Management of Bladder Cancer After Renal Transplantation.

PubMed

Demirdag, C; Citgez, S; Talat, Z; Onal, B

2017-03-01

In renal transplant recipients, the risk of developing bladder cancer and rate of diagnosis of advanced staged bladder cancer are generally higher than the general population. Also, it is more challenging to treat renal transplant recipients than the regular patient population. We aimed to evaluate the efficacy and safety of radical cystectomy (RC) and urinary diversion with ileal conduit in renal transplant recipients. We identified 2 patients with prior history of renal transplantation who underwent RC and ileal conduit urinary diversion for bladder cancer. Preoperative clinical and demographic data were presented and outcomes were assessed. The RC and ileal conduit urinary diversion were performed in the first patient 56 months after renal transplantation and in the second patient 64 months after renal transplantation. Clinical staging was high-grade T2 transitional cell cancer of the bladder for patient 1 and T2 with pure squamous cell cancer of the bladder for patient 2. No perioperative or postoperative complication and no graft dysfunction occurred in either patient. Our experience demonstrated that RC with ileal conduit reconstruction in renal transplant recipients is safe and feasible. Copyright © 2016 Elsevier Inc. All rights reserved.

Implication of androgen receptor in urinary bladder cancer: a critical mini review.

PubMed

Rahmani, Arshad H; Alzohairy, Mohammad; Babiker, Ali Yousif Y; Khan, Amjad A; Aly, Salah M; Rizvi, Moshahid A

2013-01-01

Cancer is probably the most dreaded disease of mankind and the bladder cancer is the fifth most common type of cancer worldwide. It is a major cause of cancer morbidity and mortality. From amongst the bladder cancer, the Transitional Cell Carcinoma (TCC) is the most prevalent cancer of the bladder and accounts for 90% of all bladder cancer cases. Despite such a high prevalence, the molecular mechanism involved in the induction of bladder carcinoma and its progression are poorly understood. Tumorigenesis and tumor progression of bladder carcinomas are thought to result from the accumulation of multiple genetic alterations. The Androgen Receptor (AR) gene is located on the q arm of X chromosome (q11-12) and considered as a ligand-inducible transcription factor that regulates target gene expression. The Androgen plays a vital role in the development and maintenance of the normal urinary bladder. The AR is also involved in the development and progression of urinary bladder carcinoma, which is the most common type of carcinoma. Mutation in AR alters the ligand binding ability that may cause the progression and development of bladder cancer. Tumorigenesis and tumor progression are thought to result from changes in the function of hormonal receptor gene. The accumulation of the changes in AR expressions, determines the tumor's phenotype and ultimately the patient's clinical outcome. The early detection of which may help in management and prediction, how will it behave and respond to the therapeutic regimen. The present review aimed to study the mechanism and alteration of AR gene that play a vital role in the tumorIgenesis of bladder carcinoma.

Bladder Cancer

MedlinePlus

... have an elevated risk of developing bladder cancer. Chronic bladder inflammation. Chronic or repeated urinary infections or inflammations (cystitis), ... the world, squamous cell carcinoma is linked to chronic bladder inflammation caused by the parasitic infection known as schistosomiasis. ...

Bladder Cancer Treatment (PDQ®)—Patient Version

Cancer.gov

Treatment of bladder cancer depends on the stage of the cancer. Treatment options include different types of surgery (transurethral resection, radical and partial cystectomy, and urinary diversion), radiation therapy, chemotherapy, and immunotherapy. Learn more about how bladder cancer is treated.

Microplate magnetic chemiluminescence immunoassay for detecting urinary survivin in bladder cancer.

PubMed

Chang, Yanli; Xu, Jianjun; Zhang, Qingyun

2017-10-01

Survivin is a tumor marker for bladder cancer; however the role of urinary survivin levels has not been fully elucidated due to the limitations of current detection methods. Based on two survivin-specific monoclonal antibodies (McAbs) already confirmed through enzyme linked immunosorbent assays, the present study aimed to establish a microplate magnetic chemiluminescence immunoassay (CLIA) for the detection of urinary survivin levels and evaluate its application for the diagnosis of patients with bladder cancer. Horseradish peroxidase and biotin conjugates were used to label two different anti-survivin McAbs, respectively. The labeled antibodies combined with survivin to form a sandwiched immune complex. The streptavidin magnetic particles (MPs) served as the solid phase and the separator. The relevant parameters involved in the immunoassay, including the immunoassay reagents used and the physicochemical parameters were optimized. Then, urine samples from 130 patients with bladder cancer and 113 healthy controls were detected, and analyzed using the established method. The method was linear to 1,000 ng/ml survivin with a detection limit of 0.83 ng/ml. The intra- and inter-assay coefficients of variation were <8, and <11%, respectively. The concentration of diluted survivin and the dilution ratios gave a linear correlation of 0.9989. The results demonstrated that the urinary survivin levels in patients with bladder cancer were significantly higher (P<0.001) compared with that in healthy controls. At a survivin concentration of 2.0884 ng/ml, the sensitivity and specificity were 86.9 and 61.9%, respectively. Furthermore, the urinary survivin levels were positively correlated with metastatic stage, histological stage and recurrence (P<0.01). In conclusion, the present study preliminarily proposed a microplate magnetic CLIA for survivin detection and further evaluated the value of urinary survivin as a diagnostic marker for bladder cancer.

Microplate magnetic chemiluminescence immunoassay for detecting urinary survivin in bladder cancer

PubMed Central

Chang, Yanli; Xu, Jianjun; Zhang, Qingyun

2017-01-01

Survivin is a tumor marker for bladder cancer; however the role of urinary survivin levels has not been fully elucidated due to the limitations of current detection methods. Based on two survivin-specific monoclonal antibodies (McAbs) already confirmed through enzyme linked immunosorbent assays, the present study aimed to establish a microplate magnetic chemiluminescence immunoassay (CLIA) for the detection of urinary survivin levels and evaluate its application for the diagnosis of patients with bladder cancer. Horseradish peroxidase and biotin conjugates were used to label two different anti-survivin McAbs, respectively. The labeled antibodies combined with survivin to form a sandwiched immune complex. The streptavidin magnetic particles (MPs) served as the solid phase and the separator. The relevant parameters involved in the immunoassay, including the immunoassay reagents used and the physicochemical parameters were optimized. Then, urine samples from 130 patients with bladder cancer and 113 healthy controls were detected, and analyzed using the established method. The method was linear to 1,000 ng/ml survivin with a detection limit of 0.83 ng/ml. The intra- and inter-assay coefficients of variation were <8, and <11%, respectively. The concentration of diluted survivin and the dilution ratios gave a linear correlation of 0.9989. The results demonstrated that the urinary survivin levels in patients with bladder cancer were significantly higher (P<0.001) compared with that in healthy controls. At a survivin concentration of 2.0884 ng/ml, the sensitivity and specificity were 86.9 and 61.9%, respectively. Furthermore, the urinary survivin levels were positively correlated with metastatic stage, histological stage and recurrence (P<0.01). In conclusion, the present study preliminarily proposed a microplate magnetic CLIA for survivin detection and further evaluated the value of urinary survivin as a diagnostic marker for bladder cancer. PMID:28943911

Naproxen induces cell cycle arrest and apoptosis in human urinary bladder cancer cell lines and chemically induced cancers by targeting PI3-K

PubMed Central

Kim, Mi-Sung; Kim, Jong-Eun; Lim, Do Young; Huang, Zunnan; Chen, Hanyong; Langfald, Alyssa; Lubet, Ronald A.; Grubbs, Clinton J.; Dong, Zigang; Bode, Ann M.

2014-01-01

Naproxen ((S)-6-methoxy-α-methyl-2-naphthaleneacetic acid) is a potent nonsteroidal anti-inflammatory drug that inhibits both COX-1 and COX-2 and is widely used as an over-the-counter medication. Naproxen exhibits analgesic, anti-pyretic, and anti-inflammatory activities. Naproxen, as well as other NSAIDS, has been reported to be effective in the prevention of urinary bladder cancer in rodents. However, potential targets other than the COX isozymes have not been reported. We examined potential additional targets in urinary bladder cancer cells and in rat bladder cancers. Computer kinase profiling results suggested that phosphatidylinositol 3-kinase (PI3-K) is a potential target for naproxen. In vitro kinase assay data revealed that naproxen interacts with PI3-K and inhibits its kinase activity. Pull-down binding assay data confirmed that PI3-K directly binds with naproxen in vitro and ex vivo. Western blot data showed that naproxen decreased phosphorylation of Akt, and subsequently decreased Akt signaling in UM-UC-5 and UMUC-14 urinary bladder cancer cells. Furthermore, naproxen suppressed anchorage-independent cell growth and decreased cell viability by targeting PI3-K in both cell lines. Naproxen caused an accumulation of cells at the G1 phase mediated through CDK4, cyclin D1 and p21. Moreover, naproxen induced significant apoptosis, accompanied with increased levels of cleaved caspase 3, caspase 7, and poly (ADP-ribose) polymerase (PARP) in both cell types. Naproxen-induced cell death was mainly due to apoptosis in which a prominent down-regulation of Bcl-2 and up-regulation of Bax were involved. Naproxen also caused apoptosis and inhibited Akt phosphorylation in rat urinary bladder cancers induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN). PMID:24327721

Urinary tract infections and reduced risk of bladder cancer in Los Angeles.

PubMed

Jiang, X; Castelao, J E; Groshen, S; Cortessis, V K; Shibata, D; Conti, D V; Yuan, J-M; Pike, M C; Gago-Dominguez, M

2009-03-10

We investigated the association between urinary tract infections (UTIs) and transitional cell carcinoma of the bladder in a population-based case-control study in Los Angeles covering 1586 cases and age-, gender-, and race-matched neighbourhood controls. A history of bladder infection was associated with a reduced risk of bladder cancer among women (odds ratio (OR), 0.66; 95% confidence interval (CI), 0.46-0.96). No effect was found in men, perhaps due to power limitations. A greater reduction in bladder cancer risk was observed among women with multiple infections (OR, 0.37; 95% CI, 0.18-0.78). Exclusion of subjects with a history of diabetes, kidney or bladder stones did not change the inverse association. A history of kidney infections was not associated with bladder cancer risk, but there was a weak association between a history of other UTIs and slightly increased risk among men. Our results suggest that a history of bladder infection is associated with a reduced risk of bladder cancer among women. Cytotoxicity from antibiotics commonly used to treat bladder infections is proposed as one possible explanation.

Serum Paraoxonase-1 Concentration as a Potential Predictor of Urinary Bladder Cancer Recurrence. A Five Year Follow-Up Study.

PubMed

Iftimie, Simona; García-Heredia, Anabel; Pujol-Bosch, Francesc; Pont-Salvadó, Antoni; López-Azcona, Ana Felisa; Hernández-Aguilera, Anna; Cabré, Noemí; Luciano-Mateo, Fedra; Fort-Gallifa, Isabel; Castro, Antoni; Camps, Jordi; Joven, Jorge

2018-04-23

This study provides preliminary information on the usefulness of measuring serum paraoxonase-1 (PON1) concentration and activity (and other inflammatory markers) to predict tumor recurrence in patients with urinary bladder cancer. We studied a total of 39 hospitalized patients in whom the diagnosis of urinary bladder cancer was confirmed by transurethral resection. After five years of follow-up, 29 patients presented with tumor recurrence. As control subjects, we also studied 61 healthy subjects and a further 132 hospitalized patients who had a urinary catheter-related infection due to causes other than cancer. Results showed that urinary bladder patients had lower serum PON1 concentration and activity, and higher chemokine (C-C motif) ligand 2, C-reactive protein, and procalcitonin concentrations than the control individuals. Patients with tumor recurrence had significantly lower serum PON1 concentration than patients without tumor recurrence. The mean area under the curve of the receiver operating characteristics plot for serum PON1 concentration in discriminating patients with and those without tumor recurrence was 0.755 and the best combination of sensitivity and specificity was obtained at PON1 = 100 mg/L (0.72 and 0.80, respectively). Establishing this value as a cut-off, positive predictive value was = 0.91, and negative predictive value was = 0.50. These results suggest that the measurement of serum PON1 concentration may be a high-sensitivity marker of tumor recurrence in urinary bladder cancer patients. Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.

Trends in the survival of patients diagnosed with kidney or urinary bladder cancer in the Nordic countries 1964-2003 followed up to the end of 2006.

PubMed

Engholm, Gerda; Hakulinen, Timo; Gislum, Mette; Tryggvadóttir, Laufey; Klint, Asa; Bray, Freddie; Storm, Hans H

2010-06-01

Previous studies have shown systematic differences between the Nordic Countries in population-based relative survival following a kidney or urinary bladder cancer diagnosis. Comparison of bladder cancer over time and between Nordic registries is complicated by variable coding practices with respect to the inclusion of in situ cases with invasive tumours. Five-year relative survival of patients with urinary cancer diagnosed in the Nordic countries 1964-2003 and followed up for death through 2006 was studied and contrasted with developments in incidence and mortality. The survival following bladder cancer was higher than for kidney cancer and highest for men. Survival increased over the years in all countries, more for kidney cancer than bladder cancer. For Danish kidney cancer patients, the rate of increase over all the years has been lower than in the other countries, especially among women, resulting in a survival in Denmark some 10-20% points lower than elsewhere in 1999-2003. Danish bladder cancer patient survival was in the last period 4% points lower among men and 10% points lower among women than in the other Nordic countries. The differences were mainly found in the first year following diagnosis, where a higher excess mortality in Denmark was observed. Survival decreased with higher age at diagnosis. The increasing 5-year relative survival in all the Nordic countries for both kidney and bladder cancer are promising, but for kidney cancer a higher percentage detected coincidentally during an imaging investigation for other diseases could play a role. Denmark had the lowest survival, despite their known practice of including benign conditions with invasive bladder cancers. The lower Danish survival after kidney and bladder cancer in the first year after diagnosis could be due to later diagnosis on average, a higher co-morbidity from smoking-related diseases, and perhaps, less adequate cancer treatment and management in Denmark.

Profiling the Urinary Microbiota in Male Patients With Bladder Cancer in China

PubMed Central

Wu, Peng; Zhang, Guihao; Zhao, Jie; Chen, Jiawei; Chen, Yang; Huang, Weina; Zhong, Jialei; Zeng, Jiarong

2018-01-01

Mounting evidence indicates that microbiome plays an important role in the development and progression of cancer. The dogma that urine in healthy individuals must be sterile has been overturned. Dysbiosis of the urinary microbiome has been revealed responsible for various urological disorders, including prostate cancer. The link between chronic inflammation, microbiome and solid tumors has been established for various neoplastic diseases. However, a detailed and comprehensive analysis of urinary microenvironment of bladder cancer has not been yet reported. We performed this study to characterize the potential urinary microbial community possibly associated with bladder cancer. Mid-stream urine was collected from 31 male patients with bladder cancer and 18 non-neoplastic controls. DNA was extracted from urine pellet samples and processed for high throughput 16S rRNA amplicon sequencing of the V4 region using Illumina MiSeq. Sequencing reads were filtered using QIIME and clustered using UPARSE. We observed increased bacterial richness (Observed Species, Chao 1 and Ace indexes; cancer vs. control; 120.0 vs. 56.0; 134.5 vs. 68.3; and 139.6 vs. 72.9, respectively), enrichment of some bacterial genera (e.g., Acinetobacter, Anaerococcus, and Sphingobacterium) and decrease of some bacterial genera (e.g., Serratia, Proteus, and Roseomonas) in cancer group when compared to non-cancer group. Significant difference in beta diversity was found between cancer and non-cancer group, among different risk level, but not among different tumor grade. Enrichment of Herbaspirillum, Porphyrobacter, and Bacteroides was observed in cancer patients with high risk of recurrence and progression, which means these genera maybe potential biomarkers for risk stratification. The PICRUSt showed that various functional pathways were enriched in cancer group, including Staphylococcus aureus infection, glycerolipid metabolism and retinol metabolism. To our knowledge, we performed the most comprehensive study to date to characterize the urinary microbiome associated with bladder cancer. A better understanding of the role of microbiome in the development and progression of bladder cancer could pave a new way for exploring new therapeutic options and biomarkers. PMID:29904624

Profiling the Urinary Microbiota in Male Patients With Bladder Cancer in China.

PubMed

Wu, Peng; Zhang, Guihao; Zhao, Jie; Chen, Jiawei; Chen, Yang; Huang, Weina; Zhong, Jialei; Zeng, Jiarong

2018-01-01

Mounting evidence indicates that microbiome plays an important role in the development and progression of cancer. The dogma that urine in healthy individuals must be sterile has been overturned. Dysbiosis of the urinary microbiome has been revealed responsible for various urological disorders, including prostate cancer. The link between chronic inflammation, microbiome and solid tumors has been established for various neoplastic diseases. However, a detailed and comprehensive analysis of urinary microenvironment of bladder cancer has not been yet reported. We performed this study to characterize the potential urinary microbial community possibly associated with bladder cancer. Mid-stream urine was collected from 31 male patients with bladder cancer and 18 non-neoplastic controls. DNA was extracted from urine pellet samples and processed for high throughput 16S rRNA amplicon sequencing of the V4 region using Illumina MiSeq. Sequencing reads were filtered using QIIME and clustered using UPARSE. We observed increased bacterial richness (Observed Species, Chao 1 and Ace indexes; cancer vs. control; 120.0 vs. 56.0; 134.5 vs. 68.3; and 139.6 vs. 72.9, respectively), enrichment of some bacterial genera (e.g., Acinetobacter, Anaerococcus, and Sphingobacterium ) and decrease of some bacterial genera (e.g., Serratia, Proteus , and Roseomonas ) in cancer group when compared to non-cancer group. Significant difference in beta diversity was found between cancer and non-cancer group, among different risk level, but not among different tumor grade. Enrichment of Herbaspirillum, Porphyrobacter , and Bacteroides was observed in cancer patients with high risk of recurrence and progression, which means these genera maybe potential biomarkers for risk stratification. The PICRUSt showed that various functional pathways were enriched in cancer group, including Staphylococcus aureus infection, glycerolipid metabolism and retinol metabolism. To our knowledge, we performed the most comprehensive study to date to characterize the urinary microbiome associated with bladder cancer. A better understanding of the role of microbiome in the development and progression of bladder cancer could pave a new way for exploring new therapeutic options and biomarkers.

UroMark-a urinary biomarker assay for the detection of bladder cancer.

PubMed

Feber, Andrew; Dhami, Pawan; Dong, Liqin; de Winter, Patricia; Tan, Wei Shen; Martínez-Fernández, Mónica; Paul, Dirk S; Hynes-Allen, Antony; Rezaee, Sheida; Gurung, Pratik; Rodney, Simon; Mehmood, Ahmed; Villacampa, Felipe; de la Rosa, Federico; Jameson, Charles; Cheng, Kar Keung; Zeegers, Maurice P; Bryan, Richard T; James, Nicholas D; Paramio, Jesus M; Freeman, Alex; Beck, Stephan; Kelly, John D

2017-01-01

Bladder cancer (BC) is one of the most common cancers in the western world and ranks as the most expensive to manage, due to the need for cystoscopic examination. BC shows frequent changes in DNA methylation, and several studies have shown the potential utility of urinary biomarkers by detecting epigenetic alterations in voided urine. The aim of this study is to develop a targeted bisulfite next-generation sequencing assay to diagnose BC from urine with high sensitivity and specificity. We defined a 150 CpG loci biomarker panel from a cohort of 86 muscle-invasive bladder cancers and 30 normal urothelium. Based on this panel, we developed the UroMark assay, a next-generation bisulphite sequencing assay and analysis pipeline for the detection of bladder cancer from urinary sediment DNA. The 150 loci UroMark assay was validated in an independent cohort ( n  = 274, non-cancer ( n  = 167) and bladder cancer ( n  = 107)) voided urine samples with an AUC of 97%. The UroMark classifier sensitivity of 98%, specificity of 97% and NPV of 97% for the detection of primary BC was compared to non-BC urine. Epigenetic urinary biomarkers for detection of BC have the potential to revolutionise the management of this disease. In this proof of concept study, we show the development and utility of a novel high-throughput, next-generation sequencing-based biomarker for the detection of BC-specific epigenetic alterations in urine.

Potential role of melastatin-related transient receptor potential cation channel subfamily M gene expression in the pathogenesis of urinary bladder cancer.

PubMed

Ceylan, Gülay Güleç; Önalan, Ebru Etem; Kuloğlu, Tuncay; Aydoğ, Gülten; Keleş, İbrahim; Tonyali, Şenol; Ceylan, Cavit

2016-12-01

Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities. The present study included a total of 47 subjects, of whom 40 were bladder cancer patients and 7 were controls. Following the histopathological evaluation for bladder carcinoma, the mRNA and protein expression of TRPM were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in tumor and normal tissues, in order to determine whether there is a difference in the expression of these channels in tumor and normal tissues. Immunoreactivity for TRPM2, TRPM4, TRPM7 and TRPM8 was observed in epithelial bladder cells in the two groups. RT-qPCR revealed a significant increase in TRPM7 expression in bladder cancer tissue compared to the controls (healthy bladder tissue), whereas no differences in TRPM2 or TRPM4 expression levels were observed. There were significant reductions in the expression levels of TRPM5 and TRPM8 in bladder cancer tissues. In the present study, the effects of TRP ion channels on the formation of bladder cancer was investigated. This study is instructive for TRPM2, TRPM4, TRPM5, TRPM7 and TRPM8 and their therapeutic role in bladder cancer. The results support the fact that these gens can be novel targets and can also be tested for during the treatment of bladder cancer.

Fluorescent imaging of high-grade bladder cancer using a specific antagonist for chemokine receptor CXCR4.

PubMed

Nishizawa, Koji; Nishiyama, Hiroyuki; Oishi, Shinya; Tanahara, Noriko; Kotani, Hirokazu; Mikami, Yoshiki; Toda, Yoshinobu; Evans, Barry J; Peiper, Stephen C; Saito, Ryoichi; Watanabe, Jun; Fujii, Nobutaka; Ogawa, Osamu

2010-09-01

We previously reported that the expression of CXC chemokine receptor-4 (CXCR4) was upregulated in invasive bladder cancers and that the small peptide T140 was a highly sensitive antagonist for CXCR4. In this study, we identified that CXCR4 expression was induced in high-grade superficial bladder tumors, including carcinoma in situ and invasive bladder tumors. To visualize the bladder cancer cells using urinary sediments from the patients and chemically induced mouse bladder cancer model, a novel fluorescent CXCR4 antagonist TY14003 was developed, that is a T140 derivative. TY14003 could label bladder cancer cell lines expressing CXCR4, whereas negative-control fluorescent peptides did not label them. When labeling urinary sediments from patients with invasive bladder cancer, positive-stained cells were identified in all patients with bladder cancer and positive urine cytology but not in controls. Although white blood cells in urine were also labeled with TY14003, they could be easily discriminated from urothelial cells by their shape and size. Finally, intravesical instillation of TY14003 into mouse bladder, using N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder cancer model, demonstrated that fluorescent signals were detected in the focal areas of bladder of all mice examined at 12 weeks of BBN drinking by confocal microscopy and fluorescent endoscopy. On the contrary, all the normal bladders were found to be negative for TY14003 staining. In conclusion, these results indicate that TY14003 is a promising diagnostic tool to visualize small or flat high-grade superficial bladder cancer.

IDENTIFICATION OF INTERSPECIES CONCORDANCE OF MECHANISMS OF ARSENIC INDUCED BLADDER CANCER BY GENE EXPRESSION.

EPA Science Inventory

Arsenic is a human carcinogen that induces urinary bladder cancer. Several mechanisms have been proposed for arsenic-induced cancer. Although inorganic arsenic (iAs) does not induce tumors in adult rodents, dimethylarsinic acid (DMA), a major metabolite of iAs, is a rat bladder c...

Clinical significance of serum and urinary HER2/neu protein levels in primary non-muscle invasive bladder cancer.

PubMed

Arikan, Ozgur; Yýldýrým, Asýf; Ýsbilen, Banu; Canakci, Cengiz; Atýs, Gokhan; Gurbuz, Cenk; Erol, Bulent; Ýsman, Ferruh Kemal; Ozkanli, Seyma; Caskurlu, Turhan

2015-01-01

We aimed to compare serum and urinary HER2/neu levels between healthy control group and patients with non-muscle invasive bladder cancer. Additionally, we evaluated relationship of HER2/neu levels with tumor stage, grade, recurrence and progression. Fourty-four patients with primary non-muscle invasive bladder tumors (Group 2) and 40 healthy control group (Group 1) were included the study. Blood and urinary samples were collected from all patients and HER2/neu levels were measured by ELISA method. Blood and urinary HER2/neu levels and additionally, ratio of urinary HER2/neu levels to urinary creatinine levels were recorded. Demographic data and tumor characteristics were recorded. Mean serum HER2/neu levels were similar between two groups and statistically significant difference wasn't observed. Urinary HER2/neu levels were significantly higher in group 2 than group 1. Ratio of urinary HER2/neu to urinary creatinine was significantly higher in group 2 than group 1, (p=0,021). Serum and urinary HER2/ neu levels were not associated with tumor stage, grade, recurrence and progression while ratio of urinary HER2/neu to urinary creatinin levels were significantly higher in high-grade tumors. HER2/neu, the sensitivity of the test was found to be 20.5%, and the specificity was 97.5%, also for the urinary HER2/neu/urinary creatinine ratio, the sensitivity and specificity of the test were found to be 31.8% and 87.5%, respectively. Urinary HER2/neu and ratio of urinary creatinine urine were significantly higher in patients with bladder cancer compared to healthy subjects. Large series and controlled studies are needed for use as a tumor marker.

Research progress on bladder cancer molecular genetics.

PubMed

Kang, Zhengjun; Li, Yuhui; Yu, Yang; Guo, Zhan

2014-11-01

Bladder cancer is a common malignant urinary tumor with a high rate of recurrence and quick progression, which threats human health. With the research on bladder cancer molecular genetics, the knowledge of gene modification and the development of molecular detection methods, more tumor markers have been discovered, which may have potential for early diagnosis, clinical examination and prognosis. This article reviews the research progress on bladder cancer molecular genetics.

The role of micronutrients in the risk of urinary tract cancer

PubMed Central

Bukowczan, Jakub; Sobczynski, Robert; Leszczyszyn, Jaroslaw; Chlosta, Piotr L.

2016-01-01

Prostate, bladder and kidney cancers remain the most common urological malignancies worldwide, and the prevention and treatment of these diseases pose a challenge to clinicians. In recent decades, many studies have been conducted to assess the association between supplementation with selected vitamins and elements and urinary tract tumour initiation and development. Here, we review the relationship between vitamins A, B, D, and E, in addition to calcium, selenium, and zinc, and the risk of developing prostate, kidney and bladder cancer. A relatively consistent body of evidence suggests that large daily doses of calcium (> 2,000 mg/day) increase the risk of prostate cancer. Similarly, supplementation with 400 IU/day of vitamin E carries a significant risk of prostate cancer. However, there have been many conflicting results regarding the effect of these nutrients on kidney and bladder neoplasms. Moreover, the role of other compounds in urinary tract carcinogenesis needs further clarification. PMID:27186192

INDUCTION OF TRANSTITIONAL CELL HYPERPLASIA IN THE URINARY BLADDER AND ABERRANT CRYPT FOCI IN THE COLON OF RATS TREATED WITH INDIVIDUAL AND A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS

EPA Science Inventory

ABSTRACT

Cancer of the urinary bladder and colon are significant human health concerns. Epidemiological studies have suggested a correlation between these cancers and the chronic consumption of drinking water containing disinfection by-products (DBPs). The present study...

Urinary bladder: normal appearance and mimics of malignancy at CT urography

PubMed Central

Sadow, Cheryl A.; Anik Sahni, V.; Silverman, Stuart G.

2011-01-01

Abstract The objective of this review article is to learn how to recognize anatomic variants and benign entities that mimic bladder cancer at computed tomography (CT) urography. Building on recent data that suggest that CT urography can be used to diagnose bladder cancer, recognition of anatomic variants and benign entities will help improve radiologists’ ability to diagnose bladder cancer. PMID:21771710

Case report of metastatic invasive breast lobular carcinoma to the urinary bladder.

PubMed

Al Ibraheemi, Ahmed A

2016-01-01

Breast cancer is the most common cancer in women except skin cancer. The common metastatic sites include lymph node, lung, liver and bone. However, metastasis to the bladder is extremely rare. To our knowledge, this is the first case of breast cancer metastasis to urinary bladder in Jordan which is reported. Nine years after the initial diagnosis of lobular breast carcinoma, the patient suffered from left side leg edema; Ultrasonography and Computed tomography scanning showed thickening of posterior bladder wall and bilateral hydronephrosis. The biopsy of the bladder confirmed metastatic lesion from the breast. In contrast to the primary tumor, bladder metastasis showed negative expression of estrogen (ER) and progesterone (PR) receptors. However, Her2neu test was negative in both. The reported case confirms that bladder metastasis from breast cancer tend to occur late after the diagnosis of the primary tumor. Furthermore, bladder metastasis can be asymptomatic and heterogeneous in ER and PR expression in comparison with the primary tumor. This report supports the need for careful follow-up and early intervention whenever such clinical situation is suspected. This report supports further evaluation of receptor status at time of metastasis.

Enhanced inhibition of urinary bladder cancer growth and muscle invasion by allyl isothiocyanate and celecoxib in combination

PubMed Central

Zhang, Yuesheng

2013-01-01

Allyl isothiocyanate (AITC) occurs in cruciferous vegetables that are commonly consumed by humans and has been shown to inhibit urinary bladder cancer growth and progression in previous preclinical studies. However, AITC does not significantly modulate cyclooxygenase-2 (Cox-2), whose oncogenic activity has been well documented in bladder cancer and other cancers. Celecoxib is a selective Cox-2 inhibitor and has been widely used for treatment of several diseases. Celecoxib has also been evaluated in bladder cancer patients, but its efficacy against bladder cancer as a single agent remains unclear. In a syngeneic rat model of orthotopic bladder cancer, treatment of the animals with the combination of AITC and celecoxib at low dose levels (AITC at 1mg/kg and celecoxib at 10mg/kg) led to increased or perhaps synergistic inhibition of bladder cancer growth and muscle invasion, compared with each agent used alone. The combination regime was also more effective than each single agent in inhibiting microvessel formation and stimulating microvessel maturation in the tumor tissues. The anticancer efficacy of the combination regime was associated with depletion of prostaglandin E2, a key downstream signaling molecule of Cox-2, caspase activation and downregulation of vascular endothelial growth factor in the tumor tissues. These data show that AITC and celecoxib complement each other for inhibition of bladder cancer and provide a novel combination approach for potential use for prevention or treatment of human bladder cancer. PMID:23946495

Clinical characteristics of bladder cancer in patients with spinal cord injury: the experience from a single centre.

PubMed

Böthig, Ralf; Kurze, Ines; Fiebag, Kai; Kaufmann, Albert; Schöps, Wolfgang; Kadhum, Thura; Zellner, Michael; Golka, Klaus

2017-06-01

Life expectancy for people with spinal cord injury has shown a marked increase due to modern advances in treatment methods and in neuro-urology. However, since life expectancy of people with paralysis increases, the risk of developing of urinary bladder cancer is gaining importance. Single-centre retrospective evaluation of patient data with spinal cord injuries and proven urinary bladder cancer and summary of the literature. Between 1998 and 2014, 24 (3 female, 21 male) out of a total of 6599 patients with spinal cord injury were diagnosed with bladder cancer. The average age at bladder cancer diagnosis was 57.67 years, which is well below the average for bladder cancer cases in the general population (male: 73, female: 77). All but one patient had a latency period between the onset of the spinal paralysis and tumour diagnosis of more than 10 years. The median latency was 29.83 years. The median survival for these patients was 11.5 months. Of the 24 patients, 19 (79%) had muscle invasive bladder cancer at ≥T2 at the time of diagnosis. The type of neurogenic bladder (neurogenic detrusor overactivity or acontractility) and the form of bladder drainage do not appear to influence the risk. Long-term indwelling catheter drainage played only a minor role in the investigated patients. The significantly younger age at onset and the frequency of invasive tumours at diagnosis indicate that spinal cord injury influences bladder cancer risk and prognosis as well. Early detection of bladder cancer in patients with spinal cord injury remains a challenge.

Serial urinary IL-2, IL-6, IL-8, TNFalpha, UBC, CYFRA 21-1 and NMP22 during follow-up of patients with bladder cancer receiving intravesical BCG.

PubMed

Sanchez-Carbayo, M; Urrutia, M; Romani, R; Herrero, M; Gonzalez de Buitrago, J M; Navajo, J A

2001-01-01

We evaluated the potential role of serial preinstillation levels of several interleukins, TNFalpha and urinary tumor markers to monitor patients with bladder cancer receiving intravesical BCG. 121 urine samples were collected from: patients with bladder cancer treated with BCG (group 1); patients with bladder cancer receiving other intravesical treatment (group 2) and patients with urinary tract infections (group 3). Cytokines [IL-2, IL6 and [L8] and TNFalpha and urinary tumor markers [UBC, CYFRA 21-1 and NMP22] were measured by immunoassays. In 3 out of 15 BCG non-responders that recurred over the period of the study, no cytokine peak for IL-2, IL-6 or TNFa were detected. Urinary tumor markers increased in 2 out of 3 of these patients earlier than scheduled cystoscopies. Cytokine measurement was heterogeneous among 12 out of 15 BCG-responding patients: there were low levels of IL-6 and TNFalpha and peaks of IL-2 and IL-8 in 10 out of 12 and 4 out of 12 patients, respectively. During responding patients' follow-up we observed false-positive results in 7 out of 65 urine samples for UBC, 8 out of 65 for CYFRA 21-1 and 20 out of 65 for NMP22. Urinary tract infections were the main factor associated with non-specific elevations of IL-6 and IL-8 and urinary tumor markers in all groups of patients. Although larger series are required to confirn our preliminary observations, our data argue for a potential predictive role for IL-2 of favourable response to BCG therapy. Monitoring BCG with urinary tumor markers could early detect recurrence in non-responding patients.

Receptor-targeted therapy of human experimental urinary bladder cancers with cytotoxic LH-RH analog AN-152 [AEZS- 108].

PubMed

Szepeshazi, Karoly; Schally, Andrew V; Keller, Gunhild; Block, Norman L; Benten, Daniel; Halmos, Gabor; Szalontay, Luca; Vidaurre, Irving; Jaszberenyi, Miklos; Rick, Ferenc G

2012-07-01

Many bladder cancers progress to invasion with poor prognosis; new therapeutic methods are needed. We developed a cytotoxic LH-RH analog, AN-152 (AEZS-108) containing doxorubicin (DOX), for targeted therapy of cancers expressing LHRH receptors. We investigated the expression of LH-RH receptors in clinical bladder cancers and in HT-1376, J82, RT-4 and HT-1197 human bladder cancer lines. The effect of analog, AN-152, on growth of these tumor lines xenografted into nude mice was analyzed. Using molecular and functional assays, we also evaluated the differences between the effects of AN-152, and DOX alone. We demonstrated the expression of LH-RH receptors on 18 clinical bladder cancers by immunohistochemistry and on four human urinary bladder cancer lines HT-1376, J82, RT-4 and HT-1197 by Western blotting and binding assays. AN-152 powerfully inhibited growth of these bladder cancers in nude mice. AN-152 exerted greater effects than DOX and was less toxic. DOX activated strong multidrug resistance mechanisms in RT-4 and HT-1197 cancers, while AN-152 had no or less such effect. PCR assays and in vitro studies revealed differences in the action of AN-152 and DOX on the expression of genes involved in apoptosis. These results suggest that targeted cytotoxic LH-RH analog, AN-152 (AEZS- 108), should be examined for treatment of patients with LH-RH receptor positive invasive bladder cancers.

Biomarker in Cisplatin-Based Chemotherapy for Urinary Bladder Cancer.

PubMed

Ecke, Thorsten H

2015-01-01

The treatment of metastasized bladder cancer has been evolving during recent years. Cisplatin based chemotherapy combinations are still gold standard in the treatment of advanced and metastasized bladder cancer. But new therapies are approaching. Based to this fact biological markers will become more important for decisions in bladder cancer treatment. A systematic MEDLINE search of the key words "cisplatin", "bladder cancer", "DNA marker", "protein marker", "methylation biomarker", "predictive marker", "prognostic marker" has been made. This review aims to highlight the most relevant clinical and experimental studies investigating markers for metastasized transitional carcinoma of the urothelium treated by cisplatin based regimens.

A Randomized Pilot Trial of Dietary Modification for the Chemoprevention of Non-invasive Bladder Cancer: The Dietary Intervention in Bladder Cancer Study (DIBS)

PubMed Central

Parsons, J. Kellogg; Pierce, John P.; Natarajan, Loki; Newman, Vicky A.; Barbier, Leslie; Mohler, James; Rock, Cheryl L.; Heath, Dennis D.; Guru, Khurshid; Jameson, Michael B.; Li, Hongying; Mirheydar, Hossein; Holmes, Michael A.; Marshall, James

2013-01-01

Epidemiological data suggest robust associations of high vegetable intake with decreased risks of bladder cancer incidence and mortality, but translational prevention studies have yet to be performed. We designed and tested a novel intervention to increase vegetable intake in patients with non-invasive bladder cancer. We randomized 48 patients aged 50 to 80 years with biopsy-proven non-invasive (Ta, T1, or carcinoma in situ) urothelial cell carcinoma to telephone- and Skype-based dietary counseling or a control condition that provided print materials only. The intervention behavioral goals promoted 7 daily vegetable servings, with at least 2 of these as cruciferous vegetables. Outcome variables were self-reported diet and plasma carotenoid and 24-hour urinary isothiocyanate (ITC) concentrations. We used 2-sample t-tests to assess between-group differences at 6-month follow-up. After 6 months, intervention patients had higher daily intakes of vegetable juice (p=0.02), total vegetables (p=0.02), and cruciferous vegetables (p=0.07); lower daily intakes of energy (p=0.007), (p=0.002) and energy from fat (p=0.06); and higher plasma alpha-carotene concentrations (p=0.03). Self-reported cruciferous vegetable intake correlated with urinary ITC concentrations at baseline (p<0.001) and at 6 months (p=0.03). Although urinary ITC concentrations increased in the intervention group and decreased in the control group, these changes did not attain between-group significance (p=0.32). In patients with non-invasive bladder cancer, our novel intervention induced diet changes associated with protective effects against bladder cancer. These data demonstrate the feasibility of implementing therapeutic dietary modifications to prevent recurrent and progressive bladder cancer. PMID:23867158

In vivo fluorescence imaging of an orthotopic rat bladder tumor model indicates differential uptake of intravesically instilled near-infrared labeled 2-deoxyglucose analog by neoplastic urinary bladder tissues

NASA Astrophysics Data System (ADS)

Piao, Daqing; Davis, Carole A.; Hurst, Robert E.; Slaton, Joel W.

2017-02-01

Bladder cancer is one of the most expensive cancers to manage due to frequent recurrences requiring life-long surveillance and treatment. A near-infrared labeled 2-deoxy-d-glucose probe IRDye800CW-DG targeting glucose metabolism pathway has shown to enhance the sensitivity of diagnosing several types of cancers as tested on tumor models not including bladder tumor. This pilot study has explored differential uptake of intravesically administered IRDye800CW-DG in an orthotopic rat bladder tumor model. Twenty-five female Fischer rats were randomly grouped to four conditions: no-tumor-control (n=3), no-tumor-control intravesically instilled with IRDye800CWDG (n=6), rats bearing GFP-labeled AY-27 rat bladder urothelial cell carcinoma cells and washed with saline (n=5), and rats bearing AY-27 tumors and intravesically instilled with IRDye800CW-DG (n=11). Near-infrared fluorescence was measured from the opened bladder wall of anesthetized rat at an excitation wavelength of 750nm and an emission wavelength of 776nm, by using an in-house fluorescence imaging system. There is no statistically significant difference of the peak fluorescence intensity among the no-tumor-control bladders (n=3), the no-tumorcontrol bladders instilled with IRDye800CW-DG (n=6), and the GFP-labeled AY-27 treated bladders washed by saline (n=5). When compared to that of the no-tumor-control bladders instilled with IRDye800CW-DG (n=6), the fluorescence intensity of GFP-labeled AY-27 treated bladders instilled with IRDye800CW-DG and with histology confirmed neoplastic bladder tissue (n=11) was remarkably more intense (3.34 fold of over the former) and was also statistically significant (p<0.0001). The differential uptake of IRDye800CW-DG by the neoplastic urinary bladder tissues suggests the potential for cystoscopy-adaptation to enhance diagnosis and guiding surgical management of flat urinary bladder cancer.

Developing an Instrument to Measure Socioeconomic Disparities in Quality of Care for Men with Early-Stage Prostate Cancer

DTIC Science & Technology

2011-09-01

Cystorrhaphy, suture of bladder wound), 52332 (Insertion of ureteral stent ) Diagnosis of urinary incontinence: ICD-9: 599.82 (Intrinsic...first outcome measure we will investigate will be urinary side effects of prostate cancer treatment. Because urinary continence and urinary side...initial findings have been quite striking. Most patients who undergo treatment for prostate cancer are diagnosed with some type of urinary

Gemcitabine Hydrochloride and Cisplatin With or Without Bevacizumab in Treating Patients With Advanced Urinary Tract Cancer

ClinicalTrials.gov

2018-06-11

Bladder Urothelial Carcinoma; Distal Urethral Carcinoma; Infiltrating Bladder Urothelial Carcinoma Associated With Urethral Carcinoma; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Proximal Urethral Carcinoma; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urethral Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Regional Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer AJCC v7; Stage IV Prostate Cancer AJCC v7; Stage IV Urethral Cancer AJCC v7; Ureter Carcinoma

Management of bladder neck stenosis and urethral stricture and stenosis following treatment for prostate cancer.

PubMed

Nicholson, Helen L; Al-Hakeem, Yasser; Maldonado, Javier J; Tse, Vincent

2017-07-01

The aim of this review is to examine all urethral strictures and stenoses subsequent to treatment for prostate cancer, including radical prostatectomy (RP), radiotherapy, high intensity focused ultrasound (HIFU) and cryotherapy. The overall majority respond to endoscopic treatment, including dilatation, direct visual internal urethrotomy (DVIU) or bladder neck incision (BNI). There are adjunct treatments to endoscopic management, including injections of corticosteroids and mitomycin C (MMC) and urethral stents, which remain controversial and are not currently mainstay of treatment. Recalcitrant strictures are most commonly managed with urethroplasty, while recalcitrant stenosis is relatively rare yet almost always associated with bothersome urinary incontinence, requiring bladder neck reconstruction and subsequent artificial urinary sphincter (AUS) implantation, or urinary diversion for the devastated outlet.

Management of bladder neck stenosis and urethral stricture and stenosis following treatment for prostate cancer

PubMed Central

Nicholson, Helen L.; Al-Hakeem, Yasser; Maldonado, Javier J.

2017-01-01

The aim of this review is to examine all urethral strictures and stenoses subsequent to treatment for prostate cancer, including radical prostatectomy (RP), radiotherapy, high intensity focused ultrasound (HIFU) and cryotherapy. The overall majority respond to endoscopic treatment, including dilatation, direct visual internal urethrotomy (DVIU) or bladder neck incision (BNI). There are adjunct treatments to endoscopic management, including injections of corticosteroids and mitomycin C (MMC) and urethral stents, which remain controversial and are not currently mainstay of treatment. Recalcitrant strictures are most commonly managed with urethroplasty, while recalcitrant stenosis is relatively rare yet almost always associated with bothersome urinary incontinence, requiring bladder neck reconstruction and subsequent artificial urinary sphincter (AUS) implantation, or urinary diversion for the devastated outlet. PMID:28791228

Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe).

PubMed

Häggström, Christel; Liedberg, Fredrik; Hagberg, Oskar; Aljabery, Firas; Ströck, Viveka; Hosseini, Abolfazl; Gårdmark, Truls; Sherif, Amir; Malmström, Per-Uno; Garmo, Hans; Jahnson, Staffan; Holmberg, Lars

2017-09-27

To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe). The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death. Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival. The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding author. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Prevention of chemically induced urinary bladder cancers by naproxen: protocols to reduce gastric toxicity in humans do not alter preventive efficacy.

PubMed

Lubet, Ronald A; Scheiman, James M; Bode, Ann; White, Jonathan; Minasian, Lori; Juliana, M Margaret; Boring, Daniel L; Steele, Vernon E; Grubbs, Clinton J

2015-04-01

The COX inhibitors (NSAID/Coxibs) are a major focus for the chemoprevention of cancer. The COX-2-specific inhibitors have progressed to clinical trials and have shown preventive efficacy in colon and skin cancers. However, they have significant adverse cardiovascular effects. Certain NSAIDs (e.g., naproxen) have a good cardiac profile, but can cause gastric toxicity. The present study examined protocols to reduce this toxicity of naproxen. Female Fischer-344 rats were treated weekly with the urinary bladder-specific carcinogen hydroxybutyl(butyl)nitrosamine (OH-BBN) for 8 weeks. Rats were dosed daily with NPX (40 mg/kg body weight/day, gavage) or with the proton pump inhibitor omeprazole (4.0 mg/kg body weight/day) either singly or in combination beginning 2 weeks after the final OH-BBN. OH-BBN-treated rats, 96% developed urinary bladder cancers. While omeprazole alone was ineffective (97% cancers), naproxen alone or combined with omeprazole-prevented cancers, yielding 27 and 35% cancers, respectively. In a separate study, OH-BBN -: treated rats were administered naproxen: (A) daily, (B) 1 week daily naproxen/1week vehicle, (C) 3 weeks daily naproxen/3 week vehicle, or (D) daily vehicle beginning 2 weeks after last OH-BBN treatment. In the intermittent dosing study, protocol A, B, C, and D resulted in palpable cancers in 27%, 22%, 19%, and 96% of rats (P < 0.01). Short-term naproxen treatment increased apoptosis, but did not alter proliferation in the urinary bladder cancers. Two different protocols that should decrease the gastric toxicity of NSAIDs in humans did not alter chemopreventive efficacy. This should encourage the use of NSAIDs (e.g., naproxen) in clinical prevention trials. ©2015 American Association for Cancer Research.

CHEMOPREVENTIVE EFFICACY OF NAPROXEN AND NO-NAPROXEN IN RODENT MODELS OF COLON, URINARY BLADDER, AND MAMMARY CANCERS

PubMed Central

Steele, Vernon E.; Rao, Chinthalapally V.; Zhang, Yuting; Patlolla, Jagan; Boring, Daniel; Kopelovich, Levy; Juliana, M. Margaret; Grubbs, Clinton J.; Lubet, Ronald A.

2009-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been highly effective in preventing colon, urinary bladder, and skin cancer preclinically; and also in clinical trials of colon adenoma formation. However, certain NSAIDs cause gastrointestinal (GI) ulceration and may increase cardiovascular (CV) events. Naproxen appears to cause the lowest CV events of the common NSAIDs other than aspirin. NO-naproxen was tested based on the finding that adding a nitric oxide (NO) group to NSAIDs may help alleviate GI toxicity. In the azoxymethane (AOM)-induced rat colon aberrant crypt foci (ACF) model, naproxen administered at 200 and 400 ppm in the diet reduced mean ACFs in the colon by about 45–60%, respectively. NO-naproxen was likewise administered in the diet at roughly equimolar doses (300 and 600 ppm), and reduced total ACF by 20–40%, respectively. In the hydroxybutyl (butyl) nitrosamine (OH-BBN) rat urinary bladder cancer model, NO-naproxen was given at 183 ppm or 550 ppm in the diet, and naproxen at 128 ppm. The NO-naproxen groups had 77% and 73% decreases, respectively, in the development of large urinary bladder tumors, while the 128 ppm naproxen group also showed a strong decrease (69%). If treatments were started three months after OH-BBN, NO-naproxen (550 ppm) and naproxen (400 ppm) were also highly effective (86–94% decreases). In the methylnitrosourea (MNU)-induced mammary cancer model in rats, NO-naproxen and naproxen showed non-significant inhibitions (12 and 24%) at 550 and 400 ppm, respectively. These data show that both naproxen and NO-naproxen are effective agents against urinary bladder and colon, but not mammary, carcinogenesis. PMID:19892664

Prompt diagnosis key in bladder cancer.

PubMed

DeSouza, Karen; Chowdhury, Simon; Hughes, Simon

2014-01-01

Bladder cancer is the most frequently diagnosed cancer involving the urinary tract and is the seventh most common cancer in the UK. Delayed diagnosis is associated with high-grade muscle invasive disease which has the potential to progress rapidly, metastasise and is often fatal. Urothelial cancer (transitional cell carcinoma) is the predominant histological subtype in Europe, where it accounts for 90% of all bladder cancers. Haematuria, which is typically intermittent, frank, painless and at times present throughout micturition, is the classical and most common presentation of bladder cancer. However, irritative symptoms such as dysuria, urgency, urge incontinence and frequency as well as obstructive symptoms can also be experienced. Fatigue; weight loss; anorexia; renal failure; respiratory symptoms and a suprapubic palpable mass are usually signs of advanced or metastatic malignancy. Cigarette smokers have up to four times the risk of bladder cancer compared with non-smokers. Other risk factors include: exposure to aniline dyes; use of cyclophosphamide; history of pelvic radiation; exposure to chemical carcinogens associated with certain industries; spinal cord injuries requiring long-term indwelling catheters; type 2 diabetes treated with pioglitazone and condylomata acuminata. Frank haematuria has a high diagnostic yield for malignancies involving the urinary tract and initial routine tests should be directed towards identifying a variety of potential non-malignant causes. A thorough physical examination should be undertaken to identify evidence of bleeding diathesis and metastatic malignancy. Suggested laboratory investigations include FBC, coagulation, creatinine and PSA. The diagnosis of bladder cancer is based on urine cytology, cystoscopy and pathological assessment of the bladder biopsy.

New genetic variants of LATS1 detected in urinary bladder and colon cancer.

PubMed

Saadeldin, Mona K; Shawer, Heba; Mostafa, Ahmed; Kassem, Neemat M; Amleh, Asma; Siam, Rania

2014-01-01

LATS1, the large tumor suppressor 1 gene, encodes for a serine/threonine kinase protein and is implicated in cell cycle progression. LATS1 is down-regulated in various human cancers, such as breast cancer, and astrocytoma. Point mutations in LATS1 were reported in human sarcomas. Additionally, loss of heterozygosity of LATS1 chromosomal region predisposes to breast, ovarian, and cervical tumors. In the current study, we investigated LATS1 genetic variations including single nucleotide polymorphisms (SNPs), in 28 Egyptian patients with either urinary bladder or colon cancers. The LATS1 gene was amplified and sequenced and the expression of LATS1 at the RNA level was assessed in 12 urinary bladder cancer samples. We report, the identification of a total of 29 variants including previously identified SNPs within LATS1 coding and non-coding sequences. A total of 18 variants were novel. Majority of the novel variants, 13, were mapped to intronic sequences and un-translated regions of the gene. Four of the five novel variants located in the coding region of the gene, represented missense mutations within the serine/threonine kinase catalytic domain. Interestingly, LATS1 RNA steady state levels was lost in urinary bladder cancerous tissue harboring four specific SNPs (16045 + 41736 + 34614 + 56177) positioned in the 5'UTR, intron 6, and two silent mutations within exon 4 and exon 8, respectively. This study identifies novel single-base-sequence alterations in the LATS1 gene. These newly identified variants could potentially be used as novel diagnostic or prognostic tools in cancer.

Primary adenocarcinoma of bladder.

PubMed

Wilson, T G; Pritchett, T R; Lieskovsky, G; Warner, N E; Skinner, D G

1991-09-01

Between April 1983 and December 1987, we have treated and followed 16 patients at the University of Southern California for adenocarcinoma of the bladder. In 10 patients, the cancer originated from a nonurachal source; all underwent radical cystectomy, bilateral pelvic lymph node dissection, and urinary diversion. The other 6 patients had an apparent urachal origin of their cancer. Half of these patients were treated with radical cystectomy and urinary diversion and half were treated initially with segmental cystectomy. Presenting characteristics (age, sex ratio, and symptoms) were similar for both groups. Three-year adjusted acturial tumor-free survival rates for the two groups were 48 percent and 31 percent, respectively. We advocate an aggressive approach of radical cystectomy, bilateral pelvic lymph node dissection, and urinary diversion for all invasive adenocarcinoma of the bladder, regardless of location.

Prevention of Chemically-Induced Urinary Bladder Cancers by Naproxen: Protocols to Reduce Gastric Toxicity in Humans Do Not Alter Preventive Efficacy

PubMed Central

Lubet, Ronald A.; Scheiman, James M.; Bode, Ann; White, Jonathan; Minasian, Lori; Juliana, M. Margaret; Boring, Daniel L.; Steele, Vernon E.; Grubbs, Clinton J.

2015-01-01

The COX inhibitors (NSAIDs/Coxibs) are a major focus for the chemoprevention of cancer. The COX-2 specific inhibitors have progressed to clinical trials, and have shown preventive efficacy in colon and skin cancers. However, they have significant adverse cardiovascular (CV) effects. Certain NSAIDs (e.g., naproxen (NPX)] have a good cardiac profile, but can cause gastric toxicity. The present studies examined protocols to reduce this toxicity of NPX. Female Fischer-344 rats were treated weekly with the urinary bladder specific carcinogen hydroxybutyl(butyl)nitrosamine (OH-BBN) for 8 weeks. Rats were dosed daily with NPX (40 mg/Kg BW/day, gavage) or with the proton pump inhibitor omeprazole (4.0 mg/Kg BW/day) either singly or in combination beginning 2 weeks after the final OH-BBN. OH-BBN treated rats, 96% developed urinary bladder cancers. While omeprazole alone was ineffective (97% cancers), NPX alone or combined with omeprazole prevented cancers; yielding 27 and 35% cancers, respectively. In a separate study, OH-BBN treated rats were administered NPX: (A) daily, (B) 1 week daily NPX/1wk vehicle, (C) 3 weeks daily NPX/3 week vehicle, or (D) daily vehicle beginning 2 weeks after last OH-BBN treatment. In the intermittent dosing study, protocol A, B, C and D resulted in palpable cancers in 27%, 22%, 19% and 96% of rats (P<0.01). Short-term NPX treatment increased apoptosis, but did not alter proliferation in the urinary bladder cancers. Two different protocols which should decrease the gastric toxicity of NSAIDs in humans did not alter chemopreventive efficacy. This should encourage the use of NSAIDs (e.g. NPX) in clinical prevention trials. PMID:25762530

Expression of EphA2 and Ephrin A-1 in carcinoma of the urinary bladder.

PubMed

Abraham, Shaji; Knapp, Deborah W; Cheng, Liang; Snyder, Paul W; Mittal, Suresh K; Bangari, Dinesh S; Kinch, Michael; Wu, Lan; Dhariwal, Jay; Mohammed, Sulma I

2006-01-15

The EphA2 receptor tyrosine kinase is believed to play a role in tumor growth and metastasis. The clinical significance of the expression of EphA2 was observed in breast, prostate, colon, skin, cervical, ovarian, and lung cancers. The purpose of this work was to determine the expression of EphA2 and its ligand, Ephrin A-1, and E-cadherin in carcinoma of the urinary bladder, and determine EphA2 as a new target for therapy in bladder cancer. EphA2 mRNA and protein expression was investigated by reverse transcription-PCR and Western blot, respectively, in bladder cancer cell lines. In addition, the expression of EphA2, Ephrin A-1, and E-cadherin in tissues from patients with different stages of urinary bladder cancer was determined by immunohistochemistry. Furthermore, the ability of Ephrin A-1 to inhibit growth of bladder cancer cells was also investigated using an adenoviral delivery system. Western blot analysis showed high EphA2 expression in TCCSUP, T24, and UMUC-3 cell lines. In tissues, the staining intensity of EphA2 was less in normal urothelium but increased greatly in advancing stages of urothelial carcinoma (P < 0.05). Similarly, the staining intensity of Ephrin A-1 was low in normal tissues and high in cancerous tissues, but it was similar across the various stages of urothelial carcinoma (T(a)-T(4)). E-cadherin immunoreactivity decreased in urothelial cancer. Association of EphA2 and Ephrin A-1 expression was found to be significant between T(a) stage and T(1)-T(2) (P < 0.04) and T(a) and T(3)-T(4) stages (P < 0.0001). Adenovirus delivery of Ephrin A-1 inhibited proliferation of TCCSUP cells. EphA2 may serve as a novel target for bladder cancer therapy.

[The biochemical carcinogenesis of selected heavy metals in bladder cancer].

PubMed

Rorbach-Dolata, Anna; Marchewka, Zofia; Piwowar, Agnieszka

2015-01-01

Bladder cancer takes the second place in the classification of morbidity of urinary system cancers. Many chemical factors take part in cancerogenesis. It is suggested that exposure to heavy metals such as arsenic, chromium, nickel and cadmium as well as its metabolites may trigger the bladder cancer through inducing excessive reactive oxygen species production and oxidative stress formation which are responsible for DNA damage. In patients with bladder cancer is observed the disorder of processes regulated by p-53, including apoptosis. There are many patients with bladder cancer with confirmed absence of retinoblastoma protein, which is responsible of holding on the process of coming up the cells with mutation into synthesis, where the replication process undergoes. It is mentioned that excessive expression of proto-oncogenes may also cause the bladder cancer. The article concerns biochemical effects of exposure to chosen heavy metals and their potential role in bladder cancer progression.

Metastasis of Non-Muscle-Invasive Bladder Cancer Into the Thyroid Gland: A Literature Review Accompanied by a Rare Case

PubMed Central

Tuncer, Murat; Faydaci, Gokhan; Altin, Gokhan; Kibar, Sermin; Sanli, Arif; Bilgici, Dilek

2014-01-01

Bladder cancer is the most prevalent malignancy of the urinary tract. About 90% of bladder cancers are urothelial carcinomas. Seventy percent of cases newly diagnosed are superficial diseases; roughly 30% of newly diagnosed cases are muscle-invasive metastatic diseases. Bladder urothelial carcinoma primarily metastasizes into regional lymph nodes and then into liver, lung, mediastinum, bone, and adrenal gland. In our case, non-muscle-invasive bladder cancer metastasized into the bone, mediastinum, iliac lymph node, and adrenal and thyroid glands. This is the first reported case in the current literature in which urothelial carcinoma metastasized into the thyroid gland. PMID:24648880

Quality of life in women undergoing urinary diversion for bladder cancer: results of a multicenter study among long-term disease-free survivors.

PubMed

Gacci, Mauro; Saleh, Omar; Cai, Tommaso; Gore, John L; D'Elia, Carolina; Minervini, Andrea; Masieri, Lorenzo; Giannessi, Claudia; Lanciotti, Michele; Varca, Virginia; Simonato, Alchiede; Serni, Sergio; Carmignani, Giorgio; Carini, Marco

2013-03-12

Women undergoing radical cystectomy (RC) and urinary diversion for bladder cancer experience substantial limitations in health-related quality of life (HRQOL). However, the level of discomfort caused by different urinary diversion has been never evaluated in long term survivors. The aim of this multicenter study is to evaluate differences in HRQOL among recurrence-free women undergoing cutaneous ureterostomy (CUS), Bricker's ileal conduit (BK-IC) and Orthotopic neobladder VIP (ONB-VIP) in disease-free females treated with radical cystectomy (RC), with long-term follow up (mean 60.1 months; range 36-122 months). All consecutively treated female patients from two urological institutions who underwent RC and urinary diversion from January 2000 to December 2008, with no evidence of tumor recurrence at a minimum follow up of 36 months, were included. Patients received the European Organisation for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific instruments (QLQ-BLM30) and the Functional Assessment of Cancer Therapy for Bladder Cancer (FACT-BL). Clinical data and questionnaire results were analyzed in order to evaluate the HRQOL differences among diversion groups. We identified 37 females (median age: 68, range 45-82 years), including 12 status-post CUS, 16 who underwent BK-IC, and 9 who underwent ONB-VIP. Most were healthy (24/37 with no comorbidities, 4/37 Charlson 1-2, 9/37 Charlson 3 or greater - we didn't considered bladder cancer in Charlson evaluation because bladder cancer was the main inclusion criteria). Women undergoing CUS endorsed worse FACT-BL scores compared with BK-IC and ONB-VIP patients, worse HRQOL regarding physical and emotional well-being (p=0.008 and p=0.02, respectively), and a trend toward worse EORTC QLQ-C30 scores for appetite loss and fatigue (p=0.05 for both). In our study long-term disease-free females treated with CUS endorsed worse HRQOL compared with women who underwent BK-IC or ONB-VIP, mostly due to worse physical and emotional perception of their body image.

Superficial and muscle-invasive bladder cancer: principles of management for outcomes assessments.

PubMed

Parekh, Dipen J; Bochner, Bernard H; Dalbagni, Guido

2006-12-10

Bladder cancer is a heterogeneous disease. Non-muscle-invasive bladder cancer embraces a spectrum of tumors with varying degrees of clinical behavior. Transurethral resection remains the surgical mainstay for the treatment of non-muscle-invasive bladder cancer. In an attempt to decrease the recurrence or progression rate, intravesical chemotherapy or immunotherapy is also used. Radical cystectomy with bilateral pelvic lymph node dissection remains the gold standard for treating muscle-invasive bladder cancer. Over the last decade, the orthotopic neobladder has gained widespread popularity as the preferred mode of urinary diversion in both males and females with similar oncologic and functional outcomes. Well-designed trials with effective chemotherapy have shown a beneficial role for neoadjuvant chemotherapy.

The Antineoplastic Activity of Photothermal Ablative Therapy with Targeted Gold Nanorods in an Orthotopic Urinary Bladder Cancer Model.

PubMed

Yang, Xiaoping; Su, Lih-Jen; La Rosa, Francisco G; Smith, Elizabeth Erin; Schlaepfer, Isabel R; Cho, Suehyun K; Kavanagh, Brian; Park, Wounjhang; Flaig, Thomas W

2017-07-27

Gold nanoparticles treated with near infrared (NIR) light can be heated preferentially, allowing for thermal ablation of targeted cells. The use of novel intravesical nanoparticle-directed therapy in conjunction with laser irradiation via a fiber optic cystoscope, represents a potential ablative treatment approach in patients with superficial bladder cancer. To examine the thermal ablative effect of epidermal growth factor receptor (EGFR)-directed gold nanorods irradiated with NIR light in an orthotopic urinary bladder cancer model. Gold nanorods linked to an anti-EGFR antibody (Conjugated gold NanoRods - CNR) were instilled into the bladder cavity of an orthotopic murine xenograft model with T24 bladder cancer cells expressing luciferase. NIR light was externally administered via an 808 nm diode laser. This treatment was repeated weekly for 4 weeks. The anti-cancer effect was monitored by an in vivo imaging system in a non-invasive manner, which was the primary outcome of our study. The optimal approach for an individual treatment was 2.1 W/cm 2 laser power for 30 seconds. Using this in vivo model, NIR light combined with CNR demonstrated a statistically significant reduction in tumor-associated bioluminescent activity ( n  = 16) compared to mice treated with laser alone ( n  = 14) at the end of the study ( p  = 0.035). Furthermore, the CNR+NIR light treatment significantly abrogated bioluminescence signals over a 6-week observation period, compared to pre-treatment levels ( p  = 0.045). Photothermal tumor ablation with EGFR-directed gold nanorods and NIR light proved effective and well tolerated in a murine in vivo model of urinary bladder cancer.

Cruciferous vegetables, isothiocyanates, and prevention of bladder cancer

PubMed Central

Veeranki, Omkara L.; Bhattacharya, Arup; Tang, Li; Marshall, James R.; Zhang, Yuesheng

2015-01-01

Approximately 80% of human bladder cancers (BC) are non-muscle invasive when first diagnosed and are usually treated by transurethral tumor resection. But 50–80% of patients experience cancer recurrence. Agents for prevention of primary BC have yet to be identified. Existing prophylactics against BC recurrence, e.g., Bacillus Calmette-Guerin (BCG), have limited efficacy and utility; they engender significant side effects and require urethral catheterization. Many cruciferous vegetables, rich sources of isothiocyanates (ITCs), are commonly consumed by humans. Many ITCs possess promising chemopreventive activities against BC and its recurrence. Moreover, orally ingested ITCs are selectively delivered to bladder via urinary excretion. This review is focused on urinary delivery of ITCs to the bladder, their cellular uptake, their chemopreventive activities in preclinical and epidemiological studies that are particularly relevant to prevention of BC recurrence and progression, and their chemopreventive mechanisms in BC cells and tissues. PMID:26273545

Inhibition of long non-coding RNA UCA1 by CRISPR/Cas9 attenuated malignant phenotypes of bladder cancer.

PubMed

Zhen, Shuai; Hua, Ling; Liu, Yun-Hui; Sun, Xiao-Min; Jiang, Meng-Meng; Chen, Wei; Zhao, Le; Li, Xu

2017-02-07

CRISPR/Cas9 is a novel and effective genome editing technique, but its application is not widely expanded to manipulate long non-coding RNA (lncRNA) expression. The lncRNA urothelial carcinoma-associated 1 (UCA1) is upregulated in bladder cancer and promotes the progression of bladder cancer. Here, we design gRNAs specific to UCA1 and construct CRISPR/Cas9 systems targeting UCA1. Single CRISPR/Cas9-UCA1 can effectively inhibit UCA1 expression when transfected into 5637 and T24 bladder cancer cells, while the combined transfection of the two most effective CRISPR/Cas9-UCA1s can generate more satisfied inhibitory effect. CRISPR/Cas9-UCA1s attenuate UCA1 expression via targeted genome-specific DNA cleavage, resulting in the significant inhibition of cell proliferation, migration and invasion in vitro and in vivo. The mechanisms associated with the inhibitory effect of CRISPR/Cas9-UCA1 on malignant phenotypes of bladder cancer are attributed to the induction of cell cycle arrest at G1 phase, a substantial increase of apoptosis, and an enhanced activity of MMPs. Additionally, urinary UCA1 can be used as a non-invasive diagnostic marker for bladder cancer as revealed by a meta-analysis. Collectively, our data suggest that CRISPR/Cas9 technique can be used to down-modulate lncRNA expression, and urinary UCA1 may be used as a non-invasive marker for diagnosis of bladder cancer.

DIFFERENTIAL MODULATION OF CANCER-RELATED MOLECULAR NETWORKS IN HUMAN AND RAT URINARY BLADDER CELLS EXPOSED TO TRIVALENT ARSENICALS

EPA Science Inventory

Arsenic (As) is classified as a known human carcinogen with primary targets of urinary bladder (UB), skin and lung. The most prevalent source of As exposure in humans is drinking water contaminated with inorganic As (iAs), and millions of people worldwide are exposed to drinking ...

INDUCTION OF URINARY BLADDER PATHOLOGY IN MALE AND FEMALE C3H MICE EXPOSED TO SODIUM ARSENITE FROM GESTATION THROUGH YOUNG ADULTHOOD

EPA Science Inventory

Epidemiology studies suggest that chronic exposure to inorganic arsenic is associated with cancer of the skin, urinary bladder and lung as well as the kidney and liver. Recently, an in utero animal model was developed to characterize the carcinogenic properties of inorganic arsen...

Epidemiologic survey of bladder cancer in greater New Orleans.

PubMed

Sullivan, J W

1982-08-01

Primary ancestry of the patients and controls in this study was not statistically different but the Jewish population had a significantly increased incidence of bladder cancer. Over-all, a significantly greater number of patients smoked filtered cigarettes, began drinking artificially sweetened beverages at an earlier age, drank artificially sweetened beverages for a greater number of years, consumed a greater number of glasses of artificially sweetened beverages weekly and related a history of urinary tract infections. A significantly increased incidence of bladder cancer was noted in individuals employed by certain types of companies, by certain job titles and by certain job material handled. Analysis of the data failed to show any significant difference in years of consumption of coffee, amount of various types of coffee or tea consumed, consumption of various nonalcoholic and alcoholic beverages, including source of drinking water, use of hair dye, incidence of diabetes mellitus, family history of urinary cancer and a history of pelvic irradiation or bladder stones.

Significance of Random Bladder Biopsies in Non-Muscle Invasive Bladder Cancer

PubMed Central

Kumano, Masafumi; Miyake, Hideaki; Nakano, Yuzo; Fujisawa, Masato

2013-01-01

Background/Aims To evaluate retrospectively the clinical outcome of random bladder biopsies in patients with non-muscle invasive bladder cancer (NMIBC) undergoing transurethral resection (TUR). Patients and Method This study included 234 consecutive patients with NMIBC who underwent random biopsies from normal-appearing urothelium of the bladder, including the anterior wall, posterior wall, right wall, left wall, dome, trigone and/or prostatic urethra, during TUR. Result Thirty-seven patients (15.8%) were diagnosed by random biopsies as having urothelial cancer. Among several factors available prior to TUR, preoperative urinary cytology appeared to be independently related to the detection of urothelial cancer in random biopsies on multivariate analysis. Urinary cytology prior to TUR gave 50.0% sensitivity, 91.7% specificity, 56.8% positive predictive value and 89.3% negative predictive value for predicting the findings of the random biopsies. Conclusion Biopsies of normal-appearing urothelium resulted in the additional detection of urothelial cancer in a definite proportion of NMIBC patients, and it remains difficult to find a reliable alternative to random biopsies. Collectively, these findings suggest that it would be beneficial to perform random biopsies as part of the routine management of NMIBC. PMID:24917759

What are the currently available and in development molecular markers for bladder cancer? Will they prove to be useful in the future?

PubMed

Abdulmajed, Mohamed Ismat; Sancak, Eyüp Burak; Reşorlu, Berkan; Al-Chalaby, Gydhia Zuhair

2014-12-01

Urothelial carcinoma is the 9(th) most common cancer worldwide. Most urothelial tumors are non-muscle invasive on presentation. However, two-thirds of non-invasive bladder cancers will eventually recur with a 25% risk of progression to muscle-invasive bladder cancer. Tumor stage, histological grade and pathological invasion of blood vessels and lymphatic tissue are the main indicators for urothelial cancer prognosis. The gold standard for diagnosing bladder cancer is conventional white-light cystoscopy and biopsy. Urine cytology is a highly specific, sensitive test for high-grade tumors or carcinoma in situ (CIS). Urinary NMP22 has an overall sensitivity and specificity for detecting bladder cancer of 49% and 87%, respectively. However, there are false-positive results in the presence of urinary tract infection or hematuria. The detection of specific gene mutations related to urothelial cancers has been studied and employed to reproduce markers helpful for diagnosis. According to current studies, molecular markers can be used to predict tumor recurrence. From a prognostic point of view, new molecular markers have yet to be established as reliable indicators of tumor aggressiveness. We aimed to review the molecular markers with possible prognostic significance that have been discussed in the literature. This review examined the literature for various molecular markers under development for bladder cancer in an attempt to optimize patient care and reduce the costs of treating these patients.

Near infrared imaging to identify sentinel lymph nodes in invasive urinary bladder cancer

NASA Astrophysics Data System (ADS)

Knapp, Deborah W.; Adams, Larry G.; Niles, Jacqueline D.; Lucroy, Michael D.; Ramos-Vara, Jose; Bonney, Patty L.; deGortari, Amalia E.; Frangioni, John V.

2006-02-01

Approximately 12,000 people are diagnosed with invasive transitional cell carcinoma of the urinary bladder (InvTCC) each year in the United States. Surgical removal of the bladder (cystectomy) and regional lymph node dissection are considered frontline therapy. Cystectomy causes extensive acute morbidity, and 50% of patients with InvTCC have occult metastases at the time of diagnosis. Better staging procedures for InvTCC are greatly needed. This study was performed to evaluate an intra-operative near infrared fluorescence imaging (NIRF) system (Frangioni laboratory) for identifying sentinel lymph nodes draining InvTCC. NIRF imaging was used to map lymph node drainage from specific quadrants of the urinary bladder in normal dogs and pigs, and to map lymph node drainage from naturally-occurring InvTCC in pet dogs where the disease closely mimics the human condition. Briefly, during surgery NIR fluorophores (human serum albumen-fluorophore complex, or quantum dots) were injected directly into the bladder wall, and fluorescence observed in lymphatics and regional nodes. Conditions studied to optimize the procedure including: type of fluorophore, depth of injection, volume of fluorophore injected, and degree of bladder distention at the time of injection. Optimal imaging occurred with very superficial injection of the fluorophore in the serosal surface of the moderately distended bladder. Considerable variability was noted from dog to dog in the pattern of lymph node drainage. NIR fluorescence was noted in lymph nodes with metastases in dogs with InvTCC. In conclusion, intra-operative NIRF imaging is a promising approach to improve sentinel lymph node mapping in invasive urinary bladder cancer.

[Photodynamic therapy of urinary bladder cancer using a chlorin based photosensitizer].

PubMed

Iagudaev, D M; Martov, A G; Sorokatyĭ, A E; Geĭnits, A V

2006-01-01

Photodynamic therapy (PDT) is a modem, low-invasive method of urinary bladder (UB) cancer treatment. PDT can induce complete or partial destruction of the tumor, reduce recurrence rate, provide assistance to elderly patients with compromised somatic status who are not radically operable. A combined technique improves the results of photodynamic therapy in patients with surface and invasive UB cancer of stage T2 because photodynamic impact affects not only the tumor but also all UB mucosa by light fiber with cylindric diffusor introduced in a silicon balloon with water. This leads to tumor destruction and a recurrence rate decrease.

Malakoplakia mimics urinary bladder cancer: a case report.

PubMed

Ristić-Petrović, Ana; Stojnev, Slavica; Janković-Velicković, Ljubinka; Marjanović, Goran

2013-06-01

Malakoplakia is an unusual and very rare chronic inflammatory disease. In bladder especially it can mimic malignancy and lead to serious misdiagnosis. We presented a case of a middle-aged woman with persistent macrohematuria and cystoscopically polypoid bladder mass that resembled a neoplastic process. The final diagnosis was based on cystoscopic biopsy and microscopic findings of acidophilic, foamy histiocytes with the presence of Michaelis-Gutmann inclusions which are characteristic for diagnosis of malakoplakia. Immunohistochemistry confirmed diagnosis by demonstrating CD68-positive macrophages. Urinary bladder malakoplakia should be considered in patients with persistent urinary tract infections and tumor mass at cystoscopy. Early identification with prompt antibiotic treatment can be helpful in avoiding unnecessary surgical interventions and in preventing development of possible complications.

Transitional Cell Carcinoma of the Urinary Bladder in a Beluga Whale (Delphinapterus leucas)

PubMed Central

Martineau, D.; Lagacé, A.; Massé, R.; Morin, M.; Béland, P.

1985-01-01

A transitional cell carcinoma of the urinary bladder was found in a beluga whale stranded in the St. Lawrence middle estuary. Various organs of this animal were submitted to high resolution gas chromatography coupled with mass spectrometry analysis. High frequency of urinary bladder cancer in the human population of the same area and the presence of carcinogenic compounds in the marine environment of this animal are discussed. Concurrent isolation of Edwardsiella tarda from various organs of this whale is also reported. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7.Figure 8. PMID:17422578

Panel of Urinary Diagnostic Markers for Non-Invasive Detection of Primary and Recurrent Urothelial Urinary Bladder Carcinoma.

PubMed

Soukup, Viktor; Kalousová, Marta; Capoun, Otakar; Sobotka, Roman; Breyl, Zuzana; Pešl, Michael; Zima, Tomas; Hanuš, Tomáš

2015-01-01

To determine the combination of urinary protein markers for noninvasive detection of primary and recurrent urothelial bladder carcinomas. Urinary concentrations of 27 biomarkers (NSE, ATT, AFABP, Resistin, Midkine, Clusterin, Uromodulin, ZAG2, HSP27, HSP 60, NCAM1/CD56, Angiogenin, Calreticulin, Chromogranin A, CEACAM1, CXCL1, IL13Ra2, Progranulin, VEGFA, CarbAnhydIX, Annexin-V, TIM4, Galectin1, Cystatin B, Synuclein G, ApoA1 and ApoA2) were assessed by enzyme-linked immunosorbent assay or by electrochemiluminiscence immunoassay. During the primary diagnostics, a group of 70 patients with primary occurrence of bladder cancer and 49 healthy control subjects were compared. For this clinical situation, the most accurate combination proved to be the combination of cytology with markers Midkine and Synuclein G (sensitivity 91.8%, specificity 97.5%). During the monitoring of patients with non-muscle invasive bladder cancer (NMIBC), a group of 44 patients with cancer recurrence was compared with the group of 61 patients with a history of NMIBC without current disease. For this clinical situation, the most accurate combination proved to be the combination of cytology and erythrocytes count in urine sediment with markers Midkine, ZAG2, CEACAM1, and Synuclein G (sensitivity 92.68%, specificity 90.16%). A lower accuracy of the diagnostic panel and the necessity to use more markers in the case of recurrence was connected with a different structure of patients. Multi-marker test can significantly improve the bladder cancer detection both during the primary diagnostics and monitoring of patients with NMIBC. This outcome should result in other, larger studies. © 2015 S. Karger AG, Basel.

Activated platelet-derived growth factor β receptor and Ras-mitogen-activated protein kinase pathway in natural bovine urinary bladder carcinomas.

PubMed

Corteggio, Annunziata; Di Geronimo, Ornella; Roperto, Sante; Roperto, Franco; Borzacchiello, Giuseppe

2012-03-01

Bovine papillomavirus types 1 or 2 (BPV-1/2) are involved in the aetiopathogenesis of bovine urinary bladder cancer. BPV-1/2 E5 activates the platelet-derived growth factor β receptor (PDGFβR). The aim of this study was to analyse the Ras/mitogen-activated protein kinase (MAPK) pathway in relation to activation of PDGFβR in natural bovine urinary bladder carcinomas. Co-immunoprecipitation and Western blot analysis demonstrated that recruitment of growth factor receptor bound protein 2 (GRB-2) and Sos-1 to the activated PDGFβR was increased in carcinomas compared to normal tissues. Higher grade bovine urinary bladder carcinomas were associated with activation of Ras, but not with activation of downstream mitogen-activated protein kinase/extracellular signal-regulated kinase (Mek 1/2) or extracellular signal-regulated kinase (Erk 1/2). Copyright © 2011 Elsevier Ltd. All rights reserved.

Palliative management of malignant upper urinary tract obstruction

PubMed Central

Sountoulides, P; Mykoniatis, I; Dimasis, N

2014-01-01

Malignancies of the genitourinary tract are diagnosed with increased frequency compared to the past. Currently prostate and bladder cancer account for the majority of urological malignancies. While for prostate cancer recent developments in the management of local and metastatic disease are likely to lead the majority of patients to either cure from the disease or to longer survival time, for bladder cancer advanced disease will unfortunately lead to death within months. However, the common clinical scenario in both prostate and bladder cancer includes, in high incidence, upper urinary tract obstruction in the advanced stages of these malignancies. This coupled with the fact that average life expectancy in the western world is increasing, will result in a significant patient population with either advanced, non-curable disease or with problems related to the received therapeutic surgical or medical interventions. There is no doubt that in both circumstances the room and role of palliation therapy is increasing. The care of patients with advanced urologic malignancies requires a multi-disciplinary effort from physicians of many specialties under the guiding role of the treating urologist. This review focuses on currently available palliative therapeutic options for upper urinary tract obstruction in the setting of patients with advanced malignancies of the urinary tract, as recently significant advancements have been witnessed in this field. PMID:26052193

Palliative management of malignant upper urinary tract obstruction.

PubMed

Sountoulides, P; Mykoniatis, I; Dimasis, N

2014-01-01

Malignancies of the genitourinary tract are diagnosed with increased frequency compared to the past. Currently prostate and bladder cancer account for the majority of urological malignancies. While for prostate cancer recent developments in the management of local and metastatic disease are likely to lead the majority of patients to either cure from the disease or to longer survival time, for bladder cancer advanced disease will unfortunately lead to death within months. However, the common clinical scenario in both prostate and bladder cancer includes, in high incidence, upper urinary tract obstruction in the advanced stages of these malignancies. This coupled with the fact that average life expectancy in the western world is increasing, will result in a significant patient population with either advanced, non-curable disease or with problems related to the received therapeutic surgical or medical interventions. There is no doubt that in both circumstances the room and role of palliation therapy is increasing. The care of patients with advanced urologic malignancies requires a multi-disciplinary effort from physicians of many specialties under the guiding role of the treating urologist. This review focuses on currently available palliative therapeutic options for upper urinary tract obstruction in the setting of patients with advanced malignancies of the urinary tract, as recently significant advancements have been witnessed in this field.

[Spinal cord injury with neurogenic lower urinary tract dysfunction as a potential risk factor for bladder carcinoma].

PubMed

Böthig, Ralf; Fiebag, Kai; Kowald, Birgitt; Hirschfeld, Sven; Thietje, Roland; Kurze, Ines; Schöps, Wolfgang; Böhme, Holger; Kaufmann, Albert; Zellner, Michael; Kadhum, Thura; Golka, Klaus

2018-05-29

 Life expectancy for people with spinal cord injury/disease (SCI/D) is increasing, due to modern advances in treatment methods and in neuro-urology. However, with the increased life expectancy the risk of developing urinary bladder cancer is gaining importance. How is this patient group different from the general population?  Single-centre retrospective evaluation of consecutive patient data with spinal cord injury and proven urinary bladder cancer.  Between January 1st 1998 and March 31st 2017, 32 (3 female, 29 male) out of a total of 6432 patients with SCI/D were diagnosed with bladder cancer.The average age at bladder cancer diagnosis was 54.5 years, which is well below the average for bladder cancer cases in the general population (male: 74, female: 75).Twenty-seven patients suffered from urodynamically confirmed neurogenic detrusor overactivity, while five patients (all male) had detrusor acontractility.The median latency period between the onset of SCI/D and tumor diagnosis was 29.5 years. Temporary indwelling catheterisation was found in four patients for only 1.61 % of the overall latency period of all patients.The majority of the patients (n = 27) had transitional cell carcinoma, while five had squamous cell carcinoma. Of the 32 patients, 25 (78 %) had muscle invasive bladder cancer at ≥ T2 at the time of diagnosis. Regarding tumour grading, 23 out of 32 patients showed a histologically poorly differentiated G3 carcinoma; two patients each had G2 and G1 tumours repectively (no information on tumour grading was available in five patients).The median survival for all patients was 11.5 months. The prognosis of patients with squamous cell carcinoma was even worse; 4 out of 5 died within 7 months (median 4 months).  The significantly younger age at onset and the frequency of invasive, poorly differentiated tumour at diagnosis indicate that SCI/D influences both bladder cancer risk and prognosis significantly. The latency period between paralysis and tumour disease seems to be a decisive risk parameter.The type of neurogenic bladder dysfunction and the form of bladder drainage do not appear to influence the risk. Long-term indwelling catheter drainage played only a minor role in the investigated patients.Early detection of bladder cancer in patients with spinal cord injury remains a challenge. © Georg Thieme Verlag KG Stuttgart · New York.

Discovery of urine biomarkers for bladder cancer via global metabolomics.

PubMed

Shi, Hangchuan; Li, Xiang; Zhang, Qingyang; Yang, Hongmei; Zhang, Xiaoping

2016-11-01

Bladder cancer (BC) is latent in its early stage and lethal in its late stage. Therefore, early diagnosis and intervention are essential for successful BC treatment. Considering the limitations of current diagnostic tools, noninvasive biomarkers that are both highly sensitive and specific are needed to improve the overall survival and quality of life of patients. With the advent of systems biology, "-omics" technologies have been developed over the past few decades. As a promising member, global metabolomics has increasingly been found to have clear potential for biomarker discovery. However, urinary metabolomics studies related to BC have lagged behind those of other urinary cancers, and major findings have not been systematically reported. The objective of this review is to comprehensively list the currently identified potential urinary metabolite biomarkers for BC.

The diagnostic significance of lactate dehydrogenase isoenzymes in urinary cytology.

PubMed Central

Nishikawa, A.; Tanaka, T.; Takeuchi, T.; Fujihiro, S.; Mori, H.

1991-01-01

Lactate dehydrogenase (LDH) isoenzyme distribution was examined in 106 urine samples being tested cytologically for evidence of bladder cancer; the samples were selected to have less than 20 leucocytes and erythrocytes per high power field and the LDH pattern determined by electrophoresis. The Papanicolaou stained-smears showed 68 negative, 17 suspicious and 21 positive. The LDH M-fraction of the urinary supernatant in cytologically positive cases was significantly greater than in negative cases, although the latter included a few false negative samples. Some of the false negatives gave positive results for the LDH M-fraction; these results suggest that the determination of LDH isoenzymes in the urine is useful in diagnosing urinary tract cancers, including early stage, and for follow-up of patients with bladder cancers after surgical resection. PMID:2039708

[THE SOMATIC MUTATIONS AND ABERRANT METHYLATION AS POTENTIAL GENETIC MARKERS OF URINARY BLADDER CANCER].

PubMed

Mikhailenko, D S; Kushlinskii, N E

2016-02-01

All around the world, more than 330 thousands cases of bladder cancer are registered annually hence representing actual problem of modern oncology. Still in demand are search and characteristic of new molecular markers of bladder cancer detecting in tumor cells from urinary sediment and having high diagnostic accuracy. The studies of last decade, especially using methods of genome-wide sequencing, permitted to receive a large amount of experimental data concerning development and progression of bladder cancer The review presents systematic analysis of publications available in PubMed data base mainly of last five years. The original studies of molecular genetic disorders under bladder cancer and meta-analyzes were considered This approach permitted to detected the most common local alterations of DNA under bladder cancer which can be detected using routine genetic methods indifferent clinical material and present prospective interest for development of test-systems. The molecular genetic markers of disease can be activating missense mutations in 7 and 10 exons of gene of receptor of growth factor of fibroblasts 3 (FGFR3), 9 and 20 exons of gene of Phosphatidylinositol-4,5-bi-phosphate-3-kinase (PIK3CA) and mutation in -124 and -146 nucleotides in promoter of gene of catalytic subunit telomerase (TERT). The development of test-systems on the basis of aberrant methylation of CpG-islets of genes-suppressors still is seemed as a difficult task because of differences in pattern of methylation of different primary tumors at various stages of clonal evolution of bladder cancer though they can be considered as potential markers.

[The diagnostic value of microsatellite LOH analysis and the prognostic relevance of angiogenic gene expression in urinary bladder cancer].

PubMed

Szarvas, Tibor

2009-12-01

Bladder cancer is the second most common malignancy affecting the urinary system. Currently, histology is the only tool that determines therapy and patients' prognosis. As the treatment of non-invasive (Ta/T1) and muscle invasive (T2-T4) bladder tumors are completely different, correct staging is important, although it is often hampered by disturbing factors. Molecular methods offer new prospects for early disease detection, confirmation of unclear histological findings and prognostication. Applying molecular biological methods, the present study is searching for answers to current diagnostic and prognostic problems in bladder carcinoma. We analyzed tumor, blood and/or urine samples of 334 bladder cancer patients and 117 control individuals. Genetic alterations were analyzed in urine samples of patients and controls, both by PCR-based microsatellite loss of heterozigosity (LOH) analysis using 12 fluorescently labeled primers and by DNA hybridization based UroVysion FISH technique using 4 probes, to assess the diagnostic values of these methods. Whole genome microsatellite analysis (with 400 markers) was performed in tumor and blood specimens of bladder cancer patients to find chromosomal regions, the loss of which may be associated with tumor stage. Furthermore, we assessed the prognostic value of Tie2, VEGF, Angiopoietin-1 and -2. We concluded that DNA analysis of voided urine samples by microsatellite analysis and FISH are sensitive and non-invasive methods to detect bladder cancer. Furthermore, we established a panel of microsatellite markers that could differentiate between non-invasive and invasive bladder cancer. However, further analyses in a larger cohort of patients are needed to assess their specificity and sensitivity. Finally, we identified high Ang-2 and low Tie2 gene expression as significant and independent risk factors of tumor recurrence and cancer related survival.

Lower tract neoplasm: Update of imaging evaluation.

PubMed

Hartman, Robert; Kawashima, Akira

2017-12-01

Cancers of the lower urinary tract can arise from the bladder, urachus or urethra. Urothelial carcinoma of the bladder (UCB) is the most common of these. The presentation of bladder, urachal and urethral cancers can differ but many result in hematuria as an initial indication. The diagnosis and staging of these cancers often necessitate radiologic imaging often in the form of cross-section CT urography or MR urography. The following article reviews the specific nature of lower tract cancers and their imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantitative Evaluation of Heavy Metals and Trace Elements in the Urinary Bladder: Comparison Between Cancerous, Adjacent Non-cancerous and Normal Cadaveric Tissue.

PubMed

Abdel-Gawad, Mahmoud; Elsobky, Emad; Shalaby, Mahmoud M; Abd-Elhameed, Mohamed; Abdel-Rahim, Mona; Ali-El-Dein, Bedeir

2016-12-01

The role of heavy metals and trace elements (HMTE) in the development of some cancers has been previously reported. Bladder carcinoma is a frequent malignancy of the urinary tract. The most common risk factors for bladder cancer are exposure to industrial carcinogens, cigarette smoking, gender, and possibly diet. The aim of this study was to evaluate HTME concentrations in the cancerous and adjacent non-cancerous tissues and compare them with those of normal cadaveric bladder. This prospective study included 102 paired samples of full-thickness cancer and adjacent non-cancerous bladder tissues of radical cystectomy (RC) specimens that were histologically proven as invasive bladder cancer (MIBC). We used 17 matched controls of non-malignant bladder tissue samples from cadavers. All samples were processed and evaluated for the concentration of 22 HMTE by using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). Outcome analysis was made by the Mann-Whitney U, chi-square, Kruskal-Wallis, and Wilcoxon signed ranks tests. When compared with cadaveric control or cancerous, the adjacent non-cancerous tissue had higher levels of six elements (arsenic, lead, selenium, strontium, zinc, and aluminum), and when compared with the control alone, it had a higher concentration of calcium, cadmium, chromium, potassium, magnesium, and nickel. The cancerous tissue had a higher concentration of cadmium, lead, chromium, calcium, potassium, phosphorous, magnesium, nickel, selenium, strontium, and zinc than cadaveric control. Boron level was higher in cadaveric control than cancerous and adjacent non-cancerous tissue. Cadmium level was higher in cancerous tissue with node-positive than node-negative cases. The high concentrations of cadmium, lead, chromium, nickel, and zinc, in the cancerous together with arsenic in the adjacent non-cancerous tissues of RC specimens suggest a pathogenic role of these elements in BC. However, further work-up is needed to support this conclusion by the application of these HMTE on BC cell lines.

Current trends in the management of bladder cancer.

PubMed

Patel, Amit R; Campbell, Steven C

2009-01-01

This article provides a review of bladder cancer etiology, diagnosis, and management for WOC nurses. Bladder cancer incidence continues to rise yearly in the United States, and patients with bladder cancer comprise some of the most challenging cases in urologic oncology. Nurses are involved with all aspects of the processes of care for the patient with bladder cancer, from initial diagnosis and treatment to postsurgical care and follow-up. For nonmuscle invasive bladder cancer, treatment includes transurethral resection followed by intravesical chemotherapy or immunotherapy to prevent recurrence or progression. Radical cystectomy along with chemotherapy protocols provides a survival advantage for muscle invasive bladder cancer, although the timing of chemotherapy remains controversial. Numerous factors are considered when determining the type of urinary diversion used at the time of radical cystectomy, but patient, family, surgeon, and nursing input are essential for preserving an optimal health-related quality of life and reducing morbidity. Patients with metastatic bladder cancer are generally treated with a cisplatin-based chemotherapy but continue to have a poor prognosis. Newer therapies involving novel molecular-targeted agents provide hope for the future for patients with metastatic disease.

Direct detection of hyaluronidase in urine using cationic gold nanoparticles: a potential diagnostic test for bladder cancer.

PubMed

Nossier, Ahmed Ibrahim; Eissa, Sanaa; Ismail, Manal Fouad; Hamdy, Mohamed Ahmed; Azzazy, Hassan Mohamed El-Said

2014-04-15

Hyaluronidase (HAase) was reported as a urinary marker of bladder cancer. In this study, a simple colorimetric gold nanoparticle (AuNP) assay was developed for rapid and sensitive detection of urinary HAase activity. Charge interaction between polyanionic hyaluronic acid (HA) and cationic AuNPs stabilized with cetyl trimethyl ammonium bromide (CTAB) led to formation of gold aggregates and a red to blue color shift. HAase digests HA into small fragments preventing the aggregation of cationic AuNPs. The nonspecific aggregation of AuNPs in urine samples was overcome by pre-treatment of samples with the polycationic chitosan that was able to agglomerate all negatively charged interfering moieties before performing the assay. The developed AuNP assay was compared with zymography for qualitative detection of urinary HAase activity in 40 bladder carcinoma patients, 11 benign bladder lesions patients and 15 normal individuals, the assay sensitivity was 82.5% vs. 65% for zymography, while the specificity for both assays was 96.1%. The absorption ratio, A530/A620 of the reacted AuNP solution was used to quantify the HAase activity. The best cut off value was 93.5 μU/ng protein, at which the sensitivity was 90% and the specificity was 80.8%.The developed colorimetric AuNP HAase assay is simple, inexpensive, and can aid noninvasive diagnosis of bladder cancer. © 2013 Elsevier B.V. All rights reserved.

Prognostic Significance of Selected Lifestyle Factors in Urinary Bladder Cancer

PubMed Central

Wakai, Kenji; Ohno, Yoshiyuki; Obata, Kohji; Aoki, Kunio

1993-01-01

To examine the prognostic significance of lifestyle factors in urinary bladder cancer, we conducted a follow‐up study of 258 incident bladder cancer patients, who were originally recruited in a case‐control study in metropolitan Nagoya. Information on individual survivals was obtained from the computer data‐file of the tumor registry of the Nagoya Bladder Cancer Research Group. Univariate analyses revealed significant associations of 5‐year survivorship with educational attainment, marital status, drinking habits and consumption of green tea in males, and age at first consultation, histological type and grade of tumor, stage and distant metastasis in both sexes. After adjustment for age, stage, histology (histological type and grade) and distant metastasis by means of a proportional hazards model, drinking of alcoholic beverages was significantly associated with the prognosis of bladder cancer in males. Its adjusted hazard ratio was 0.46 (95% confidence interval: 0.26–0.79), favoring patients who had taken alcoholic beverages. In detailed analysis, ex‐drinkers and all levels of current drinkers demonstrated hazard ratios smaller than unity, although no clear dose‐response relationship was detected. No prognostic significance was found for such lifestyle factors as smoking habit, uses of artificial sweeteners and hairdye, and consumption of coffee, black tea, matcha (powdered green tea) and cola. PMID:8294212

Prognostic significance of selected lifestyle factors in urinary bladder cancer.

PubMed

Wakai, K; Ohno, Y; Obata, K; Aoki, K

1993-12-01

To examine the prognostic significance of lifestyle factors in urinary bladder cancer, we conducted a follow-up study of 258 incident bladder cancer patients, who were originally recruited in a case-control study in metropolitan Nagoya. Information on individual survivals was obtained from the computer data-file of the tumor registry of the Nagoya Bladder Cancer Research Group. Univariate analyses revealed significant associations of 5-year survivorship with educational attainment, marital status, drinking habits and consumption of green tea in males, and age at first consultation, histological type and grade of tumor, stage and distant metastasis in both sexes. After adjustment for age, stage, histology (histological type and grade) and distant metastasis by means of a proportional hazards model, drinking of alcoholic beverages was significantly associated with the prognosis of bladder cancer in males. Its adjusted hazard ratio was 0.46 (95% confidence interval: 0.26-0.79), favoring patients who had taken alcoholic beverages. In detailed analysis, ex-drinkers and all levels of current drinkers demonstrated hazard ratios smaller than unity, although no clear dose-response relationship was detected. No prognostic significance was found for such lifestyle factors as smoking habit, uses of artificial sweeteners and hairdye, and consumption of coffee, black tea, matcha (powdered green tea) and cola.

Transcriptional Modulation of the ERK1/2 MAPK and NF-kB pathways in Human Urothelial cells after trivalent arsenical exposure: Implications for urinary bladder cancer

EPA Science Inventory

Chronic exposure to drinking water contaminated with inorganic arsenic (iAs) is associated with an increased risk ofurinary bladder (DB) cancers in humans. Rodent models administered particular arsenicals have indicated urothelial necrosis followed by regenerative proliferation i...

Urinary retinoic acid receptor-β2 gene promoter methylation and hyaluronidase activity as noninvasive tests for diagnosis of bladder cancer.

PubMed

Eissa, Sanaa; Zohny, Samir F; Shehata, Hanan Hussien; Hegazy, Marwa G A; Salem, Ahmed M; Esmat, Mohamed

2012-04-01

We evaluated the significance of urinary retinoic acid receptor-β2 (RAR-β2) gene promoter methylation and hyaluronidase activity in comparison with voided urine cytology (VUC) in diagnosis of bladder cancer. This study included 100 patients diagnosed with bladder cancer, 65 patients with benign urological disorders and 51 healthy volunteers. Urine supernatant was used for determining hyaluronidase activity by zymography while urine sediment was used for cytology and detection of methylated RAR-β2 gene promoter by methylation specific nested PCR. The sensitivity and specificity were 53% and 90.5% for VUC, 65% and 89.7% for percent methylation fraction of RAR-β2 gene promoter, and 89% and 90.5% for hyaluronidase activity; combination of the three parameters increased sensitivity to 95%. A significant association was observed between investigated markers and advanced grade tumor. Combined use of RAR-β2 gene promoter methylation, hyaluronidase activity and VUC is promising non-invasive tool for bladder cancer detection. Copyright © 2012. Published by Elsevier Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Jun; Wanibuchi, Hideki; Waalkes, Michael P.

Epidemiological studies indicated that human arsenic exposure can induce urinary bladder cancer. Methylation of inorganic arsenic can generate more reactive and toxic organic arsenical species. In this regard, it was recently reported that the methylated arsenical metabolite, dimethylarsinic acid [DMA(V)], induced urinary bladder tumors in rats. However, other methylated metabolites, like monomethylarsonic acid [MMA(V)] and trimethylarsine oxide (TMAO) were not carcinogenic to the urinary bladder. In order to compare the early effects of DMA(V), MMA(V), and TMAO on the urinary bladder transitional cell epithelium at the scanning electron microscope (SEM) level, we investigated the sub-chronic (13 weeks) toxicological effects ofmore » MMA(V) (187 ppm), DMA(V) (184 ppm), TMAO (182 ppm) given in the drinking water to male and female F344 rats with a focus on the urinary bladder in this study. Obvious pathological changes, including ropy microridges, pitting, increased separation of epithelial cells, exfoliation, and necrosis, were found in the urinary bladders of both sexes, but particularly in females receiving carcinogenic doses of DMA(V). Urine arsenical metabolic differences were found between males and females, with levels of MMA(III), a potential genotoxic form, higher in females treated with DMA(V) than in males. Thus, this study provides clear evidence that DMA(V) is more toxic to the female urinary bladder, in accord with sensitivity to carcinogenesis. Important gender-related metabolic differences including enhanced presentation of MMA(III) to the urothelial cells might possibly account for heightened sensitivity in females. However, the potential carcinogenic effects of MMA(III) need to be further elucidated.« less

Predictive values of urinary bladder tumor markers survivin and soluble-Fas comparison with cystoscopy and bladder tumor antigen.

PubMed

Ganas, V; Kalaitzis, C; Sountoulides, P; Giannakopoulos, S; Touloupidis, S

2012-12-01

The aim of the study was to evaluate the predictive values of two novel urinary markers for bladder cancer: survivin and soluble-Fas (s-Fas). The study included 84 individuals divided in two groups. The first group contained 47 patients, who underwent transurethral bladder tumor resection and the second, control, group 20 patients with non-malignant conditions, who underwent cystoscopy and 17 health volunteers. Fresh, second morning voided urine was collected for measurement of s-Fas, survivin, BTA and for cytology. Sensitivity, specificity, positive and negative predictive values and accuracy were calculated. Bladder tumor patients had significantly higher survivin urine levels in comparison to the controls. Survivin correlated also with the tumor stage. Combination of survivin with BTA had a sensitivity of 86.4% but still lower than that of cystoscopy (97.8%). Only the specificity of the combination between survivin and BTA was higher than that of cystoscopy (86.4% and 75.6%, respectively). Survivin was a better marker for tumor detection than s-Fas and was better enough to discriminate cancer stage. Combination of survivin and BTA had a specificity of 86.4% to exclude bladder malignancy and the combination of s-Fas with survivin and BTA had a sensitivity of 93.6% to detect bladder cancer.

Quality of life in patients with muscle invasive and non-muscle invasive bladder cancer.

PubMed

Singer, S; Ziegler, C; Schwalenberg, T; Hinz, A; Götze, H; Schulte, T

2013-05-01

Compared to the literature on other malignancies, data on quality of life (QoL) in bladder cancer are sparse. This study sought answers to the following questions: In what QoL domains do patients with bladder cancer differ from the general population? Do patients with radical cystectomy differ in QoL compared to those who received conservative treatment? Do patients with neobladder generally have better QoL compared to patients with other diversion methods? At the beginning of inpatient rehabilitation, N = 823 patients with bladder cancer were assessed. Data of a representative community sample (N = 2037) were used for comparison. The questionnaire EORTC QLQ-C30 was used to measure QoL. Multivariate linear regression models were computed to investigate differences between groups. Patients with both non-muscle invasive and muscle invasive bladder cancer reported significantly more problems and worse functioning than the general population. Radiotherapy is associated with clinically relevant more pain, dyspnoea, constipation, appetite loss and decreased social functioning while chemotherapy is associated more with dyspnoea. Cystectomy patients reported more fatigue, appetite loss and decreased role functioning. Male patients ≥70 years with conduit experienced more sleep and emotional problems. These effects of urinary diversion were not observed in women and younger patients. Patients with bladder cancer experience various QoL concerns at the beginning of inpatient rehabilitation. These problems can partly be explained by the type of treatment the patients receive. Type of urinary diversion is relevant for QoL in subgroups of patients.

Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer.

PubMed

Weber, Lea; Schulz, Wolfgang A; Philippou, Stathis; Eckardt, Josephine; Ubrig, Burkhard; Hoffmann, Michéle J; Tannapfel, Andrea; Kalbe, Benjamin; Gisselmann, Günter; Hatt, Hanns

2018-01-01

Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca 2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

Urinary tract cancers: An overview for general practice

PubMed Central

Yaxley, Julian P.

2016-01-01

Urinary tract cancers are common and comprise a gamut of lesions ranging from small benign tumors to aggressive neoplasms with high mortality. The predominant urinary tract malignancy is bladder cancer. The clinical challenge is early detection and adequate follow-up because recurrence is high and delayed diagnosis is associated with poor prognosis. Primary care physicians form a key part of the management apparatus for these patients and may be responsible for ensuring adequate ongoing surveillance. This article aims to outline the evaluation of patients in whom urinary tract cancer is suspected and briefly review the general principles of treatment. PMID:28217578

[Concomitant oncopathological changes in the prostate of urinary bladder cancer patients undergoing radical cystoprostateectomy].

PubMed

Komyakov, B K; Sergeev, A V; Fadeev, V A; Ismailov, K I; Ulyanov, A Yu; Shmelev, A Yu; Onoshko, M V

2017-09-01

To determine the incidence of spreading bladder transitional cell carcinoma and primary adenocarcinoma to the prostate in patients with bladder cancer undergoing radical cystectomy. From 1995 to 2016, 283 men underwent radical cystectomy with removal of the bladder, perivesical tissue, prostate, seminal vesicles and pelvic lymph nodes. Prostate sparing cystectomy was performed in 45 (13.7%) patients. The whole prostate and the apex of the prostate were preserved in 21 (6.4%) and 24 (7.3%) patients, respectively. The spread of transitional cell cancer of the bladder to the prostate occurred in 50 (15.2%) patients. Twelve (3.6%) patients were found to have primary prostate adenocarcinoma. Clinically significant prostate cancer was diagnosed in 4 (33.3%) patients. We believe that the high oncological risk of prostate sparing cystectomy, despite some functional advantages, dictates the need for complete removal of the prostate in the surgical treatment of bladder cancer.

Risk of Late Urinary Complications Following Image Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer: Refining Bladder Dose-Volume Parameters.

PubMed

Manea, Elena; Escande, Alexandre; Bockel, Sophie; Khettab, Mohamed; Dumas, Isabelle; Lazarescu, Ioana; Fumagalli, Ingrid; Morice, Philippe; Deutsch, Eric; Haie-Meder, Christine; Chargari, Cyrus

2018-06-01

To study correlations between dose-volume parameters of the whole bladder and bladder trigone and late urinary toxicity in locally advanced cervical cancer patients treated with pulsed-dose-rate brachytherapy. Patients with locally advanced cervical cancer treated with chemoradiation therapy and pulsed-dose-rate brachytherapy from 2004 to 2015 were included. Cumulative dose-volume parameters of the whole bladder and bladder trigone were converted into 2-Gy/fraction equivalents (EQD2, with α/β = 3 Gy); these parameters, as well as clinical factors, were analyzed as predictors of toxicity in patients without local relapse. A total of 297 patients fulfilled the inclusion criteria. The median follow-up period was 4.9 years (95% confidence interval 4.5-5.3 years). In patients without local relapse (n = 251), the Kaplan-Meier estimated grade 2 or higher urinary toxicity rates at 3 years and 5 years were 25.4% and 32.1%, respectively. Minimal dose to the most exposed 2 cm 3 of the whole bladder [Formula: see text] , bladder International Commission on Radiation Units & Measurements (ICRU) (B ICRU ) dose, and trigone dose-volume parameters correlated with grade 2 or higher toxicity. At 3 years, the cumulative incidence of grade 2 or higher complications was 22.8% (standard error, 2.9%) for bladder [Formula: see text]  < 80 Gy EQD2 versus 61.8% (standard error, 12.7%) for [Formula: see text]  ≥ 80 Gy EQD2 (P = .001). In the subgroup of patients with bladder [Formula: see text]  ≤ 80 Gy EQD2 , a trigone dose delivered to 50% of the volume (D 50% ) > 60 Gy EQD2 was significant for grade 2 or higher toxicity (P = .027). The probability of grade 3 or higher toxicities increased with bladder [Formula: see text]  > 80 Gy EQD2 (16.7% vs 1.6%; hazard ratio [HR], 5.77; P = .039), B ICRU dose > 65 Gy EQD2 (4.9% vs 1.3%; HR, 6.36; P = .018), and trigone D 50%  > 60 Gy EQD2 (3.1% vs 1.2%; HR, 6.29; P = .028). Pearson correlation coefficients showed a moderate correlation between bladder [Formula: see text] , B ICRU dose, and bladder trigone D 50% (P < .0001). These data suggest that [Formula: see text]  ≤ 80 Gy EQD2 should be advised for minimizing the risk of severe urinary complications (<15%). Bladder trigone dose was also predictive of severe late urinary toxicity. These constraints need further confirmation in a multicenter prospective setting. Copyright © 2018 Elsevier Inc. All rights reserved.

Stenting Prior to Cystectomy is an Independent Risk Factor for Upper Urinary Tract Recurrence.

PubMed

Kiss, Bernhard; Furrer, Marc A; Wuethrich, Patrick Y; Burkhard, Fiona C; Thalmann, George N; Roth, Beat

2017-12-01

Patients with bladder cancer who present with hydronephrosis may require drainage of the affected kidney before receiving further cancer treatment. Drainage can be done by retrograde stenting or percutaneously. However, retrograde stenting carries the risk of tumor cell spillage to the upper urinary tract. The aim of this study was to evaluate whether patients with bladder cancer are at higher risk for upper urinary tract recurrence if retrograde stenting has been performed prior to radical cystectomy. We retrospectively analyzed the records of 1,005 consecutive patients with bladder cancer who underwent radical cystectomy at our department between January 2000 and June 2016. Negative intraoperative ureteral margins were mandatory for study inclusion. Patients received regular followup according to our institutional protocol, including imaging of the upper urinary tract and urine cytology. Preoperative drainage of the upper urinary tract was performed in 114 of the 1,005 patients (11%), including in 53 (46%) by Double-J® stenting and in 61 (54%) by percutaneous nephrostomy. Recurrence developed in the upper urinary tract in 31 patients (3%) at a median of 17 months after cystectomy, including 7 of 53 (13%) in the Double-J group, 0% in the nephrostomy group and 24 of 891 (3%) in the no drainage group. Multivariate regression analysis revealed a higher risk of upper urinary tract recurrence if patients underwent Double-J stenting (HR 4.54, 95% CI 1.43-14.38, p = 0.01) and preoperative intravesical instillations (HR 2.94, 95% CI 1.40-6.16, p = 0.004). Patients who undergo Double-J stenting prior to radical cystectomy are at higher risk for upper urinary tract recurrence. If preoperative upper urinary tract drainage is required, percutaneous drainage might be recommended. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Immune Response Following Photodynamic Therapy For Bladder Cancer

NASA Astrophysics Data System (ADS)

Raymond K.

1989-06-01

This study was undertaken to determine if photodynamic therapy (PDT) produces an immunologic response in patients treated for bladder cancer. Gamma interferon, interleukin 1-beta, interleukin 2 and tumor necrosis factor-alpha were assayed in the urine of four patients treated with photodynamic therapy for bladder cancer, in seven patients undergoing transurethral procedures, and in five healthy control subjects. Quantifiable concentrations of all cytokines, except gamma interferon, were measured in urine samples from the PDT patients treated with the highest light energies, while no urinary cytokines were found in the PDT patient who received the lowest light energy or in the control subjects. These findings suggest that a local immunologic response may occur following PDT for bladder cancer. Such an immunologic response activated by PDT may be an additional mechanism involved in bladder tumor destruction.

Safety of three sequential whole bladder photodynamic therapy (WBPDT) treatments in the management of resistant bladder cancer

NASA Astrophysics Data System (ADS)

Mejia, Maria C.; Nseyo, Unyime O.

2009-02-01

INTRODUCTION: WBPDT has been used to treat resistant superficial bladder cancer, with clinical benefits and associated dose-dependent side effects. OBJECTIVE: The objective of this study was to assess the safety of three sequential WBPDT treatments in patients with resistant non-muscle invasive (NMI) bladder cancer. MATERIALS AND METHODS: 12 males and one female provided written informed consent in this Phase II study. Each patient received intravenous injection of Photofrin® (AXCAN Parma Inc, Canada) at 1.5 mg/kg two days prior to whole bladder laser (630nm) treatment. Assessment of safety and efficacy included weekly urinary symptoms; cystoscopy, biopsy and cytology; and measurement of bladder volume quarterly after each treatment at baseline, six and 12 months. Treatment #2 and/or #3 occurred only in the absence of bladder contracture, and/or disease progression. RESULTS: 13 patients: 12 males and one female have been enrolled and average age of enrollees is 67.1(52 - 87) years. Four patients had Ta-T1/Grade I-III tumors; two patients had CIS associated with T1/GI-III; and seven patients had carcinoma in situ (CIS) only. Three patients received 3/3 treatments, and are evaluable for toxicity; three patients received two treatments only; and seven patients received one treatment only. There was no bladder contracture; transient mild to moderate bladder irritative voiding symptoms of dysuria, urinary frequency, nocturia and urgency occurred in all patients. The three evaluable patients were without evidence of disease at average of 13.1 (7-20) months. CONCLUSION: Three sequential WBPDT treatments might have a favorable toxicity profile in the management of recurrent/ refractory non-muscle invasive bladder cancer.

Gelatin-modified gold nanoparticles for direct detection of urinary total gelatinase activity: Diagnostic value in bladder cancer.

PubMed

Nossier, Ahmed I; Mohammed, Ola S; Fakhr El-Deen, Rasha R; Zaghloul, Ashraf S; Eissa, Sanaa

2016-12-01

Matrix metalloproteinases (MMPs), in particularly gelatinases (MMP-2 and MMP-9) were reported as urinary markers of bladder cancer. In this work, we developed a simple colorimetric gold nanoparticle (AuNP) assay for rapid and sensitive detection of urinary total gelatinase activity based on the surface plasmon resonance (SPR) property of AuNPs. Gelatin-modified AuNPs were stably suspended in solution even upon addition of an aggregation inducer as 6-mercaptohexan-1-ol (6-MCH). Gelatinases digest gelatin capping. Subsequently, addition of 6-MCH leads to AuNPs aggregation with red to blue color shift. In a pilot study, results of the developed AuNP assay were consistent with zymography for qualitative detection of urinary total gelatinase activity. The sensitivity and specificity of both assays were 80% and 90.9% respectively. The absorption ratios, A 625 /A 530 of the reacted AuNP solutions were used to quantify the total gelatinase concentration. The best cut off value was 0.01895ng/μg protein, at which the sensitivity was 87.5% and the specificity was 86.4%. The developed AuNP assay is simple, low-cost and can aid non-invasive diagnosis of bladder cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

NMP22 BladderChek Test: point-of-care technology with life- and money-saving potential.

PubMed

Tomera, Kevin M

2004-11-01

A new, relatively obscure tumor marker assay, the NMP22 BladderChek Test (Matritech, Inc.), represents a paradigm shift in the diagnosis and management of urinary bladder cancer (transitional cell carcinoma). Specifically, BladderChek should be employed every time a cystoscopy is performed, with corresponding changes in the diagnostic protocol and the guidelines of the American Urological Association for the diagnosis and management of bladder cancer. Currently, cystoscopy is the reference standard and NMP22 BladderChek Test in combination with cystoscopy improves the performance of cystoscopy. At every stage of disease, BladderChek provides a higher sensitivity for the detection of bladder cancer than cytology, which now represents the adjunctive standard of care. Moreover, BladderChek is four-times more sensitive than cytology and is available at half the cost. Early detection of bladder cancer improves prognosis, quality of life and survival. BladderChek may be analogous to the prostate-specific antigen test and eventually expand beyond the urologic setting into the primary care setting for the testing of high-risk patients characterized by smoking history, occupational exposures or age.

Possible distinct molecular carcinogenic pathways for bladder cancer in Ukraine, before and after the Chernobyl disaster.

PubMed

Morimura, Keiichirou; Romanenko, Alina; Min, Wei; Salim, Elsayed I; Kinoshita, Anna; Wanibuchi, Hideki; Vozianov, Alexander; Fukushima, Shoji

2004-04-01

After the Chernobyl accident in 1986, the incidence of urinary bladder cancers in the Ukraine increased gradually from 26.2 to 43.3 per 100,000 people between 1986 and 2001. In the areas of low level but persistent cesium-137 (137Cs) radio-contamination, a unique atypical radiation-related urinary bladder cystitis named 'Chernobyl cystitis', a possible pre-neoplastic condition in humans, has been detected. We have previously documented high incidences of bladder lesions, including severe dysplasias and/or carcinoma in situ, in association with this cystitis and correlating with oxidative DNA damage. To further investigate the molecular mechanisms underlying bladder carcinogenesis with this specific etiology, mutation analysis of p53 gene (exon 5-8) was performed for 11 and 18 paraffin-embedded bladder cancers in Ukrainians, respectively collected before and after the Chernobyl disaster. DNAs were extracted and subjected to nested PCR-single-strand conformational polymorphism analysis followed by direct DNA sequencing, as well as p53 immunohistochemistry (IHC). The incidences of p53 gene mutation were 54.5 and 16.7% for before and after the Chernobyl disaster, respectively, the difference being statistically significant. Also a tendency for higher p53 IHC score was apparent in the earlier group of lesions. No significant difference was noted for the proportions of historical types. These results point to possible distinct molecular carcinogenic pathways of bladder cancer formation, before and after the Chernobyl disaster, on the basis of variation in p53 gene alteration.

Cytology exam of urine

MedlinePlus

Urine cytology; Bladder cancer - cytology; Urethral cancer - cytology; Renal cancer - cytology ... The test is done to detect cancer of the urinary tract. It is often done when blood is seen in the urine. It is also useful for monitoring people ...

A Systematic Review of the Diagnostic and Prognostic Value of Urinary Protein Biomarkers in Urothelial Bladder Cancer

PubMed Central

D’Costa, Jamie J.; Goldsmith, James C.; Wilson, Jayne S.; Bryan, Richard T.; Ward, Douglas G.

2016-01-01

For over 80 years, cystoscopy has remained the gold-standard for detecting tumours of the urinary bladder. Since bladder tumours have a tendency to recur and progress, many patients are subjected to repeated cystoscopies during long-term surveillance, with the procedure being both unpleasant for the patient and expensive for healthcare providers. The identification and validation of bladder tumour specific molecular markers in urine could enable tumour detection and reduce reliance on cystoscopy, and numerous classes of biomarkers have been studied. Proteins represent the most intensively studied class of biomolecule in this setting. As an aid to researchers searching for better urinary biomarkers, we report a comprehensive systematic review of the literature and a searchable database of proteins that have been investigated to date. Our objective was to classify these proteins as: 1) those with robustly characterised sensitivity and specificity for bladder cancer detection; 2) those that show potential but further investigation is required; 3) those unlikely to warrant further investigation; and 4) those investigated as prognostic markers. This work should help to prioritise certain biomarkers for rigorous validation, whilst preventing wasted effort on proteins that have shown no association whatsoever with the disease, or only modest biomarker performance despite large-scale efforts at validation. PMID:27500198

Endoscopic Optical Coherence Tomography in Urology

NASA Astrophysics Data System (ADS)

Pan, Yingtian; Waltzer, Wayne; Ye, Zhangqun

Clinical statistics has shown a stable prevalence of bladder cancer in recent years, which by far remains among the most common types of malignancy in the USA. With smoking as the most well-established risk factor, bladder cancer is the fourth most common cancer occurrences in male population [1]. In the year of 2014, an estimated 74,690 new cases are expected to occur with estimated 15,580 deaths. Bladder cancer often refers to transitional cell carcinoma (TCC) as it originates primarily from the epithelial cell layer (i.e., urothelium) of the bladder. Unlike prostate-specific antigen (PSA) for prostate cancer screening, there is currently no effective screening technique approved or recommended for the population at average risk [2-5]. As a result, hematuria (i.e., blood in the urine) is often the first clinical symptom of bladder cancer. Fortunately, urinary bladder is more accessible than prostate glands endoscopically; thus cytology following white-light cystoscopy has been the gold standard for current clinical detection of bladder cancer. This is important because bladder cancer if diagnosed prior to muscle invasion (e.g., superficial or at

Sniffer mice discriminate urine odours of patients with bladder cancer: A proof-of-principle study for non-invasive diagnosis of cancer-induced odours.

PubMed

Sato, Takaaki; Katsuoka, Yoji; Yoneda, Kimihiko; Nonomura, Mitsuo; Uchimoto, Shinya; Kobayakawa, Reiko; Kobayakawa, Ko; Mizutani, Yoichi

2017-11-07

Similar to fingerprints, humans have unique, genetically determined body odours. In case of urine, the odour can change due to variations in diet as well as upon infection or tumour formation. We investigated the use of mice in a manner similar to "sniffer dogs" to detect changes in urine odour in patients with bladder cancer. We measured the odour discrimination thresholds of mice in a Y-maze, using urine mixtures from patients with bladder cancer (Stage I) and healthy volunteers (dietary variations) as well as occult blood- or antibiotic drug metabolite-modulated samples. Threshold difference indicated that intensities of urinary olfactory cues increase in the following order: dietary variation < bladder cancer < occult blood < antibiotic drug metabolites. After training with patient urine mixtures, sniffer mice discriminated between urine odours of pre- and post-transurethral resection in individual patients with bladder cancer in an equal-occult blood diluted condition below the detection level of dietary variations, achieving a success rate of 100% (11/11). Furthermore, genetic ablation of all dorsal olfactory receptors elevated the discrimination thresholds of mice by ≥ 10 5 -fold. The marked reduction in discrimination sensitivity indicates an essential role of the dorsal olfactory receptors in the recognition of urinary body odours in mice.

An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer

PubMed Central

Liang, Li-Guo; Kong, Meng-Qi; Zhou, Sherry; Sheng, Ye-Feng; Wang, Ping; Yu, Tao; Inci, Fatih; Kuo, Winston Patrick; Li, Lan-Juan; Demirci, Utkan; Wang, ShuQi

2017-01-01

Extracellular vesicles (EVs), including exosomes and microvesicles, are present in a variety of bodily fluids, and the concentration of these sub-cellular vesicles and their associated biomarkers (proteins, nucleic acids, and lipids) can be used to aid clinical diagnosis. Although ultracentrifugation is commonly used for isolation of EVs, it is highly time-consuming, labor-intensive and instrument-dependent for both research laboratories and clinical settings. Here, we developed an integrated double-filtration microfluidic device that isolated and enriched EVs with a size range of 30–200 nm from urine, and subsequently quantified the EVs via a microchip ELISA. Our results showed that the concentration of urinary EVs was significantly elevated in bladder cancer patients (n = 16) compared to healthy controls (n = 8). Receiver operating characteristic (ROC) analysis demonstrated that this integrated EV double-filtration device had a sensitivity of 81.3% at a specificity of 90% (16 bladder cancer patients and 8 healthy controls). Thus, this integrated device has great potential to be used in conjunction with urine cytology and cystoscopy to improve clinical diagnosis of bladder cancer in clinics and at point-of-care (POC) settings. PMID:28436447

Bladder cancer exosomes contain EDIL-3/Del1 and facilitate cancer progression.

PubMed

Beckham, Carla J; Olsen, Jayme; Yin, Peng-Nien; Wu, Chia-Hao; Ting, Huei-Ju; Hagen, Fred K; Scosyrev, Emelian; Messing, Edward M; Lee, Yi-Fen

2014-08-01

High grade bladder cancer is an extremely aggressive malignancy associated with high rates of morbidity and mortality. Understanding how exosomes may affect bladder cancer progression could reveal novel therapeutic targets. Exosomes derived from human bladder cancer cell lines and the urine of patients with high grade bladder cancer were assessed for the ability to promote cancer progression in standard assays. Exosomes purified from the high grade bladder cancer cell line TCC-SUP and the nonmalignant urothelial cell line SV-HUC were submitted for mass spectrometry analysis. EDIL-3 was identified and selected for further analysis. Western blot was done to determine EDIL-3 levels in urinary exosomes from patients with high grade bladder cancer. shRNA gene knockdown and recombinant EDIL-3 were applied to study EDIL-3 function. Exosomes isolated from high grade bladder cancer cells and the urine of patients with high grade bladder cancer promoted angiogenesis and migration of bladder cancer cells and endothelial cells. We silenced EDIL-3 expression and found that shEDIL-3 exosomes did not facilitate angiogenesis, and urothelial and endothelial cell migration. Moreover, exosomes purified from the urine of patients with high grade bladder cancer contained significantly higher EDIL-3 levels than exosomes from the urine of healthy controls. EDIL-3 activated epidermal growth factor receptor signaling while blockade of epidermal growth factor receptor signaling abrogated this EDIL-3 induced bladder cell migration. Exosomes derived from the urine of patients with bladder cancer contains bioactive molecules such as EDIL-3. Identifying these components and their associated oncogenic pathways could lead to novel therapeutic targets and treatment strategies. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Symptom clusters and related factors in bladder cancer patients three months after radical cystectomy.

PubMed

Ren, Hongyan; Tang, Ping; Zhao, Qinghua; Ren, Guosheng

2017-08-23

To identify symptom distress and clusters in patients 3 months after radical cystectomy and to explore their potential predictors. A cross-sectional design was used to investigate 99 bladder cancer patients 3 months after radical cystectomy. Data were collected by demographic and disease characteristic questionnaires, the symptom experience scale of the M.D. Anderson symptom inventory, two additional symptoms specific to radical cystectomy, and the functional assessment of cancer therapy questionnaire. A factor analysis, stepwise regression, and correlation analysis were applied. Three symptom clusters were identified: fatigue-malaise, gastrointestinal, and psycho-urinary. Age, complication severity, albumin post-surgery (negative), orthotropic neobladder reconstruction, adjuvant chemotherapy and American Society of Anesthesiologists (ASA) scores were significant predictors of fatigue-malaise. Adjuvant chemotherapy, orthotropic neobladder reconstruction, female gender, ASA scores and albumin (negative) were significant predictors of gastrointestinal symptoms. Being unmarried, having a higher educational level and complication severity were significant predictors of psycho-urinary symptoms. The correlations between clusters and for each cluster with quality of life were significant, with the highest correlation observed between the psycho-urinary cluster and quality of life. Bladder cancer patients experience concurrent symptoms that appear to cluster and are significantly correlated with quality of life. Moreover, symptom clusters may be predicted by certain demographic and clinical characteristics.

Thirty-five years of noninvasive bladder carcinoma: a plea for the use of papillary intraurothelial neoplasia as new terminology.

PubMed

Van der Kwast, Theodorus H; Zlotta, Alexandre R; Fleshner, Neil; Jewett, Michael; Lopez-Beltran, Antonio; Montironi, Roldolfo

2008-12-01

Since the introduction of the World Health Organization (WHO) 1973 terminology for bladder cancer, noninvasive epithelial bladder tumors have consistently been labeled bladder carcinomas. In the WHO 2004 classification the removal of the "carcinoma" label from a small subset of noninvasive bladder carcinomas with indolent behavior created the entity of papillary urothelial neoplasms of low malignant potential, but the remaining noninvasive carcinomas of the urothelial tract retained this label. In this overview, we analyze clinical, pathologic and molecular-genomic findings to support a more evidence-based nomenclature of papillary neoplastic lesions of the urinary tract. In line with the tendency during the last few decades to label flat precancerous lesions of various organs intraepithelial neoplasms, we may now also refer to dysplasia and carcinoma in situ of the urinary tract as low and high grade intraurothelial neoplasia, respectively. To harmonize nomenclature, we now propose that the terms low and high grade papillary urothelial carcinoma be replaced by low and high grade papillary intraurothelial neoplasiafor all noninvasive urothelial cancers.

Evaluation of associations between lifetime exposure to drinking water disinfection by-products and bladder cancer in dogs.

PubMed

Backer, Lorraine C; Coss, Angela M; Wolkin, Amy F; Flanders, W Dana; Reif, John S

2008-06-01

To assess the risk of bladder cancer in dogs from exposure to drinking water disinfection by-products and determine whether dogs could serve as sentinels for human bladder cancer associated with such exposures. Case-control study. 100 dogs with cancer of the urinary bladder and 100 control dogs. Case and control dogs were frequency-matched by age (within 2 years) and sex. Owners of dogs enrolled provided verbal informed consent and were interviewed by telephone. The telephone questionnaire included a complete residence history for each dog. Each dog's total exposure history to trihalomethanes was reconstructed from its residence history and corresponding drinking water utility company data. No association was detected between increasing years of exposure to chlorinated drinking water and risk of bladder cancer. Dogs with bladder cancer were exposed to higher total trihalomethanes concentrations than control dogs; however, the difference was not significant. Although humans and their dogs live in the same household, the activity patterns of dogs may lead to lower exposures to household tap water. Thus, although exposure to disinfection by-products in tap water may be a risk factor for human bladder cancer, this may not be true for canine bladder cancer at the concentrations at which dogs are exposed.

In vitro and in vivo effects of CpG-Oligodeoxynucleotides (CpG-ODN) on murine transitional cell carcinoma and on the native murine urinary bladder wall.

PubMed

Olbert, Peter Jochen; Schrader, Andres Jan; Simon, Corinna; Dalpke, Alexander; Barth, Peter; Hofmann, Rainer; Hegele, Axel

2009-06-01

Intravesical BCG instillation is established and efficient in the prophylaxis of recurrent transitional cell carcinoma. A Th-1 biased immune response is postulated. Recent work has proven the efficacy of synthetic CpG-Oligodeoxynucleotides (ODN) as inducers and adjuvants for a strong Th1-response and there is evidence for a direct and/or adjuvant anti-neoplastic effect. The purpose of this study was to examine the local effects of CpG-ODN on the murine bladder wall after intravesical instillation and the effects on cytokine expression in an orthotopic murine bladder cancer model. Histopathology, immunohistochemistry and fluorescence microscopy were performed after different instillation schedules of stimulatory, non-stimulatory biotinylized and FITC-labelled CpG-ODN into the murine bladder. MB-49 murine bladder cancer cells were tested for TLR-9 expression to exclude a potential direct responsiveness to CpG-ODN. Furthermore induction of apoptosis was tested by annexin V staining and FACS analysis of CpG-ODN stimulated tumor cells. In an orthotopic C57/Bl6 murine bladder cancer model, the expressions of IL-12, IFNgamma, IL-10 and TGF-beta were evaluated after repeated CpG-ODN treatment. Single and repeated instillation of CpG-ODN induced subepithelial and urothelial lymphocytic infiltrations with consecutive apoptoses. PBS and non-stimulative ODN induced no visible reaction. Bladder submucosa stained positive for biotin. Controls showed no endogenic biotin staining. FITC-labelled ODN adhered to the bladder mucosa and penetration of the mucosal barrier was not detected. MB-49 TCC cells did not express TLR-9 and CpG-ODN did not induce apoptosis in these cells. Repeated intravesical instillations of CpG-ODN in orthotopic murine tumor bearing urinary bladders resulted in significant up-regulation of both Th-1 and Th-2 cytokines. CpG-ODNs have promising anti-neoplastic potential. They exert a pronounced immunological response both in the native murine urinary bladder and in murine TCC. The mechanisms of action appear to be mediated immunologically, There was no direct effect of CpG-ODN on the tumor cells in this model.

THE SIGNIFICANCE OF EPIDERMAL GROWTH FACTOR RECEPTOR AND SURVIVIN EXPRESSION IN BLADDER CANCER TISSUE AND URINE CYTOLOGY OF PATIENTS WITH TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER.

PubMed

Kehinde, E O; Al-Maghrebi, M; Anim, J T; Kapila, K; George, S S; Al-Juwaiser, A; Memon, A

2013-01-01

To assess whether epidermal growth factor receptor (EGFR) and survivin immunostaining of tumour cells in urinary cytology and tissue of patients with bladder cancer has a prognostic significance. Prospective study Department of Surgery (Division of Urology), Mubarak Al-Kabeer Teaching Hospital and Faculty of Medicine, Kuwait University, Kuwait Urine cytology smears obtainedpriorto cystoscopy in patients with transitional cell carcinoma (TCC) of the bladder were immunostained for EGFR and survivin. Bladder cancer tissue resected at surgery was also immunostained for EGFR and survivin expression. Tissue expression of EGFR and survivin in TCC of the bladder was compared to their expression in urine cytology and relationship to tumour grade and stage. 178 patients were studied (43 newly diagnosed bladder cancer, 58 with recurrent TCC and 77 in disease remission). Twenty five patients with normal urothelium served as controls. The mean sensitivity of urine cytology, tissue survivin immunohistochemistry (IHC) and tissue EGFR IHC was 30.5%, 62% and 59% respectively. The corresponding mean specificity was 95%, 79% and 38% respectively. For grades 1, 2 and 3 bladder tumors, tissue expression positivity for EGFR was 47.8%, 92.9%, 100% and for tissue survivin it was 27.8%, 18.2% and 33.3% respectively. For grades 1, 2 and 3 bladder tumors, urine expression positivity for EGFR was 35.7%, 40% and 67.7% and for urine survivin it was 8.3%, 42.9% and 33.3% respectively. Positive EGFR immunostaining of urine cytology specimen or tumour tissue increases with histological grade of TCC of the bladder. Survivin expression is less consistent in both urine cytology specimen and tissue samples. EGFR immunostaining may provide a useful tool in the grading of bladder TCC and aid in the selection of patients that may benefit from administration of EGFR inhibitors.

Predictors of Urinary Morbidity in Cs-131 Prostate Brachytherapy Implants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Ryan P., E-mail: smithrp@upmc.edu; Jones, Heather A.; Beriwal, Sushil

2011-11-01

Purpose: Cesium-131 is a newer radioisotope being used in prostate brachytherapy (PB). This study was conducted to determine the predictors of urinary morbidity with Cs-131 PB. Methods and Materials: A cohort of 159 patients underwent PB with Cs-131 at our institution and were followed by using Expanded Prostate Cancer Index Composite (EPIC) surveys to determine urinary morbidity over time. EPIC scores were obtained preoperatively and postoperatively at 2 and 4 weeks, and 3 and 6 months. Different factors were evaluated to determine their individual effect on urinary morbidity, including patient characteristics, disease characteristics, treatment, and dosimetry. Multivariate analysis of covariancemore » was carried out to identify baseline determinants affecting urinary morbidity. Factors contributing to the need for postoperative catheterization were also studied and reported. Results: At 2 weeks, patient age, dose to 90% of the organ (D90), bladder neck maximum dose (D{sub max}), and external beam radiation therapy (EBRT) predicted for worse function. At 4 weeks, age and EBRT continued to predict for worse function. At the 3-month mark, better preoperative urinary function, preoperative alpha blockers, bladder neck D{sub max}, and EBRT predicted for worse urinary morbidity. At 6 months, better preoperative urinary function, preoperative alpha blockers, bladder neck D{sub max}, and EBRT were predictive of increased urinary problems. High bladder neck D{sub max} and poor preoperative urinary function predicted for the need for catheterization. Conclusions: The use of EBRT plus Cs-131 PB predicts for worse urinary toxicity at all time points studied. Patients should be cautioned about this. Age was a consistent predictor of worsened morbidity immediately following Cs-131 PB, while bladder D{sub max} was the only consistent dosimetric predictor. Paradoxically, patients with better preoperative urinary function had worse urinary morbidity at 3 and 6 months, consistent with recently published literature.« less

Epigenetics application in the diagnosis and treatment of bladder cancer.

PubMed

Harb-de la Rosa, Alfredo; Acker, Matthew; Kumar, Raj A; Manoharan, Murugesan

2015-10-01

Bladder cancer is the sixth most common cancer in the Western world. Patients with bladder cancer require close monitoring, which may include frequent cystoscopy and urine cytology. Such monitoring results in significant health care cost. The application of epigenetics may allow for a risk adapted approach and more cost-effective method of monitoring. A number of epigenetic changes have been described for many cancer sites, including the urinary bladder. In this review, we discuss the use of epigenetics in bladder cancer and the potential diagnostic and therapeutic applications. A comprehensive search of the English medical literature was conducted in PubMed using the terms microRNA regulation, DNA methylation, histone modification and bladder cancer. The most important epigenetic changes include DNA methylation, histone modification and microRNA regulation. Both DNA hypomethylation and hypermethylation have been associated with higher rate of cancer. The association of epigenetic changes with bladder cancer has led to the research of its diagnostic and prognostic implications as well as to the development of novel drugs to target these changes with the aim of achieving a survival benefit. Recently, epigenetics has been shown to play a much greater role than previously anticipated in the initiation and propagation of many tumors. The use of epigenetics for the diagnosis and treatment of bladder cancer is an evolving and promising field. The possibility of reversing epigenetic changes may facilitate additional cancer treatment options in the future.

Urinary fibronectin levels in patients treated with intravesical bacillus Calmette-Guérin for superficial bladder cancer.

PubMed

Danişman, A; Bulut, K; Kukul, E; Ozen, I; Sevük, M

2000-01-01

Intravesical bacillus Calmette-Guérin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma (TCC) of the bladder, but the precise mechanism of action of BCG remains poorly understood. Fibronectin (FN), an important component of the extracellular matrix, has been found to play a role in BCG therapy. Some studies have shown that the soluble form of FN can compete efficiently with the matrix form of binding to the specific receptors on the bacteria and could consequently diminish the effect of BCG treatment. To evaluate a possible correlation between the urinary levels of FN and the efficacy of BCG therapy, we determined prospectively the urinary FN levels in 38 patients with TCC of the bladder and in 25 control subjects without malignancy matched for age and sex. All TCC patients were treated with transurethral tumor resection plus 6 weekly intravesical BCG instillations. After an average follow-up of 30 months, 8 patients (21.1%) had recurrent tumors, while 30 (78.9%) were free of tumor after intravesical BCG therapy. Urinary levels of FN in cancer patients have been shown to be significantly higher than controls (p < 0.001). These elevated levels were not decreased significantly after the operation (p > 0. 05). It was also found that the mean urinary FN levels were not statistically significant between patients with recurrence and complete remission. The data suggest that BCG-bladder tumor cell binding is not influenced by soluble fibronectin and urinary FN may not be a ideal marker for selecting patients to BCG therapy. Copyright 2000 S. Karger AG, Basel

Can renal and bladder ultrasound replace CT urogram in patients investigated for microscopic hematuria?

PubMed

Tan, Wei Shen; Sarpong, Rachael; Khetrapal, Pramit; Rodney, Simon; Mostafid, Hugh; Cresswell, Joanne; Hicks, James; Rane, Abhay; Henderson, Alastair; Watson, Dawn; Cherian, Jacob; Williams, Norman; Brew-Graves, Chris; Feber, Andrew; Kelly, John D

2018-04-24

Computed tomography urogram (CTU) is recommended when investigating patients with hematuria. We determine the incidence of urinary tract cancer and compare the diagnostic accuracy of CTU and renal and bladder ultrasound (RBUS) at identifying urinary tract cancer. The DETECT I study (clinicaltrials.gov NCT02676180) is a prospective observational study recruiting patients ≥18 years following a presentation of macroscopic or microscopic haematuria at 40 hospitals. All patients had cystoscopy and upper tract imaging (CTU, RBUS or both). 3,556 patients with a median age of 68 years were recruited, of which 2166 had RBUS and 1692 had CTU in addition to cystoscopy. The incidence of bladder, renal and upper tract urothelial cancer (UTUC) were 11.0%, 1.4% and 0.8% respectively in macroscopic hematuria patients. Patients with microscopic hematuria had a 2.7%, 0.4% and 0% incidence of bladder, renal and UTUC respectively. The sensitivity and negative predictive value (NPV) of RBUS for the detection of renal cancer was 85.7% and 99.9% respectively but 14.3% and 99.7% for the detection of UTUC. RBUS was poor at identifying renal calculi. Sensitivity of RBUS was lower than CTU for the detection of bladder cancer (both <85%). Cystoscopy has a specificity and PPV of 98.3% and 83.9% respectively. CTU can be safely replaced with RBUS in patients with microscopic hematuria. The incidence of UTUC is 0.8% in patients with macroscopic hematuria and CTU is recommended. Patients with suspected renal calculi will require non-contrast renal tract CT. Imaging cannot replace cystoscopy to diagnose bladder cancer. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Commentary on "tissue-specific mutagenesis by N-butyl-N-(4-hydroxybutyl) nitrosamine as the basis for urothelial cell carcinogenesis." He Z, Kosinska W, Zhao ZL, Wu XR, Guttenplan JB, Department of Basic Science, New York University Dental College, NY, USA.: Mutat Res 2012;742(1-2):92-5 [Epub 2011 Dec 4].

PubMed

Scherr, Douglas S

2014-02-01

Bladder cancer is one of the few cancers that have been linked to carcinogens in the environment and tobacco smoke. Of the carcinogens tested in mouse chemical carcinogenesis models, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is one that reproducibly causes high-grade, invasive cancers in the urinary bladder, but not in any other tissues. However, the basis for such a high-level tissue-specificity has not been explored. Using mutagenesis in lacI (Big Blue™) mice, we show here that BBN is a potent mutagen and it causes high-level of mutagenesis specifically in the epithelial cells (urothelial) of the urinary bladder. After a 2-6-week treatment of 0.05% BBN in the drinking water, mutagenesis in urothelial cells of male and female mice was about two orders of magnitude greater than the spontaneous mutation background. In contrast, mutagenesis in smooth muscle cells of the urinary bladder was about five times lower than in urothelial tissue. No appreciable increase in mutagenesis was observed in kidney, ureter, liver or forestomach. In lacI (Big Blue™) rats, BBN mutagenesis was also elevated in urothelial cells, albeit not nearly as profoundly as in mice. This provides a potential explanation as to why rats are less prone than mice to the formation of aggressive form of bladder cancer induced by BBN. Our results suggest that the propensity to BBN-triggered mutagenesis of urothelial cells underlies its heightened susceptibility to this carcinogen and that mutagenesis induced by BBN represents a novel model for initiation of bladder carcinogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

Overexpression of HER-2 via immunohistochemistry in canine urinary bladder transitional cell carcinoma - A marker of malignancy and possible therapeutic target.

PubMed

Millanta, F; Impellizeri, J; McSherry, L; Rocchigiani, G; Aurisicchio, L; Lubas, G

2018-06-01

Transitional cell carcinoma (TCC) is the most commonly diagnosed neoplasm in the urinary bladder. Distant metastases to the regional lymph nodes, lungs, abdominal organs or bones are noted in up to 50% of dogs at time of death. Surgical excision is often not practical as TCC typically involve the trigone of the bladder and/or occurs multifocally throughout the bladder with field cancerization. Therapeutic approaches are very challenging and the requirement to evaluate alternative therapeutic protocols that may prolong survival times in dogs bearing these tumours is compelling. We assessed the immunohistochemical expression of HER-2 in 23 cases of canine TCCs of the urinary bladder and compare it with non-neoplastic urothelium in order to evaluate a rationale for targeted therapies and gene-based vaccines. HER-2 positivity was recorded in 13/23 (56%) neoplastic lesions. The receptor was significantly overexpressed in neoplastic than in non-neoplastic samples (P = .015). According to our preliminary results, it would be of interest to further evaluate the role of HER-2 in canine TCCs as a marker of malignancy and a therapeutic target for cancer vaccine and antibodies. Moreover, the significantly different overexpression of HER-2 in TCCs than in non-neoplastic urothelium further supports to investigate its role in the progression toward malignancy of non-neoplastic lesions. © 2017 John Wiley & Sons Ltd.

Insights from animal models of bladder cancer: recent advances, challenges, and opportunities

PubMed Central

John, Bincy Anu; Said, Neveen

2017-01-01

Bladder cancer (urothelial cancer of the bladder) is the most common malignancy affecting the urinary system with increasing incidence and mortality. Treatment of bladder cancer has not advanced in the past 30 years. Therefore, there is a crucial unmet need for novel therapies, especially for high grade/stage disease that can only be achieved by preclinical model systems that faithfully recapitulate the human disease. Animal models are essential elements in bladder cancer research to comprehensively study the multistep cascades of carcinogenesis, progression and metastasis. They allow for the investigation of premalignant phases of the disease that are not clinically encountered. They can be useful for identification of diagnostic and prognostic biomarkers for disease progression and for preclinical identification and validation of therapeutic targets/candidates, advancing translation of basic research to clinic. This review summarizes the latest advances in the currently available bladder cancer animal models, their translational potential, merits and demerits, and the prevalent tumor evaluation modalities. Thereby, findings from these model systems would provide valuable information that can help researchers and clinicians utilize the model that best answers their research questions. PMID:28915710

Small-cell carcinoma of the urinary bladder: where do we stand?

PubMed

Ghervan, Liviu; Zaharie, Andreea; Ene, Bogdan; Elec, Florin I

2017-01-01

Small-cell carcinoma of the urinary bladder is a very rare pathology, but with a very aggressive behavior and disappointing prognosis. The literature concerning this type of cancer is scarce and physicians may encounter difficulty trying to manage it. Most articles involve the study of case series, without definite results due to the small number of patients. The present article aims at gathering the most significant articles and results in order to offer a broad perspective on the existing literature concerning this pathology.

Measurement of DNA damage in rat urinary bladder transitional cells: improved selective harvest of transitional cells and detailed Comet assay protocols.

PubMed

Wang, Amy; Robertson, John L; Holladay, Steven D; Tennant, Alan H; Lengi, Andrea J; Ahmed, S Ansar; Huckle, William R; Kligerman, Andrew D

2007-12-01

Urinary bladder transitional epithelium is the main site of bladder cancer, and the use of transitional cells to study carcinogenesis/genotoxicity is recommended over the use of whole bladders. Because the transitional epithelium is only a small fraction of the whole bladder, the alkaline single cell gel electrophoresis assay (Comet assay), which requires only a small number of cells per sample, is especially suitable for measuring DNA damage in transitional cells. However, existed procedures of cell collection did not yield transitional cells with a high purity, and pooling of samples was needed for Comet assay. The goal of this study was to develop an optimized protocol to evaluate DNA damage in the urinary bladder transitional epithelium. This was achieved by an enzymatic stripping method (trypsin-EDTA incubation plus gentle scraping) to selectively harvest transitional cells from rat bladders, and the use of the alkaline Comet assay to detect DNA strand breaks, alkaline labile sites, and DNA-protein crosslinks. Step by step procedures are reported here. Cells collected from a single rat bladder were sufficient for multiple Comet assays. With this new protocol, increases in DNA damage were detected in transitional cells after in vitro exposure to the positive control agents, hydrogen peroxide or formaldehyde. Repair of the induced DNA damage occurred within 4h. This indicated the capacity for DNA repair was maintained in the harvested cells. The new protocol provides a simple and inexpensive method to detect various types of DNA damage and to measure DNA damage repair in urinary bladder transitional cells.

Genome-wide association studies in bladder cancer: first results and potential relevance.

PubMed

Kiemeney, Lambertus A; Grotenhuis, Anne J; Vermeulen, Sita H; Wu, Xifeng

2009-09-01

The role of genetic susceptibility in the development of urinary bladder cancer is unclear, as it is in many other types of cancer. Since 2007, however, an innovative research approach (i.e. genome-wide association studies or GWASs) has led to the identification of numerous genomic loci that harbor susceptibility factors for one or more cancer sites. All GWASs have been published in high-impact journals and the strengths of the design are acknowledged by all experts, but there is criticism about the relevance of the results. Late 2008, the first GWAS in bladder cancer was published. In this review, the principles of GWASs are explained, as well as their strengths and limitations. The study in bladder cancer among 4000 cases and 38,000 controls identified three new susceptibility loci at 8q24, 3q28, and 5p15 that increase the risk of bladder cancer by 22, 19, and 16%, respectively. The results of two other GWASs in bladder cancer are expected to appear this year. Joint analysis of the three studies will probably identify additional susceptibility loci. The results of bladder cancer GWASs may point the way to yet unknown disease mechanisms. So far, the findings are not sufficiently discriminative for risk predictions to be used in clinical care or public health.

[Study on different responses of rats' small intestine mucous membrane and bladder transitional epithelium in the same carcinogenic urine environment].

PubMed

Wu, B; Pan, C; Song, G

2001-10-25

To preliminarily verify the tentative idea of replacement of bladder transitional epithelium with small intestine mucous membrane to prevent recurrence of carcinoma of bladder. A certain segment of small intestine was transplanted to the urinary bladder of the same body in 17 rats. Then N-butyl-N-(4-hydroxy-butyl) nitrosamine (BBN) was used to induce carcinoma of bladder. BBN was used to 11 control rats that did not undergo operation. Bladder carcinoma failed to be found in the transplanted small intestine mucous membrane in all experimental rats except one. After stimulation of BBN, carcinoma of urinary bladder occurred in all rats' bladder transitional epithelium. 1) The carcinogenic substances in the urine of rats suffering from BBN-induced bladder carcinoma are carcinogenic only to bladder transitional epithelium and have no effect on small intestine epithelium. 2) Bladder transitional epithelium may be more sensitive to the urine carcinogenic substances and easier to be cancerized than small intestine epithelium. 3) The tentative idea of substitution of small intestine mucous membrane for bladder transitional epithelium to prevent the recurrence of bladder carcinoma is worth further studying.

Urinary adverse effects of pelvic radiotherapy

PubMed Central

Liberman, Daniel; Mehus, Brian

2014-01-01

Objective Radiation is an integral part of the treatment of many pelvic tumors. The cellular death induced by radiotherapy (RT) benefits cancer control but can also result in adverse effects (AEs) on the organ being treated or those adjacent to it. RT for cancers of the pelvis (bladder, prostate, rectum, uterus or cervix) can result in AEs in the urinary tract. While the acute urinary AEs of pelvic RT are well described, late AEs are less well characterized. The burden of treatment for late AEs may be large given the prevalence of tumors in the pelvis and the high utilization of RT to treat them. Review For prostate cancer, grade 1 and 2 urinary AEs following external beam radiation therapy (EBRT) are reported to occur in 20-43% and 7-19%, respectively, with a follow up of 10 years. Three-year cumulative risk for grade ≥2 urinary AEs is 28-30%. Following brachytherapy (BT), rates of urinary AEs at 5 years are reported to be 36%, 24%, 6.2% and 0.1% for Radiation Therapy Oncology Group (RTOG) grade 1, 2, 3, and 4, respectively. For bladder cancer, with a median follow-up of 5 years, 7-12% of patients who receive RT experience urinary AEs of grade 3 or more. For cervical cancer, there remains a 0.25% per year risk of severe AEs for at least 25 years following RT, and ureteral stricture is a well-described AE. For endometrial cancer, severe urinary AEs are rare, but at 13 years of follow up, patients report a significantly worse quality of life with respect to urinary function. In rectal cancer, preoperative RT has a lower risk of AEs than postoperative RT, and few urinary AEs are reported in the literature. Conclusions Urinary AEs can manifest long after RT, and there is a paucity of studies describing rates of these long-term AEs. It is important that the possible complications of RT are recognized by providers and properly communicated to patients so that they are able to make informed decisions about their cancer treatment. PMID:26813159

Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancer

PubMed Central

Selinski, Silvia; Blaszkewicz, Meinolf; Ickstadt, Katja; Gerullis, Holger; Otto, Thomas; Roth, Emanuel; Volkert, Frank; Ovsiannikov, Daniel; Moormann, Oliver; Banfi, Gergely; Nyirady, Peter; Vermeulen, Sita H; Garcia-Closas, Montserrat; Figueroa, Jonine D; Johnson, Alison; Karagas, Margaret R; Kogevinas, Manolis; Malats, Nuria; Schwenn, Molly; Silverman, Debra T; Koutros, Stella; Rothman, Nathaniel; Kiemeney, Lambertus A; Hengstler, Jan G; Golka, Klaus

2017-01-01

Abstract Little is known whether genetic variants identified in genome-wide association studies interact to increase bladder cancer risk. Recently, we identified two- and three-variant combinations associated with a particular increase of bladder cancer risk in a urinary bladder cancer case–control series (Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), 1501 cases, 1565 controls). In an independent case–control series (Nijmegen Bladder Cancer Study, NBCS, 1468 cases, 1720 controls) we confirmed these two- and three-variant combinations. Pooled analysis of the two studies as discovery group (IfADo-NBCS) resulted in sufficient statistical power to test up to four-variant combinations by a logistic regression approach. The New England and Spanish Bladder Cancer Studies (2080 cases and 2167 controls) were used as a replication series. Twelve previously identified risk variants were considered. The strongest four-variant combination was obtained in never smokers. The combination of rs1014971[AA] near apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and chromobox homolog 6 (CBX6), solute carrier family 1s4 (urea transporter), member 1 (Kidd blood group) (SLC14A1) exon single nucleotide polymorphism (SNP) rs1058396[AG, GG], UDP glucuronosyltransferase 1 family, polypeptide A complex locus (UGT1A) intron SNP rs11892031[AA] and rs8102137[CC, CT] near cyclin E1 (CCNE1) resulted in an unadjusted odds ratio (OR) of 2.59 (95% CI = 1.93–3.47; P = 1.87 × 10−10), while the individual variant ORs ranged only between 1.11 and 1.30. The combination replicated in the New England and Spanish Bladder Cancer Studies (ORunadjusted = 1.60, 95% CI = 1.10–2.33; P = 0.013). The four-variant combination is relatively frequent, with 25% in never smoking cases and 11% in never smoking controls (total study group: 19% cases, 14% controls). In conclusion, we show that four high-risk variants can statistically interact to confer increased bladder cancer risk particularly in never smokers. PMID:29028944

Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats.

PubMed

Fujioka, Masaki; Gi, Min; Kawachi, Satoko; Tatsumi, Kumiko; Ishii, Naomi; Doi, Kenichiro; Kakehashi, Anna; Wanibuchi, Hideki

2016-11-01

Arsenic is a well-known human bladder and liver carcinogen, but its exact mechanism of carcinogenicity is not fully understood. Dimethylarsinic acid (DMA V ) is a major urinary metabolite of sodium arsenite (iAs III ) and induces urinary bladder cancers in rats. DMA V and iAs III are negative in in vitro mutagenicity tests. However, their in vivo mutagenicities have not been determined. The purpose of present study is to evaluate the in vivo mutagenicities of DMA V and iAs III in rat urinary bladder epithelium and liver using gpt delta F344 rats. Ten-week old male gpt delta F344 rats were randomized into 3 groups and administered 0, 92mg/L DMA V , or 87mg/L iAs III (each 50mg/L As) for 13weeks in the drinking water. In the mutation assay, point mutations are detected in the gpt gene by 6-thioguanine selection (gpt assay) and deletion mutations are identified in the red/gam genes by Spi - selection (Spi - assay). Results of the gpt and Spi - assays showed that DMA V and iAs III had no effects on the mutant frequencies or mutation spectrum in urinary bladder epithelium or liver. These findings indicate that DMA V and iAs III are not mutagenic in urinary bladder epithelium or liver in rats. Copyright © 2016. Published by Elsevier B.V.

Occupational risk of bladder cancer among Iranian male workers

PubMed Central

Aminian, Omid; Saburi, Amin; Mohseni, Hossein; Akbari, Hamed; Chavoshi, Farzaneh; Akbari, Hesam

2014-01-01

Background: Approximately 5-10% of human cancers are thought to be caused by occupational exposure to carcinogens. Compare to other cancers, bladder cancer is most strongly linked to occupational exposure to chemical toxins. This study has been performed to understand which occupations and exposures are related to bladder cancer in Iran. Materials and Methods: This study is a case-control study which is conducted on cases with bladder cancer (160 cases) diagnosed in Baharlou hospital in 2007-2009. One hundred sixty cases without any occupational exposure were considered as controls matched for demographic characteristics. Demographic data and characteristics of occupation were compared. Results: Mean age of cases and controls were 63.7 and 64 years, respectively (P = 0.841). History of urinary tract stone had significantly difference in two groups (P = 0.039). Occupations such as bus and truck driving, road and asphalt making, mechanics, working in refinery and Petrochemical, plastic, metal manufactory, welding, and pipeline founded a higher risk for bladder cancer rather than controls. Conclusion: Our findings on Iranian workers are concurrent and compatible with findings of previous reports about occupational and environmental risk factors of bladder cancer. Although our study population was PMID:24833825

Low awareness of risk factors among bladder cancer survivors: New evidence and a literature overview.

PubMed

Westhoff, Ellen; Maria de Oliveira-Neumayer, Julia; Aben, Katja K; Vrieling, Alina; Kiemeney, Lambertus A

2016-06-01

Data on urinary bladder cancer (UBC) patients' perceptions about causes of bladder cancer is limited, while this may be important knowledge for health prevention and education. We evaluated self-reported perceptions and beliefs about the causes of bladder cancer among UBC survivors in the Netherlands. UBC survivors identified through the Netherlands Cancer Registry from 2007 to 2012 were invited to participate. Patients who consented were asked to fill out a questionnaire, including questions on lifestyle characteristics, occupational and medical history, and family history of cancer. The final question was 'You have been diagnosed with bladder cancer. Do you have any idea what may have been the cause of your cancer?'. Of the 1793 UBC survivors included, 366 (20%) reported a possible cause for their bladder cancer. The most frequently reported suspected causes were smoking (10%), occupational exposure (5%), and heredity (2%). Smoking, occupational exposure and heredity were mentioned only slightly more frequently by participants with these risk factors (11%, 8%, and 5%, respectively) compared to the total population. Most UBC survivors did not suspect any cause that might have contributed to the development of their cancer. Even among participants with established risk factors for bladder cancer, these risk factors were not commonly perceived. This finding probably reflects the superficial knowledge of risk factors for bladder cancer in the population and highlights the importance of effective education on cancer prevention. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Platelet-derived growth factor receptor beta: a novel urinary biomarker for recurrence of non-muscle-invasive bladder cancer.

PubMed

Feng, Jiayu; He, Weifeng; Song, Yajun; Wang, Ying; Simpson, Richard J; Zhang, Xiaorong; Luo, Gaoxing; Wu, Jun; Huang, Chibing

2014-01-01

Non-muscle-invasive bladder cancer (NMIBC) is one of the most common malignant tumors in the urological system with a high risk of recurrence, and effective non-invasive biomarkers for NMIBC relapse are still needed. The human urinary proteome can reflect the status of the microenvironment of the urinary system and is an ideal source for clinical diagnosis of urinary system diseases. Our previous work used proteomics to identify 1643 high-confidence urinary proteins in the urine from a healthy population. Here, we used bioinformatics to construct a cancer-associated protein-protein interaction (PPI) network comprising 16 high-abundance urinary proteins based on the urinary proteome database. As a result, platelet-derived growth factor receptor beta (PDGFRB) was selected for further validation as a candidate biomarker for NMIBC diagnosis and prognosis. Although the levels of urinary PDGFRB showed no significant difference between patients pre- and post-surgery (n = 185, P>0.05), over 3 years of follow-up, urinary PDGFRB was shown to be significantly higher in relapsed patients (n = 68) than in relapse-free patients (n = 117, P<0.001). The levels of urinary PDGFRB were significantly correlated with the risk of 3-year recurrence of NMIBC, and these levels improved the accuracy of a NMIBC recurrence risk prediction model that included age, tumor size, and tumor number (area under the curve, 0.862; 95% CI, 0.809 to 0.914) compared to PDGFR alone. Therefore, we surmise that urinary PDGFRB could serve as a non-invasive biomarker for predicting NMIBC recurrence.

Modeling and simulation of a low-grade urinary bladder carcinoma.

PubMed

Bunimovich-Mendrazitsky, Svetlana; Pisarev, Vladimir; Kashdan, Eugene

2015-03-01

In this work, we present a mathematical model of the initiation and progression of a low-grade urinary bladder carcinoma. We simulate the crucial processes affecting tumor growth, such as oxygen diffusion, carcinogen penetration, and angiogenesis, within the framework of the urothelial cell dynamics. The cell dynamics are modeled using the discrete technique of cellular automata, while the continuous processes of carcinogen penetration and oxygen diffusion are described by nonlinear diffusion-absorption equations. As the availability of oxygen is necessary for tumor progression, processes of oxygen transport to the tumor growth site seem most important. Our model yields a theoretical insight into the main stages of development and growth of urinary bladder carcinoma with emphasis on the two most common types: bladder polyps and carcinoma in situ. Analysis of histological structure of bladder tumor is important to avoid misdiagnosis and wrong treatment. We expect our model to be a valuable tool in the study of bladder cancer progression due to the exposure to carcinogens and the oxygen dependent expression of genes promoting tumor growth. Our numerical simulations have good qualitative agreement with in vivo results reported in the corresponding medical literature. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early dynamic imaging in 68Ga- PSMA-11 PET/CT allows discrimination of urinary bladder activity and prostate cancer lesions.

PubMed

Uprimny, Christian; Kroiss, Alexander Stephan; Decristoforo, Clemens; Fritz, Josef; Warwitz, Boris; Scarpa, Lorenza; Roig, Llanos Geraldo; Kendler, Dorota; von Guggenberg, Elisabeth; Bektic, Jasmin; Horninger, Wolfgang; Virgolini, Irene Johanna

2017-05-01

PET/CT with 68 Ga-labelled prostate-specific membrane antigen (PSMA)-ligands has been proven to establish a promising imaging modality in the work-up of prostate cancer (PC) patients with biochemical relapse. Despite a high overall detection rate, the visualisation of local recurrence may be hampered by high physiologic tracer accumulation in the urinary bladder on whole body imaging, usually starting 60 min after injection. This study sought to verify whether early dynamic 68 Ga-PSMA-11 (HBED-CC)PET/CT can differentiate pathologic PC-related tracer uptake from physiologic tracer accumulation in the urinary bladder. Eighty consecutive PC patients referred to 68 Ga -PSMA-11 PET/CT were included in this retrospective analysis (biochemical relapse: n = 64; primary staging: n = 8; evaluation of therapy response/restaging: n = 8). In addition to whole-body PET/CT acquisition 60 min post injection early dynamic imaging of the pelvis in the first 8 min after tracer injection was performed. SUV max of pathologic lesions was calculated and time-activity curves were generated and compared to those of urinary bladder and areas of physiologic tracer uptake. A total of 55 lesions consistent with malignancy on 60 min whole body imaging exhibited also pathologic 68 Ga-PSMA-11 uptake during early dynamic imaging (prostatic bed/prostate gland: n = 27; lymph nodes: n = 12; bone: n = 16). All pathologic lesions showed tracer uptake within the first 3 min, whereas urinary bladder activity was absent within the first 3 min of dynamic imaging in all patients. Suv max was significantly higher in PC lesions in the first 6 min compared to urinary bladder accumulation (p < 0.001). In the subgroup of PC patients with biochemical relapse the detection rate of local recurrence could be increased from 20.3 to 29.7%. Early dynamic imaging in 68 Ga-PSMA-11 PET/CT reliably enables the differentiation of pathologic tracer uptake in PC lesions from physiologic bladder accumulation. Performance of early dynamic imaging in addition to whole body imaging 60 min after tracer injection might improve the detection rate of local recurrence in PC patients with biochemical relapse referred for 68 Ga-PSMA-11 PET/CT.

Identification of differentially expressed proteins during human urinary bladder cancer progression.

PubMed

Memon, Ashfaque A; Chang, Jong W; Oh, Bong R; Yoo, Yung J

2005-01-01

Comparative proteome analysis was performed between RT4 (grade-1) and T24 (grade-3) bladder cancer cell lines, in an attempt to identify differentially expressed proteins during bladder cancer progression. Among those relatively abundant proteins, seven spots changed more than two-fold reproducibly and identified by peptide mass fingerprinting using mass spectrometry and database search. We found most extensive and reproducible down-regulation of NADP dependent isocitrate dehydrogenase cytoplasmic (IDPc) and peroxiredoxin-II (Prx-II), in poorly differentiated T24 compared to well-differentiated RT4 bladder cancer cell line. Subsequent Western blotting analysis of human biopsy samples from bladder cancer patient revealed significant loss of IDPc and Prx-II in more advance tumor samples, in agreement with data on cell lines. These results suggest that loss of IDPc and Prx-II during tumor development may involve in tumor progression and metastasis. However, additional investigations are needed on large number of human samples to further verify these findings.

Differentiation of human endometrial stem cells into urothelial cells on a three-dimensional nanofibrous silk-collagen scaffold: an autologous cell resource for reconstruction of the urinary bladder wall.

PubMed

Shoae-Hassani, Alireza; Mortazavi-Tabatabaei, Seyed Abdolreza; Sharif, Shiva; Seifalian, Alexander Marcus; Azimi, Alireza; Samadikuchaksaraei, Ali; Verdi, Javad

2015-11-01

Reconstruction of the bladder wall via in vitro differentiated stem cells on an appropriate scaffold could be used in such conditions as cancer and neurogenic urinary bladder. This study aimed to examine the potential of human endometrial stem cells (EnSCs) to form urinary bladder epithelial cells (urothelium) on nanofibrous silk-collagen scaffolds, for construction of the urinary bladder wall. After passage 4, EnSCs were induced by keratinocyte growth factor (KGF) and epidermal growth factor (EGF) and seeded on electrospun collagen-V, silk and silk-collagen nanofibres. Later we tested urothelium-specific genes and proteins (uroplakin-Ia, uroplakin-Ib, uroplakin-II, uroplakin-III and cytokeratin 20) by immunocytochemistry, RT-PCR and western blot analyses. Scanning electron microscopy (SEM) and histology were used to detect cell-matrix interactions. DMEM/F12 supplemented by KGF and EGF induced EnSCs to express urothelial cell-specific genes and proteins. Either collagen, silk or silk-collagen scaffolds promoted cell proliferation. The nanofibrous silk-collagen scaffolds provided a three-dimensional (3D) structure to maximize cell-matrix penetration and increase differentiation of the EnSCs. Human EnSCs seeded on 3D nanofibrous silk-collagen scaffolds and differentiated to urothelial cells provide a suitable source for potential use in bladder wall reconstruction in women. Copyright © 2013 John Wiley & Sons, Ltd.

Modulation of gene expression and cell-cycle signaling pathways by the EGFR inhibitor gefitinib (Iressa) in rat urinary bladder cancer.

PubMed

Lu, Yan; Liu, Pengyuan; Van den Bergh, Francoise; Zellmer, Victoria; James, Michael; Wen, Weidong; Grubbs, Clinton J; Lubet, Ronald A; You, Ming

2012-02-01

The epidermal growth factor receptor inhibitor Iressa has shown strong preventive efficacy in the N-butyl-N-(4-hydroxybutyl)-nitrosamine (OH-BBN) model of bladder cancer in the rat. To explore its antitumor mechanism, we implemented a systems biology approach to characterize gene expression and signaling pathways in rat urinary bladder cancers treated with Iressa. Eleven bladder tumors from control rats, seven tumors from rats treated with Iressa, and seven normal bladder epithelia were profiled by the Affymetrix Rat Exon 1.0 ST Arrays. We identified 713 downregulated and 641 upregulated genes in comparing bladder tumors versus normal bladder epithelia. In addition, 178 genes were downregulated and 96 genes were upregulated when comparing control tumors versus Iressa-treated tumors. Two coexpression modules that were significantly correlated with tumor status and treatment status were identified [r = 0.70, P = 2.80 × 10(-15) (bladder tumor vs. normal bladder epithelium) and r = 0.63, P = 2.00 × 10(-42) (Iressa-treated tumor vs. control tumor), respectively]. Both tumor module and treatment module were enriched for genes involved in cell-cycle processes. Twenty-four and twenty-one highly connected hub genes likely to be key drivers in cell cycle were identified in the tumor module and treatment module, respectively. Analysis of microRNA genes on the array chips showed that tumor module and treatment module were significantly associated with expression levels of let-7c (r = 0.54, P = 3.70 × 10(-8) and r = 0.73, P = 1.50 × 10(-65), respectively). These results suggest that let-7c downregulation and its regulated cell-cycle pathway may play an integral role in governing bladder tumor suppression or collaborative oncogenesis and that Iressa exhibits its preventive efficacy on bladder tumorigenesis by upregulating let-7 and inhibiting the cell cycle. Cell culture study confirmed that the increased expression of let-7c decreases Iressa-treated bladder tumor cell growth. The identified hub genes may also serve as pharmacodynamic or efficacy biomarkers in clinical trials of chemoprevention in human bladder cancer. ©2011 AACR.

Who Should Be Investigated for Haematuria? Results of a Contemporary Prospective Observational Study of 3556 Patients.

PubMed

Tan, Wei Shen; Feber, Andrew; Sarpong, Rachael; Khetrapal, Pramit; Rodney, Simon; Jalil, Rumana; Mostafid, Hugh; Cresswell, Joanne; Hicks, James; Rane, Abhay; Henderson, Alastair; Watson, Dawn; Cherian, Jacob; Williams, Norman; Brew-Graves, Chris; Kelly, John D

2018-07-01

There remains a lack of consensus among guideline relating to which patients require investigation for haematuria. We determined the incidence of urinary tract cancer in a prospective observational study of 3556 patients referred for investigation of haematuria across 40 hospitals between March 2016 and June 2017 (DETECT 1; ClinicalTrials.gov: NCT02676180) and the appropriateness of age at presentation in cases with visible (VH) and nonvisible (NVH) haematuria. The overall incidence of urinary tract cancer was 10.0% (bladder cancer 8.0%, renal parenchymal cancer 1.0%, upper tract transitional cell carcinoma 0.7%, and prostate cancer 0.3%). Patients with VH were more likely to have a diagnosis of urinary tract cancer compared with NVH patients (13.8% vs 3.1%). Older patients, male gender, and smoking history were independently associated with urinary tract cancer diagnosis. Of bladder cancers diagnosed following NVH, 59.4% were high-risk cancers, with 31.3% being muscle invasive. The incidence of cancer in VH patients <45 yr of age was 3.5% (n=7) and 1.0% (n=4) in NVH patients <60 yr old. Our results suggest that patients with VH should be investigated regardless of age. Although the risk of urinary tract cancer in NVH patients is low, clinically significant cancers are detected below the age threshold for referral for investigation. This study highlights the requirement to investigate all patients with visible blood in the urine and an age threshold of ≥60 yr, as recommended in some guidelines, as the investigation of nonvisible blood in the urine will miss a significant number of urinary tract cancers. Patient preference is important, and evidence that patients are willing to submit to investigation should be considered in reaching a consensus recommendation for the investigation of haematuria. International consensus to guide that patients will benefit from investigation should be developed. Copyright © 2018. Published by Elsevier B.V.

Excess risk of urinary tract cancers in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study.

PubMed

Bourrier, A; Carrat, F; Colombel, J-F; Bouvier, A-M; Abitbol, V; Marteau, P; Cosnes, J; Simon, T; Peyrin-Biroulet, L; Beaugerie, L

2016-01-01

The risk of urinary tract cancers, including kidney and bladder cancers, was increased in transplant recipients receiving thiopurines. To assess the risk of urinary tract cancers in patients with inflammatory bowel disease (IBD) receiving thiopurines in the CESAME observational cohort. Between May 2004 and June 2005, 19 486 patients with IBD, 30.1% of whom were receiving thiopurines, were enrolled. Median follow-up was 35 months (IQR: 29-40). Ten and six patients developed respectively kidney and bladder cancer. The incidence rates of urinary tract cancer were 0.48/1000 patient-years in patients receiving thiopurines (95% CI: 0.21-0.95), 0.10/1000 patient-years in patients who discontinued thiopurines (95% CI: 0.00-0.56) and 0.30/1000 patient-years in patients never treated with thiopurines (95% CI: 0.12-0.62) at entry. The standardised incidence ratio of urinary tract cancer was 3.40 (95% CI: 1.47-6.71, P = 0.006) in patients receiving thiopurines, 0.64 (95% CI: 0.01-3.56, P = 0.92) in patients previously exposed to thiopurines and 1.17 (95% CI: 0.47-12.42, P = 0.78) in patients never treated with thiopurines. The multivariate-adjusted hazard ratio (HR) of urinary tract cancer between patients receiving thiopurines and those not receiving thiopurines was 2.82 (95% CI: 1.04-7.68, P = 0.04). Other significant risk factors were male gender (HR: 3.98, 95% CI: 1.12-14.10, P = 0.03) and increasing age (HR after 65 years (ref <50): 13.26, 95% CI: 3.52-50.03, P = 0.0001). Patients with IBD receiving thiopurines have an increased risk of urinary tract cancers. Clinically relevant excess risk is observed in older men. © 2015 John Wiley & Sons Ltd.

Unusual asymptomatic presentation of bladder cancer metastatic to the penis.

PubMed

Giunchi, Francesca; Vasuri, Francesco; Valerio, Vagnoni; Montagnani, Ilaria; Nelli, Federico; Fiorentino, Michelangelo; Raspollini, Maria Rosaria

2017-06-01

Penile metastasis is an extremely rare event and mainly originate from primary pelvic tumor sites such us urinary bladder, gastro-intestinal tract and prostate and more rarely from respiratory system, bone tumors and melanoma. Here we describe the unusual presentation of two bladder urothelial cancer metastatic to the penis with no relevant clinical symptoms. Namely, a 69 years-old man with a warthy lesions of the foreskin and the glans misunderstood for a condylomata that at histological and immunohistochemical analysis showed a bladder urothelial carcinoma; and a 71 years-old man with reddish skin lesion of the glans, a previous history of bladder and urethral carcinoma and histological pagetoid spread of urothelial cancer to the glans. Recurrent bladder urothelial carcinoma is usually a visceral disease that rarely presents as a superficial asymptomatic skin lesion. The two reported cases were asymptomatic superficial penis metastases with a relatively slow growth and a fairy good prognosis after conservative surgical approach. Accurate clinical examination of the penis is mandatory for males with history of bladder cancer. Copyright © 2016 Elsevier GmbH. All rights reserved.

17-DMAG induces heat shock protein 90 functional impairment in human bladder cancer cells: knocking down the hallmark traits of malignancy.

PubMed

Karkoulis, Panagiotis K; Stravopodis, Dimitrios J; Voutsinas, Gerassimos E

2016-05-01

Heat shock protein 90 (Hsp90) is a molecular chaperone that maintains the structural and functional integrity of various protein clients involved in multiple oncogenic signaling pathways. Hsp90 holds a prominent role in tumorigenesis, as numerous members of its broad clientele are involved in the generation of the hallmark traits of cancer. 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) specifically targets Hsp90 and interferes with its function as a molecular chaperone, impairing its intrinsic ATPase activity and undermining proper folding of multiple protein clients. In this study, we have examined the effects of 17-DMAG on the regulation of Hsp90-dependent tumorigenic signaling pathways directly implicated in cell cycle progression, survival, and motility of human urinary bladder cancer cell lines. We have used MTT-based assays, FACS analysis, Western blotting, semiquantitative PCR (sqPCR), immunofluorescence, and scratch-wound assays in RT4 (p53(wt)), RT112 (p53(wt)), T24 (p53(mt)), and TCCSUP (p53(mt)) human urinary bladder cancer cell lines. We have demonstrated that, upon exposure to 17-DMAG, bladder cancer cells display prominent cell cycle arrest and commitment to apoptotic and autophagic cell death, in a dose-dependent manner. Furthermore, 17-DMAG administration induced pronounced downregulation of multiple Hsp90 protein clients and other downstream oncogenic effectors, therefore causing inhibition of cell proliferation and decline of cell motility due to the molecular "freezing" of critical cytoskeletal components. In toto, we have clearly demonstrated the dose-dependent and cell type-specific effects of 17-DMAG on the hallmark traits of cancer, appointing Hsp90 as a key molecular component in bladder cancer targeted therapy.

Urinary Exosomes: The Potential for Biomarker Utility, Intercellular Signaling and Therapeutics in Urological Malignancy.

PubMed

Franzen, Carrie A; Blackwell, Robert H; Foreman, Kimberly E; Kuo, Paul C; Flanigan, Robert C; Gupta, Gopal N

2016-05-01

Exosomes are small secreted vesicles that contain proteins, mRNA and miRNA with the potential to alter signaling pathways in recipient cells. While exosome research has flourished, few publications have specifically considered the role of genitourinary cancer shed exosomes in urine, their implication in disease progression and their usefulness as noninvasive biomarkers. In this review we examined the current literature on the role of exosomes in intercellular communication and as biomarkers, and their potential as delivery vehicles for therapeutic applications in bladder, prostate and renal cancer. We searched PubMed® and Google® with the key words prostate cancer, bladder cancer, kidney cancer, exosomes, microvesicles and urine. Relevant articles, including original research studies and reviews, were selected based on contents. A review of this literature was generated. Cancer exosomes can be isolated from urine using various techniques. Cancer cells have been found to secrete more exosomes than normal cells. These exosomes have a role in cellular communication by interacting with and depositing their cargo in target cells. Bladder, prostate and renal cancer exosomes have been shown to enhance migration, invasion and angiogenesis. These exosomes have also been shown to increase proliferation, confer drug resistance and promote immune evasion. Urinary exosomes can be isolated from bladder, kidney and prostate cancer. They serve as a potential reservoir for biomarker identification. Exosomes also have potential for therapeutics as siRNA or pharmacological agents can be loaded into exosomes. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Effect of furosemide administration before F-18 fluorodeoxyglucose positron emission tomography/computed tomography on urine radioactivity and detection of uterine cervical cancer.

PubMed

d'Amico, Andrea; Gorczewska, Izabela; Gorczewski, Kamil; Turska-d'Amico, Maria; Di Pietro, Marco

2014-01-01

In evaluating uterine cervical cancer with ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT), there may be overlap between the FDG activity at tumor sites and nonspecific radioactivity in the urine. We evaluated the efficacy of furosemide premedication with routine hydration to obtain better contrast and less overlap between cervical cancer and the urinary bladder. We retrospectively evaluated 166 patients who had primary or relapsed cervical cancer and underwent FDG PET/CT scanning with (133 patients) or without (33 patients) furosemide premedication (10 mg intravenous, slowly injected 30 min before the scan). We calculated bladder and tumor maximum and median standardized uptake value (SUVmax and SUVmed), and overlap between tumor and urinary activity was detected visually. Overlap between urinary and tumor radioactivity was observed in 8 of 133 scans (6%) in patients who receive furosemide and in 3 of 33 scans (9%) in patients who did not receive furosemide. The SUVmax and SUVmed for the bladder were significantly lower in patients who were pretreated with furosemide (SUVmax, 6.3; SUVmed, 4.6) than patients who were not pretreated with furosemide (SUVmax, 8.8 [P ≤ 0.008]; SUVmed, 6.5 [P ≤ 0.002]). The tumor SUVmax and SUVmed were similar between the patient groups. Furosemide premedication before FDG PET/CT scanning may enable improved evaluation of activity and extension of cervical cancer.

Urinary long noncoding RNAs in nonmuscle-invasive bladder cancer: new architects in cancer prognostic biomarkers.

PubMed

Terracciano, Daniela; Ferro, Matteo; Terreri, Sara; Lucarelli, Giuseppe; D'Elia, Carolina; Musi, Gennaro; de Cobelli, Ottavio; Mirone, Vincenzo; Cimmino, Amelia

2017-06-01

Several reports over the last 10 years provided evidence that long noncoding RNAs (lncRNAs) are often altered in bladder cancers. lncRNAs are longer than 200 nucleotides and function as important regulators of gene expression, interacting with the major pathways of cell growth, proliferation, differentiation, and survival. A large number of lncRNAs has oncogenic function and is more expressed in tumor compared with normal tissues. Their overexpression may be associated with tumor formation, progression, and metastasis in a variety of tumors including bladder cancer. Although lncRNAs have been shown to have critical regulatory roles in cancer biology, the biological functions and prognostic values in nonmuscle-invasive bladder cancer remain largely unknown. Nevertheless, a growing body of evidence suggests that several lncRNAs expression profiles in bladder malignancies are associated with poor prognosis, and they can be detected in biological fluids, such as urines. Here, we review current progress in the biology and the implication of lncRNAs associated with bladder cancer, and we discuss their potential use as diagnosis and prognosis biomarkers in bladder malignancies with a focus on their role in high-risk nonmuscle-invasive tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

Speciation of arsenic in exfoliated urinary bladder epithelial cells from individuals exposed to arsenic in drinking water.

PubMed

Hernández-Zavala, Araceli; Valenzuela, Olga L; Matousek, Tomás; Drobná, Zuzana; Dĕdina, Jirí; García-Vargas, Gonzalo G; Thomas, David J; Del Razo, Luz M; Stýblo, Miroslav

2008-12-01

The concentration of arsenic in urine has been used as a marker of exposure to inorganic As (iAs). Relative proportions of urinary metabolites of iAs have been identified as potential biomarkers of susceptibility to iAs toxicity. However, the adverse effects of iAs exposure are ultimately determined by the concentrations of iAs metabolites in target tissues. In this study we examined the feasibility of analyzing As species in cells that originate in the urinary bladder, a target organ for As-induced cancer in humans. Exfoliated bladder epithelial cells (BECs) were collected from urine of 21 residents of Zimapan, Mexico, who were exposed to iAs in drinking water. We determined concentrations of iAs, methyl-As (MAs), and dimethyl-As (DMAs) in urine using conventional hydride generation-cryotrapping-atomic absorption spectrometry (HG-CT-AAS). We used an optimized HG-CT-AAS technique with detection limits of 12-17 pg As for analysis of As species in BECs. All urine samples and 20 of 21 BEC samples contained detectable concentrations of iAs, MAs, and DMAs. Sums of concentrations of these As species in BECs ranged from 0.18 to 11.4 ng As/mg protein and in urine from 4.8 to 1,947 ng As/mL. We found no correlations between the concentrations or ratios of As species in BECs and in urine. These results suggest that urinary levels of iAs metabolites do not necessarily reflect levels of these metabolites in the bladder epithelium. Thus, analysis of As species in BECs may provide a more effective tool for risk assessment of bladder cancer and other urothelial diseases associated with exposures to iAs.

Non-invasive quantification of tumour heterogeneity in water diffusivity to differentiate malignant from benign tissues of urinary bladder: a phase I study.

PubMed

Nguyen, Huyen T; Shah, Zarine K; Mortazavi, Amir; Pohar, Kamal S; Wei, Lai; Jia, Guang; Zynger, Debra L; Knopp, Michael V

2017-05-01

To quantify the heterogeneity of the tumour apparent diffusion coefficient (ADC) using voxel-based analysis to differentiate malignancy from benign wall thickening of the urinary bladder. Nineteen patients with histopathological findings of their cystectomy specimen were included. A data set of voxel-based ADC values was acquired for each patient's lesion. Histogram analysis was performed on each data set to calculate uniformity (U) and entropy (E). The k-means clustering of the voxel-wised ADC data set was implemented to measure mean intra-cluster distance (MICD) and largest inter-cluster distance (LICD). Subsequently, U, E, MICD, and LICD for malignant tumours were compared with those for benign lesions using a two-sample t-test. Eleven patients had pathological confirmation of malignancy and eight with benign wall thickening. Histogram analysis showed that malignant tumours had a significantly higher degree of ADC heterogeneity with lower U (P = 0.016) and higher E (P = 0.005) than benign lesions. In agreement with these findings, k-means clustering of voxel-wise ADC indicated that bladder malignancy presented with significantly higher MICD (P < 0.001) and higher LICD (P = 0.002) than benign wall thickening. The quantitative assessment of tumour diffusion heterogeneity using voxel-based ADC analysis has the potential to become a non-invasive tool to distinguish malignant from benign tissues of urinary bladder cancer. • Heterogeneity is an intrinsic characteristic of tumoral tissue. • Non-invasive quantification of tumour heterogeneity can provide adjunctive information to improve cancer diagnosis accuracy. • Histogram analysis and k-means clustering can quantify tumour diffusion heterogeneity. • The quantification helps differentiate malignant from benign urinary bladder tissue.

Phase I/II Study of IMMU-132 in Patients With Epithelial Cancers

ClinicalTrials.gov

2018-04-23

Colorectal Cancer; Gastric Adenocarcinoma; Esophageal Cancer; Hepatocellular Carcinoma; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Ovarian Epithelial Cancer; Carcinoma Breast Stage IV; Hormone-refractory Prostate Cancer; Pancreatic Ductal Adenocarcinoma; Head and Neck Cancers- Squamous Cell; Renal Cell Cancer; Urinary Bladder Neoplasms; Cervical Cancer; Endometrial Cancer; Follicular Thyroid Cancer; Glioblastoma Multiforme; Triple Negative Breast Cancer

Oncogenic role of fibroblast growth factor receptor 3 in tumorigenesis of urinary bladder cancer.

PubMed

Pandith, Arshad A; Shah, Zafar A; Siddiqi, Mushtaq A

2013-05-01

Bladder cancer is the second most common genitourinary tumor and constitutes a very heterogeneous disease. Molecular and pathologic studies suggest that low-grade noninvasive and high-grade invasive urothelial cell carcinoma (UCC) arise via distinct pathways. Low-grade noninvasive UCC represent the majority of tumors at presentation. A high proportion of patients with low-grade UCC develop recurrences but usually with no progression to invasive disease. At presentation, a majority of the bladder tumors (70%-80%) are low-grade noninvasive (pTa). Several genetic changes may occur in bladder cancer, but activating mutations in the fibroblast growth factor receptor 3 (FGFR3) genes are the most common and most specific genetic abnormality in bladder cancer. Interestingly, these mutations are associated with bladder tumors of low stage and grade, which makes the FGFR3 mutation the first marker that can be used for diagnosis of noninvasive bladder tumors. Since the first report of FGFR3 involvement in bladder tumors, numerous studies have been conducted to understand its function and thereby confirm the oncogenic role of this receptor particularly in noninvasive groups. Efforts are on to exploit this receptor as a therapeutic target, which holds much promise in the treatment of bladder cancer, particularly low-grade noninvasive tumors. Further studies need to explore the potential use of FGFR3 mutations in bladder cancer diagnosis, prognosis, and in surveillance of patients with bladder cancer. This review focuses on the role of FGFR3 in bladder tumors in the backdrop of various studies published. Copyright © 2013 Elsevier Inc. All rights reserved.

Pitfalls and Limitations of Diffusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Urinary Bladder Cancer

PubMed Central

Lin, Wei-Ching; Chen, Jeon-Hor

2015-01-01

Adequately selecting a therapeutic approach for bladder cancer depends on accurate grading and staging. Substantial inaccuracy of clinical staging with bimanual examination, cystoscopy, and transurethral resection of bladder tumor has facilitated the increasing utility of magnetic resonance imaging to evaluate bladder cancer. Diffusion-weighted imaging (DWI) is a noninvasive functional magnetic resonance imaging technique. The high tissue contrast between cancers and surrounding tissues on DWI is derived from the difference of water molecules motion. DWI is potentially a useful tool for the detection, characterization, and staging of bladder cancers; it can also monitor posttreatment response and provide information on predicting tumor biophysical behaviors. Despite advancements in DWI techniques and the use of quantitative analysis to evaluate the apparent diffusion coefficient values, there are some inherent limitations in DWI interpretation related to relatively poor spatial resolution, lack of cancer specificity, and lack of standardized image acquisition protocols and data analysis procedures that restrict the application of DWI and reproducibility of apparent diffusion coefficient values. In addition, inadequate bladder distension, artifacts, thinness of bladder wall, cancerous mimickers of normal bladder wall and benign lesions, and variations in the manifestation of bladder cancer may interfere with diagnosis and monitoring of treatment. Recognition of these pitfalls and limitations can minimize their impact on image interpretation, and carefully applying the analyzed results and combining with pathologic grading and staging to clinical practice can contribute to the selection of an adequate treatment method to improve patient care. PMID:26055180

Colon pouch (Mainz III) for continent urinary diversion.

PubMed

Stolzenburg, Jens-Uwe; Schwalenberg, Thilo; Liatsikos, Evangelos N; Sakelaropoulos, George; Rödder, Kilian; Hohenfellner, Rudolph; Fisch, Margit

2007-06-01

To evaluate the use of a continent cutaneous pouch made exclusively of colon (Mainz pouch III), as excellent results with the Mainz pouch III in irradiated patients suggested that the indication for this type of urinary diversion could be extended. The outcome of 24 patients with continent cutaneous urinary diversions using colon segments (Mainz pouch III) was investigated retrospectively. Overall, 22 of the patients had a malignant disease and two a benign disease; 16 had a hysterectomy and pelvic exenteration for gynaecological tumours; two men with a rhabdomyosarcoma of the prostate had a radical cystoprostatectomy; one woman had pelvic exenteration for bladder cancer; one man had a simultaneous rectum resection due to infiltrating rectal cancer, and another a left nephrectomy with cystectomy for concomitant kidney and bladder tumour. Benign indications were hyper-reflexive bladder after polytrauma and two cases of neurogenic bladder dysfunction. Eighteen patients had radiotherapy (32-48 Gy) before the urinary diversion. The mean (range) follow-up was 35 (12-65) months. The mean pouch capacity was 293.8 mL. Three patients died during the follow-up (two from disease progression and one suicide); 20 patients were fully continent, four with reduced pouch capacity (<300 mL) had slight incontinence and are wearing a protective pad (band-aid at the umbilicus). All patients use intermittent self-catheterization (mean catheterization frequency 6.8/day, range 6-12). Complications related to the pouch were one outlet stenosis that required revision. Postoperative pouchograms showed asymptomatic reflux in four patients. None of the patients developed metabolic acidosis or diarrhoea. The Mainz pouch III is an alternative to other types of continent urinary diversion.

Small-cell carcinoma of the urinary bladder: where do we stand?

PubMed Central

GHERVAN, LIVIU; ZAHARIE, ANDREEA; ENE, BOGDAN; ELEC, FLORIN I.

2017-01-01

Small-cell carcinoma of the urinary bladder is a very rare pathology, but with a very aggressive behavior and disappointing prognosis. The literature concerning this type of cancer is scarce and physicians may encounter difficulty trying to manage it. Most articles involve the study of case series, without definite results due to the small number of patients. The present article aims at gathering the most significant articles and results in order to offer a broad perspective on the existing literature concerning this pathology. PMID:28246491

Risk factors for bladder cancer: challenges of conducting a literature search using PubMed.

PubMed

Joshi, Ashish; Preslan, Elicia

2011-04-01

The objective of this study was to assess the risk factors for bladder cancer using PubMed articles from January 2000 to December 2009. The study also aimed to describe the challenges encountered in the methodology of a literature search for bladder cancer risk factors using PubMed. Twenty-six categories of risk factors for bladder cancer were identified using the National Cancer Institute Web site and the Medical Subject Headings (MeSH) Web site. A total of 1,338 PubMed searches were run using the term "urinary bladder cancer" and a risk factor term (e.g., "cigarette smoking") and were screened to identify 260 articles for final analysis. The search strategy had an overall precision of 3.42 percent, relative recall of 12.64 percent, and an F-measure of 5.39 percent. Although search terms derived from MeSH had the highest overall precision and recall, the differences did not reach significance, which indicates that for generalized, free-text searches of the PubMed database, the searchers' own terms are generally as effective as MeSH terms.

Low Temperature Plasma Kills SCaBER Cancer Cells

NASA Astrophysics Data System (ADS)

Barekzi, Nazir; van Way, Lucas; Laroussi, Mounir

2013-09-01

Squamous cell carcinoma of the bladder is a rare type of bladder cancer that forms as a result of chronic irritation of the epithelial lining of the bladder. The cell line used in this study is SCaBER (ATCC® HTB-3™) derived from squamous cell carcinoma of the human urinary bladder. Current treatments of bladder cancer include surgery, radiation and chemotherapy. However, the cost of these treatments, the potential toxicity of the chemotherapeutic agents and the systemic side-effects warrant an alternative to current cancer treatment. This paper represents preliminary studies to determine the effects of biologically tolerant plasma (BTP) on a cell line of human bladder cancer cells. Previous work by our group using the plasma pencil revealed the efficacy of BTP on leukemia cells suspended in solution. Based on these earlier findings we hypothesized that the plasma exposure would elicit a similar programmed cell death in the SCaBER cells. Trypan blue exclusion and MTT assays revealed the cell killing after exposure to BTP. Our study indicates that low temperature plasma generated by ionizing helium gas and the reactive species may be a suitable and safe alternative for cancer therapy.

Sex disparities in diagnosis of bladder cancer after initial presentation with hematuria: a nationwide claims-based investigation.

PubMed

Cohn, Joshua A; Vekhter, Benjamin; Lyttle, Christopher; Steinberg, Gary D; Large, Michael C

2014-02-15

Women have disproportionately higher mortality rates relative to incidence for bladder cancer. Multiple etiologies have been proposed, including delayed diagnosis and treatment. Guidelines recommend ruling out malignancy in men and women presenting with hematuria. This study sought to determine the difference in timing from presentation with hematuria to diagnosis of bladder cancer in women versus men. This is a retrospective population-based study examining the timing from presentation with hematuria to diagnosis of bladder cancer, based on data from the MarketScan databases, which include enrollees of more than 100 health insurance plans of approximately 40 large US employers from 2004 through 2010. All study patients presented with hematuria and were subsequently diagnosed with bladder cancer. The primary outcome measure was number of days between initial presentation with hematuria and diagnosis of bladder cancer by sex. A total of 5416 men and 2233 women met inclusion criteria. Mean days from initial hematuria claim to bladder cancer claim was significantly longer in women (85.4 versus 73.6 days, P < .001), and the proportion of women with >6 month delay in bladder cancer diagnosis was significantly higher (17.3% versus 14.1%, P < .001). Women were more likely to be diagnosed with urinary tract infection (odds ratio = 2.32, 95% confidence interval = 2.07-2.59) and less likely to undergo abdominal or pelvic imaging (odds ratio = 0.80, 95% confidence interval = 0.71-0.89). Both men and women experience significant delays between presentation with hematuria and diagnosis of bladder cancer, with longer delays for women. This may be partly responsible for the sex-based discrepancy in outcomes associated with bladder cancer. © 2013 American Cancer Society.

Protoporphyrin IX induced by 5-aminolevulinic acid in bladder cancer cells in voided urine can be extracorporeally quantified using a spectrophotometer.

PubMed

Nakai, Yasushi; Anai, Satoshi; Onishi, Sayuri; Masaomi, Kuwada; Tatsumi, Yoshihiro; Miyake, Makito; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

2015-06-01

We evaluated the feasibility of photodynamic diagnosis of bladder cancer by spectrophotometric analysis of voided urine samples after extracorporeal treatment with 5-aminolevulinic acid (ALA). Sixty-one patients with bladder cancer, confirmed histologically after the transurethral resection of a bladder tumor, were recruited as the bladder cancer group, and 50 outpatients without history of urothelial carcinoma or cancer-related findings were recruited as the control group. Half of the voided urine sample was incubated with ALA (ALA-treated sample), and the rest was incubated without treatment (ALA-untreated sample). For detecting cellular protoporphyrin IX levels, intensity of the samples at the excitation wavelength of 405 nm was measured using a spectrophotometer. The difference between the intensity of the ALA-treated and ALA-untreated samples at 635 nm was calculated. The differences in the bladder cancer group were significantly greater than those in the control group (p < 0.001). These differences were also significantly greater in patients with high-grade tumors than in those with low-grade tumors (p = 0.004), and also in patients with invasive bladder cancer than in those with noninvasive bladder cancer (p = 0.007). The area under the curve was 0.84. Sensitivity and specificity of the method were 82% and 80%, respectively. We demonstrated that protoporphyrin IX levels in urinary cells treated with ALA could be quantitatively detected by spectrophotometer in patients with bladder cancer. Therefore, this cancer detection system has a potential for clinical use. Copyright © 2015 Elsevier B.V. All rights reserved.

Urinary incontinence a first presentation of central pontine myelinolysis: a case report.

PubMed

Syed, Asmah Hassan; Shak, Joanna; Alsawaf, Ali

2015-09-01

An 84-year-old lady was treated for hyperosmolar hyperglycaemia with IV insulin, fluids and catheterisation for fluid balance monitoring. Trial without catheter failed as the patient complained of new-onset urinary incontinence and lack of awareness of bladder filling. In light of her breast cancer history, we excluded cauda equina. Ultrasound KUB showed an enlarged bladder. Whole-body MRI revealed a lesion in the pons which was highly suggestive of central pontine myelinolysis (CPM). Her electrolytes were normal throughout her admission; thus, the rapid fluctuation in osmolality, secondary to her hyperglycaemic state, was the likely cause of CPM. CPM has been reported secondary to hyperglycaemia; however, this is the first reported case of CPM presenting as urinary incontinence and loss of bladder sensation. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Optimal Timing of Chemotherapy and Surgery in Patients with Muscle-Invasive Bladder Cancer and Upper Urinary Tract Urothelial Carcinoma.

PubMed

Tabayoyong, William; Li, Roger; Gao, Jianjun; Kamat, Ashish

2018-05-01

Radical cystectomy with bilateral pelvic lymph node dissection is the standard of care for patients with clinically localized muscle-invasive bladder cancer. Survival after radical cystectomy is associated with final pathologic staging. Survival decreases with increasing pT stage because of the presence of occult micrometastases, indicating the need for systemic chemotherapy. Systemic chemotherapy is delivered as either neoadjuvant therapy preoperatively, or as adjuvant therapy postoperatively. This article reviews the evidence for neoadjuvant and adjuvant chemotherapy for the treatment of muscle-invasive bladder and upper tract urothelial cancer and offers recommendations based on these data and recently updated clinical guidelines. Copyright © 2018 Elsevier Inc. All rights reserved.

Impact of dosimetric and clinical parameters on clinical side effects in cervix cancer patients treated with 3D pulse-dose-rate intracavitary brachytherapy.

PubMed

Levitchi, Mihai; Charra-Brunaud, Claire; Quetin, Philippe; Haie-Meder, Christine; Kerr, Christine; Castelain, Bernard; Delannes, Martine; Thomas, Laurence; Desandes, Emmanuel; Peiffert, Didier

2012-06-01

To assess the association between dosimetric/clinical parameters and gastrointestinal/urinary grade 2-4 side effects in cervix cancer patients treated with 3D pulse dose rate brachytherapy. Three hundred and fifty-two patients received brachytherapy associated with external-beam radiotherapy (EBRT) for 266 of them; 236 patients underwent surgery. The doses for the most exposed 2, and 0.1 cm(3) (D(2cc) and D(0.1cc)) volumes of the rectum and bladder as well as bladder ICRU point dose (D(ICRU)) were converted into isoeffective doses in 2-Gy fractions. The clinical parameters analyzed were: age, smoking habits, arteritis, diabetes, previous pelvic surgery, FIGO stage, nodal status, pathology, pelvic surgery, EBRT and chemotherapy. Side effects were prospectively assessed using the CTCAEv3.0. Cutoff dose levels were defined separately for patients treated with EBRT and brachytherapy (Group 1) and with preoperative brachytherapy (Group 2). The median follow-up was 23.4months. In Group 1 a significant predictive value of rectum D(0.1cc) and D(2cc), bladder D(0.1cc) and D(ICRU) for gastrointestinal and urinary toxicity was found using as cutoff 83, 68, 109 and 68Gy(α)(/)(β)(3). In Group 2 a significant predictive value of bladder D(0.1cc), D(2cc) and D(ICRU) for urinary toxicity was found using as cutoff 141, 91 and 67Gy(α)(/)(β)(3), but not for the rectum D(0.1cc) and D(2cc); smoking had a significant predictive value on urinary toxicity. For patients treated with brachytherapy and EBRT, rectum D(0.1cc) and D(2cc) and bladder D(0.1cc) and D(ICRU) had a predictive value for toxicity. For patients treated with preoperative brachytherapy, bladder D(0.1cc), D(2cc) and D(ICRU) and smoking had a predictive value for urinary toxicity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Urinary bladder cancer risk factors in an area of former coal, iron, and steel industries in Germany.

PubMed

Krech, Eugen; Selinski, Silvia; Blaszkewicz, Meinolf; Bürger, Hannah; Kadhum, Thura; Hengstler, Jan G; Truss, Michael C; Golka, Klaus

2017-01-01

This study was performed to investigate the frequency of bladder cancer in patients with an occupational history such as underground hard coal mining and/or painting after the structural change in the local industry. A total of 206 patients with bladder cancer and 207 controls were enlisted regarding occupational and nonoccupational bladder cancer risk factors by questionnaire. The phase II enzymes N-acetyltransferase 2 (NAT2), glutathione S-transferases M1 (GSTM1), and T1 (GSTT1) and the single nucleotide polymorphism (SNP) rs11892031[A/C] reported to be associated with bladder cancer in genome-wide association studies were genotyped. The bladder cancer risk in varnishers and underground hard coal miners was increased as previously shown in a study in this area performed in the 1980s. The occupation of a car mechanic was associated with a significantly elevated bladder cancer risk and higher in the case of underground hard coal miners even though the mine was closed in 1987. The frequency of GSTM1 negative genotype was comparable in cases and controls (53% versus 54%). In the case of NAT2, the slow NAT2 genotype was more frequent (62% versus 58%) and ultra-slow NAT2 genotype (NAT2*6A and/or *7B alleles only) was 23% versus 15%. An occupational history of a varnisher or an underground hard coal miner remains a risk factor for bladder cancer occurrence. Data indicate that in the case of bladder cancer, GSTM1 is a susceptibility factor related to environmental and/or occupational exposure.

Hem-o-lok clip: a neglected cause of severe bladder neck contracture and consequent urinary incontinence after robot-assisted laparoscopic radical prostatectomy.

PubMed

Cormio, Luigi; Massenio, Paolo; Lucarelli, Giuseppe; Di Fino, Giuseppe; Selvaggio, Oscar; Micali, Salvatore; Carrieri, Giuseppe

2014-02-20

Hem-o-lok clips are widely used during robot-assisted and laparoscopic radical prostatectomy to control the lateral pedicles. There are a few reports of hem-o-lok clip migration into the bladder or vesico-urethral anastomosis and only four cases of hem-o-lok clip migration resulting into bladder neck contracture. Herein, we describe the first case, to our knowledge, of hem-o-lok clip migration leading to severe bladder neck contracture and subsequent stress urinary incontinence. A 62-year-old Caucasian man underwent robot-assisted laparoscopic radical prostatectomy for a T1c Gleason 8 prostate cancer. One month after surgery the patient was fully continent; however, three months later, he presented with acute urinary retention requiring suprapubic drainage. Urethroscopy showed a hem-o-lok clip strongly attached to the area between the vesico-urethral anastomosis and the urethral sphincter and a severe bladder neck contracture behind it. Following cold-knife urethral incision and clip removal, the bladder neck contracture was widely resected. At 3-month follow-up, the patient voided spontaneously with a peak flow rate of 9.5 ml/sec and absence of post-void residual urine, but leaked 240 ml urine at the 24-hour pad test. To date, at 1-year follow-up, his voiding situation remains unchanged. The present report provides further evidence for the risk of hem-o-lok clip migration causing bladder neck contracture, and is the first to demonstrate the potential of such complication to result into stress urinary incontinence.

Recommended oral sodium bicarbonate administration for urine alkalinization did not affect the concentration of mitomycin-C in non-muscle invasive bladder cancer patients.

PubMed

Seo, Ho Kyung; Kim, Sung Han; Ahn, Kyung-Ohk; Lee, Sang-Jin; Park, Weon Seo; Kim, Sohee; Hwang, Sang-Hyun; Lee, Do Hoon; Joung, Jae Young; Chung, Jinsoo; Joo, Jungnam; Jeong, Kyung-Chae

2017-11-10

Sodium bicarbonate has been reported to maximize the efficacy of intravesical instillation of mitomycin-C (IVI-MMC) therapy by urine alkalinization in non-muscle-invasive bladder cancer (NMIBC). This study aimed to analyze the changes in MMC concentration according to urinary pH and evaluate the efficacy of sodium bicarbonate to maintain the concentration of active form of MMC during IVI-MMC. We prospectively enrolled 26 patients with NMIBC after transurethral resection of bladder tumor. Patients with very high-risk and low-risk NMIBC were excluded. Urinary creatinine, volume, pH, and concentrations of MMC and its degraded form were measured immediately before and after IVI-MMC. The patients were administered 1.5 g of oral sodium bicarbonate during the preceding evening, in the morning, and immediately before the fourth cycle of the six-cycle IVI-MMC. The correlation between MMC concentration and urinary pH changes was explored with or without oral bicarbonate therapy. Recurrence without progression to muscle-invasive disease was noted in 4 of 26 patients in a 23.7-month follow-up. The mean urinary pH before and after the therapy increased from 6.03 to 6.50, and 6.46 to 7.24, without or with oral SB therapy, respectively. Despite this increase, the concentration of active form of MMC did not change significantly. No correlation was found between urinary pH and MMC concentration. Urine alkalinization by SB administration did not maintain the high concentration of urinary MMC. Urine alkalinization by sodium bicarbonate administration for IVI-MMC did not maintain the high concentration of active urinary MMC in NMIBC.

[Local application of dimethyl sulfoxide at different concentrations to the prevention of radiation-induced damages in patient with cancer of the cervix uteri].

PubMed

Neklasova, N Iu; Sharinov, G M; Vinokurov, V L; Skrynditsa, G M

2006-01-01

to study the efficacy of dimethyl sulfoxide ((DMSO) at different concentrations in preventing radiation-induced rectal and urinary bladder damages in patients with cervix uteri cancer (CUC). combined radiation therapy (RT) was performed in 807 patients with CUC. In the control group (n = 221), RT was made, without applying radio-modified agents. An hour prior to a session of intracavitary irradiation, 10% DMSO solution was instilled into the rectum and urinary bladder in 113 patients and applications of metronidazole (MN) dissolved in 100% DSMO were made in 473 patients. Teleradiotherapy was performed, by using megavolt irradiation sources in the conventional fractionation mode; the total focal dose (TFD) was increased up to 40-46 Gy. Intracavitary irradiation was carried out on "AGAT-V" and "AGAT-VU" devices once weekly; the single focal dose in point A was 7 Gy; TFD was 49-56 Gy. 10% DMSO instillations reduced the incidence of late radiation-induced damages to the rectum and urinary bladder. In the control group, the incidence of these conditions was 19.0 and 9.5%, respectively; with the use of 10% DMSO, that was 8.8 and 7.1%. Applications of MN dissolved in 100% DMSO reduced the incidence of late radiation-induced damages to 1.7%. Local application of DMSO is a method for preventing late radiation-induced damages to the rectum and urinary bladder in patients with CUC. When the concentration of DMSO is increased, its preventive effect increases.

Management of transitional cell carcinoma of the urinary bladder in dogs: a review.

PubMed

Fulkerson, Christopher M; Knapp, Deborah W

2015-08-01

Transitional cell carcinoma (TCC), also referred to as urothelial carcinoma, is the most common form of urinary bladder cancer in dogs, affecting tens of thousands of dogs worldwide each year. Canine TCC is usually a high grade invasive cancer. Problems associated with TCC include urinary tract obstruction, distant metastases in >50% of affected dogs, and clinical signs that are troubling both to the dogs and to their owners. Risk factors for TCC include exposure to older types of flea control products and lawn chemicals, obesity, female sex, and a very strong breed-associated risk. This knowledge is allowing pet owners to take steps to reduce the risk of TCC in their dog. The diagnosis of TCC is made by histopathology of tissue biopsies obtained by cystoscopy, surgery, or catheter. Percutaneous aspirates and biopsies should be avoided due to the risk of tumor seeding. TCC is most commonly located in the trigone region of the bladder precluding complete surgical resection. Medical treatment is the mainstay for TCC therapy in dogs. Although TCC is not usually curable in dogs, multiple drugs have activity against it. Approximately 75% of dogs respond favorably to TCC treatment and can enjoy several months to a year or more of good quality life. Many promising new therapies for TCC are emerging and with the close similarity between TCC in dogs and high grade invasive bladder cancer in humans, new treatment strategies found to be successful in canine studies are expected to help dogs and to be subsequently translated to humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

Severity of hydronephrosis correlates with tumour invasiveness and urinary bladder recurrence of ureteric cancer.

PubMed

Luo, Hao Lun; Kang, Chih Hsiung; Chen, Yen Ta; Chuang, Yao Chi; Lee, Wei Ching; Cheng, Yuan Tso; Chiang, Po Hui

2013-08-01

To explore the prognostic role of hydronephrosis grade in patients with pure ureteric cancer. The study included 162 patients with pure ureteric cancer who were treated between January 2005 and December 2010 at a single tertiary referral centre. The association between hydronephrosis grade with pathological findings and oncological outcomes was assessed using multivariate Cox regression analysis. Hydronephrosis grade >2 was independently associated with non-organ-confined ureteric cancer (P = 0.003). Hydronephrosis grade <2 was highly prevalent in organ-confined disease. Hydronephrosis grade >2 and bladder cancer history independently predict bladder cancer recurrence (P = 0.021 and P = 0.002, respectively) Hydronephrosis of grade >2 was found to be associated with local and distant recurrence only in univariate analysis; non-organ-confined pathology independently predicted local and distant oncological failure (P ≤ 0.001 and P = 0.002, respectively). Hydronephrosis grade >2 is associated with non-organ-confined ureteric cancer and with bladder cancer recurrence. Non-organ-confined pathology is still the most important predictor for local and distant oncological failure. © 2013 BJU International.

Dynamic Real-time Microscopy of the Urinary Tract Using Confocal Laser Endomicroscopy

PubMed Central

Wu, Katherine; Liu, Jen-Jane; Adams, Winifred; Sonn, Geoffrey A.; Mach, Kathleen E.; Pan, Ying; Beck, Andrew H.; Jensen, Kristin C.; Liao, Joseph C.

2014-01-01

OBJECTIVES To develop the diagnostic criteria for benign and neoplastic conditions of the urinary tract using probe-based confocal laser endomicroscopy (pCLE), a new technology for dynamic, in vivo imaging with micron-scale resolution. The suggested diagnostic criteria will formulate a guide for pCLE image interpretation in urology. METHODS Patients scheduled for transurethral resection of bladder tumor (TURBT) or nephrectomy were recruited. After white-light cystoscopy (WLC), fluorescein was administered as contrast. Different areas of the urinary tract were imaged with pCLE via direct contact between the confocal probe and the area of interest. Confocal images were subsequently compared with standard hematoxylin and eosin analysis. RESULTS pCLE images were collected from 66 participants, including 2 patients who underwent nephrectomy. We identified key features associated with different anatomic landmarks of the urinary tract, including the kidney, ureter, bladder, prostate, and urethra. In vivo pCLE of the bladder demonstrated distinct differences between normal mucosa and neoplastic tissue. Using mosaicing, a post hoc image-processing algorithm, individual image frames were juxtaposed to form wideangle views to better evaluate tissue microarchitecture. CONCLUSIONS In contrast to standard pathologic analysis of fixed tissue with hematoxylin and eosin, pCLE provides real time microscopy of the urinary tract to enable dynamic interrogation of benign and neoplastic tissues in vivo. The diagnostic criteria developed in this study will facilitate adaptation of pCLE for use in conjunction with WLC to expedite diagnosis of urinary tract pathology, particularly bladder cancer. PMID:21601243

Biomarkers in patients treated with BCG: an update.

PubMed

Klap, Julia; Schmid, Marianne; Loughlin, Kevin R

2014-08-01

Bacillus Calmette-Guerin (BCG) instillations are the recommended treatment for non-muscle invasive bladder cancer but high recurrence and progression rates remain after treatment. Despite patients risk stratification, BCG effectiveness remains unpredictable. A close, invasive and expensive follow up is mandatory. To improve or even replace this heavy surveillance in this high risk population, validated biomarkers were developed. To identify the useful tools for the urologist in monitoring bladder cancer patients, we reviewed the literature focusing on plasma and urinary biomarkers of BCG-therapy outcome. Articles dated from 1988 to 2013 including specific keywords (urinary bladder neoplasm, biological markers, intravesical administration, recurrence) were examined and relevant papers were selected. Before treatment initiation, genetic polymorphisms of multiple agents (cytokines, matrix-metalloproteinases) were found to become very useful to tailor therapy and monitoring. Those biomarkers belong to personalized medicine which is a topic of great interest today, but still need to be validated in cohorts from different ethnicities. During instillations, cytokines (IL-2, IL-8, IL-6/IL-10) were reported to be reliable to determine treatment response and efficacy. Further studies are needed to confirm results and standardize thresholds. After treatment, UroVysion, the FDA-approved fluorescence in situ hybridization (FISH), appeared to be the most robust marker of all the clinical parameters reviewed; but is not yet validated for BCG-treated patients. No recommendations for everyday practice can be established today, but a combination of several markers and clinicopathological characteristics may be the future. As bladder cancer diagnosis and management are evolving, practicing urologists should be aware of and utilize bladder cancer markers in clinical practice.

Prognostic Relevance of Urinary Bladder Cancer Susceptibility Loci

PubMed Central

Grotenhuis, Anne J.; Dudek, Aleksandra M.; Verhaegh, Gerald W.; Witjes, J. Alfred; Aben, Katja K.; van der Marel, Saskia L.; Vermeulen, Sita H.; Kiemeney, Lambertus A.

2014-01-01

In the last few years, susceptibility loci have been identified for urinary bladder cancer (UBC) through candidate-gene and genome-wide association studies. Prognostic relevance of most of these loci is yet unknown. In this study, we used data of the Nijmegen Bladder Cancer Study (NBCS) to perform a comprehensive evaluation of the prognostic relevance of all confirmed UBC susceptibility loci. Detailed clinical data concerning diagnosis, stage, treatment, and disease course of a population-based series of 1,602 UBC patients were collected retrospectively based on a medical file survey. Kaplan-Meier survival analyses and Cox proportional hazard regression were performed, and log-rank tests calculated, to evaluate the association between 12 confirmed UBC susceptibility variants and recurrence and progression in non-muscle invasive bladder cancer (NMIBC) patients. Among muscle-invasive or metastatic bladder cancer (MIBC) patients, association of these variants with overall survival was tested. Subgroup analyses by tumor aggressiveness and smoking status were performed in NMIBC patients. In the overall NMIBC group (n = 1,269), a statistically significant association between rs9642880 at 8q24 and risk of progression was observed (GT vs. TT: HR = 1.08 (95% CI: 0.76–1.54), GG vs. TT: HR = 1.81 (95% CI: 1.23–2.66), P for trend = 2.6×10−3). In subgroup analyses, several other variants showed suggestive, though non-significant, prognostic relevance for recurrence and progression in NMIBC and survival in MIBC. This study provides suggestive evidence that genetic loci involved in UBC etiology may influence disease prognosis. Elucidation of the causal variant(s) could further our understanding of the mechanism of disease, could point to new therapeutic targets, and might aid in improvement of prognostic tools. PMID:24586564

The health economics of bladder cancer: an updated review of the published literature.

PubMed

Yeung, Christina; Dinh, Tuan; Lee, Joseph

2014-11-01

The purpose of this paper is to provide a current view of the economic burden of bladder cancer, with a focus on the cost effectiveness of available interventions. This review updates a previous systematic review and includes 72 new papers published between 2000 and 2013. Bladder cancer continues to be one of the most common and expensive malignancies. The annual cost of bladder cancer in the USA during 2010 was $US4 billion and is expected to rise to $US5 billion by 2020. Ten years ago, urinary markers held the potential to lower treatment costs of bladder cancer. However, subsequent real-world experiments have demonstrated that further work is necessary to identify situations in which these technologies can be applied in a cost-effective manner. Adjunct cytology remains a part of diagnostic standard of care, but recent research suggests that it is not cost effective due to its low diagnostic yield. Analysis of intravesical chemotherapy after transurethral resection of bladder tumor (TURBT), neo-adjuvant therapy for cystectomy, and robot-assisted laparoscopic cystectomy suggests that these technologies are cost effective and should be implemented more widely for appropriate patients. The existing literature on the cost effectiveness of bladder cancer treatments has improved substantially since 2000. The body of work now includes many new models, registry analyses, and real-world studies. However, there is still a need for new implementation guidelines, new risk modeling tools, and a better understanding of the empirical burden of bladder cancer.

Complicated Genitourinary Tract Infections and Mimics.

PubMed

Yu, Michael; Robinson, Kathryn; Siegel, Cary; Menias, Christine

This article provides pictorial review of complicated upper and lower genitourinary infections and their mimics. Imaging features of upper urinary tract infections including uncomplicated acute pyelonephritis, xanthogranulomatous pyelonephritis (XGPN), emphysematous pyelonephritis, perirenal abscess, and pyonephrosis are first reviewed and then followed by pictorial review of their mimics including contrast-associated nephrotoxicity, renal infarcts, malakoplakia, renal cell cancer, leukemia or lymphoma and Castleman's disease. Next, imaging features of lower urinary tract infections including cystitis, emphysematous cystitis, enterovesical, colovesical and vesicovaginal fistulas, Fournier gangrene, prostatitis, epididymitis, and orchitis are reviewed and then followed by pictorial review of their mimics including gas in the bladder and perineum related to instrumentation, radiation cystitis, bladder cancer, testicular torsion, testicular trauma, and testicular cancer and lymphoma. Recognizing imaging characteristics of complicated genitourinary infections and their mimics would allow clinicians to provide appropriate timely management. Copyright © 2016 Elsevier Inc. All rights reserved.

Arsenic Methylation and Lung and Bladder Cancer in a Case-control Study in Northern Chile

PubMed Central

Melak, Dawit; Ferreccio, Catterina; Kalman, David; Parra, Roxana; Acevedo, Johanna; Pérez, Liliana; Cortés, Sandra; Smith, Allan H; Yuan, Yan; Liaw, Jane; Steinmaus, Craig

2014-01-01

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., <200 μg/L). In this study, urinary arsenic metabolites were measured in 94 lung and 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.99–3.67), and 3.26 (1.76–6.04) (p-trend <0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.06–3.11), and 2.02 (1.15–3.54) (p-trend <0.001). In analyses confined to subjects only with arsenic water concentrations <200 μg/L (median=60 μg/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared to subjects in the lower two tertiles were 2.48 (1.08–5.68) and 2.37 (1.01–5.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations. PMID:24296302

Bladder Control Problems: Medications for Treating Urinary Incontinence

MedlinePlus

Bladder control: Medications for urinary problems Learn about medications used to treat bladder control problems, including how they work to treat urinary ... your doctor's suggestions for bladder retraining. But bladder control remains a problem. What else can you do? ...

[Multidisciplinary approach to the treatment of colorectal cancer, complicated by urinary tract invasion].

PubMed

Likhter, M S; Shelygin, Iu A; Achkasov, S I

2012-01-01

Results of treatment of 277 patients with colorectal cancer stage IV complicated by the urinary tract invasion, were analyzed. Men were 168 (60.7%); women - 109 (39.3%). Patients aged 31-79 years (59.6±5.7) years. All patients were operated on radically with the resection of the invaded parts of the urinary tract en bloc. Both abdominal surgeons and urologists took part in the operation. The study proved that the invasion of the urinary tract by colorectal cancer should not become a reason for the surgery refusal. The subtotal resection of the urinary bladder by its cancer invasion demonstrated the appropriate radicalism and functional postoperative results. The efficacy of such combined operations was proved by the high level of social adaptation of the operated patients - 18 (51.4%) of 35 followed up patients came back to the previous level of social activity. Urinary tracts' resection did not influenced the level of postoperative lethality.

Spontaneous puerperal extraperitoneal bladder wall rupture in young woman with diagnostic dilemma

PubMed Central

Sabat, Debabrat Kumar; Panigrahi, Pradeep Kumar; Sahoo, Ranjan Kumar; Acharya, Mousumi; Sahu, Mahesh Ch

2015-01-01

A young female presented with an acute abdominal pain and oliguria for 1 week following normal vaginal delivery. No history of hematuria was present. Patient was having lochia rubra. Sealed uterine rupture was suspected clinically. Initial ultrasound of the patient showed distended urinary bladder containing Foley catheter ballon with clamping of Foley catheter and particulate ascites. Abdominal paracentesis revealed hemorrhagic fluid. Contrast-enhanced computed tomography of abdomen revealed ascites, distended urinary bladder and no extraluminal contrast extravasation in delayed scan. As patient condition deteriorated, repeat ultrasound guided abdominal paracentesis was done which revealed transudative peritoneal collection with distended bladder. Cystoscopy revealed urinary bladder ruptures with exudate sealing the rupture site. Exploratory laparotomy was done and a diagnosis of extraperitoneal bladder rupture was confirmed. The rent was repaired in layers. She was put on continuous bladder drainage for 3 weeks followed by bladder training. It presented in a unique way as there was hemorrhagic peritoneal tap, no macroscopic hematuria and urinary bladder was distended in spite of urinary bladder wall rupture which delayed the diagnosis and treatment. Complete emptying of urinary bladder before second stage of labor and during postpartum period with perineal repair is mandatory to prevent urinary bladder rupture. PMID:26985426

Spontaneous puerperal extraperitoneal bladder wall rupture in young woman with diagnostic dilemma.

PubMed

Sabat, Debabrat Kumar; Panigrahi, Pradeep Kumar; Sahoo, Ranjan Kumar; Acharya, Mousumi; Sahu, Mahesh Ch

2015-01-01

A young female presented with an acute abdominal pain and oliguria for 1 week following normal vaginal delivery. No history of hematuria was present. Patient was having lochia rubra. Sealed uterine rupture was suspected clinically. Initial ultrasound of the patient showed distended urinary bladder containing Foley catheter ballon with clamping of Foley catheter and particulate ascites. Abdominal paracentesis revealed hemorrhagic fluid. Contrast-enhanced computed tomography of abdomen revealed ascites, distended urinary bladder and no extraluminal contrast extravasation in delayed scan. As patient condition deteriorated, repeat ultrasound guided abdominal paracentesis was done which revealed transudative peritoneal collection with distended bladder. Cystoscopy revealed urinary bladder ruptures with exudate sealing the rupture site. Exploratory laparotomy was done and a diagnosis of extraperitoneal bladder rupture was confirmed. The rent was repaired in layers. She was put on continuous bladder drainage for 3 weeks followed by bladder training. It presented in a unique way as there was hemorrhagic peritoneal tap, no macroscopic hematuria and urinary bladder was distended in spite of urinary bladder wall rupture which delayed the diagnosis and treatment. Complete emptying of urinary bladder before second stage of labor and during postpartum period with perineal repair is mandatory to prevent urinary bladder rupture.

[Nitric oxide pathway and female lower urinary tract. Physiological and pathophysiological role].

PubMed

Gamé, X; Rischmann, P; Arnal, J-F; Malavaud, B

2013-09-01

The aim was to review the literature on nitric oxide and female lower urinary tract. A literature review through the PubMed library until December, 31 2012 was carried out using the following keywords: lower urinary tract, bladder, urethra, nervous central system, innervation, female, women, nitric oxide, phosphodiesterase, bladder outlet obstruction, urinary incontinence, overactive bladder, urinary tract infection. Two nitric oxide synthase isoforms, the neuronal (nNOS) and the endothelial (eNOS), are constitutively expressed in the lower urinary tract. Nevertheless, nNOS is mainly expressed in the bladder neck and the urethra. In the bladder, NO modulates the afferent neurons activity. In pathological condition, inducible NOS expression induces an increase in detrusor contractility and bladder wall thickness and eNOS facilitates Escherichia coli bladder wall invasion inducing recurrent urinary tract infections. In the urethra, NO play a major role in smooth muscle cells relaxation. The NO pathway plays a major role in the female lower urinary tract physiology and physiopathology. While it acts mainly on bladder outlet, in pathological condition, it is involved in bladder dysfunction occurrence. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Spontaneous Urinary Bladder Leiomyoma in a Rhesus Macaque (Macaca mulatta).

PubMed

Scott, Kathleen E; Frydman, Galit; Fox, James G; Bakthavatchalu, Vasudevan

2018-06-01

Here we report the case of a urinary bladder leiomyoma in a rhesus macaque. The animal was clinically normal and had a lipoma localized to the stifle. Endovesicular leiomyomas are the most common form of urinary bladder leiomyoma in humans. In contrast, this macaque's tumor exhibited extravesicular localization in the bladder. Urinary bladder leiomyomas account for less than 0.5% of all bladder tumors in humans, with only 250 cases reported in total.

Cellular autofluorescence imaging for early diagnosis of cancers

NASA Astrophysics Data System (ADS)

Steenkeste, Karine; Deniset, Ariane; Lecart, Sandrine; Leveque-Fort, Sandrine; Fontaine-Aupart, Marie-Pierre; Ferlicot, Sophie; Eschwege, Pascal

2005-08-01

Urinary cytology is employed in diagnostic guidelines of bladder cancer in anatomo-pathological laboratories mostly for its ability to diagnose non detectable cancers using cystoscopy, but also because it is a non-invasive and non-constraining technique for a regular follow-up of the more exposed populations. The impossibility to detect such cancers is mainly due to their localization either in the bladder or in the upper urinary tract and the prostate. However, urinary cytology lacks sensitivity, especially for the detection of low grade low stage tumors due to inherent limitation of morphological criteria to distinguish low grade tumor cells from normal urothelial cells. For this purpose, we developed, in addition to urinary cytology, an original screening of these cytological slides by using spectrally-resolved and time-resolved fluorescence as a contrast factor, without changing any parameters in the cytological slide preparation. This method takes advantage of a femtosecond Ti:sapphire laser, continuously tunable in the spectral range 700-950 nm allowing the observation of most endogenous cellular chromophores by biphotonic excitation. A commercial confocal microscope was also used in the measurements allowing an excitation of the samples between 458 nm and 633 nm. We observed that the fluorescence emission is differentially distributed in normal and pathological urothelial cells. Spectral- and time-resolved measurements attested this difference over about one hundred cases which have been tested to confirm the high accuracy of this non-invasive technique.

Effects of Cyclooxygenase on the Urothelium of the Urinary Bladder of Mice Exposed to Pelvic Radiation.

PubMed

Ozbilgin, M Kemal; Onal, Tuna; Ozcan, Cemil; Temel, Merve; Aktas, Caner; Gareveran, Manuchehr Salehi; Uluer, Elgin Turkoz; Inan, Sevinc; Kurtman, Cengiz

2016-04-01

To determine the role of cyclooxygenase (COX) expression in the urothelium of the urinary bladder during radiation injury caused by pelvic radiotherapy for cancer therapy. Twenty-four male Swiss Albino mice were separated into 4 groups. The first group was the control group (Group 1) and the second, third, and fourth groups were euthanized after 24 hours (Group 2), 48 hours (Group 3), and 7 days (Group 4), respectively. A single-fractioned 10 Gy of ionizing radiation was applied to all mice's pelvic zone with Co-60. Bladders were removed completely from the pelvic region. Histochemical analysis using hematoxylin and eosin and immunohistochemical analysis using anti-COX-1 and COX-2 antibodies were performed on tissue samples. The immunoreactivities of the urinary bladder were quantified using H-score measurement, and statistical comparison was performed. In the immunohistochemical examination the COX-1 immunoreactivities were found to be higher in the urothelium of the bladder in the radiation exposed groups than in the normal control group (group 1) (p < 0.005). Additionally, high immunoreactivity of COX-2 molecule was established in groups 2, 3, and 4 of radiation groups as compared to group 1 (p < 0.005) in examination of the urothelium. COX-1 and COX-2 immunoreactivities in the submucosa were detected higher in group 4 than in the other groups (p < 0.005). COX-1 and COX-2 expressions in the urothelium and subepithelium of the urinary bladder were investigated in mice during the acute radiation response. The expression of COX-1 and COX-2 in the urothelium seems to prevent bladder damage from radiation, supplying differentiation and restoration of the urothelium.

Proteomic Analysis of Arsenic-Induced Oxidative Stress in Human Epidermal Keratinocytes

EPA Science Inventory

Chronic exposure to inorganic arsenic (IAs) has been associated with the development of several human cancers, including those found in the skin, lung, urinary bladder, liver, prostate and kidney. The precise mechanisms by which arsenic causes cancer are unknown. Defining the mod...

The Urinary Bladder Transcriptome and Proteome Defined by Transcriptomics and Antibody-Based Profiling

PubMed Central

Habuka, Masato; Fagerberg, Linn; Hallström, Björn M.; Pontén, Fredrik; Yamamoto, Tadashi; Uhlen, Mathias

2015-01-01

To understand functions and diseases of urinary bladder, it is important to define its molecular constituents and their roles in urinary bladder biology. Here, we performed genome-wide deep RNA sequencing analysis of human urinary bladder samples and identified genes up-regulated in the urinary bladder by comparing the transcriptome data to those of all other major human tissue types. 90 protein-coding genes were elevated in the urinary bladder, either with enhanced expression uniquely in the urinary bladder or elevated expression together with at least one other tissue (group enriched). We further examined the localization of these proteins by immunohistochemistry and tissue microarrays and 20 of these 90 proteins were localized to the whole urothelium with a majority not yet described in the context of the urinary bladder. Four additional proteins were found specifically in the umbrella cells (Uroplakin 1a, 2, 3a, and 3b), and three in the intermediate/basal cells (KRT17, PCP4L1 and ATP1A4). 61 of the 90 elevated genes have not been previously described in the context of urinary bladder and the corresponding proteins are interesting targets for more in-depth studies. In summary, an integrated omics approach using transcriptomics and antibody-based profiling has been used to define a comprehensive list of proteins elevated in the urinary bladder. PMID:26694548

Does increased urination frequency protect against bladder cancer?

PubMed

Silverman, Debra T; Alguacil, Juan; Rothman, Nathaniel; Real, Francisco X; Garcia-Closas, Montserrat; Cantor, Kenneth P; Malats, Nuria; Tardon, Adonina; Serra, Consol; Garcia-Closas, Reina; Carrato, Alfredo; Lloreta, Josep; Samanic, Claudine; Dosemeci, Mustafa; Kogevinas, Manolis

2008-10-01

Experimental studies suggest that increased urination frequency may reduce bladder cancer risk if carcinogens are present in the urine. Only 2 small studies of the effect of increased urination frequency on bladder cancer risk in humans have been conducted with conflicting results. Our purpose was to evaluate the effect of urination frequency on risk of bladder cancer in a large, multicenter case-control study. We analyzed data based on interviews conducted with 884 patients with newly diagnosed, bladder cancer and 996 controls from 1998 to 2001 in Spain. We observed a consistent, inverse trend in risk with increasing nighttime voiding frequency in both men (p = 0.0003) and women (p = 0.07); voiding at least 2 times per night was associated with a significant, 40-50% risk reduction. The protective effect of nocturia was apparent among study participants with low, moderate and high water consumption. The risk associated with cigarette smoking was reduced by nocturia. Compared with nonsmokers who did not urinate at night, current smokers who did not urinate at night had an OR of 7.0 (95% CI = 4.7-10.2), whereas those who voided at least twice per night had an OR of 3.3 (95% CI = 1.9-5.8) (p value for trend = 0.0005). Our findings suggest a strong protective effect of nocturia on bladder cancer risk, providing evidence in humans that bladder cancer risk is related to the contact time of the urothelium with carcinogens in urine. Increased urination frequency, coupled with possible dilution of the urine from increased water intake, may diminish the effect of urinary carcinogens on bladder cancer risk.

GENE EXPRESSION CAN DIFFERENTIATE CARCINOGENIC FROM NON-CARCINOGENIC DOSES OF DIMETHYLARSINIC ACID (DMAv) IN THE TRANSITIONAL EPITHELIUM OF THE URINARY BLADDER FROM FEMALE F344 RATS

EPA Science Inventory

Arsenic is an environmental concern worldwide, and drinking arsenic contaminated water has been associated with increased incidences of skin, lung and bladder cancer. Dimethylarsinic acid (DMAv) is a major metabolite of inorganic arsenic in rodents and humans and is the predomina...

Roles of polyuria and hyperglycemia in bladder dysfunction in diabetes.

PubMed

Xiao, Nan; Wang, Zhiping; Huang, Yexiang; Daneshgari, Firouz; Liu, Guiming

2013-03-01

Diabetes mellitus causes diabetic bladder dysfunction. We identified the pathogenic roles of polyuria and hyperglycemia in diabetic bladder dysfunction in rats. A total of 72 female Sprague-Dawley® rats were divided into 6 groups, including age matched controls, and rats with sham urinary diversion, urinary diversion, streptozotocin induced diabetes mellitus after sham urinary diversion, streptozotocin induced diabetes mellitus after urinary diversion and 5% sucrose induced diuresis after sham urinary diversion. Urinary diversion was performed by ureterovaginostomy 10 days before diabetes mellitus induction. Animals were evaluated 20 weeks after diabetes mellitus or diuresis induction. We measured 24-hour drinking and voiding volumes, and cystometry. Bladders were harvested to quantify smooth muscle, urothelium and collagen. We measured nitrotyrosine and Mn superoxide dismutase in the bladder. Diabetes and diuresis caused increases in drinking and voiding volume, and bladder weight. Bladder weight decreased in the urinary diversion group and the urinary diversion plus diabetes group. The intercontractile interval, voided volume and compliance increased in the diuresis and diabetes groups, decreased in the urinary diversion group and further decreased in the urinary diversion plus diabetes group. Total cross-sectional tissue, smooth muscle and urothelium areas increased in the diuresis and diabetes groups, and decreased in the urinary diversion and urinary diversion plus diabetes groups. As a percent of total tissue area, collagen decreased in the diuresis and diabetes groups, and increased in the urinary diversion and urinary diversion plus diabetes groups. Smooth muscle and urothelium decreased in the urinary diversion and urinary diversion plus diabetes groups. Nitrotyrosine and Mn superoxide dismutase increased in rats with diabetes and urinary diversion plus diabetes. Polyuria induced bladder hypertrophy, while hyperglycemia induced substantial oxidative stress in the bladder, which may have a pathogenic role in late stage diabetic bladder dysfunction. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bladder Control Problems in Women

MedlinePlus

... Prostate Enlargement (Benign Prostatic Hyperplasia) Urinary Diversion Urinary Retention Urine Blockage in Newborns Vesicoureteral Reflux (VUR) The ... Conditions & Diseases Bladder Control Problems & Nerve Disease Urinary Retention Bladder Infection (Urinary Tract Infection—UTI) in Adults ...

Suppression of the PI3K pathway in vivo reduces cystitis-induced bladder hypertrophy and restores bladder capacity examined by magnetic resonance imaging.

PubMed

Qiao, Zhongwei; Xia, Chunmei; Shen, Shanwei; Corwin, Frank D; Liu, Miao; Guan, Ruijuan; Grider, John R; Qiao, Li-Ya

2014-01-01

This study utilized magnetic resonance imaging (MRI) to monitor the real-time status of the urinary bladder in normal and diseased states following cyclophosphamide (CYP)-induced cystitis, and also examined the role of the phosphoinositide 3-kinase (PI3K) pathway in the regulation of urinary bladder hypertrophy in vivo. Our results showed that under MRI visualization the urinary bladder wall was significantly thickened at 8 h and 48 h post CYP injection. The intravesical volume of the urinary bladder was also markedly reduced. Treatment of the cystitis animals with a specific PI3K inhibitor LY294002 reduced cystitis-induced bladder wall thickening and enlarged the intravesical volumes. To confirm the MRI results, we performed H&E stain postmortem and examined the levels of type I collagen by real-time PCR and western blot. Inhibition of the PI3K in vivo reduced the levels of type I collagen mRNA and protein in the urinary bladder ultimately attenuating cystitis-induced bladder hypertrophy. The bladder mass calculated according to MRI data was consistent to the bladder weight measured ex vivo under each drug treatment. MRI results also showed that the urinary bladder from animals with cystitis demonstrated high magnetic signal intensity indicating considerable inflammation of the urinary bladder when compared to normal animals. This was confirmed by examination of the pro-inflammatory factors showing that interleukin (IL)-1α, IL-6 and tumor necrosis factor (TNF)α levels in the urinary bladder were increased with cystitis. Our results suggest that MRI can be a useful technique in tracing bladder anatomy and examining bladder hypertrophy in vivo during disease development and the PI3K pathway has a critical role in regulating bladder hypertrophy during cystitis.

Primary Bladder Neurofibroma: A Rare Case with Clinical Implications and Diagnostic Challenges.

PubMed

Umakanthan, Srikanth; Naik, Ramadas; Bukelo, Maryann Margaret; Rai, Sharada; Prabhu, Laxman

2015-09-01

Neurofibroma of the genito-urinary tract is rare. Urinary bladder is the commonest organ involved in cases of urinary tract involvement. Patients present early in life and there is male preponderance. We discuss here a case of primary neurofibroma of the urinary bladder in a 52-year-male presenting with haematuria, irritative bladder symptoms and pelvic mass. Cystoscopy showed a swelling in the left lateral wall. A transurethral biopsy revealed neurofibroma of the urinary bladder. Immunohistochemical studies confirmed the diagnosis.

Primary Bladder Neurofibroma: A Rare Case with Clinical Implications and Diagnostic Challenges

PubMed Central

Naik, Ramadas; Bukelo, Maryann Margaret; Rai, Sharada; Prabhu, Laxman

2015-01-01

Neurofibroma of the genito-urinary tract is rare. Urinary bladder is the commonest organ involved in cases of urinary tract involvement. Patients present early in life and there is male preponderance. We discuss here a case of primary neurofibroma of the urinary bladder in a 52-year-male presenting with haematuria, irritative bladder symptoms and pelvic mass. Cystoscopy showed a swelling in the left lateral wall. A transurethral biopsy revealed neurofibroma of the urinary bladder. Immunohistochemical studies confirmed the diagnosis. PMID:26500913

Deep Sequencing of Urinary RNAs for Bladder Cancer Molecular Diagnostics.

PubMed

Sin, Mandy L Y; Mach, Kathleen E; Sinha, Rahul; Wu, Fan; Trivedi, Dharati R; Altobelli, Emanuela; Jensen, Kristin C; Sahoo, Debashis; Lu, Ying; Liao, Joseph C

2017-07-15

Purpose: The majority of bladder cancer patients present with localized disease and are managed by transurethral resection. However, the high rate of recurrence necessitates lifetime cystoscopic surveillance. Developing a sensitive and specific urine-based test would significantly improve bladder cancer screening, detection, and surveillance. Experimental Design: RNA-seq was used for biomarker discovery to directly assess the gene expression profile of exfoliated urothelial cells in urine derived from bladder cancer patients ( n = 13) and controls ( n = 10). Eight bladder cancer specific and 3 reference genes identified by RNA-seq were quantitated by qPCR in a training cohort of 102 urine samples. A diagnostic model based on the training cohort was constructed using multiple logistic regression. The model was further validated in an independent cohort of 101 urines. Results: A total of 418 genes were found to be differentially expressed between bladder cancer and controls. Validation of a subset of these genes was used to construct an equation for computing a probability of bladder cancer score (P BC ) based on expression of three markers ( ROBO1, WNT5A , and CDC42BPB ). Setting P BC = 0.45 as the cutoff for a positive test, urine testing using the three-marker panel had overall 88% sensitivity and 92% specificity in the training cohort. The accuracy of the three-marker panel in the independent validation cohort yielded an AUC of 0.87 and overall 83% sensitivity and 89% specificity. Conclusions: Urine-based molecular diagnostics using this three-marker signature could provide a valuable adjunct to cystoscopy and may lead to a reduction of unnecessary procedures for bladder cancer diagnosis. Clin Cancer Res; 23(14); 3700-10. ©2017 AACR . ©2017 American Association for Cancer Research.

Vitamin B12 deficiency after irradiation for bladder carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kinn, A.C.; Lantz, B.

1984-05-01

Vitamin B12 deficiency was found in 10 of 41 patients who underwent radiotherapy before cystectomy with Bricker urinary diversion for carcinoma of the bladder. Of 13 patients given full irradiation because of inoperable bladder cancer 5 had malabsorption of vitamin B12. Serum folic acid was normal in these patients, indicating predominantly ileal irradiation sequelae. Routine evaluation of serum vitamin B12 after radiotherapy is recommended so that appropriate medication can be given, if possible before neurological symptoms appear.

Clinical results of conformal versus intensity-modulated radiotherapy using a focal simultaneous boost for muscle-invasive bladder cancer in elderly or medically unfit patients.

PubMed

Lutkenhaus, Lotte J; van Os, Rob M; Bel, Arjan; Hulshof, Maarten C C M

2016-03-18

For elderly or medically unfit patients with muscle-invasive bladder cancer, cystectomy or chemotherapy are contraindicated. This leaves radical radiotherapy as the only treatment option. It was the aim of this study to retrospectively analyze the treatment outcome and associated toxicity of conformal versus intensity-modulated radiotherapy (IMRT) using a focal simultaneous tumor boost for muscle-invasive bladder cancer in patients not suitable for cystectomy. One hundred eighteen patients with T2-4 N0-1 M0 bladder cancer were analyzed retrospectively. Median age was 80 years. Treatment consisted of either a conformal box technique or IMRT and included a simultaneous boost to the tumor. To enable an accurate boost delivery, fiducial markers were placed around the tumor. Patients were treated with 40 Gy in 20 fractions to the elective treatment volumes, and a daily tumor boost up to 55-60 Gy. Clinical complete response was seen in 87 % of patients. Three-year overall survival was 44 %, with a locoregional control rate of 73 % at 3 years. Toxicity was low, with late urinary and intestinal toxicity rates grade ≥ 2 of 14 and 5 %, respectively. The use of IMRT reduced late intestinal toxicity, whereas fiducial markers reduced acute urinary toxicity. Radical radiotherapy using a focal boost is feasible and effective for elderly or unfit patients, with a 3-year locoregional control of 73 %. Toxicity rates were low, and were reduced by the use of IMRT and fiducial markers.

Arsenic methylation and lung and bladder cancer in a case-control study in northern Chile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melak, Dawit; Ferreccio, Catterina; Kalman, David

2014-01-15

In humans, ingested inorganic arsenic is metabolized to monomethylarsenic (MMA) then to dimethylarsenic (DMA), although this process is not complete in most people. The trivalent form of MMA is highly toxic in vitro and previous studies have identified associations between the proportion of urinary arsenic as MMA (%MMA) and several arsenic-related diseases. To date, however, relatively little is known about its role in lung cancer, the most common cause of arsenic-related death, or about its impacts on people drinking water with lower arsenic concentrations (e.g., < 200 μg/L). In this study, urinary arsenic metabolites were measured in 94 lung andmore » 117 bladder cancer cases and 347 population-based controls from areas in northern Chile with a wide range of drinking water arsenic concentrations. Lung cancer odds ratios adjusted for age, sex, and smoking by increasing tertiles of %MMA were 1.00, 1.91 (95% confidence interval (CI), 0.99–3.67), and 3.26 (1.76–6.04) (p-trend < 0.001). Corresponding odds ratios for bladder cancer were 1.00, 1.81 (1.06–3.11), and 2.02 (1.15–3.54) (p-trend < 0.001). In analyses confined to subjects only with arsenic water concentrations < 200 μg/L (median = 60 μg/L), lung and bladder cancer odds ratios for subjects in the upper tertile of %MMA compared to subjects in the lower two tertiles were 2.48 (1.08–5.68) and 2.37 (1.01–5.57), respectively. Overall, these findings provide evidence that inter-individual differences in arsenic metabolism may be an important risk factor for arsenic-related lung cancer, and may play a role in cancer risks among people exposed to relatively low arsenic water concentrations. - Highlights: • Urine arsenic metabolites were measured in cancer cases and controls from Chile. • Higher urine %MMA values were associated with increased lung and bladder cancer. • %MMA-cancer associations were seen at drinking water arsenic levels < 200 μg/L.« less

Using transurethral Ho:YAG-laser resection to treat urethral stricture and bladder neck contracture

NASA Astrophysics Data System (ADS)

Bo, Juanjie; Dai, Shengguo; Huang, Xuyuan; Zhu, Jing; Zhang, Huiguo; Shi, Hongmin

2005-07-01

Objective: Ho:YAG laser had been used to treat the common diseases of urinary system such as bladder cancer and benign prostatic hyperplasia in our hospital. This study is to assess the efficacy and safety of transurethral Ho:YAG-laser resection to treat the urethral stricture and bladder neck contracture. Methods: From May 1997 to August 2004, 26 cases of urethral stricture and 33 cases of bladder neck contracture were treated by transurethral Ho:YAG-laser resection. These patients were followed up at regular intervals after operation. The uroflow rate of these patients was detected before and one-month after operation. The blood loss and the energy consumption of holmium-laser during the operation as well as the complications and curative effect after operation were observed. Results: The therapeutic effects were considered successful, with less bleeding and no severe complications. The Qmax of one month postoperation increased obviously than that of preoperation. Of the 59 cases, restenosis appeared in 11 cases (19%) with the symptoms of dysuria and weak urinary stream in 3-24 months respectively. Conclusions: The Ho:YAG-laser demonstrated good effect to treat the obstructive diseases of lower urinary tract such as urethral stricture and bladder neck contracture. It was safe, minimal invasive and easy to operate.

Pure Lymphoepithelioma-Like Carcinoma Originating from the Urinary Bladder

PubMed Central

Nagai, Takashi; Naiki, Taku; Kawai, Noriyasu; Iida, Keitaro; Etani, Toshiki; Ando, Ryosuke; Hamamoto, Shuzo; Sugiyama, Yosuke; Okada, Atsushi; Mizuno, Kentaro; Umemoto, Yukihiro; Yasui, Takahiro

2016-01-01

Lymphoepithelioma-like carcinoma of the urinary bladder (LELCB) is a rare variant of infiltrating urothelial carcinoma. We report a case of LELCB in a 43-year-old man. Ultrasonography and cystoscopy revealed two bladder tumors, one on the left side of the trigone and the other on the right side of the trigone. Transurethral resection of the bladder tumors was performed and pathological analysis revealed undifferentiated carcinoma. We therefore performed radical cystectomy and urinary diversion. Immunohistochemically the tumor cells were positive for cytokeratin, but negative for Epstein-Barr virus-encoded small RNA in situ hybridization as found for previous cases of LELCB. The final pathological diagnosis was a lymphoepithelioma-like variant of urothelial carcinoma with perivesical soft tissue invasion. For adjuvant systemic chemotherapy, three courses of cisplatin were administered. The patient subsequently became free of cancer 72 months postoperatively. Based on the literature, pure or predominant LELCB types show favorable prognoses due to their sensitivity to chemotherapy or radiotherapy. An analysis of the apparent diffusion coefficient (ADC) values of bladder tumors examined in our institution revealed that the ADC value measured for this LELCB was relatively low compared to conventional urothelial carcinomas. This suggests that measuring the ADC value of a lymphoepithelioma-like carcinoma prior to operation may be helpful in predicting LELCB. PMID:27099604

Prospective comparison of molecular signatures in urothelial cancer of the bladder and the upper urinary tract--is there evidence for discordant biology?

PubMed

Krabbe, Laura-Maria; Lotan, Yair; Bagrodia, Aditya; Gayed, Bishoy A; Darwish, Oussama M; Youssef, Ramy F; Bolenz, Christian; Sagalowsky, Arthur I; Raj, Ganesh V; Shariat, Shahrokh F; Kapur, Payal; Margulis, Vitaly

2014-04-01

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

Bladder Cancer Treatment Response Assessment in CT using Radiomics with Deep-Learning.

PubMed

Cha, Kenny H; Hadjiiski, Lubomir; Chan, Heang-Ping; Weizer, Alon Z; Alva, Ajjai; Cohan, Richard H; Caoili, Elaine M; Paramagul, Chintana; Samala, Ravi K

2017-08-18

Cross-sectional X-ray imaging has become the standard for staging most solid organ malignancies. However, for some malignancies such as urinary bladder cancer, the ability to accurately assess local extent of the disease and understand response to systemic chemotherapy is limited with current imaging approaches. In this study, we explored the feasibility that radiomics-based predictive models using pre- and post-treatment computed tomography (CT) images might be able to distinguish between bladder cancers with and without complete chemotherapy responses. We assessed three unique radiomics-based predictive models, each of which employed different fundamental design principles ranging from a pattern recognition method via deep-learning convolution neural network (DL-CNN), to a more deterministic radiomics feature-based approach and then a bridging method between the two, utilizing a system which extracts radiomics features from the image patterns. Our study indicates that the computerized assessment using radiomics information from the pre- and post-treatment CT of bladder cancer patients has the potential to assist in assessment of treatment response.

Neoadjuvant chemotherapy for primary adenocarcinomas of the urinary bladder: a single-site experience.

PubMed

Yu, Bin; Zhou, Jin; Cai, Hongzhou; Xu, Ting; Xu, Zicheng; Zou, Qing; Gu, Min

2015-01-28

Adenocarcinoma of the urinary bladder is a rare malignancy. Radical surgery is suggested as the best available treatment for early-stage disease, but there is currently no consensus on standard chemotherapy regimen for advanced stage. We assessed the feasibility and effect of neoadjuvant chemotherapy with gemcitabine and cisplatin (GC) plus S-1 for patients with locally advanced primary adenocarcinomas of the urinary bladder. Six patients with locally advanced urachal or non-urachal (n = 3, each) primary adenocarcinoma of the bladder were treated from October 2010 to October 2013 at a single center. All the patients were treated with 3 cycles (21d, each) of GC plus S-1 (gemcitabine, 1000 mg/m2, days 1 and 8; cisplatin, 70 mg/m2, day 2; and S-1, 50 mg bid, day 1-14). After neoadjuvant chemotherapy, patients with urachal cancer were treated with en bloc radical cystectomy and umbilectomy; the remaining 3 patients were treated with cystectomy. All patients successfully completed the neoadjuvant chemotherapy without serious side effects. Two patients were assessed as complete response, 2 as partial response, 1 as stable disease and 1 as progressive disease. Despite the limitations of a small study population, the GC plus S-1 regimen for locally advanced primary adenocarcinoma of the urinary bladder was effective, and facilitated the success of surgery to a certain extent. Short follow-up time was also a limitation of our study. More studies are needed to evaluate the results.

Effect of coffee drinking on cell proliferation in rat urinary bladder epithelium.

PubMed

Lina, B A; Rutten, A A; Woutersen, R A

1993-12-01

A possible effect of freshly brewed drip coffee on urinary bladder carcinogenesis was investigated in male Wistar rats using cell proliferation in urinary bladder epithelium as the indicator of tumour promotion. Male rats were given either undiluted coffee brew (100% coffee), coffee diluted 10 times (10% coffee) or tap water (controls), as their only source of drinking fluid for 2 or 6 wk. Uracil, known to induce cell proliferation in urinary bladder epithelium, was included in the study as a positive control. In rats receiving 100% coffee, body weights, liquid intake and urinary volume were decreased. Neither histopathological examination of urinary bladder tissue nor the bromodeoxyuridine labelling index revealed biologically significant differences between rats receiving coffee and the tap water controls. Uracil increased the labelling index and induced hyperplasia of the urinary bladder epithelium, as expected. It was concluded that these results produced no evidence that drinking coffee predisposes to tumour development in the urinary bladder.

Real time diagnosis of bladder cancer with probe-based confocal laser endomicroscopy

NASA Astrophysics Data System (ADS)

Liu, Jen-Jane; Wu, Katherine; Adams, Winifred; Hsiao, Shelly T.; Mach, Kathleen E.; Beck, Andrew H.; Jensen, Kristin C.; Liao, Joseph C.

2011-02-01

Probe-based confocal laser endomicroscopy (pCLE) is an emerging technology for in vivo optical imaging of the urinary tract. Particularly for bladder cancer, real time optical biopsy of suspected lesions will likely lead to improved management of bladder cancer. With pCLE, micron scale resolution is achieved with sterilizable imaging probes (1.4 or 2.6 mm diameter), which are compatible with standard cystoscopes and resectoscopes. Based on our initial experience to date (n = 66 patients), we have demonstrated the safety profile of intravesical fluorescein administration and established objective diagnostic criteria to differentiate between normal, benign, and neoplastic urothelium. Confocal images of normal bladder showed organized layers of umbrella cells, intermediate cells, and lamina propria. Low grade bladder cancer is characterized by densely packed monomorphic cells with central fibrovascular cores, whereas high grade cancer consists of highly disorganized microarchitecture and pleomorphic cells with indistinct cell borders. Currently, we are conducting a diagnostic accuracy study of pCLE for bladder cancer diagnosis. Patients scheduled to undergo transurethral resection of bladder tumor are recruited. Patients undergo first white light cystocopy (WLC), followed by pCLE, and finally histologic confirmation of the resected tissues. The diagnostic accuracy is determined both in real time by the operative surgeon and offline after additional image processing. Using histology as the standard, the sensitivity, specificity, positive and negative predictive value of WLC and WLC + pCLE are calculated. With additional validation, pCLE may prove to be a valuable adjunct to WLC for real time diagnosis of bladder cancer.

Radical surgery for treatment of primary localized bladder amyloidosis: could prostate-sparing robot-assisted cystectomy with intracorporeal urinary diversion be an option?

PubMed

Hosseini, Abolfazl; Ploumidis, Achilles; Adding, Christofer; Wiklund, N Peter

2013-02-01

Primary localized bladder amyloidosis is a rare pathology that mimics urothelial cancer. Systemic disease and lymphoproliferative disorders should be excluded. Transurethral resection is the mainstay of treatment, although in cases of extensive bladder involvement or massive haematuria radical cystectomy has been reported. To the authors' knowledge, this is the first robot-assisted prostate-sparing simple cystectomy with intracorporeal neobladder and preservation of the seminal vesicles and vas deferens reported in the literature, in a patient with primary localized amyloidosis of the bladder.

Pathogenesis of Bladder Calculi in the Presence of Urinary Stasis

PubMed Central

Childs, M. Adam; Mynderse, Lance A.; Rangel, Laureano J.; Wilson, Torrence M.; Lingeman, James E.; Krambeck, Amy E.

2013-01-01

Purpose Although minimal evidence exists, bladder calculi in men with benign prostatic hyperplasia are thought to be secondary to bladder outlet obstruction induced urinary stasis. We performed a prospective, multi-institutional clinical trial to determine whether metabolic differences were present in men with and without bladder calculi undergoing surgical intervention for benign prostatic hyperplasia induced bladder outlet obstruction. Materials and Methods Men who elected surgery for bladder outlet obstruction secondary to benign prostatic hyperplasia with and without bladder calculi were assessed prospectively and compared. Men without bladder calculi retained more than 150 ml urine post-void residual urine. Medical history, serum electrolytes and 24-hour urinary metabolic studies were compared. Results Of the men 27 had bladder calculi and 30 did not. Bladder calculi were associated with previous renal stone disease in 36.7% of patients (11 of 30) vs 4% (2 of 27) and gout was associated in 13.3% (4 of 30) vs 0% (0 of 27) (p <0.01 and 0.05, respectively). There was no observed difference in the history of other medical conditions or in serum electrolytes. Bladder calculi were associated with lower 24-hour urinary pH (median 5.9 vs 6.4, p = 0.02), lower 24-hour urinary magnesium (median 106 vs 167 mmol, p = 0.01) and increased 24-hour urinary uric acid supersaturation (median 2.2 vs 0.6, p <0.01). Conclusions In this comparative prospective analysis patients with bladder outlet obstruction and benign prostatic hyperplasia with bladder calculi were more likely to have a renal stone disease history, low urinary pH, low urinary magnesium and increased urinary uric acid supersaturation. These findings suggest that, like the pathogenesis of nephrolithiasis, the pathogenesis of bladder calculi is likely complex with multiple contributing lithogenic factors, including metabolic abnormalities and not just urinary stasis. PMID:23159588

Bladder biopsy

MedlinePlus

... than usual ( oliguria ). You cannot urinate despite a strong urge to do so. Alternative Names Biopsy - bladder Images Bladder catheterization, female Bladder catheterization, male Female urinary tract Male urinary tract Bladder biopsy ...

Summary and Recommendations from the National Cancer Institute’s Clinical Trials Planning Meeting on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer

PubMed Central

Lerner, Seth P.; Bajorin, Dean F.; Dinney, Colin P.; Efstathiou, Jason A.; Groshen, Susan; Hahn, Noah M.; Hansel, Donna; Kwiatkowski, David; O’Donnell, Michael; Rosenberg, Jonathan; Svatek, Robert; Abrams, Jeffrey S.; Al-Ahmadie, Hikmat; Apolo, Andrea B.; Bellmunt, Joaquim; Callahan, Margaret; Cha, Eugene K.; Drake, Charles; Jarow, Jonathan; Kamat, Ashish; Kim, William; Knowles, Margaret; Mann, Bhupinder; Marchionni, Luigi; McConkey, David; McShane, Lisa; Ramirez, Nilsa; Sharabi, Andrew; Sharpe, Arlene H.; Solit, David; Tangen, Catherine M.; Amiri, Abdul Tawab; Van Allen, Eliezer; West, Pamela J.; Witjes, J. A.; Quale, Diane Zipursky

2016-01-01

The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from NCI, FDA, National Clinical Trials Network (NCTN), advocacy and the pharmaceutical and biotech industry. The meeting goals and objectives were to: 1) create a collaborative environment in which the greater bladder research community can pursue future optimally designed novel clinical trials focused on the theme of molecular targeted and immune-based therapies in NMIBC; 2) frame the clinical and translational questions that are of highest priority; and 3) develop two clinical trial designs focusing on immunotherapy and molecular targeted therapy. Despite successful development and implementation of large Phase II and Phase III trials in bladder and upper urinary tract cancers, there are no active and accruing trials in the NMIBC space within the NCTN. Disappointingly, there has been only one new FDA approved drug (Valrubicin) in any bladder cancer disease state since 1998. Although genomic-based data for bladder cancer are increasingly available, translating these discoveries into practice changing treatment is still to come. Recently, major efforts in defining the genomic characteristics of NMIBC have been achieved. Aligned with these data is the growing number of targeted therapy agents approved and/or in development in other organ site cancers and the multiple similarities of bladder cancer with molecular subtypes in these other cancers. Additionally, although bladder cancer is one of the more immunogenic tumors, some tumors have the ability to attenuate or eliminate host immune responses. Two trial concepts emerged from the meeting including a window of opportunity trial (Phase 0) testing an FGFR3 inhibitor and a second multi-arm multi-stage trial testing combinations of BCG or radiotherapy and immunomodulatory agents in patients who recur after induction BCG (BCG failure). PMID:27376138

Quantitative elasticity measurement of urinary bladder wall using laser-induced surface acoustic waves.

PubMed

Li, Chunhui; Guan, Guangying; Zhang, Fan; Song, Shaozhen; Wang, Ruikang K; Huang, Zhihong; Nabi, Ghulam

2014-12-01

The maintenance of urinary bladder elasticity is essential to its functions, including the storage and voiding phases of the micturition cycle. The bladder stiffness can be changed by various pathophysiological conditions. Quantitative measurement of bladder elasticity is an essential step toward understanding various urinary bladder disease processes and improving patient care. As a nondestructive, and noncontact method, laser-induced surface acoustic waves (SAWs) can accurately characterize the elastic properties of different layers of organs such as the urinary bladder. This initial investigation evaluates the feasibility of a noncontact, all-optical method of generating and measuring the elasticity of the urinary bladder. Quantitative elasticity measurements of ex vivo porcine urinary bladder were made using the laser-induced SAW technique. A pulsed laser was used to excite SAWs that propagated on the bladder wall surface. A dedicated phase-sensitive optical coherence tomography (PhS-OCT) system remotely recorded the SAWs, from which the elasticity properties of different layers of the bladder were estimated. During the experiments, series of measurements were performed under five precisely controlled bladder volumes using water to estimate changes in the elasticity in relation to various urinary bladder contents. The results, validated by optical coherence elastography, show that the laser-induced SAW technique combined with PhS-OCT can be a feasible method of quantitative estimation of biomechanical properties.

Filtration Device for On-Site Collection, Storage and Shipment of Cells from Urine and Its Application to DNA-Based Detection of Bladder Cancer.

PubMed

Andersson, Elin; Dahmcke, Christina M; Steven, Kenneth; Larsen, Louise K; Guldberg, Per

2015-01-01

Molecular analysis of cells from urine provides a convenient approach to non-invasive detection of bladder cancer. The practical use of urinary cell-based tests is often hampered by difficulties in handling and analyzing large sample volumes, the need for rapid sample processing to avoid degradation of cellular content, and low sensitivity due to a high background of normal cells. We present a filtration device, designed for home or point-of-care use, which enables collection, storage and shipment of urinary cells. A special feature of this device is a removable cartridge housing a membrane filter, which after filtration of urine can be transferred to a storage unit containing an appropriate preserving solution. In spiking experiments, the use of this device provided efficient recovery of bladder cancer cells with elimination of >99% of excess smaller-sized cells. The performance of the device was further evaluated by DNA-based analysis of urinary cells collected from 57 patients subjected to transurethral resection following flexible cystoscopy indicating the presence of a tumor. All samples were tested for FGFR3 mutations and seven DNA methylation markers (BCL2, CCNA1, EOMES, HOXA9, POU4F2, SALL3 and VIM). In the group of patients where a transitional cell tumor was confirmed at histopathological evaluation, urine DNA was positive for one or more markers in 29 out of 31 cases (94%), including 19 with FGFR3 mutation (61%). In the group of patients with benign histopathology, urine DNA was positive for methylation markers in 13 out of 26 cases (50%). Only one patient in this group was positive for a FGFR3 mutation. This patient had a stage Ta tumor resected 6 months later. The ability to easily collect, store and ship diagnostic cells from urine using the presented device may facilitate non-invasive testing for bladder cancer.

Filtration Device for On-Site Collection, Storage and Shipment of Cells from Urine and Its Application to DNA-Based Detection of Bladder Cancer

PubMed Central

Andersson, Elin; Dahmcke, Christina M.; Steven, Kenneth; Larsen, Louise K.; Guldberg, Per

2015-01-01

Molecular analysis of cells from urine provides a convenient approach to non-invasive detection of bladder cancer. The practical use of urinary cell-based tests is often hampered by difficulties in handling and analyzing large sample volumes, the need for rapid sample processing to avoid degradation of cellular content, and low sensitivity due to a high background of normal cells. We present a filtration device, designed for home or point-of-care use, which enables collection, storage and shipment of urinary cells. A special feature of this device is a removable cartridge housing a membrane filter, which after filtration of urine can be transferred to a storage unit containing an appropriate preserving solution. In spiking experiments, the use of this device provided efficient recovery of bladder cancer cells with elimination of >99% of excess smaller-sized cells. The performance of the device was further evaluated by DNA-based analysis of urinary cells collected from 57 patients subjected to transurethral resection following flexible cystoscopy indicating the presence of a tumor. All samples were tested for FGFR3 mutations and seven DNA methylation markers (BCL2, CCNA1, EOMES, HOXA9, POU4F2, SALL3 and VIM). In the group of patients where a transitional cell tumor was confirmed at histopathological evaluation, urine DNA was positive for one or more markers in 29 out of 31 cases (94%), including 19 with FGFR3 mutation (61%). In the group of patients with benign histopathology, urine DNA was positive for methylation markers in 13 out of 26 cases (50%). Only one patient in this group was positive for a FGFR3 mutation. This patient had a stage Ta tumor resected 6 months later. The ability to easily collect, store and ship diagnostic cells from urine using the presented device may facilitate non-invasive testing for bladder cancer. PMID:26151138

[Analysis for related factors of upper urinary tract deterioration in patients with spinal cord injury].

PubMed

Jing, Hua-fang; Liao, Li-min; Fu, Guang; Wu, Juan; Ju, Yan-he; Chen, Guo-qing

2014-08-18

To evaluate the related factors of upper urinary tract deterioration in spinal cord injured patients. Medical records of spinal cord injured patients from Jan.2002 to Sep.2009 were retrospectively reviewed. All the patients were divided into the upper urinary tract deterioration group and non-deterioration group according to the diagnostic criteria. Indexes such as demographic characteristic (gender, age), spinal cord injury information (cause, level, completeness), statuses of urinary tract system (bladder management, urine routine, urine culture, ultrasound, serum creatinine, fever caused by urinary tract infection) and urodynamics information(bladder compliance, bladder stability, bladder sensation, detrusor sphincter dyssynergia, detrusor leak point pressure, maximum cystometric capacity, relative safe bladder capacity, maximum flow rate, maximum urethra closure pressure) were compared between the two groups.Then Logistic regression analysis were performed. There was significantly difference between the two groups in spinal cord injury level(χ(2) = 8.840, P = 0.031),bladder management(χ(2) = 11.362, P = 0.045), urinary rutine(χ(2) = 17.983, P = 0.000), fever caused by urinary tract infection(χ(2)= 64.472, P = 0.000), bladder compliance(χ(2) = 6.531, P = 0.011), bladder sensation(χ(2) = 11.505, P = 0.009), maximum cystometric capacity(t = 2.209, P = 0.043), and detrusor-sphincter dyssynergia(χ(2) = 4.247, P = 0.039). The multiple-factor non-conditional Logistic regression analysis showed that bladder management (OR = 1.114, P = 0.006), fever caused by urinary tract infection(OR = 1.018,P = 0.000), bladder compliance (OR = 1.588, P = 0.040) and detrusor-sphincter dyssynergia(OR = 1.023, P = 0.034) were the key factors of upper urinary tract deterioration in spinal cord injured patients. Urinary tract infection, lower bladder compliance, detrusor-sphincter dyssynergia and unreasonable bladder management are the risk factors of upper urinary tract deterioration in spinal cord injured patients.

Nitrative DNA damage and Oct3/4 expression in urinary bladder cancer with Schistosomahaematobium infection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Ning; Thanan, Raynoo; Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Mie

Highlights: {yields} Oct3/4-positive cells increase in Schistosoma haematobium (SH)-associated bladder cancer. {yields} iNOS-dependent DNA lesion, 8-nitroguanine, was formed in Oct3/4-positive cells. {yields} 8-Nitroguanine formed in stem-like cells plays a role in SH-induced carcinogenesis. {yields} Mutant stem cells may participate in inflammation-related carcinogenesis. -- Abstract: To investigate whether mutant stem cells participate in inflammation-related carcinogenesis, we performed immunohistochemical analysis to examine nitrative and oxidative DNA lesions (8-nitroguanine and 8-oxodG) and a stem cell marker Oct3/4 in bladder tissues obtained from cystitis and bladder cancer patients infected with Schistosomahaematobium (S. haematobium). We also detected the expression of nuclear factor-{kappa}B (NF-{kappa}B) and induciblemore » nitric oxide synthase (iNOS), which lead to 8-nitroguanine formation. The staining intensity of 8-nitroguanine and 8-oxodG was significantly higher in bladder cancer and cystitis tissues than in normal tissues. iNOS expression was colocalized with NF-{kappa}B in 8-nitroguanine-positive tumor cells from bladder cancer patients. Oct3/4 expression was significantly increased in cells from S. haematobium-associated bladder cancer tissues in comparison to normal bladder and cancer tissues without infection. Oct3/4 was also expressed in epithelial cells of cystitis patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in S. haematobium-associated cystitis and cancer tissues. In conclusion, inflammation by S.haematobium infection may increase the number of mutant stem cells, in which iNOS-dependent DNA damage occurs via NF-{kappa}B activation, leading to tumor development.« less

Sonography of tumors and tumor-like lesions that mimic carcinoma of the urinary bladder

PubMed Central

Szopiński, Tomasz; Gołąbek, Tomasz; Ostasz, Oksana; Bojko, Stefania

2014-01-01

One of the basic abdominal organs that is assessed during transabdominal ultrasound examination for urological reasons is the urinary bladder. The bladder must be filled with urine. This is a prerequisite for a reliable assessment and, at the same time, an acoustic window in examining adjacent structures and organs, for instance the prostate gland. In some cases, doubts occur with respect to the nature of lesions detected. The paper presents anatomic lesions, defects and pathologies which might be erroneously interpreted as tumors of the urinary bladder, i.e. transitional cell carcinoma of the urinary bladder. The following lesions are discussed: 1) anatomic defects (including urachus remnants, ligaments that stabilize the bladder or cyst in the opening of the ureter into the bladder – ureterocele); 2) tumor- like lesions in the lumen of the urinary bladder (such as blood clots, fungus balls, stones or foreign bodies); 3) bladder wall pathologies (i.e. cystitis or endometriosis), focal decidual transformation of stromal cells or inflammatory pseudotumor; 4) lesions impressing on the bladder from the outside (the mesentery of the sigmoid colon, the bowel, pathological lesions in organs adjacent to the urinary bladder, inflammatory infiltration, vasogenic compression of the bladder, pelvic lipomatosis, pathological lesions of the pubic symphysis); 5) postoperative lesions. All these lesions may mimic carcinoma of the urinary bladder in sonography. Bearing this fact in mind is significant in establishing a diagnosis. Due to the malignant character of carcinoma of the urinary bladder and the need for aggressive surgical treatment, a correct diagnosis of this disease is essential for patients, particularly because the lack of adequate treatment and delayed treatment considerably affect prognosis. PMID:26672732

Leiomyoma of Urinary Bladder Presenting with Febrile Urinary Tract Infection: A Case Report.

PubMed

Haddad, Ra'ed Ghassan; Murshidi, Mujalli Mhailan; Abu Shahin, Nisreen; Murshidi, Muayyad Mujalli

2016-01-01

Leiomyomas of urinary bladder constitute only about 0.43% of all bladder tumors. Only about 250 cases were reported in English literature. This is the first reported case of bladder leiomyoma to present with febrile urinary tract infection. We report a case of a 37- year old male who presented with febrile urinary tract infection. Imaging showed a bladder lesion. This lesion was managed by transurethral resection. Pathologic diagnosis was bladder leiomyoma. Although bladder leiomyomas are benign, they can cause serious sequelae, including serious urinary tract infections as the case we present here shows. This is why it is important to early diagnose and treat this condition. This case highlights the importance of early introduction of imaging in patients presenting with severe urinary tract infections. Failure to diagnose this lesion as the underlying cause of infection may have easily led to recurrence of similar severe life-threatening infections. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Immunohistochemical study of parathyroid hormone-related protein in vesical transitional epithelium of patients with spinal cord injury.

PubMed

Vaidyanathan, S; McCreavy, D T; McDicken, I W; Soni, B M; Mansour, P; Wlodarski, B; Carron, J A; Fraser, W D; Singh, G; Sett, P; Gallagher, J A

1999-11-01

Parathyroid hormone-related protein (PTHrP), in addition to the well-established role in endochrondral bone development, is believed to be an important mediator of cellular growth and differentiation in a number of non-bony tissues. To compare the immunohistochemical staining of vesical transitional epithelium to antibodies raised to synthetic peptides of PTHrP composed of amino acid sequences 43 - 52 and 127 - 138 in patients with spinal cord injury (SCI) and neuropathic bladder (n=14), and control patients with intact neuraxis and no history of bladder cancer (n=10). Male SCI patients registered with Regional Spinal Injuries Centre, Southport, England. Endoscopic cold cup biopsy from the trigone of the urinary bladder was taken from patients with SCI while they were undergoing a therapeutic procedure in the urinary bladder. The control samples of bladder biopsies were taken from the archives of the Department of Histopathology, District General Hospital, Southport. Immunohistochemistry was performed using rabbit antibodies raised against synthetic peptides of human PTHrP (43 - 52) and PTHrP (127 - 138). The biopsies were examined for immunostaining of transitional epithelium. Of the 14 biopsies of SCI patients, positive immunostaining using antibodies to both the PTHrP peptides was found in four cases; five biopsies showed positive immunostaining only to anti-PTHrP (43 - 52); and five biopsies showed no immunostaining with either of the PTHrP peptides. In contrast, transitional epithelium in the biopsy specimens of ten control subjects with no history of bladder cancer showed no immunostaining with either of the PTHrP peptides. This study revealed that the transitional epithelium of neuropathic urinary bladder exhibits increased predilection for positive immunohistochemical staining for PTHrP (43 - 52), and to a lesser extent, to PTHrP (127 - 138), as compared to the vesical transitional epithelium of able bodied individuals with no history of vesical malignancy. The possible role of PTHrP in the cellular differentiation of urothelium of neuropathic bladder, and thereby, in the pathogenesis of cystitis in SCI patients, needs to be explored.

Identification of potential bladder cancer markers in urine by abundant-protein depletion coupled with quantitative proteomics.

PubMed

Chen, Chien-Lun; Lin, Tsung-Shih; Tsai, Cheng-Han; Wu, Chih-Ching; Chung, Ting; Chien, Kun-Yi; Wu, Maureen; Chang, Yu-Sun; Yu, Jau-Song; Chen, Yi-Ting

2013-06-24

In this study, we evaluated the reproducibility of abundant urine protein depletion by hexapeptide-based library beads and an antibody-based affinity column using the iTRAQ technique. The antibody-based affinity-depletion approach, which proved superior, was then applied in conjunction with iTRAQ to discover proteins that were differentially expressed between pooled urine samples from hernia and bladder cancer patients. Several proteins, including seven apolipoproteins, TIM, SAA4, and proEGF were further verified in 111 to 203 individual urine samples from patients with hernia, bladder cancer, or kidney cancer. Six apolipoproteins (APOA1, APOA2, APOB, APOC2, APOC3, and APOE) were able to differentiate bladder cancer from hernia. SAA4 was significantly increased in bladder cancer subgroups, whereas ProEGF was significantly decreased in bladder cancer subgroups. Additionally, the combination of SAA4 and ProEGF exhibited higher diagnostic capacity (AUC=0.80 and p<0.001) in discriminating bladder cancer from hernia than either marker alone. Using MetaCore software to interpret global changes of the urine proteome caused by bladder cancer, we found that the most notable alterations were in immune-response/alternative complement and blood-coagulation pathways. This study confirmed the clinical significance of the urine proteome in the development of non-invasive biomarkers for the detection of bladder cancer. In this study, we evaluated the reproducibility of abundant urine protein depletion by hexapeptide-based library beads and an antibody-based affinity column using the iTRAQ technique. The antibody-based affinity-depletion approach, which proved superior, was then applied in conjunction with iTRAQ to discover proteins that were differentially expressed between pooled urine samples from hernia and bladder cancer patients. Several proteins, including seven apolipoproteins, TIM, SAA4, and proEGF were further verified in 111 to 203 individual urine samples from patients with hernia, bladder cancer, or kidney cancer. SAA4 was significantly increased in bladder cancer subgroups, whereas ProEGF was significantly decreased in bladder cancer subgroups. Additionally, the combination of SAA4 and ProEGF exhibited higher diagnostic capacity in discriminating bladder cancer from hernia than either marker alone. A marker panel composed by two novel biomarker candidates, SAA4 and proEGF, was first discovered and verified successfully using Western blotting. To the best of our knowledge, the associations of urinary SAA4 and proEGF with bladder tumor and kidney cancer have not been mentioned before. In the present study, we discovered and verified SAA4 and proEGF as potential bladder cancer biomarker for the first time. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Bladder accumulated dose in image-guided high-dose-rate brachytherapy for locally advanced cervical cancer and its relation to urinary toxicity

NASA Astrophysics Data System (ADS)

Zakariaee, Roja; Hamarneh, Ghassan; Brown, Colin J.; Gaudet, Marc; Aquino-Parsons, Christina; Spadinger, Ingrid

2016-12-01

The purpose of this study was to estimate locally accumulated dose to the bladder in multi-fraction high-dose-date (HDR) image-guided intracavitary brachytherapy (IG-ICBT) for cervical cancer, and study the locally-accumulated dose parameters as predictors of late urinary toxicity. A retrospective study of 60 cervical cancer patients who received five HDR IG-ICBT sessions was performed. The bladder outer and inner surfaces were segmented for all sessions and a bladder-wall contour point-set was created in MATLAB. The bladder-wall point-sets for each patient were registered using a deformable point-set registration toolbox called coherent point drift (CPD), and the fraction doses were accumulated. Various dosimetric and volumetric parameters were calculated using the registered doses, including r{{\\text{D}}n \\text{c{{\\text{m}}\\text{3}}}} (minimum dose to the most exposed n-cm3 volume of bladder wall), r V n Gy (wall volume receiving at least m Gy), and r\\text{EQD}{{2}n \\text{c{{\\text{m}}\\text{3}}}} (minimum equivalent biologically weighted dose to the most exposed n-cm3 of bladder wall), where n  =  1/2/5/10 and m  =  3/5/10. Minimum dose to contiguous 1 and 2 cm3 hot-spot volumes was also calculated. The unregistered dose volume histogram (DVH)-summed equivalent of r{{\\text{D}}n \\text{c{{\\text{m}}3}}} and r\\text{EQD}{{2}n \\text{c{{\\text{m}}3}}} parameters (i.e. s{{\\text{D}}n \\text{c{{\\text{m}}\\text{3}}}} and s\\text{EQD}{{2}n \\text{c{{\\text{m}}3}}} ) were determined for comparison. Late urinary toxicity was assessed using the LENT-SOMA scale, with toxicity Grade 0-1 categorized as Controls and Grade 2-4 as Cases. A two-sample t-test was used to identify the differences between the means of Control and Case groups for all parameters. A binomial logistic regression was also performed between the registered dose parameters and toxicity grouping. Seventeen patients were in the Case and 43 patients in the Control group. Contiguous values were on average 16 and 18% smaller than parameters for 1 and 2 cm3 volumes, respectively. Contiguous values were on average 26 and 27% smaller than parameters. The only statistically significant finding for Case versus Control based on both methods of analysis was observed for r V3 Gy (p  =  0.01). DVH-summed parameters based on unregistered structure volumes overestimated the bladder dose in our patients, particularly when contiguous high dose volumes were considered. The bladder-wall volume receiving at least 3 Gy of accumulated dose may be a parameter of interest in further investigations of Grade 2+  urinary toxicity.

Impaired M3 and enhanced M2 muscarinic receptor contractile function in a streptozotocin model of mouse diabetic urinary bladder

PubMed Central

Pak, K. J.; Ostrom, R. S.; Matsui, M.

2010-01-01

We investigated the contractile roles of M2 and M3 muscarinic receptors in urinary bladder from streptozotocin-treated mice. Wild-type and M2 muscarinic receptor knockout (M2 KO) mice were given a single injection of vehicle or streptozotocin (125 mg kg−1) 2–24 weeks prior to bladder assays. The effect of forskolin on contractions elicited to the muscarinic agonist, oxotremorine-M, was measured in isolated urinary bladder (intact or denuded of urothelium). Denuded urinary bladder from vehicle-treated wild-type and M2 KO mice exhibited similar contractile responses to oxotremorine-M, when contraction was normalized relative to that elicited by KCl (50 mM). Eight to 9 weeks after streptozotocin treatment, the EC50 value of oxotremorine-M increased 3.1-fold in urinary bladder from the M2 KO mouse (N = 5) compared to wild type (N = 6; P < 0.001). Analogous changes were observed in intact bladder. In denuded urinary bladder from vehicle-treated mice, forskolin (5 µM) caused a much greater inhibition of contraction in M2 KO bladder compared to wild type. Following streptozotocin treatment, this forskolin effect increased 1.6-fold (P = 0.032). At the 20- to 24-week time point, the forskolin effect increased 1.7-fold for denuded as well as intact bladders (P = 0.036, 0.01, respectively). Although streptozotocin treatment inhibits M3 receptor-mediated contraction in denuded urinary bladder, muscarinic contractile function is maintained in wild-type bladder by enhanced M2 contractile function. M2 receptor activation opposes forskolin-induced relaxation of the urinary bladder, and this M2 function is enhanced following streptozotocin treatment. PMID:20349044

Impaired M3 and enhanced M2 muscarinic receptor contractile function in a streptozotocin model of mouse diabetic urinary bladder.

PubMed

Pak, K J; Ostrom, R S; Matsui, M; Ehlert, F J

2010-05-01

We investigated the contractile roles of M2 and M3 muscarinic receptors in urinary bladder from streptozotocin-treated mice. Wild-type and M2 muscarinic receptor knockout (M2 KO) mice were given a single injection of vehicle or streptozotocin (125 mg kg(-1)) 2-24 weeks prior to bladder assays. The effect of forskolin on contractions elicited to the muscarinic agonist, oxotremorine-M, was measured in isolated urinary bladder (intact or denuded of urothelium). Denuded urinary bladder from vehicle-treated wild-type and M2 KO mice exhibited similar contractile responses to oxotremorine-M, when contraction was normalized relative to that elicited by KCl (50 mM). Eight to 9 weeks after streptozotocin treatment, the EC(50) value of oxotremorine-M increased 3.1-fold in urinary bladder from the M2 KO mouse (N = 5) compared to wild type (N = 6; P < 0.001). Analogous changes were observed in intact bladder. In denuded urinary bladder from vehicle-treated mice, forskolin (5 microM) caused a much greater inhibition of contraction in M2 KO bladder compared to wild type. Following streptozotocin treatment, this forskolin effect increased 1.6-fold (P = 0.032). At the 20- to 24-week time point, the forskolin effect increased 1.7-fold for denuded as well as intact bladders (P = 0.036, 0.01, respectively). Although streptozotocin treatment inhibits M3 receptor-mediated contraction in denuded urinary bladder, muscarinic contractile function is maintained in wild-type bladder by enhanced M2 contractile function. M2 receptor activation opposes forskolin-induced relaxation of the urinary bladder, and this M(2) function is enhanced following streptozotocin treatment.

Classification of bladder cancer cell lines using Raman spectroscopy: a comparison of excitation wavelength, sample substrate and statistical algorithms

NASA Astrophysics Data System (ADS)

Kerr, Laura T.; Adams, Aine; O'Dea, Shirley; Domijan, Katarina; Cullen, Ivor; Hennelly, Bryan M.

2014-05-01

Raman microspectroscopy can be applied to the urinary bladder for highly accurate classification and diagnosis of bladder cancer. This technique can be applied in vitro to bladder epithelial cells obtained from urine cytology or in vivo as an optical biopsy" to provide results in real-time with higher sensitivity and specificity than current clinical methods. However, there exists a high degree of variability across experimental parameters which need to be standardised before this technique can be utilized in an everyday clinical environment. In this study, we investigate different laser wavelengths (473 nm and 532 nm), sample substrates (glass, fused silica and calcium fluoride) and multivariate statistical methods in order to gain insight into how these various experimental parameters impact on the sensitivity and specificity of Raman cytology.

Genetic variation in the base excision repair pathway and bladder cancer risk.

PubMed

Figueroa, Jonine D; Malats, Núria; Real, Francisco X; Silverman, Debra; Kogevinas, Manolis; Chanock, Stephen; Welch, Robert; Dosemeci, Mustafa; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Castaño-Vinyals, Gemma; Rothman, Nathaniel; García-Closas, Montserrat

2007-04-01

Genetic polymorphisms in DNA repair genes may impact individual variation in DNA repair capacity and alter cancer risk. In order to examine the association of common genetic variation in the base-excision repair (BER) pathway with bladder cancer risk, we analyzed 43 single nucleotide polymorphisms (SNPs) in 12 BER genes (OGG1, MUTYH, APEX1, PARP1, PARP3, PARP4, XRCC1, POLB, POLD1, PCNA, LIG1, and LIG3). Using genotype data from 1,150 cases of urinary bladder transitional cell carcinomas and 1,149 controls from the Spanish Bladder Cancer Study we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. SNPs in three genes showed significant associations with bladder cancer risk: the 8-oxoG DNA glycosylase gene (OGG1), the Poly (ADP-ribose) polymerase family member 1 (PARP1) and the major gap filling polymerase-beta (POLB). Subjects who were heterozygous or homozygous variant for an OGG1 SNP in the promoter region (rs125701) had significantly decreased bladder cancer risk compared to common homozygous: OR (95%CI) 0.78 (0.63-0.96). Heterozygous or homozygous individuals for the functional SNP PARP1 rs1136410 (V762A) or for the intronic SNP POLB rs3136717 were at increased risk compared to those homozygous for the common alleles: 1.24 (1.02-1.51) and 1.30 (1.04-1.62), respectively. In summary, data from this large case-control study suggested bladder cancer risk associations with selected BER SNPs, which need to be confirmed in other study populations.

Automobile industry occupations and bladder cancer: a population-based case-control study in southeastern Michigan, USA.

PubMed

Kobrosly, R W; Meliker, J R; Nriagu, J O

2009-10-01

To determine whether employees in the automobile industry in Michigan are at elevated risk of urinary bladder cancer. The authors conducted a population-based case-control study including 418 cases and 571 controls. History of employment within the automobile industry was coded according to the US Census Bureau Index of Occupations. Logistic regression analyses were adjusted for age at interview, cigarette smoking status, and highest education level, and used to assess associations between bladder cancer and (1) ever working in particular occupations within the automobile industry; and (2) usual occupation - defined as occupation of longest duration for each subject. Ever having worked in the automobile industry and usual employment within the industry exhibited elevated non-significant risks for bladder cancer among assembly line workers, painters and foremen. A higher risk was seen for those who worked for 20 or more years on the assembly line (OR = 2.10, 95% CI 1.15 to 3.80). Statistical interaction between usual employment on the assembly line and smoking status (>5 pack-years) was demonstrated (OR = 6.19, 95% CI 2.69 to 14.24). Among workers on the assembly line for at least 20 years, we observed an approximately twofold risk for bladder cancer. Heavy smokers working on the assembly line experience a sixfold risk for bladder cancer. Further research is necessary to verify this finding, identify the exposures that might be contributing to bladder cancer on the assembly line, and examine whether those exposures continue to persist in today's workplace.

Urinary Calculi and Risk of Cancer

PubMed Central

Shih, Chia-Jen; Chen, Yung-Tai; Ou, Shuo-Ming; Yang, Wu-Chang; Chen, Tzeng-Ji; Tarng, Der-Cherng

2014-01-01

Abstract Previous studies have shown that urinary calculi are associated with increased risks of urinary tract cancers. However, the association between urinary calculi and overall cancers is a largely undefined body of knowledge. We conducted a nationwide population-based cohort study using Taiwan's National Health Insurance Research Database from 2000 and 2009. Patients were excluded if they had antecedent cancers or urinary calculi before the enrollment. All study subjects were followed until the occurrence of cancer, dropout from the NHI program, death, or the end of 2010. Patterns of cancer incidence in patients with urinary calculi were compared with those of the general population using standardized incidence ratio (SIR). A total of 43,516 patients with urinary calculi were included. After a median follow-up of 5.3 years, 1891 patients developed cancer. The risk of overall cancers was significantly increased (SIR, 1.75; 95% confidence interval [CI], 1.68–1.83). We observed that urinary calculi was associated with higher risk of cancers of kidney (4.24; 95% CI, 3.47–5.13), bladder (3.30; 95% CI, 2.69–4.00), thyroid (2.50; 95% CI, 1.78–3.40), hematologic origin (2.41; 95% CI, 1.92–2.99), breast (1.84; 95% CI, 1.54–2.20), lung (1.82; 95% CI, 1.59–2.07), digestive tract (1.69; 95% CI, 1.57–1.82), and head and neck (1.54; 95% CI, 1.32–1.79), respectively. Our study shows that urinary calculi are associated with higher risk of systemic cancers in addition to urinary tract cancers. Further study is required to validate this association. PMID:25546684

Suppression of urinary bladder urothelial carcinoma cell by the ethanol extract of pomegranate fruit through cell cycle arrest and apoptosis.

PubMed

Lee, Song-Tay; Lu, Min-Hua; Chien, Lan-Hsiang; Wu, Ting-Feng; Huang, Li-Chien; Liao, Gwo-Ing

2013-12-21

Pomegranate possesses many medicinal properties such as antioxidant, anti-inflammation and antitumor. It has been extensively used as a folk medicine by many cultures. Pomegranate fruit has been shown to have the inhibitory efficacy against prostate cancer and lung cancer in vitro and in vivo. It can be exploited in chemoprevention and chemotherapy of prostate cancer. In this study we examined the anti-cancer efficacy of pomegranate fruit grown in Taiwan against urinary bladder urothelial carcinoma (UBUC) and its mechanism of action. Edible portion of Taiwanese pomegranate was extracted using ethanol and the anti-cancer effectiveness of ethanol extract was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry and western immunoblotting were exploited to uncover the molecular pathways underlying anti-UBUC activity of Taiwanese pomegranate ethanol extract. This study demonstrated that Taiwanese pomegranate fruit ethanol extract (PEE) could effectively restrict the proliferation of UBUC T24 and J82 cells. Cell cycle analyses indicated that the S phase arrest induced by PEE treatment might be caused by an increase in cyclin A protein level and a decrease in the expression of cyclin-dependent kinase 1. The results of western immunoblotting demonstrated that PEE treatment could not only evoke the activation of pro-caspase-3, -8,-9 but also increase Bax/Bcl-2 ratio in T24 cells. The above observations implicated that PEE administration might trigger the apoptosis in T24 cells through death receptor signaling and mitochondrial damage pathway. Besides we found that PEE exposure to T24 cells could provoke intensive activation of procaspase-12 and enhance the expressions of CHOP and Bip, endoplasmic reticulum (ER) stress marker, suggesting that ER stress might be the cardinal apoptotic mechanism of PEE-induced inhibition of bladder cancer cell. The analytical results of this study help to provide insight into the molecular mechanism of induced bladder cancer cell apoptosis by pomegranate and to develop novel mechanism-based chemopreventive strategy for bladder cancer.

Suppression of urinary bladder urothelial carcinoma cell by the ethanol extract of pomegranate fruit through cell cycle arrest and apoptosis

PubMed Central

2013-01-01

Background Pomegranate possesses many medicinal properties such as antioxidant, anti-inflammation and antitumor. It has been extensively used as a folk medicine by many cultures. Pomegranate fruit has been shown to have the inhibitory efficacy against prostate cancer and lung cancer in vitro and in vivo. It can be exploited in chemoprevention and chemotherapy of prostate cancer. In this study we examined the anti-cancer efficacy of pomegranate fruit grown in Taiwan against urinary bladder urothelial carcinoma (UBUC) and its mechanism of action. Methods Edible portion of Taiwanese pomegranate was extracted using ethanol and the anti-cancer effectiveness of ethanol extract was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry and western immunoblotting were exploited to uncover the molecular pathways underlying anti-UBUC activity of Taiwanese pomegranate ethanol extract. Results This study demonstrated that Taiwanese pomegranate fruit ethanol extract (PEE) could effectively restrict the proliferation of UBUC T24 and J82 cells. Cell cycle analyses indicated that the S phase arrest induced by PEE treatment might be caused by an increase in cyclin A protein level and a decrease in the expression of cyclin-dependent kinase 1. The results of western immunoblotting demonstrated that PEE treatment could not only evoke the activation of pro-caspase-3, -8,-9 but also increase Bax/Bcl-2 ratio in T24 cells. The above observations implicated that PEE administration might trigger the apoptosis in T24 cells through death receptor signaling and mitochondrial damage pathway. Besides we found that PEE exposure to T24 cells could provoke intensive activation of procaspase-12 and enhance the expressions of CHOP and Bip, endoplasmic reticulum (ER) stress marker, suggesting that ER stress might be the cardinal apoptotic mechanism of PEE-induced inhibition of bladder cancer cell. Conclusions The analytical results of this study help to provide insight into the molecular mechanism of induced bladder cancer cell apoptosis by pomegranate and to develop novel mechanism-based chemopreventive strategy for bladder cancer. PMID:24359437

Muscle invasive bladder cancer: examining survivor burden and unmet needs.

PubMed

Mohamed, Nihal E; Chaoprang Herrera, Phapichaya; Hudson, Shawna; Revenson, Tracey A; Lee, Cheryl T; Quale, Diane Z; Zarcadoolas, Christina; Hall, Simon J; Diefenbach, Michael A

2014-01-01

Although improvements in perioperative care have decreased surgical morbidity after radical cystectomy for muscle invasive bladder cancer, treatment side effects still have a negative impact on patient quality of life. We examined unmet patient needs along the illness trajectory. A total of 30 patients (26.7% women) treated with cystectomy and urinary diversion for muscle invasive bladder cancer participated in the study. Patients were recruited from the Department of Urology at Mount Sinai and through advertisements on the Bladder Cancer Advocacy Network (BCAN) website between December 2011 and September 2012. Data were collected at individual interviews, which were audiotaped and transcribed. Transcribed data were quantitatively analyzed to explore key unmet needs. At diagnosis unmet informational needs were predominant, consisting of insufficient discussion of certain topics, including urinary diversion options and their side effects, self-care, the recovery process and medical insurance. Unmet psychological needs related to depression, and worries about changes in body image and sexual function were reported. Postoperative unmet needs revolved around medical needs (eg pain and bowel dysfunction) and instrumental needs (eg need of support for stomal appliances, catheters and incontinence). During survivorship (ie 6 to 72 months postoperatively) unmet needs centered around psychological support (ie depression, poor body image and sexual dysfunction) and instrumental support (eg difficulty adjusting to changes in daily living). Meeting patient needs is imperative to ensure adequate patient involvement in health care and enhance postoperative quality of life. An effective support provision plan should follow changes in patient needs. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Risk factors for development of primary bladder squamous cell carcinoma

PubMed Central

Hubbard, R; Swallow, D; Finch, W; Wood, SJ; Biers, SM

2017-01-01

INTRODUCTION The aim of this study was to investigate the prevalence of risk factors for primary squamous cell carcinoma (SCC) of the bladder. MATERIALS A total of 90 cases of primary SCC of the bladder were identified through multicentre analysis. Patient demographics, stage and grade of cancer at presentation, management and outcomes were recorded. The presence of known risk factors (catheter use, neuropathic bladder, smoking history, recurrent urinary tract infection and bladder stones) was also documented. RESULTS Over half of the patients had at least one identifiable risk factor for the development of primary bladder SCC: 13.9% of patients had a history of catheter use (clean intermittent self-catheterisation [CISC] in 11.1%), 10.0% of patients had a neuropathic bladder, 27.8% were smokers or ex-smokers and 20.0% had a documented history of recurrent urinary tract infection. Statistical analysis of the results showed no association between risk factors and grade of tumour at presentation. CONCLUSIONS These data further support the association between primary bladder SCC and several of the well documented risk factors for its development. Chronic use of CISC may confer a greater risk for development of SCC than thought previously. Further evidence of the role of CISC in primary SCC is required to justify routine screening and to determine exactly when surveillance of the bladder should begin for this group of patients. PMID:27869492

Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs.

PubMed

Fulkerson, Christopher M; Dhawan, Deepika; Ratliff, Timothy L; Hahn, Noah M; Knapp, Deborah W

2017-01-01

Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

PubMed Central

Fulkerson, Christopher M.; Ratliff, Timothy L.; Hahn, Noah M.

2017-01-01

Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed. PMID:28487862

Sequence variant on 8q24 confers susceptibility to urinary bladder cancer

PubMed Central

Kiemeney, Lambertus A.; Thorlacius, Steinunn; Sulem, Patrick; Geller, Frank; Aben, Katja K.H.; Stacey, Simon N.; Gudmundsson, Julius; Jakobsdottir, Margret; Bergthorsson, Jon T.; Sigurdsson, Asgeir; Blondal, Thorarinn; Witjes, J. Alfred; Vermeulen, Sita H.; Hulsbergen-van de Kaa, Christina A.; Swinkels, Dorine W.; Ploeg, Martine; Cornel, Erik B.; Vergunst, Henk; Thorgeirsson, Thorgeir E.; Gudbjartsson, Daniel; Gudjonsson, Sigurjon A.; Thorleifsson, Gudmar; Kristinsson, Kari T.; Mouy, Magali; Snorradottir, Steinunn; Placidi, Donatella; Campagna, Marcello; Arici, Cecilia; Koppova, Kvetoslava; Gurzau, Eugene; Rudnai, Peter; Kellen, Eliane; Polidoro, Silvia; Guarrera, Simonetta; Sacerdote, Carlotta; Sanchez, Manuel; Saez, Berta; Valdivia, Gabriel; Ryk, Charlotta; de Verdier, Petra; Lindblom, Annika; Golka, Klaus; Bishop, D. Timothy; Knowles, Margaret A.; Nikulasson, Sigfus; Petursdottir, Vigdis; Jonsson, Eirikur; Geirsson, Gudmundur; Kristjansson, Baldvin; Mayordomo, Jose I.; Steineck, Gunnar; Porru, Stefano; Buntinx, Frank; Zeegers, Maurice P.; Fletcher, Tony; Kumar, Rajiv; Matullo, Giuseppe; Vineis, Paolo; Kiltie, Anne E.; Gulcher, Jeffrey R.; Thorsteinsdottir, Unnur; Kong, Augustine; Rafnar, Thorunn; Stefansson, Kari

2015-01-01

We conducted a genome wide SNP association study on 1,803 Urinary Bladder Cancer (UBC) cases and 34,336 controls from Iceland and the Netherlands and follow up studies in seven additional case control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30kb upstream of the c-Myc gene (allele specific OR=1.22; P=9.34×10−12). Approximately 20% of individuals of European ancestry are homozygous for rs9642880 (T) and their estimated risk of developing UBC is 1.49 times that of non-carriers with population attributable risk (PAR) of 17%. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome wide significance, was captured by rs710521 (A) located near the TP63 gene on chromosome 3q28 (allele specific OR=1.19; P=1. 15× 10−7). PMID:18794855

Increased risks of upper tract urothelial carcinoma in male and female chinese herbalists.

PubMed

Yang, Hsiao-Yu; Wang, Jung-Der; Lo, Tsai-Chang; Chen, Pau-Chung

2011-03-01

It has been shown that herbs that contain aristolochic acid induce urological cancer. Chinese herbalists have easy access to such herbs. Our previous mortality study has shown a significantly increased risk of urological cancer in female but not male herbalists. To re-examine this risk in male herbalists, the incidence of urological cancer was analyzed. We enrolled all 6550 Chinese herbalists in Taiwan registered during 1985-2000, and we retrospectively followed the development of cancer until 2001 by analysis of data collected from the Taiwan Cancer Registry. Standardized incidence ratios (SIRs) were calculated for urological cancers in herbalists and compared with those for the general population in Taiwan. There were 30 newly diagnosed cases of urological cancer and most of them were transitional cell carcinoma (93.1%). The mean age at diagnosis for urothelial carcinoma was 51.6 years, and 51.9% were in the upper urinary tract. After adjustment for age and sex, the SIR for all urological cancers was 3.51 [(95% confidence interval (CI): 2.37-5.01]. When stratified by location, the SIRs for kidney and upper urinary tract cancers and bladder cancer were 4.24 (95% CI: 2.47-6.80) and 2.86 (95% CI: 1.52-4.89), respectively. When analyzed by sex, the SIRs for all urological cancers, kidney and upper urinary tract cancers, and bladder cancer were also significantly increased in male herbalists. The significant risk of urothelial carcinoma noted in male herbalists increases our suspicion that this is an occupational disease that renders regular health assessment of herbalists an urgent necessity. Copyright © 2011 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.

Wide-field lifetime-based FRET imaging for the assessment of early functional distribution of transferrin-based delivery in breast tumor-bearing small animals

NASA Astrophysics Data System (ADS)

Sinsuebphon, Nattawut; Rudkouskaya, Alena; Barroso, Margarida; Intes, Xavier

2016-02-01

Targeted drug delivery is a critical aspect of successful cancer therapy. Assessment of dynamic distribution of the drug provides relative concentration and bioavailability at the target tissue. The most common approach of the assessment is intensity-based imaging, which only provides information about anatomical distribution. Observation of biomolecular interactions can be performed using Förster resonance energy transfer (FRET). Thus, FRET-based imaging can assess functional distribution and provide potential therapeutic outcomes. In this study, we used wide-field lifetime-based FRET imaging for the study of early functional distribution of transferrin delivery in breast cancer tumor models in small animals. Transferrin is a carrier for cancer drug delivery. Its interaction with its receptor is within a few nanometers, which is suitable for FRET. Alexa Fluor® 700 and Alexa Fluor® 750 were conjugated to holo-transferrin which were then administered via tail vein injection to the mice implanted with T47D breast cancer xenografts. Images were continuously acquired for 60 minutes post-injection. The results showed that transferrin was primarily distributed to the liver, the urinary bladder, and the tumor. The cellular uptake of transferrin, which was indicated by the level of FRET, was high in the liver but very low in the urinary bladder. The results also suggested that the fluorescence intensity and FRET signals were independent. The liver showed increasing intensity and increasing FRET during the observation period, while the urinary bladder showed increasing intensity but minimal FRET. Tumors gave varied results corresponding to their FRET progression. These results were relevant to the biomolecular events that occurred in the animals.

Transcriptional and Translational Plasticity in Rodent Urinary Bladder TRP Channels with Urinary Bladder Inflammation, Bladder Dysfunction or Postnatal Maturation

PubMed Central

Merrill, Liana; Girard, Beatrice M.; May, Victor; Vizzard, Margaret A.

2013-01-01

These studies examined transcriptional and translational plasticity of three transient receptor potential (TRP) channels (TRPA1, TRPV1, TRPV4) with established neuronal and non-neuronal expression and functional roles in the lower urinary tract. Mechanosensor and nociceptor roles in either physiological or pathological lower urinary tract states have been suggested for TRPA1, TRPV1 and TRPV4. We have previously demonstrated neurochemical, organizational and functional plasticity in micturition reflex pathways following induction of urinary bladder inflammation using the antineoplastic agent, cyclophosphamide (CYP). More recently, we have characterized similar plasticity in micturition reflex pathways in a transgenic mouse model with chronic urothelial overexpression (OE) of nerve growth factor (NGF) and in a transgenic mouse model with deletion of vasoactive intestinal polypeptide (VIP). In addition, the micturition reflex undergoes postnatal maturation that may also reflect plasticity in urinary bladder TRP channel expression. Thus, we examined plasticity in urinary bladder TRP channel expression in diverse contexts using a combination of quantitative, real-time PCR and western blotting approaches. We demonstrate transcriptional and translational plasticity of urinary bladder TRPA1, TRPV1 and TRVP4 expression. Although the functional significance of urinary bladder TRP channel plasticity awaits further investigation, these studies demonstrate context-(inflammation, postnatal development, NGF-OE, VIP deletion) and tissue-dependent (urothelium + suburothelium, detrusor) plasticity. PMID:22865090

Rhabdomyosarcoma of the urinary bladder in adults: predilection for alveolar morphology with anaplasia and significant morphologic overlap with small cell carcinoma.

PubMed

Paner, Gladell P; McKenney, Jesse K; Epstein, Jonathan I; Amin, Mahul B

2008-07-01

Rhabdomyosarcoma (RMS) represents the most common malignant soft tissue tumor in children and adolescents with the urinary bladder representing a frequent site. Most of these urinary bladder tumors are embryonal RMS, predominantly the botryoid subtype. RMSs of the urinary bladder in adults are distinctively rare and the subject of only case reports. We report the clinicopathologic features of 5 bladder neoplasms with rhabdomyosarcomatous differentiation in adults and emphasize the differential diagnosis in the adult setting. The patients, 4 men and 1 woman, ranged in age from 23 to 85 years (mean 65.4 y). Gross hematuria was the most common initial symptom, although 2 patients had metastatic disease at presentation. Four cases were pure primary RMSs of the bladder and 1 case was a sarcomatoid urothelial carcinoma with RMS representing the extensive heterologous component. All 5 cases demonstrated a diffuse growth pattern (ie, non-nested), of which 4 cases had nuclear anaplasia (Wilms criteria without the atypical mitotic figure requirement); only 1 case (the sarcomatoid carcinoma) showed obvious rhabdomyoblastic differentiation (ie, strap cells). Three cases were of the alveolar subtype (1 admixed with embryonal histology) and 2 were RMS, not further classified. Microscopically, all tumors had a primitive undifferentiated morphology with cells containing scant cytoplasm, varying round to fusiform nuclei with even chromatin distribution, and frequent mitoses. The degree of morphologic overlap with small cell carcinoma of the bladder, a relatively more common round cell tumor in adults, was striking. The epithelial component of the sarcomatoid carcinoma was high-grade invasive urothelial carcinoma with glandular differentiation. No other case had previous history of bladder cancer or concurrent carcinoma in situ or invasive urothelial carcinoma. All tumors showed immunohistochemical expression for desmin, myogenin, and/or MyoD1. Synaptophysin was performed in 4 cases, and 3 showed weak cytoplasmic immunoreactivity. Two patients received chemotherapy, 2 underwent cystectomy, and 1 had transurethral resection alone. Outcome data were available in 4 cases, and all 4 died of disease (1, 4, 8, and 8 mo). In conclusion, (1) RMS of the urinary bladder in adults more commonly presents as a primitive round blue cell neoplasm that has significant morphologic and immunohistochemical overlap with small cell carcinoma of the bladder. (2) Although RMS in children generally have a botryoid embryonal histology with favorable outcome, bladder RMS in adults frequently demonstrates alveolar or unclassified histology, commonly with anaplasia, and have a uniformly aggressive clinical course.

Neurogenic Bladder

PubMed Central

Dorsher, Peter T.; McIntosh, Peter M.

2012-01-01

Congenital anomalies such as meningomyelocele and diseases/damage of the central, peripheral, or autonomic nervous systems may produce neurogenic bladder dysfunction, which untreated can result in progressive renal damage, adverse physical effects including decubiti and urinary tract infections, and psychological and social sequelae related to urinary incontinence. A comprehensive bladder-retraining program that incorporates appropriate education, training, medication, and surgical interventions can mitigate the adverse consequences of neurogenic bladder dysfunction and improve both quantity and quality of life. The goals of bladder retraining for neurogenic bladder dysfunction are prevention of urinary incontinence, urinary tract infections, detrusor overdistension, and progressive upper urinary tract damage due to chronic, excessive detrusor pressures. Understanding the physiology and pathophysiology of micturition is essential to select appropriate pharmacologic and surgical interventions to achieve these goals. Future perspectives on potential pharmacological, surgical, and regenerative medicine options for treating neurogenic bladder dysfunction are also presented. PMID:22400020

Analysis on pathogenesis of 50 cases of bladder proliferative lesions.

PubMed

Chen, Zhiqiang; Lan, Ruzhu; Ye, Zhangqun; Yang, Weimin

2003-01-01

In order to study the pathogenesis, clinical and pathological characteristics of proliferative lesions of the bladder, 50 cases of proliferative lesions of the bladder from 150 patients with complaints of frequency, urgency, hematuria and dysuria were subjected to cystoscopic biopsy of the suspicious foci in the bladder. In combination with the symptoms, urine and urodynamics, the relationship of proliferative lesions of the bladder to the inflammation and obstruction of the lower urinary tract was analyzed. Of the 50 cases of proliferative bladder lesions, 44 cases (88%) had lower urinary tract infection and 29 (58%) lower urinary tract obstruction. The patients with lower urinary tract obstruction were all complicated with infection. Three cases were associated with transitional cell carcinoma. Malignant cells were detected in 1 case by urinary cytologic examination. Proliferative lesions of the bladder, especially those without other obvious mucosa changes under cystoscopy, are common histological variants of urothelium in the patients with chronic inflammation and obstruction of the lower urinary tract. Chronic inflammation and obstruction of the lower urinary tract might be the causes for proliferative lesions of the bladder. It is suggested that different treatments should be applied according to the scope and histological type of the proliferative lesions.

Therapeutic options for intractable hematuria in advanced bladder cancer.

PubMed

Abt, Dominik; Bywater, Mirjam; Engeler, Daniel Stephan; Schmid, Hans-Peter

2013-07-01

Intractable hematuria is a common and severe complication in patients with inoperable bladder carcinoma. The aim was to provide an overview of therapeutic options for such cases, and analyze their effectiveness and risk profile, so a systematic literature search of peer-reviewed papers published up to September 2012 was carried out. Various options are available to treat hematuria in patients with inoperable bladder cancer; these include orally administered epsilon-aminocaproic acid, intravesical formalin, alum or prostaglandin irrigation, hydrostatic pressure, urinary diversion, radiotherapy, embolization and intraarterial mitoxantrone perfusion. These treatment options are associated with different prospects of success, risks and side-effects. Well-designed and large studies comparing options are completely lacking. Despite various treatment options, management of intractable hematuria in patients with inoperable bladder cancer remains a challenge, and most of the reported methods should be seen as experimental. Interventional radiology and alum instillation seem to be suitable alternative options for patients who, after critical consideration, cannot be treated by irrigation, transurethral resection or palliative cystectomy. © 2013 The Japanese Urological Association.

Frequency of CD4+CD25+Foxp3+ cells in peripheral blood in relation to urinary bladder cancer malignancy indicators before and after surgical removal.

PubMed

Jóźwicki, Wojciech; Brożyna, Anna A; Siekiera, Jerzy; Slominski, Andrzej T

2016-03-08

Tumor cells communicate with stromal cells, including cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), to form microenvironment inhibiting immune responses. Regulatory T cells (Tregs, CD4+CD25+FoxP3+) stimulate immune tolerance and facilitate tumor progression. We analyzed the changes in Treg frequencies assessed using flow cytometry in the peripheral blood of patients with urothelial bladder cancer before and after tumor-removal. Changes in Treg frequency were investigated in relation to clinicopathomorphological indicators of tumor malignancy and expression of RCAS1 on CAFs and TAMs. Higher Treg frequencies were observed in early phase of tumor growth (pTa-pT2), in larger tumors, with more aggressive type of invasion, and with expression of RCAS1. The later phase of tumor development, accompanied by a nonclassic differentiations and pT3-pT4 advancement, had lower number of tumor infiltrating lymphocytes (TILs) and lower Treg frequency. Furthermore, in pT2-pT4 tumors, a decreased post-surgery Treg frequency was associated with poorer prognosis: patients with the lowest frequency of Tregs died first. These findings strongly suggest that the Treg frequencies at later phase of tumor growth, associated with a low anti-tumor response, represent a new and important prognostic indicator in urinary bladder cancer.

Systematic Review of Studies Reporting Positive Surgical Margins After Bladder Neck Sparing Radical Prostatectomy.

PubMed

Bellangino, Mariangela; Verrill, Clare; Leslie, Tom; Bell, Richard W; Hamdy, Freddie C; Lamb, Alastair D

2017-11-07

Bladder neck preservation (BNP) during radical prostatectomy (RP) has been proposed as a method to improve early recovery of urinary continence after radical prostatectomy. However, there is concern over a possible increase in the risk of positive surgical margins and prostate cancer recurrence rate. A recent systematic review and meta-analysis reported improved early recovery and overall long-term urinary continence without compromising oncologic control. The aim of our study was to perform a critical review of the literature to assess the impact on bladder neck and base margins after bladder neck sparing radical prostatectomy. We carried out a systematic review of the literature using Pubmed, Scopus and Cochrane library databases in May 2017 using medical subject headings and free-text protocol according to PRISMA guidelines. We used the following search terms: bladder neck preservation, prostate cancer, radical prostatectomy and surgical margins. Studies focusing on positive surgical margins (PSM) in bladder neck sparing RP pertinent to the objective of this review were included. Overall, we found 15 relevant studies reporting overall and site-specific positive surgical margins rate after bladder neck sparing radical prostatectomy. This included two RCTs, seven prospective comparative studies, two retrospective comparative studies and four case series. All studies were published between 1993 and 2015 with sample sizes ranging between 50 and 1067. Surgical approaches included open, laparoscopic and robot-assisted radical prostatectomy. The overall and base-specific PSM rates ranged between 7-36% and 0-16.3%, respectively. Mean base PSM was 4.9% in those patients where bladder neck sparing was performed, but only 1.85% in those without sparing. Bladder neck preservation during radical prostatectomy may increase base-positive margins. Further studies are needed to better investigate the impact of this technique on oncological outcomes. A future paradigm could include modification of intended approach to bladder neck dissection when anterior base lesions are identified on pre-operative MRI.

The Promise of Novel Molecular Markers in Bladder Cancer

PubMed Central

Miremami, Jahan; Kyprianou, Natasha

2014-01-01

Bladder cancer is the fourth most common malignancy in the US and is associated with the highest cost per patient. A high likelihood of recurrence, mandating stringent surveillance protocols, has made the development of urinary markers a focus of intense pursuit with the hope of decreasing the burden this disease places on patients and the healthcare system. To date, routine use of markers is not recommended for screening or diagnosis. Interests include the development of a single urinary marker that can be used in place of or as an adjunct to current screening and surveillance techniques, as well identifying a molecular signature for an individual’s disease that can help predict progression, prognosis, and potential therapeutic response. Markers have shown potential value in improving diagnostic accuracy when used as an adjunct to current modalities, risk-stratification of patients that could aid the clinician in determining aggressiveness of surveillance, and allowing for a decrease in invasive surveillance procedures. This review discusses the current understanding of emerging biomarkers, including miRNAs, gene signatures and detection of circulating tumor cells in the blood, and their potential clinical value in bladder cancer diagnosis, as prognostic indicators, and surveillance tools, as well as limitations to their incorporation into medical practice. PMID:25535079

Bladder cancer diagnosis with CT urography: test characteristics and reasons for false-positive and false-negative results.

PubMed

Trinh, Tony W; Glazer, Daniel I; Sadow, Cheryl A; Sahni, V Anik; Geller, Nina L; Silverman, Stuart G

2018-03-01

To determine test characteristics of CT urography for detecting bladder cancer in patients with hematuria and those undergoing surveillance, and to analyze reasons for false-positive and false-negative results. A HIPAA-compliant, IRB-approved retrospective review of reports from 1623 CT urograms between 10/2010 and 12/31/2013 was performed. 710 examinations for hematuria or bladder cancer history were compared to cystoscopy performed within 6 months. Reference standard was surgical pathology or 1-year minimum clinical follow-up. False-positive and false-negative examinations were reviewed to determine reasons for errors. Ninety-five bladder cancers were detected. CT urography accuracy: was 91.5% (650/710), sensitivity 86.3% (82/95), specificity 92.4% (568/615), positive predictive value 63.6% (82/129), and negative predictive value was 97.8% (568/581). Of 43 false positives, the majority of interpretation errors were due to benign prostatic hyperplasia (n = 12), trabeculated bladder (n = 9), and treatment changes (n = 8). Other causes include blood clots, mistaken normal anatomy, infectious/inflammatory changes, or had no cystoscopic correlate. Of 13 false negatives, 11 were due to technique, one to a large urinary residual, one to artifact. There were no errors in perception. CT urography is an accurate test for diagnosing bladder cancer; however, in protocols relying predominantly on excretory phase images, overall sensitivity remains insufficient to obviate cystoscopy. Awareness of bladder cancer mimics may reduce false-positive results. Improvements in CTU technique may reduce false-negative results.

Androgen receptor signals regulate UDP-glucuronosyltransferases in the urinary bladder: a potential mechanism of androgen-induced bladder carcinogenesis.

PubMed

Izumi, Koji; Zheng, Yichun; Hsu, Jong-Wei; Chang, Chawnshang; Miyamoto, Hiroshi

2013-02-01

UDP-glucuronosyltransferases (UGTs), major phase II drug metabolism enzymes, play an important role in urinary bladder cancer initiation by detoxifying carcinogens. We aimed to determine if androgens regulate UGT expression via the androgen receptor (AR) pathway in the bladder. Real-time reverse transcription-polymerase chain reaction and Western blot analyses were used to assess UGT1A levels in the normal urothelium SVHUC cell line stably expressed with AR and in bladder tissues from AR knockout (ARKO) and castrated male mice. Immunohistochemistry was also performed in radical cystectomy specimens. Dihydrotestosterone (DHT) treatment in SVHUC-AR reduced mRNA expression of all the UGT1A subtypes (19-75% decrease), and hydroxyflutamide antagonized the DHT effects. In contrast, DHT showed only marginal effects on UGT1A expression in SVHUC-Vector. Of note were higher expression levels of UGT1As in SVHUC-Vector than in SVHUC-AR. In ARKO mice, all the Ugt1a subtypes were up-regulated, compared to wild-type littermates. In wild-type male mice, castration increased the expression of Ugt1a8, Ugt1a9, and Ugt1a10. Additionally, wild-type female mice had higher levels of Ugt1a than wild-type males. Immunohistochemical studies showed strong (3+) UGT1A staining in 11/24 (46%) cancer tissues, which was significantly lower than in corresponding benign tissues [17/18 (94%) cases (P = 0.0009)]. These results suggest that androgen-mediated AR signals promote bladder carcinogenesis by down-regulating the expression of UGTs in the bladder. Copyright © 2011 Wiley Periodicals, Inc.

Ultrasound-guided urinary bladder biopsy through a urinary catheter in a bitch.

PubMed

Lopez, Julio; Norman, Brian C

2014-01-01

A 34.4 kg 5 yr old spayed female mixed-breed dog was presented for evaluation of a urinary bladder mass. The dog had a recent onset of hematuria and stranguria but otherwise appeared to be healthy. Abdominal ultrasound revealed a mass in the urinary bladder. The dog was sedated and a 10-French rubber catheter that had the blunt end removed was passed from the urethra to the urinary bladder. Using ultrasound guidance, ellipsoid cup biopsy forceps were advanced through the rubber catheter to the urinary bladder mass and biopsies were successfully obtained. The dog was discharged from the hospital a few hours after the procedure. Histopathology of the mass was consistent with polypoid cystitis. Follow-up surgical removal of the polyp was uneventful, and histopathology confirmed the presurgical biopsy diagnosis. Procurement of urinary bladder biopsies through a urinary catheter with ultrasound guidance was used as a minimally invasive alternative to either cystoscopy or surgery in a bitch. Use of this technique achieved a diagnosis without the need for specialized endoscopic equipment, anesthesia, or surgery.

Probiotics to prevent urinary tract infections: the rationale and evidence.

PubMed

Reid, Gregor; Bruce, Andrew W

2006-02-01

For over 30 years, urologists have recognized in females, that urinary pathogens almost always infect the host through ascension from the rectum, vagina to the urethra and bladder. Likewise, the Lactobacillus organisms that predominate in the vagina of healthy women, spread from the rectum and perineum and form a barrier in the vagina to bladder entry by uropathogens. The concept of artificially boosting the lactobacilli numbers through probiotic instillation has long been conceived, but only in recent years shown to be possible. Not all lactobacilli are effective, and to date clinical efficacy only exists for Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri B-54 and RC-14. These strains are only commercially available in Austria, and therefore for most urologists, while some probiotic organisms may reduce the recurrences of bladder cancer or oxaluria, no probiotics can be recommended widely to prevent UTI at present.

The microbiome of the urinary tract--a role beyond infection.

PubMed

Whiteside, Samantha A; Razvi, Hassan; Dave, Sumit; Reid, Gregor; Burton, Jeremy P

2015-02-01

Urologists rarely need to consider bacteria beyond their role in infectious disease. However, emerging evidence shows that the microorganisms inhabiting many sites of the body, including the urinary tract--which has long been assumed sterile in healthy individuals--might have a role in maintaining urinary health. Studies of the urinary microbiota have identified remarkable differences between healthy populations and those with urologic diseases. Microorganisms at sites distal to the kidney, bladder and urethra are likely to have a profound effect on urologic health, both positive and negative, owing to their metabolic output and other contributions. Connections between the gut microbiota and renal stone formation have already been discovered. In addition, bacteria are also used in the prevention of bladder cancer recurrence. In the future, urologists will need to consider possible influences of the microbiome in diagnosis and treatment of certain urological conditions. New insights might provide an opportunity to predict the risk of developing certain urological diseases and could enable the development of innovative therapeutic strategies.

Bovine papillomavirus type 2 (BPV-2) E5 oncoprotein binds to the subunit D of the V₁-ATPase proton pump in naturally occurring urothelial tumors of the urinary bladder of cattle.

PubMed

Roperto, Sante; Russo, Valeria; Borzacchiello, Giuseppe; Urraro, Chiara; Lucà, Roberta; Esposito, Iolanda; Riccardi, Marita Georgia; Raso, Cinzia; Gaspari, Marco; Ceccarelli, Dora Maria; Galasso, Rocco; Roperto, Franco

2014-01-01

Active infection by bovine papillomavirus type 2 (BPV-2) was documented for fifteen urinary bladder tumors in cattle. Two were diagnosed as papillary urothelial neoplasm of low malignant potential (PUNLMP), nine as papillary and four as invasive urothelial cancers. In all cancer samples, PCR analysis revealed a BPV-2-specific 503 bp DNA fragment. E5 protein, the major oncoprotein of the virus, was shown both by immunoprecipitation and immunohistochemical analysis. E5 was found to bind to the activated (phosphorylated) form of the platelet derived growth factor β receptor. PDGFβR immunoprecipitation from bladder tumor samples and from normal bladder tissue used as control revealed a protein band which was present in the pull-down from bladder cancer samples only. The protein was identified with mass spectrometry as "V₁-ATPase subunit D", a component of the central stalk of the V₁-ATPase vacuolar pump. The subunit D was confirmed in this complex by coimmunoprecipitation investigations and it was found to colocalize with the receptor. The subunit D was also shown to be overexpressed by Western blot, RT-PCR and immunofluorescence analyses. Immunoprecipitation and immunofluorescence also revealed that E5 oncoprotein was bound to the subunit D. For the first time, a tri-component complex composed of E5/PDGFβR/subunit D has been documented in vivo. Previous in vitro studies have shown that the BPV-2 E5 oncoprotein binds to the proteolipid c ring of the V₀-ATPase sector. We suggest that the E5/PDGFβR/subunit D complex may perturb proteostasis, organelle and cytosol homeostasis, which can result in altered protein degradation and in autophagic responses.

Bladder Control and Nerve Disease

MedlinePlus

... VUR) The Urinary Tract & How It Works Bladder Control Problems & Nerve Disease For the urinary system to ... the bladder do not work properly. What bladder control problems does nerve damage cause? Nerves that work ...

Problems arising in the diagnosis of primary ovarian transitional cell carcinoma after the occurrence of a transitional cell carcinoma of the bladder: a report of a difficult case and a critical review of literature.

PubMed

Raspollini, Maria Rosaria; Paglierani, Milena; Taddei, Gian Luigi

2009-03-01

Transitional cell carcinoma (TCC) of the ovary is a recently recognized subtype of ovarian surface epithelial-stromal cancer that morphologically resembles a TCC of the bladder. The most frequent metastases to ovaries come from the gastrointestinal tract and from breast carcinoma, but metastatic TCCs from the urinary tract to the ovary have been reported. TCC of the bladder is the sixth most common cancer in European and North American countries and its incidence has been increasing. We recently observed a woman, who previously had undergone endoscopic resection of a TCC of the bladder. She was affected by an ovarian bilateral tumor with features of malignant transitional cell tumor, characterized by papillae with multilayered transitional epithelium infiltrating the ovarian stroma. In this study, we showed the utility of WT1 and a panel of immunohistochemical markers in the difficult differential diagnosis between bladder and ovarian TCC.

Urinary Bladder Lesions after the Chernobyl Accident: Immunohistochemical Assessment of p53, Proliferating Cell Nuclear Antigen, Cyclin D1 and p21WAF1/Cip1

PubMed Central

Romanenko, Alina; Lee, Chyi Chia R.; Yamamoto, Shinji; Hori, Taka‐aki; Wanibuchi, Hideki; Zaparin, Wadim; Vinnichenko, Wladimir; Vozianov, Alexander

1999-01-01

During the 11‐year period subsequent to the Chernobyl accident, the incidence of urinary bladder cancer in Ukraine has increased from 26.2 to 36.1 per 100,000 population. Cesium‐137 (137Cs) accounts for 80–90% of the incorporated radioactivity in this population, which has been exposed to long‐term, low‐dose ionizing radiation, and 80% of the more labile pool of cesium is excreted via the urine. The present study was performed to evaluate the histopathological features and the immunohistochemical status of p53, p21WAF1/Cip1, cyclin D1 and PCNA (proliferating cell nuclear antigen) in urinary bladder mucos a of 55 males (49‐92 years old) with benign prostatic hyperplasia who underwent surgery in Kiev, Ukraine, in 1995 and 1996. Group I (28 patients) inhabiting radiocontaminated areas of the country, group II (17 patients) from Kiev city with less radiocontamination and a control group III (10 patients) living in so‐called “clean” areas of Ukraine were compared. In groups I and II, an increase in multiple areas of moderate or severe dysplasia or carcinoma in situ was seen in 42 (93%) of 45 cases. In addi tion, two small transitional cell carcinomas were found in one patient in each of groups I and II. Nuclear accumulation of p53, PCNA, cyclin D1, and to a lesser extent p21WAF1/Cip1, was significantly increased in both groups I and II as compared with the control group III, indicating possible transformation events or enhancement of repair activities, that may precede the defect in the regulatory pathway itself, at least in the G1 phase of the cell cycle. Our results suggest that early malignant transformation is taking place in the bladder urothelium of people in the radiocontaminated areas of Ukraine and that this could possibly lead sometime in the future to an increased incidence of urinary bladder cancer. PMID:10189884

Cuscuta chinensis Ameliorates Immunosuppression and Urotoxic Effect of Cyclophosphamide by Regulating Cytokines - GM-CSF and TNF-Alpha.

PubMed

Raju, Nidhi; Sakthivel, Kunnathur Murugesan; Kannan, Narayanan; Vinod Prabhu, Venugopal; Guruvayoorappan, Chandrasekaran

2015-06-01

Cancer is the leading cause of death worldwide. Cyclophosphamide (CTX) is commonly used as anticancer drug which causes toxicity by its reactive metabolites such as acroline and phosphoramide mustard. In this study, Cuscuta chinensis (C. chinensis) (family: Convolvulaceae) was assessed for ability to restore mice against CTX-induced toxicity. Coadministration of C. chinensis extract (10 mg/kg BW, IP, daily) for ten consecutive days reduced CTX-induced (25 mg/kg BW, IP, daily) toxicity. Treatment with C. chinensis extract significantly (p < 0.01) increased the relative organ weight and body weight. Moreover, administration of C. chinensis extract significantly increased bone marrow cellulatity and α-esterase activity in CTX-treated mice which suggested its protective role on the hematopoietic system. The GSH content was drastically reduced by CTX administration in urinary bladder which was enhanced by treatment with C. chinensis extract, indicating that preventing acroline-mediated tissue damage or cell toxicity and also the extract decreased the urinary bladder nitric oxide (NO) level which proves recovery over urinary tract injury associated with CTX treatment. The administration of C. chinensis extract decreased serum urea, creatinine, and bilirubin levels when compared to CTX-alone-treated group. Histopathological analysis of the urinary bladder of CTX-alone-treated group showed necrotic damage whereas the C. chinensis-treated group showed normal bladder architecture. The above data clearly demonstrates chemoprotective role of C. chinensis against CTX-induced toxicities by regulating antioxidant and inflammatory mediators.

Social stress induces changes in urinary bladder function, bladder NGF content, and generalized bladder inflammation in mice

PubMed Central

Peterson, Abbey; Erickson, Cuixia Shi; Nelson, Mark T.; Vizzard, Margaret A.

2014-01-01

Social stress may play a role in urinary bladder dysfunction in humans, but the underlying mechanisms are unknown. In the present study, we explored changes in bladder function caused by social stress using mouse models of stress and increasing stress. In the stress paradigm, individual submissive FVB mice were exposed to C57BL/6 aggressor mice directly/indirectly for 1 h/day for 2 or 4 wk. Increased stress was induced by continuous, direct/indirect exposure of FVB mice to aggressor mice for 2 wk. Stressed FVB mice exhibited nonvoiding bladder contractions and a decrease in both micturition interval (increased voiding frequency) and bladder capacity compared with control animals. ELISAs demonstrated a significant increase in histamine protein expression with no change in nerve growth factor protein expression in the urinary bladder compared with controls. Unlike stressed mice, mice exposed to an increased stress paradigm exhibited increased bladder capacities and intermicturition intervals (decreased voiding frequency). Both histamine and nerve growth factor protein expression were significantly increased with increased stress compared with control bladders. The change in bladder function from increased voiding frequency to decreased voiding frequency with increased stress intensity suggests that changes in social stress-induced urinary bladder dysfunction are context and duration dependent. In addition, changes in the bladder inflammatory milieu with social stress may be important contributors to changes in urinary bladder function. PMID:25100077

Quality of life after radical cystectomy for bladder cancer in men with an ileal conduit or continent urinary diversion: A comparative study

PubMed Central

Asgari, M. A.; Safarinejad, M. R.; Shakhssalim, N.; Soleimani, M.; Shahabi, A.; Amini, E.

2013-01-01

Aim: To investigate quality of life (QoL) domains with three forms of urinary diversions, including ileal conduit, MAINZ pouch, and orthotopic ileal neobladder after radical cystectomy in men with muscle-invasive bladder cancer. Materials and Methods: In a prospective study, 149 men underwent radical cystectomy and urinary diversion (70 ileal conduit, 16 MAINZ pouch, and 63 orthotopic ileal neobladder). Different domains of QoL, including general and physical conditions, psychological status, social status, sexual life, diversion-related symptoms, and satisfaction with the treatment were assessed using an author constructed questionnaire. Assessment was performed at three months postoperatively. Results: In questions addressing psychological status, social status, and sexual life, patients with continent diversion had a more favorable outcome (P = 0.002, P = 0.01, and P = 0.002, respectively). The rate of erectile dysfunction did not differ significantly between the three groups (P = 0.21). The rate and global satisfaction was higher with the MAINZ pouch (68.7%) and ileal neobladder (76.2%) as compared with the ileal conduit group (52.8%) (P = 0.002). Conclusion: Continent urinary diversion after radical cystectomy provides better results in terms of QoL as compared with ileal conduit diversion. PMID:24049384

Chronic arsenic exposure increases TGFalpha concentration in bladder urothelial cells of Mexican populations environmentally exposed to inorganic arsenic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valenzuela, Olga L.; Germolec, Dori R.; Borja-Aburto, Victor H.

Inorganic arsenic (iAs) is a well-established carcinogen and human exposure has been associated with a variety of cancers including those of skin, lung, and bladder. High expression of transforming growth factor alpha (TGF-{alpha}) has associated with local relapses in early stages of urinary bladder cancer. iAs exposures are at least in part determined by the rate of formation and composition of iAs metabolites (MAs{sup III}, MAs{sup V}, DMAs{sup III}, DMAs{sup V}). This study examines the relationship between TGF-{alpha} concentration in exfoliated bladder urothelial cells (BUC) separated from urine and urinary arsenic species in 72 resident women (18-51 years old) frommore » areas exposed to different concentrations of iAs in drinking water (2-378 ppb) in central Mexico. Urinary arsenic species, including trivalent methylated metabolites were measured by hydride generation atomic absorption spectrometry method. The concentration of TGF-{alpha} in BUC was measured using an ELISA assay. Results show a statistically significant positive correlation between TGF-{alpha} concentration in BUC and each of the six arsenic species present in urine. The multivariate linear regression analyses show that the increment of TGF-{alpha} levels in BUC was importantly associated with the presence of arsenic species after adjusting by age, and presence of urinary infection. People from areas with high arsenic exposure had a significantly higher TGF-{alpha} concentration in BUC than people from areas of low arsenic exposure (128.8 vs. 64.4 pg/mg protein; p < 0.05). Notably, exfoliated cells isolated from individuals with skin lesions contained significantly greater amount of TGF-{alpha} than cells from individuals without skin lesions: 157.7 vs. 64.9 pg/mg protein (p = 0.003). These results suggest that TGF-{alpha} in exfoliated BUC may serve as a susceptibility marker of adverse health effects on epithelial tissue in arsenic-endemic areas.« less

Chronic arsenic exposure increases TGFalpha concentration in bladder urothelial cells of Mexican populations environmentally exposed to inorganic arsenic☆

PubMed Central

Valenzuela, Olga L.; Germolec, Dori R.; Borja-Aburto, Víctor H.; Contreras-Ruiz, José; García-Vargas, Gonzalo G.; Del Razo, Luz M.

2009-01-01

Inorganic arsenic (iAs) is a well-established carcinogen and human exposure has been associated with a variety of cancers including those of skin, lung, and bladder. High expression of transforming growth factor alpha (TGF-α) has associated with local relapses in early stages of urinary bladder cancer. iAs exposures are at least in part determined by the rate of formation and composition of iAs metabolites (MAsIII, MAsV, DMAsIII, DMAsV). This study examines the relationship between TGF-α concentration in exfoliated bladder urothelial cells (BUC) separated from urine and urinary arsenic species in 72 resident women (18-51 years old) from areas exposed to different concentrations of iAs in drinking water (2-378 ppb) in central Mexico. Urinary arsenic species, including trivalent methylated metabolites were measured by hydride generation atomic absorption spectrometry method. The concentration of TGF-α in BUC was measured using an ELISA assay. Results show a statistically significant positive correlation between TGF-α concentration in BUC and each of the six arsenic species present in urine. The multivariate linear regression analyses show that the increment of TGF-α levels in BUC was importantly associated with the presence of arsenic species after adjusting by age, and presence of urinary infection. People from areas with high arsenic exposure had a significantly higher TGF-α concentration in BUC than people from areas of low arsenic exposure (128.8 vs. 64.4 pg/mg protein; p<0.05). Notably, exfoliated cells isolated from individuals with skin lesions contained significantly greater amount of TGF-α than cells from individuals without skin lesions: 157.7 vs. 64.9 pg/mg protein (p=0.003). These results suggest that TGF-α in exfoliated BUC may serve as a susceptibility marker of adverse health effects on epithelial tissue in arsenic-endemic areas. PMID:17267001

Next generation of optical diagnostics for bladder cancer using probe-based confocal laser endomicroscopy

NASA Astrophysics Data System (ADS)

Liu, Jen-Jane; Chang, Timothy C.; Pan, Ying; Hsiao, Shelly T.; Mach, Kathleen E.; Jensen, Kristin C.; Liao, Joseph C.

2012-02-01

Real-time imaging with confocal laser endomicroscopy (CLE) probes that fit in standard endoscopes has emerged as a clinically feasible technology for optical biopsy of bladder cancer. Confocal images of normal, inflammatory, and neoplastic urothelium obtained with intravesical fluorescein can be differentiated by morphologic characteristics. We compiled a confocal atlas of the urinary tract using these diagnostic criteria to be used in a prospective diagnostic accuracy study. Patients scheduled to undergo transurethral resection of bladder tumor underwent white light cystoscopy (WLC), followed by CLE, and histologic confirmation of resected tissue. Areas that appeared normal by WLC were imaged and biopsied as controls. We imaged and prospectively analyzed 135 areas in 57 patients. We show that CLE improves the diagnostic accuracy of WLC for diagnosing benign tissue, low and high grade cancer. Interobserver studies showed a moderate level of agreement by urologists and nonclinical researchers. Despite morphologic differences between inflammation and cancer, real-time differentiation can still be challenging. Identification of bladder cancer-specific contrast agents could provide molecular specificity to CLE. By using fluorescently-labeled antibodies or peptides that bind to proteins expressed in bladder cancer, we have identified putative molecular contrast agents for targeted imaging with CLE. We describe one candidate agent - anti-CD47 - that was instilled into bladder specimens. The tumor and normal urothelium were imaged with CLE, with increased fluorescent signal demonstrated in areas of tumor compared to normal areas. Thus, cancer-specificity can be achieved using molecular contrast agents ex vivo in conjunction with CLE.

Transcription Factor KLF5 Binds a Cyclin E1 Polymorphic Intronic Enhancer to Confer Increased Bladder Cancer Risk

PubMed Central

Pattison, Jillian M.; Posternak, Valeriya; Cole, Michael D.

2016-01-01

It is well established that environmental toxins, such as exposure to arsenic, are risk factors in the development of urinary bladder cancer, yet recent genome-wide association studies (GWAS) provide compelling evidence that there is a strong genetic component associated with disease predisposition. A single nucleotide polymorphism (SNP), rs8102137, was identified on chromosome 19q12, residing 6 kb upstream of the important cell cycle regulator and proto-oncogene, Cyclin E1 (CCNE1). However, the functional role of this variant in bladder cancer predisposition has been unclear since it lies within a non-coding region of the genome. Here, it is demonstrated that bladder cancer cells heterozygous for this SNP exhibit biased allelic expression of CCNE1 with 1.5-fold more transcription occurring from the risk allele. Furthermore, using chromatin immunoprecipitation assays, a novel enhancer element was identified within the first intron of CCNE1 that binds Kruppel-like Factor 5 (KLF5), a known transcriptional activator in bladder cancer. Moreover, the data reveal that the presence of rs200996365, a SNP in high linkage disequilibrium with rs8102137 residing in the center of a KLF5 motif, alters KLF5 binding to this genomic region. Through luciferase assays and CRISPR-Cas9 genome editing, a novel polymorphic intronic regulatory element controlling CCNE1 transcription is characterized. These studies uncover how a cancer-associated polymorphism mechanistically contributes to an increased predisposition for bladder cancer development. Implications A polymorphic KLF5 binding site near the CCNE1 gene explains genetic risk identified through genome wide association studies. PMID:27514407

Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2

DOE PAGES

Ho, Melissa E.; Quek, Sue -Ing; True, Lawrence D.; ...

2016-02-15

Anterior gradient 2 (AGR2) is a cancer-associated secreted protein found predominantly in adenocarcinomas. Given its ubiquity in solid tumors, cancer-secreted AGR2 could be a useful biomarker in urine or blood for early detection. Normal organs express AGR2 and might also secrete AGR2, which would impact on the utility of AGR2 as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is, however, secreted by the urothelial cells as no measurable amounts could be detected in urine. The urinary proteomes of healthy people contain no listing for AGR2. The blood proteomes also contain no significantmore » peptide counts for AGR2 suggesting that little urothelial secretion into capillaries of the lamina propria. Expression is lost in urothelial carcinoma, but 25% primary tumors retained AGR2 expression in a cohort of lymph node positive cases. AGR2 is secreted by the urothelial carcinoma cells as urinary AGR2 was measured in the voided urine of 25% of the cases analyzed in a cohort of cancer vs. non-cancer urine, which matched the frequency of AGR2-positive urothelial carcinoma. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. In addition to secretion, AGR2 is also localized to the cell surface. Thus, secretion/cell surface localization of AGR2 is pecific to cancer while expression itself is not. Lastly, since AGR2 is found in many solid tumor types, this tumor-associated antigen constitutes a highly promising therapeutic target.« less

Bladder cancer cells secrete while normal bladder cells express but do not secrete AGR2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ho, Melissa E.; Quek, Sue -Ing; True, Lawrence D.

Anterior gradient 2 (AGR2) is a cancer-associated secreted protein found predominantly in adenocarcinomas. Given its ubiquity in solid tumors, cancer-secreted AGR2 could be a useful biomarker in urine or blood for early detection. Normal organs express AGR2 and might also secrete AGR2, which would impact on the utility of AGR2 as a cancer biomarker. Uniform AGR2 expression is found in the normal bladder urothelium. Little AGR2 is, however, secreted by the urothelial cells as no measurable amounts could be detected in urine. The urinary proteomes of healthy people contain no listing for AGR2. The blood proteomes also contain no significantmore » peptide counts for AGR2 suggesting that little urothelial secretion into capillaries of the lamina propria. Expression is lost in urothelial carcinoma, but 25% primary tumors retained AGR2 expression in a cohort of lymph node positive cases. AGR2 is secreted by the urothelial carcinoma cells as urinary AGR2 was measured in the voided urine of 25% of the cases analyzed in a cohort of cancer vs. non-cancer urine, which matched the frequency of AGR2-positive urothelial carcinoma. Since cancer cells secrete AGR2 while normal cells do not, its measurement in body fluids could be used to indicate tumor presence. In addition to secretion, AGR2 is also localized to the cell surface. Thus, secretion/cell surface localization of AGR2 is pecific to cancer while expression itself is not. Lastly, since AGR2 is found in many solid tumor types, this tumor-associated antigen constitutes a highly promising therapeutic target.« less

The Role(s) of Cytokines/Chemokines in Urinary Bladder Inflammation and Dysfunction

PubMed Central

Gonzalez, Eric J.; Arms, Lauren; Vizzard, Margaret A.

2014-01-01

Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome characterized by pain, pressure, or discomfort perceived to be bladder related and with at least one urinary symptom. It was recently concluded that 3.3–7.9 million women (>18 years old) in the United States exhibit BPS/IC symptoms. The impact of BPS/IC on quality of life is enormous and the economic burden is significant. Although the etiology and pathogenesis of BPS/IC are unknown, numerous theories including infection, inflammation, autoimmune disorder, toxic urinary agents, urothelial dysfunction, and neurogenic causes have been proposed. Altered visceral sensations from the urinary bladder (i.e., pain at low or moderate bladder filling) that accompany BPS/IC may be mediated by many factors including changes in the properties of peripheral bladder afferent pathways such that bladder afferent neurons respond in an exaggerated manner to normally innocuous stimuli (allodynia). The goals for this review are to describe chemokine/receptor (CXCL12/CXCR4; CCL2/CCR2) signaling and cytokine/receptor (transforming growth factor (TGF-β)/TGF-β type 1 receptor) signaling that may be valuable LUT targets for pharmacologic therapy to improve urinary bladder function and reduce somatic sensitivity associated with urinary bladder inflammation. PMID:24738044

Occupational exposures to polycyclic aromatic hydrocarbons, and respiratory and urinary tract cancers: a quantitative review to 2005.

PubMed

Bosetti, C; Boffetta, P; La Vecchia, C

2007-03-01

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been reported in several industries, including those of the aluminum production, coal gasification, coke production, iron and steel foundries, coal tar and related products, carbon black and carbon electrodes production. This paper reviews the results from cohort studies conducted on workers exposed to PAHs in these industries, with a focus on cancers of the respiratory and urinary tract. An excess risk from lung/respiratory cancers was found in most industries, the pooled relative risk (RR) being 2.58 (95% CI 2.28-2.92) for coal gasification, 1.58 (95% CI 1.47-1.69) for coke production, 1.40 (95% CI 1.31-1.49) for iron and steel foundries, 1.51 (95% CI 1.28-1.78) for roofers and 1.30 (95% CI 1.06-1.59) for carbon black production. The evidence for cancers of the bladder and of the urinary system is less consistent, with a significant increased risk only for workers in aluminum production (pooled RR = 1.29, 95% CI 1.12-1.49), coal gasification (pooled RR = 2.39, 95% CI 1.36-4.21), and iron and steel foundries (pooled RR = 1.29, 95% CI 1.06-1.57). Increased risks from lung and bladder cancers were found in PAH-related occupations. These were modest in most industries, apart from those for coal gasification, and whether they are due at least partially to some bias or confounding remains open to discussion.

Surgical technique for en bloc transurethral resection of bladder tumour with a Hybrid Knife(®).

PubMed

Islas-García, J J O; Campos-Salcedo, J G; López-Benjume, B I; Torres-Gómez, J J; Aguilar-Colmenero, J; Martínez-Alonso, I A; Gil-Villa, S A

2016-05-01

Bladder cancer is the second most common malignancy of the urinary tract and the 9th worldwide. Latin American has an incidence of 5.6 per 100,000 inhabitants per year. Seventy-five percent of newly diagnosed cases are nonmuscle invasive bladder cancer, and 25% of cases present as muscle invasive. The mainstay of treatment for nonmuscle invasive bladder cancer is loop transurethral resection. In 2013, the group led by Dr Mundhenk of the University Hospital of Tübingen, Germany, was the first to describe the Hybrid Knife(®) equipment for performing en bloc bladder tumour resection, with favourable functional and oncological results. To describe the surgical technique of en bloc bladder tumour resection with a Hybrid Knife(®) as an alternative treatment for nonmuscle invasive bladder tumours. A male patient was diagnosed by urotomography and urethrocystoscopy with a bladder tumour measuring 2×1cm on the floor. En bloc transurethral resection of the bladder tumour was performed with a Hybrid Knife(®). Surgery was performed for 35min, with 70 watts for cutting and 50 watts for coagulation, resecting and evacuating en bloc the bladder tumour, which macroscopically included the muscle layer of the bladder. There were no complications. The technique of en bloc bladder tumour resection with Hybrid Knife(®) is an effective alternative to bipolar loop transurethral resection. Resection with a Hybrid Knife(®) is a procedure with little bleeding and good surgical vision and minimises the risk of bladder perforation and tumour implants. The procedure facilitates determining the positivity of the neoplastic process, vascular infiltration and bladder muscle invasion in the histopathology study. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Arsenic in drinking water and urinary tract cancers: a systematic review of 30 years of epidemiological evidence.

PubMed

Saint-Jacques, Nathalie; Parker, Louise; Brown, Patrick; Dummer, Trevor Jb

2014-06-02

Arsenic in drinking water is a public health issue affecting hundreds of millions of people worldwide. This review summarizes 30 years of epidemiological studies on arsenic exposure in drinking water and the risk of bladder or kidney cancer, quantifying these risks using a meta-analytical framework. Forty studies met the selection criteria. Seventeen provided point estimates of arsenic concentrations in drinking water and were used in a meta-analysis of bladder cancer incidence (7 studies) and mortality (10 studies) and kidney cancer mortality (2 studies). Risk estimates for incidence and mortality were analyzed separately using Generalized Linear Models. Predicted risks for bladder cancer incidence were estimated at 10, 50 and 150 μg/L arsenic in drinking water. Bootstrap randomizations were used to assess robustness of effect size. Twenty-eight studies observed an association between arsenic in drinking water and bladder cancer. Ten studies showed an association with kidney cancer, although of lower magnitude than that for bladder cancer. The meta-analyses showed the predicted risks for bladder cancer incidence were 2.7 [1.2-4.1]; 4.2 [2.1-6.3] and; 5.8 [2.9-8.7] for drinking water arsenic levels of 10, 50, and 150 μg/L, respectively. Bootstrapped randomizations confirmed this increased risk, but, lowering the effect size to 1.4 [0.35-4.0], 2.3 [0.59-6.4], and 3.1 [0.80-8.9]. The latter suggests that with exposures to 50 μg/L, there was an 83% probability for elevated incidence of bladder cancer; and a 74% probability for elevated mortality. For both bladder and kidney cancers, mortality rates at 150 ug/L were about 30% greater than those at 10 μg/L. Arsenic in drinking water is associated with an increased risk of bladder and kidney cancers, although at lower levels (<150 μg/L), there is uncertainty due to the increased likelihood of exposure misclassification at the lower end of the exposure curve. Meta-analyses suggest exposure to 10 μg/L of arsenic in drinking water may double the risk of bladder cancer, or at the very least, increase it by about 40%. With the large number of people exposed to these arsenic concentrations worldwide the public health consequences of arsenic in drinking water are substantial.

Epithelial-Mesenchymal Interactions in Urinary Bladder and Small Intestine and How to Apply Them in Tissue Engineering.

PubMed

Jerman, Urška Dragin; Kreft, Mateja Erdani; Veranič, Peter

2015-12-01

Reciprocal interactions between the epithelium and mesenchyme are essential for the establishment of proper tissue morphology during organogenesis and tissue regeneration as well as for the maintenance of cell differentiation. With this review, we highlight the importance of epithelial-mesenchymal cross talk in healthy tissue and further discuss its significance in engineering functional tissues in vitro. We focus on the urinary bladder and small intestine, organs that are often compromised by disease and are as such in need of research that would advance effective treatment or tissue replacement. To date, the understanding of epithelial-mesenchymal reciprocal interactions has enabled the development of in vitro biomimetic tissue equivalents that have provided many possibilities in treating defective, damaged, or even cancerous tissues. Although research of the past several years has advanced the field of bladder and small intestine tissue engineering, one must be aware of its current limitations in successfully and above all safely introducing tissue-engineered constructs into clinical practice. Special attention is in particular needed when treating cancerous tissues, as initially successful tumor excision and tissue reconstruction may later on result in cancer recurrence due to oncogenic signals originating from an altered stroma. Recent rather poor outcomes in pioneering clinical trials of bladder reconstructions should serve as a reminder that recreating a functional organ to replace a dysfunctional one is an objective far more difficult to reach than initially foreseen. When considering effective tissue engineering approaches for diseased tissues in humans, it is imperative to introduce animal models with dysfunctional or, even more importantly, cancerous organs, which would greatly contribute to predicting possible complications and, hence, reducing risks when translating to the clinic.

The prognostic value of family history among patients with urinary bladder cancer.

PubMed

Egbers, Lieke; Grotenhuis, Anne J; Aben, Katja K; Alfred Witjes, J; Kiemeney, Lambertus A; Vermeulen, Sita H

2015-03-01

A history of urinary bladder cancer (UBC) in first-degree relatives increases UBC risk by twofold. The influence of positive family history on UBC prognosis is unknown. Here, we investigated association of first-degree UBC family history with clinicopathological characteristics and prognosis of UBC patients. Detailed clinical data of 1,465 non-muscle-invasive bladder cancer (NMIBC) and 250 muscle-invasive or metastatic bladder cancer (MIBC) patients, diagnosed from 1995 to 2010, were collected through medical file review. Competing risk analyses were used to compare recurrence-free survival (RFS) and progression-free survival (PFS) of NMIBC patients according to self-reported UBC family history. Overall survival in MIBC patients was estimated using Kaplan-Meier analysis. The added value of family history in prediction of NMIBC prognosis was quantified with Harrell's concordance-index. Hundred (6.8%) NMIBC and 14 (5.6%) MIBC patients reported UBC in first-degree relatives. Positive family history was statistically significantly associated with smaller tumor size and non-significantly with more favorable distribution of other tumor characteristics. In univariable analyses, positive family history correlated with longer RFS (p = 0.11) and PFS (p = 0.04). Hazard ratios for positive vs. negative family history after adjustment for clinicopathological characteristics were 0.75 (95% CI = 0.53-1.07) and 0.45 (95% CI = 0.18-1.12) for RFS and PFS, respectively. Five familial and 48 sporadic MIBC patients (Kaplan-Meier 10-year risk: 41% and 25%) died within 10 years. Family history did not improve the c-index of prediction models. This study shows that a first-degree family history of UBC is not clearly associated with NMIBC prognosis. Family history does not aid in prediction of NMIBC recurrence or progression. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

Interesting Layering of Excreted 18F-FDG in the Urinary Bladder in Patients with Urinary Tract Infection and Distended Bladder.

PubMed

Shen, Guohua; Zhang, Wenjie; Jia, Zhiyun; Deng, Houfu

2015-09-01

Settling of (18)F-FDG in the bladder is often noted on whole-body PET/CT images, but this phenomenon has never received any careful attention and the mechanism has been unclear. The 2 patients described in this report, one with a T1 pathologic fracture and another with widespread bone and lymph node metastases from an unknown primary tumor, underwent PET/CT. Both had urinary tract infection and a distended bladder during scanning. The interesting layering of (18)F-FDG in the urinary bladder was observed in both patients. The presence of this phenomenon demands careful evaluation of the urine by the clinician, and the mechanism is hypothesized to be slow (18)F-FDG excretion in patients with a distended urinary bladder, resulting in delayed mixing with urine. In addition, urinary tract infection may be a potential cause. Images showing this interesting layering should be interpreted with care. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Fibrosarcoma of the urinary bladder in a cat

PubMed Central

Capasso, Angelo; Raiano, Vera; Sontuoso, Antonio; Olivero, Daniela

2015-01-01

Case summary A 5-year-old female spayed domestic shorthair cat was presented with haematuria, pollakiuria and stranguria of 2 months’ duration, and a firm non-painful mass in the urinary bladder was palpated. Abdominal radiographs showed thickening and irregular cranial margins of the urinary bladder wall. Abdominal ultrasound showed a vascularised mass of mixed echogenicity almost entirely occupying the urinary bladder lumen. During explorative laparotomy, the mass appeared pedunculated and was totally excised. Histopathology was characterised by infiltration of the mucosal, submucosal and muscular layers by proliferated atypical mesenchymal cells; immunochemistry confirmed the diagnosis of fibrosarcoma. The cat was discharged with normal urination 5 days after surgery. The owner declined any imaging follow-up but reported the cat to be free of any clinical signs at 16 months after surgery. Relevance and novel information To the best of our knowledge, this is the first case of primary fibrosarcoma of the urinary bladder in the cat. Fibrosarcoma should be included in the differential diagnosis of urinary bladder neoplasia. PMID:28491352

Fibrosarcoma of the urinary bladder in a cat.

PubMed

Capasso, Angelo; Raiano, Vera; Sontuoso, Antonio; Olivero, Daniela; Greci, Valentina

2015-01-01

A 5-year-old female spayed domestic shorthair cat was presented with haematuria, pollakiuria and stranguria of 2 months' duration, and a firm non-painful mass in the urinary bladder was palpated. Abdominal radiographs showed thickening and irregular cranial margins of the urinary bladder wall. Abdominal ultrasound showed a vascularised mass of mixed echogenicity almost entirely occupying the urinary bladder lumen. During explorative laparotomy, the mass appeared pedunculated and was totally excised. Histopathology was characterised by infiltration of the mucosal, submucosal and muscular layers by proliferated atypical mesenchymal cells; immunochemistry confirmed the diagnosis of fibrosarcoma. The cat was discharged with normal urination 5 days after surgery. The owner declined any imaging follow-up but reported the cat to be free of any clinical signs at 16 months after surgery. To the best of our knowledge, this is the first case of primary fibrosarcoma of the urinary bladder in the cat. Fibrosarcoma should be included in the differential diagnosis of urinary bladder neoplasia.

Human urinary bladder regeneration through tissue engineering - an analysis of 131 clinical cases.

PubMed

Pokrywczynska, Marta; Adamowicz, Jan; Sharma, Arun K; Drewa, Tomasz

2014-03-01

Replacement of urinary bladder tissue with functional equivalents remains one of the most challenging problems of reconstructive urology over the last several decades. The gold standard treatment for urinary diversion after radical cystectomy is the ileal conduit or neobladder; however, this technique is associated with numerous complications including electrolyte imbalances, mucus production, and the potential for malignant transformation. Tissue engineering techniques provide the impetus to construct functional bladder substitutes de novo. Within this review, we have thoroughly perused the literature utilizing PubMed in order to identify clinical studies involving bladder reconstruction utilizing tissue engineering methodologies. The idea of urinary bladder regeneration through tissue engineering dates back to the 1950s. Many natural and synthetic biomaterials such as plastic mold, gelatin sponge, Japanese paper, preserved dog bladder, lyophilized human dura, bovine pericardium, small intestinal submucosa, bladder acellular matrix, or composite of collagen and polyglycolic acid were used for urinary bladder regeneration with a wide range of outcomes. Recent progress in the tissue engineering field suggest that in vitro engineered bladder wall substitutes may have expanded clinical applicability in near future but preclinical investigations on large animal models with defective bladders are necessary to optimize the methods of bladder reconstruction by tissue engineering in humans.

Two differentially structured collagen scaffolds for potential urinary bladder augmentation: proof of concept study in a Göttingen minipig model.

PubMed

Leonhäuser, Dorothea; Stollenwerk, Katja; Seifarth, Volker; Zraik, Isabella M; Vogt, Michael; Srinivasan, Pramod K; Tolba, Rene H; Grosse, Joachim O

2017-01-04

The repair of urinary bladder tissue is a necessity for tissue loss due to cancer, trauma, or congenital abnormalities. Use of intestinal tissue is still the gold standard in the urological clinic, which leads to new problems and dysfunctions like mucus production, stone formation, and finally malignancies. Therefore, the use of artificial, biologically derived materials is a promising step towards the augmentation of this specialised tissue. The aim of this study was to investigate potential bladder wall repair by two collagen scaffold prototypes, OptiMaix 2D and 3D, naïve and seeded with autologous vesical cells, as potential bladder wall substitute material in a large animal model. Six Göttingen minipigs underwent cystoplastic surgery for tissue biopsy and cell isolation followed by implantation of unseeded scaffolds. Six weeks after the first operation, scaffolds seeded with the tissue cultured autologous urothelial and detrusor smooth muscle cells were implanted into the bladder together with additional unseeded scaffolds for comparison. Cystography and bladder ultrasound were performed to demonstrate structural integrity and as leakage test of the implantation sites. Eighteen, 22, and 32 weeks after the first operation, two minipigs respectively were sacrificed and the urinary tract was examined via different (immunohistochemical) staining procedures and the usage of two-photon laser scanning microscopy. Both collagen scaffold prototypes in vivo had good ingrowth capacity into the bladder wall including a quick lining with urothelial cells. The ingrowth of detrusor muscle tissue, along with the degradation of the scaffolds, could also be observed throughout the study period. We could show that the investigated collagen scaffolds OptiMaix 2D and 3D are a potential material for bladder wall substitution. The material has good biocompatible properties, shows a good cell growth of autologous cells in vitro, and a good integration into the present bladder tissue in vivo.

Positive feedback loop for cystitis cystica: the effect of recurrent urinary tract infection on the number of bladder wall mucosa nodules.

PubMed

Vrljicak, Kristina; Turudić, Daniel; Bambir, Ivan; Gradiski, Ivan Pavao; Spajić, Borislav; Batinić, Danica; Topalović-Grković, Marija; Spajić, Marija; Batinić, Danko; Milosević, Danko

2013-12-01

The main purpose of this study was to demonstrate positive feedback loop between bladder wall nodules (nodules being one of the key diagnostic factors), bladder wall thickness, and recurrent urinary tract infections. Cystitis cystica was diagnosed in 115 prepubertal girls (mean age 7.79 +/- 3.05 years) by optic examination of bladder mucosal nodules and by ultrasonographic measurement of bladder wall thickness. Bladder wall thickness increased with the frequency of recurrent urinary tract infections as well as with the number of nodules on bladder wall mucosa (3.52 +/- 0.522 mm < or = 5 nodules vs. 4.42 +/- 0.429 mm 6-10 nodules vs. 5.20 +/- 0.610 mm > 10 nodules, respectively). Study results suggested that early control of urinary tract infections by chemoprophylaxis could prevent higher grades of bladder wall mucosal changes and consequently shorten the length of chemoprophylaxis.

Bladder preservation in non-metastatic muscle-invasive bladder cancer (MIBC): a single-institution experience

PubMed Central

Gerardi, Marianna A.; Jereczek-Fossa, Barbara A.; Zerini, Dario; Surgo, Alessia; Dicuonzo, Samantha; Spoto, Ruggero; Fodor, Cristiana; Verri, Elena; Rocca, Maria Cossu; Nolè, Franco; Muto, Matteo; Ferro, Matteo; Musi, Gennaro; Bottero, Danilo; Matei, Deliu V.; De Cobelli, Ottavio; Orecchia, Roberto

2016-01-01

The aim of this study is to access the feasibility, toxicity profile, and tumour outcome of an organ preservation curative approach in non-metastatic muscle-invasive bladder cancer. A retrospective analysis was conducted on patients affected by M0 bladder cancer, who refused cystectomy and were treated with a curative approach. The standard bladder preservation scheme included maximal transurethral resection of bladder tumour (TURBT) and combination of radiotherapy and platin-based chemotherapy, followed by endoscopic evaluation, urine cytology, and instrumental evaluation. Thirteen patients fulfilled the inclusion criteria. TNM stage was cT2cN0M0 and cT2cNxM0, in 12 and one patients, respectively. All patients had transitional cell cancer. Twelve patients completed the whole therapeutic programme (a bimodal treatment without chemotherapy for one patient). Median follow-up is 36 months. None of the patients developed severe urinary or intestinal acute toxicity. In 10 patients with a follow-up > 6 months, no cases of severe late toxicity were observed. Response evaluated in 12 patients included complete response and stable disease in 11 patients (92%), and one patient (8%), respectively. At the time of data analysis (March 2016), 10 patients (77%) are alive with no evidence of disease, two patients (15%) died for other reasons, and one patient has suspicious persistent local disease. The trimodality approach, including maximal TURBT, radiotherapy, and chemotherapy for muscle-invasive bladder cancer, is well-tolerated and might be considered a valid and feasible option in fit patients who refuse radical cystectomy. PMID:27563352

Bladder preservation in non-metastatic muscle-invasive bladder cancer (MIBC): a single-institution experience.

PubMed

Gerardi, Marianna A; Jereczek-Fossa, Barbara A; Zerini, Dario; Surgo, Alessia; Dicuonzo, Samantha; Spoto, Ruggero; Fodor, Cristiana; Verri, Elena; Rocca, Maria Cossu; Nolè, Franco; Muto, Matteo; Ferro, Matteo; Musi, Gennaro; Bottero, Danilo; Matei, Deliu V; De Cobelli, Ottavio; Orecchia, Roberto

2016-01-01

The aim of this study is to access the feasibility, toxicity profile, and tumour outcome of an organ preservation curative approach in non-metastatic muscle-invasive bladder cancer. A retrospective analysis was conducted on patients affected by M0 bladder cancer, who refused cystectomy and were treated with a curative approach. The standard bladder preservation scheme included maximal transurethral resection of bladder tumour (TURBT) and combination of radiotherapy and platin-based chemotherapy, followed by endoscopic evaluation, urine cytology, and instrumental evaluation. Thirteen patients fulfilled the inclusion criteria. TNM stage was cT2cN0M0 and cT2cNxM0, in 12 and one patients, respectively. All patients had transitional cell cancer. Twelve patients completed the whole therapeutic programme (a bimodal treatment without chemotherapy for one patient). Median follow-up is 36 months. None of the patients developed severe urinary or intestinal acute toxicity. In 10 patients with a follow-up > 6 months, no cases of severe late toxicity were observed. Response evaluated in 12 patients included complete response and stable disease in 11 patients (92%), and one patient (8%), respectively. At the time of data analysis (March 2016), 10 patients (77%) are alive with no evidence of disease, two patients (15%) died for other reasons, and one patient has suspicious persistent local disease. The trimodality approach, including maximal TURBT, radiotherapy, and chemotherapy for muscle-invasive bladder cancer, is well-tolerated and might be considered a valid and feasible option in fit patients who refuse radical cystectomy.

Dithiothreitol-based protein equalization technology to unravel biomarkers for bladder cancer.

PubMed

Araújo, J E; López-Fernández, H; Diniz, M S; Baltazar, Pedro M; Pinheiro, Luís Campos; da Silva, Fernando Calais; Carrascal, Mylène; Videira, Paula; Santos, H M; Capelo, J L

2018-04-01

This study aimed to assess the benefits of dithiothreitol (DTT)-based sample treatment for protein equalization to assess potential biomarkers for bladder cancer. The proteome of plasma samples of patients with bladder carcinoma, patients with lower urinary tract symptoms (LUTS) and healthy volunteers, was equalized with dithiothreitol (DTT) and compared. The equalized proteomes were interrogated using two-dimensional gel electrophoresis and matrix assisted laser desorption ionization time of flight mass spectrometry. Six proteins, namely serum albumin, gelsolin, fibrinogen gamma chain, Ig alpha-1 chain C region, Ig alpha-2 chain C region and haptoglobin, were found dysregulated in at least 70% of bladder cancer patients when compared with a pool of healthy individuals. One protein, serum albumin, was found overexpressed in 70% of the patients when the equalized proteome of the healthy pool was compared with the equalized proteome of the LUTS patients. The pathways modified by the proteins differentially expressed were analyzed using Cytoscape. The method here presented is fast, cheap, of easy application and it matches the analytical minimalism rules as outlined by Halls. Orthogonal validation was done using western-blot. Overall, DTT-based protein equalization is a promising methodology in bladder cancer research. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of Novel Gene Targets and Putative Regulators of Arsenic-Associated DNA Methylation in Human Urothelial Cells and Bladder Cancer

PubMed Central

Rager, Julia E.; Miller, Sloane; Tulenko, Samantha E.; Smeester, Lisa; Ray, Paul D.; Yosim, Andrew; Currier, Jenna M.; Ishida, María C.; González-Horta, Maria del Carmen; Sánchez-Ramírez, Blanca; Ballinas-Casarrubias, Lourdes; Gutiérrez-Torres, Daniela S.; Drobná, Zuzana; Del Razo, Luz M.; García-Vargas, Gonzalo G.; Kim, William Y.; Zhou, Yi-Hui; Wright, Fred A.; Stýblo, Miroslav; Fry, Rebecca C.

2016-01-01

There is strong epidemiologic evidence linking chronic exposure to inorganic arsenic (iAs) to a myriad of adverse health effects, including cancer of the bladder. The present study set out to identify DNA methylation patterns associated with iAs and its metabolites in exfoliated urothelial cells (EUCs) that originate primarily from the urinary bladder, one of the targets of arsenic (As)-induced carcinogenesis. Genome-wide, gene-specific promoter DNA methylation levels were assessed in EUCs from 46 residents of Chihuahua, Mexico, and the relationship was examined between promoter methylation profiles and the intracellular concentrations of total As (tAs) and As species. A set of 49 differentially methylated genes was identified with increased promoter methylation associated with EUC tAs, iAs, and/or monomethylated As (MMAs) enriched for their roles in metabolic disease and cancer. Notably, no genes had differential methylation associated with EUC dimethylated As (DMAs), suggesting that DMAs may influence DNA methylation-mediated urothelial cell responses to a lesser extent than iAs or MMAs. Further analysis showed that 22 of the 49 As-associated genes (45%) are also differentially methylated in bladder cancer tissue identified using The Cancer Genome Atlas repository. Both the As- and cancer-associated genes are enriched for the binding sites of common transcription factors known to play roles in carcinogenesis, demonstrating a novel potential mechanistic link between iAs exposure and bladder cancer. PMID:26039340

In Vivo Demonstration of PSMA Expression in Adenocarcinoma Urinary Bladder Using 68Ga-PSMA 11 PET/CT.

PubMed

Roy, Shambo Guha; Parida, Girish Kumar; Tripathy, Sarthak; Singhal, Abhinav; Tripathi, Madhavi; Bal, Chandrasekhar

2017-07-01

In vitro and in vivo studies have demonstrated prostate-specific membrane antigen (PSMA) expression in various malignant and benign tumors. Based on the recent immunohistochemical study showing PSMA expression in adenocarcinoma of urinary bladder, we hypothesized that PSMA expression in adenocarcinoma of urinary bladder can be demonstrated in vivo using Ga-PSMA 11 PET/CT. We present a man with exstrophy bladder, presenting with adenocarcinoma urinary bladder referred for staging PET/CT. Both F-FDG and Ga-PSMA-11 PET/CT were done, which showed PSMA expression in the primary tumor as well as metastatic lymph nodes.

Bladder rupture caused by postpartum urinary retention.

PubMed

Dueñas-García, Omar Felipe; Rico, Hugo; Gorbea-Sanchez, Viridiana; Herrerias-Canedo, Tomas

2008-08-01

Postpartum bladder rupture is an uncommon surgical emergency and a diagnostic challenge. A primigravida delivered a healthy newborn without complications at 39.4 weeks of gestation. The patient was admitted 80 hours postpartum with abdominal pain, oliguria, hematuria, and pain that worsened during the previous 4 hours. An inserted Foley catheter drained only a small amount of urine, and serum creatinine was elevated (3.5 mg/dL). A laparotomy was performed and revealed a 10-cm hole in the urinary bladder. The bladder was repaired and the patient was discharged 15 days after surgery. The follow-up cystoscopy revealed adequate healing of the bladder. Urinary retention can lead to serious complications, including bladder rupture. Postpartum bladder rupture due to urinary retention should be ruled out if there is a history of abdominal pain, oliguria, and elevated of serum creatinine.

Lifetime exposure to arsenic in drinking water and bladder cancer: a population-based case–control study in Michigan, USA

PubMed Central

Slotnick, Melissa J.; AvRuskin, Gillian A.; Schottenfeld, David; Jacquez, Geoffrey M.; Wilson, Mark L.; Goovaerts, Pierre; Franzblau, Alfred; Nriagu, Jerome O.

2014-01-01

Objective Arsenic in drinking water has been linked with the risk of urinary bladder cancer, but the dose–response relationships for arsenic exposures below 100 µg/L remain equivocal. We conducted a population-based case–control study in southeastern Michigan, USA, where approximately 230,000 people were exposed to arsenic concentrations between 10 and 100 µg/L. Methods This study included 411 bladder cancer cases diagnosed between 2000 and 2004, and 566 controls recruited during the same period. Individual lifetime exposure profiles were reconstructed, and residential water source histories, water consumption practices, and water arsenic measurements or modeled estimates were determined at all residences. Arsenic exposure was estimated for 99% of participants’ person-years. Results Overall, an increase in bladder cancer risk was not found for time-weighted average lifetime arsenic exposure >10 µg/L when compared with a reference group exposed to <1 µg/L (odds ratio (OR) = 1.10; 95% confidence interval (CI): 0.65, 1.86). Among ever-smokers, risks from arsenic exposure >10 µg/L were similarly not elevated when compared to the reference group (OR = 0.94; 95% CI: 0.50, 1.78). Conclusions We did not find persuasive evidence of an association between low-level arsenic exposure and bladder cancer. Selecting the appropriate exposure metric needs to be thoughtfully considered when investigating risk from low-level arsenic exposure. PMID:20084543

Defining Priorities to Improve Patient Experience in Non-Muscle Invasive Bladder Cancer.

PubMed

Garg, Tullika; Connors, Jill Nault; Ladd, Ilene G; Bogaczyk, Tyler L; Larson, Sharon L

2018-01-20

Although approximately 75% of bladder cancers are non-muscle invasive (NMIBC) at diagnosis, most research tends to focus on invasive disease (e.g., experiences related to radical cystectomy and urinary diversion). There is a lack of studies on quality of life, and especially qualitative research, in bladder cancer generally. As a result, relatively little is known about the experiences and needs of NMIBC patients. To understand patient experience, define care priorities, and identify targets for care improvement in NMIBC across the cancer continuum. Through focus groups, patients treated for NMIBC (stage

[Effective dimethyl sulfoxide (DMSO) occlusive dressing technique for amyloidosis of the urinary bladder].

PubMed

Hasegawa, Yoshihiro; Kanda, Hideki; Miki, Manabu; Masui, Satoru; Yoshio, Yuko; Yamada, Yasushi; Soga, Norihito; Arima, Kiminobu; Sugimura, Yoshiki

2013-10-01

A 48-year-old married woman complaining of macroscopic hematuria and cystitis symptom was admitted to our institute. Flexible cystoscopy revealed many yellowish, nodular masses at the paries posterior of the urinary bladder, and cold-punch biopsy proved it to be amyloidosis. Serum amyloid protein A (SAA) was high, and suggested systemic amyloidosis. Renal biopsy and colon fiberscopy did not reveal any abnormalities. We therefore diagnosed a primary localized amyloidosis of the urinary bladder. Transurethral resection and dimethyl sulfoxide (DMSO) infusion therapy are used to treat amyloidosis of the urinary bladder. However there is no definite cure for amyloidosis of the urinary bladder. Therefore we selected DMSO occlusive dressing technique therapy. After 5 years of therapy, there was no evidence of a recurrence of amyloidosis.

Prostatic Artery Embolization as an Alternative to Indwelling Bladder Catheterization to Manage Benign Prostatic Hyperplasia in Poor Surgical Candidates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rampoldi, Antonio; Barbosa, Fabiane, E-mail: fabiane001@hotmail.com; Secco, Silvia

PurposeTo prospectively assess discontinuation of indwelling bladder catheterization (IBC) and relief of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) following prostate artery embolization (PAE) in poor surgical candidates.MethodsPatients ineligible for surgical intervention were offered PAE after at least 1 month of IBC for management of urinary retention secondary to BPH; exclusion criteria for PAE included eligibility for surgery, active bladder cancer or known prostate cancer. Embolization technical and clinical success were defined as bilateral prostate embolization and removal of IBC, respectively. Patients were followed for at least 6 months and evaluated for International Prostate Symptom Score, quality ofmore » life, prostate size and uroflowmetric parameters.ResultsA total of 43 patients were enrolled; bilateral embolization was performed in 33 (76.7%), unilateral embolization was performed in 8 (18.6%), and two patients could not be embolized due to tortuous and atherosclerotic pelvic vasculature (4.7%). Among the patients who were embolized, mean prostate size decreased from 75.6 ± 33.2 to 63.0 ± 23.2 g (sign rank p = 0.0001, mean reduction of 19.6 ± 17.3%), and IBC removal was achieved in 33 patients (80.5%). Clavien II complications were reported in nine patients (21.9%) and included urinary tract infection (three patients, 7.3%) and recurrent acute urinary retention (six patients, 14.6%). Nine patients (22.0%) experienced post-embolization syndrome.ConclusionsPAE is a safe and feasible for the relief of LUTS and IBC in highly comorbid patients without surgical treatment options.« less

Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls.

PubMed

Kim, Won Tae; Yun, Seok Joong; Yan, Chunri; Jeong, Pildu; Kim, Ye Hwan; Lee, Il Seok; Kang, Ho Won; Park, Sunghyouk; Moon, Sung Kwon; Choi, Yung Hyun; Choi, Young Deuk; Kim, Isaac Yi; Kim, Jayoung; Kim, Wun Jae

2016-07-01

Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed. Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (CPT1A, CPT1B, CPT1C, CPT2, SLC25A20, and CRAT) or tryptophan metabolism (TPH1 and IDO1) was assessed by RT-PCR in our BCA cohort (n=135). CPT1B, CPT1C, SLC25A20, CRAT, TPH1, and IOD1 were significantly downregulated in tumor tissues compared to normal bladder tissues (p<0.05 all) of patients with non-muscle invasive BCA, whereas CPT1B, CPT1C, CRAT, and TPH1 were downregulated in those with muscle invasive BCA (p<0.05), with no changes in IDO1 expression. Alterations in the expression of genes associated with the carnitine-acylcarnitine and tryptophan metabolic pathways, which were the most perturbed pathways in BCA, were determined.

Urological outcomes following pelvic exenteration for advanced pelvic cancer are not inferior to those following radical cystectomy.

PubMed

Aslim, Edwin J; Chew, Min Hoe; Chew, Ghee Kheng; Lee, Lui Shiong

2018-06-12

Pelvic exenteration (PE) for locally advanced pelvic malignancy requires a multi-disciplinary approach and is associated with significant morbidity. Urinary reconstruction forms a major component of this procedure. The aim of the study is to review the urological outcomes following PE in a newly established pelvic oncology unit, to compare with those following radical cystectomy (RC) for bladder cancer. Patients were identified from prospectively maintained PE and bladder cancer databases, inclusive of all cases performed between January 2012 and December 2016. Those without urinary reconstructions and follow-up durations of less than 3 months were excluded. The outcomes of PE and RC cases were compared, stratifying surgical complications using the Clavien-Dindo classification. Statistical significance was defined as P < 0.05. There were 22 PE cases and 27 RC cases. The median age at surgery was 56 and 65 years, with a median follow-up of 11.7 and 19.8 months, in the PE and RC groups, respectively. Urinary reconstructions comprised n = 20 (91%) conduit diversions and n = 2 (9%) ureteral reimplantations in the PE group, and n = 5 (19%) orthotopic bladder substitutes and n = 22 (81%) ileal conduits in the RC group. The 30-day urological complication rate was 23% in the PE group (n = 4 Clavien-Dindo Grade 1-2, and n = 1 Grade 3) versus 11% in the RC group (n = 1 Grade 1-2, and n = 2 Grade 3), P = 0.801. There were no Grade 4-5 complications in this series. The urological outcomes following PE in complex pelvic oncology are reasonable and not inferior to those after primary RC alone. © 2018 Royal Australasian College of Surgeons.

Sexual function, incontinence, and wellbeing in women after rectal cancer--a review of the evidence.

PubMed

Panjari, Mary; Bell, Robin J; Burney, Susan; Bell, Stephen; McMurrick, Paul J; Davis, Susan R

2012-11-01

Colorectal cancer (CRC) is the second most common cancer. One-third of these cancers occur in the rectum. Treatment of rectal cancer involves surgery with/without radiotherapy and chemotherapy. Surgery is undertaken to prevent damage to the nerves controlling bladder, bowel, and sexual organs, whether this translates into preservation of urinary and fecal continence and sexual function and, ultimately, quality of life (QoL) is not known. The aim of this review was to summarize the literature regarding the impact of treatment for rectal cancer on bladder and bowel continence, sexual function and QoL in women. A comprehensive review of the current literature on sexual function, incontinence and wellbeing in women after treatment for rectal cancer highlighting prevalence rates, trial design, and patient population. We conducted a systematic search of the literature using A systematic search of the literature using Medline (Ovid, 1946-present) and PubMed (1966-2011) for English-language studies that included the following search terms: "colorectal cancer," or "rectal cancer," or "rectal neoplasm," and "sexual function," or "sexual dysfunction," or "wellbeing," or "QoL," or "urinary or fecal incontinence." Although around 1/3 of women aged 50 to 70 years report lack of sexual desire, sexual function problems after treatment for rectal cancer are in the order of 60% among women. QoL improves with length of survival. Urinary and fecal incontinence are ongoing concerns for many women after treatment with rates up to 60%. There is a gap in our knowledge of the effects of rectal cancer and its treatment on urinary and fecal continence, sexual function and QoL in women. There is a need for studies of sufficient size and duration to gain a better understanding of the disease and its management and the long-term effects on these parameters. This information is needed to develop preventative health care plans for women treated for rectal cancer that target those most at risk for these adverse outcomes. © 2012 International Society for Sexual Medicine.

A sensitive and selective magnetic graphene composite-modified polycrystalline-silicon nanowire field-effect transistor for bladder cancer diagnosis.

PubMed

Chen, Hsiao-Chien; Chen, Yi-Ting; Tsai, Rung-Ywan; Chen, Min-Cheng; Chen, Shi-Liang; Xiao, Min-Cong; Chen, Chien-Lun; Hua, Mu-Yi

2015-04-15

In this study, we describe the urinary quantification of apolipoprotein A II protein (APOA2 protein), a biomarker for the diagnosis of bladder cancer, using an n-type polycrystalline silicon nanowire field-effect transistor (poly-SiNW-FET). The modification of poly-SiNW-FET by magnetic graphene with long-chain acid groups (MGLA) synthesized via Friedel-Crafts acylation was compared with that obtained using short-chain acid groups (MGSA). Compared with MGSA, the MGLA showed a higher immobilization degree and bioactivity to the anti-APOA2 antibody (Ab) due to its lower steric hindrance. In addition, the magnetic properties enabled rapid separation and purification during Ab immobilization, ultimately preserving its bioactivity. The Ab-MGLA/poly-SiNW-FET exhibited a linear dependence of relative response to the logarithmical concentration in a range between 19.5pgmL(-1) and 1.95µgmL(-1), with a limit of detection (LOD) of 6.7pgmL(-1). An additional washing step before measurement aimed at excluding the interfering biocomponents ensured the reliability of the assay. We conclude that our biosensor efficiently distinguishes mean values of urinary APOA2 protein concentrations between patients with bladder cancer (29-344ngmL(-1)) and those with hernia (0.425-9.47ngmL(-1)). Copyright © 2014 Elsevier B.V. All rights reserved.

A case-control study on the association between bladder cancer and prior bladder calculus.

PubMed

Chung, Shiu-Dong; Tsai, Ming-Chieh; Lin, Ching-Chun; Lin, Herng-Ching

2013-03-15

Bladder calculus is associated with chronic irritation and inflammation. As there is substantial documentation that inflammation can play a direct role in carcinogenesis, to date the relationship between stone formation and bladder cancer (BC) remains unclear. This study aimed to examine the association between BC and prior bladder calculus using a population-based dataset. This case-control study included 2,086 cases who had received their first-time diagnosis of BC between 2001 and 2009 and 10,430 randomly selected controls without BC. Conditional logistic regressions were employed to explore the association between BC and having been previously diagnosed with bladder calculus. Of the sampled subjects, bladder calculus was found in 71 (3.4%) cases and 105 (1.1%) controls. Conditional logistic regression analysis revealed that the odds ratio (OR) of having been diagnosed with bladder calculus before the index date for cases was 3.42 (95% CI = 2.48-4.72) when compared with controls after adjusting for monthly income, geographic region, hypertension, diabetes, coronary heart disease, and renal disease, tobacco use disorder, obesity, alcohol abuse, and schistosomiasis, bladder outlet obstruction, and urinary tract infection. We further analyzed according to sex and found that among males, the OR of having been previously diagnosed with bladder calculus for cases was 3.45 (95% CI = 2.39-4.99) that of controls. Among females, the OR was 3.05 (95% CI = 1.53-6.08) that of controls. These results add to the evidence surrounding the conflicting reports regarding the association between BC and prior bladder calculus and highlight a potential target population for bladder cancer screening.

Bladder Morphology Using 2 Different Catheter Designs

ClinicalTrials.gov

2017-04-10

Urologic Injuries; Urologic Diseases; Bladder Infection; Urinary Tract Infections; Mucosal Inflammation; Mucosal Infection; Bladder Injury; Catheter-Related Infections; Catheter Complications; Catheter; Infection (Indwelling Catheter); Pelvic Floor Disorders; Urinary Incontinence

Localization of P2X receptor subtypes 2, 3 and 7 in human urinary bladder.

PubMed

Svennersten, Karl; Hallén-Grufman, Katarina; de Verdier, Petra J; Wiklund, N Peter; Poljakovic, Mirjana

2015-08-08

Voiding dysfunctions are a common problem that has a severe negative impact on the quality of life. Today there is a need for new drug targets for these conditions. The role of ATP receptors in bladder physiology has been studied for some time, primarily in animal models. The aim of this work is to investigate the localization of the ATP receptors P2X2, P2X3 and P2X7 and their colocalization with vimentin and actin in the human urinary bladder. Immunohistochemical analysis was conducted on full-thickness bladder tissues from fundus and trigonum collected from 15 patients undergoing open radical cystectomy due to chronic cystitis, bladder cancer or locally advanced prostate cancer. Colocalization analyses were performed between the three different P2X subtypes and the structural proteins vimentin and actin. Specimens were examined using epifluorescence microscopy and correlation coefficients were calculated for each costaining as well as the mean distance from the laminin positive basal side of the urothelium to the vimentin positive cells located in the suburothelium. P2X2 was expressed in vimentin positive cells located in the suburothelium. Less distinct labelling of P2X2 was also observed in actin positive smooth muscle cells and in the urothelium. P2X3 was expressed in vimentin positive cells surrounding the smooth muscle, and in vimentin positive cells located in the suburothelium. Weaker P2X3 labelling was seen in the urothelium. P2X7 was expressed in the smooth muscle cells and the urothelium. In the suburothelium, cells double positive for P2X2 and vimentin where located closer to the urothelium while cells double positive for P2X3 and vimentin where located further from the urothelium. The results from this study demonstrate that there is a significant difference in the expression of the purinergic P2X2, P2X3 and P2X7 receptors in the different histological layers of the human urinary bladder.

Enteric-coated, highly standardized cranberry extract reduces risk of UTIs and urinary symptoms during radiotherapy for prostate carcinoma

PubMed Central

Bonetta, Alberto; Di Pierro, Francesco

2012-01-01

Background Cranberry (Vaccinium macrocarpon) proanthocyanidins can interfere with adhesion of bacteria to uroepithelial cells, potentially preventing lower urinary tract infections (LUTIs). Because LUTIs are a common side effect of external beam radiotherapy (EBRT) for prostate cancer, we evaluated the clinical efficacy of enteric-coated tablets containing highly standardized V. msacrocarpon (ecVM) in this condition. Methods A total of 370 consecutive patients were entered into this study. All patients received intensity-modulated radiotherapy for prostate cancer; 184 patients were also treated with ecVM while 186 served as controls. Cranberry extract therapy started on the simulation day, at which time a bladder catheterization was performed. During EBRT (over 6–7 weeks), all patients underwent weekly examination for urinary tract symptoms, including regular urine cultures during the treatment period. Results Compliance was excellent, with no adverse effects or allergic reactions being observed, apart from gastric pain in two patients. In the cranberry cohort (n = 184), 16 LUTIs (8.7%) were observed, while in the control group (n = 186) 45 LUTIs (24.2%) were recorded. This difference was statistically significant. Furthermore, lower rates of nocturia, urgency, micturition frequency, and dysuria were observed in the group that received cranberry extract. Conclusion Cranberry extracts have been reported to reduce the incidence of LUTIs significantly in women and children. Our data extend these results to patients with prostate cancer undergoing irradiation to the pelvis, who had a significant reduction in LUTIs compared with controls. These results were accompanied by a statistically significant reduction in urinary tract symptoms (dysuria, nocturia, urinary frequency, urgency), suggesting a generally protective effect of cranberry extract on the bladder mucosa. PMID:22977312

Large-Scale SRM Screen of Urothelial Bladder Cancer Candidate Biomarkers in Urine.

PubMed

Duriez, Elodie; Masselon, Christophe D; Mesmin, Cédric; Court, Magali; Demeure, Kevin; Allory, Yves; Malats, Núria; Matondo, Mariette; Radvanyi, François; Garin, Jérôme; Domon, Bruno

2017-04-07

Urothelial bladder cancer is a condition associated with high recurrence and substantial morbidity and mortality. Noninvasive urinary tests that would detect bladder cancer and tumor recurrence are required to significantly improve patient care. Over the past decade, numerous bladder cancer candidate biomarkers have been identified in the context of extensive proteomics or transcriptomics studies. To translate these findings in clinically useful biomarkers, the systematic evaluation of these candidates remains the bottleneck. Such evaluation involves large-scale quantitative LC-SRM (liquid chromatography-selected reaction monitoring) measurements, targeting hundreds of signature peptides by monitoring thousands of transitions in a single analysis. The design of highly multiplexed SRM analyses is driven by several factors: throughput, robustness, selectivity and sensitivity. Because of the complexity of the samples to be analyzed, some measurements (transitions) can be interfered by coeluting isobaric species resulting in biased or inconsistent estimated peptide/protein levels. Thus the assessment of the quality of SRM data is critical to allow flagging these inconsistent data. We describe an efficient and robust method to process large SRM data sets, including the processing of the raw data, the detection of low-quality measurements, the normalization of the signals for each protein, and the estimation of protein levels. Using this methodology, a variety of proteins previously associated with bladder cancer have been assessed through the analysis of urine samples from a large cohort of cancer patients and corresponding controls in an effort to establish a priority list of most promising candidates to guide subsequent clinical validation studies.

Urinary metabotyping of bladder cancer using two-dimensional gas chromatography time-of-flight mass spectrometry.

PubMed

Pasikanti, Kishore Kumar; Esuvaranathan, Kesavan; Hong, Yanjun; Ho, Paul C; Mahendran, Ratha; Raman Nee Mani, Lata; Chiong, Edmund; Chan, Eric Chun Yong

2013-09-06

Cystoscopy is the gold standard clinical diagnosis of human bladder cancer (BC). As cystoscopy is expensive and invasive, it compromises patients' compliance toward surveillance screening and challenges the detection of recurrent BC. Therefore, the development of a noninvasive method for the diagnosis and surveillance of BC and the elucidation of BC progression become pertinent. In this study, urine samples from 38 BC patients and 61 non-BC controls were subjected to urinary metabotyping using two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOFMS). Subsequent to data preprocessing and chemometric analysis, the orthogonal partial least-squares discriminant analysis (OPLS-DA, R2X=0.278, R2Y=0.904 and Q2Y (cumulative)=0.398) model was validated using permutation tests and receiver operating characteristic (ROC) analysis. Marker metabolites were further screened from the OPLS-DA model using statistical tests. GC×GC-TOFMS urinary metabotyping demonstrated 100% specificity and 71% sensitivity in detecting BC, while 100% specificity and 46% sensitivity were observed via cytology. In addition, the model revealed 46 metabolites that characterize human BC. Among the perturbed metabolic pathways, our clinical finding on the alteration of the tryptophan-quinolinic metabolic axis in BC suggested the potential roles of kynurenine in the malignancy and therapy of BC. In conclusion, global urinary metabotyping holds potential for the noninvasive diagnosis and surveillance of BC in clinics. In addition, perturbed metabolic pathways gleaned from urinary metabotyping shed new and established insights on the biology of human BC.

Urinary bladder cancer T-staging from T2-weighted MR images using an optimal biomarker approach

NASA Astrophysics Data System (ADS)

Wang, Chuang; Udupa, Jayaram K.; Tong, Yubing; Chen, Jerry; Venigalla, Sriram; Odhner, Dewey; Guzzo, Thomas J.; Christodouleas, John; Torigian, Drew A.

2018-02-01

Magnetic resonance imaging (MRI) is often used in clinical practice to stage patients with bladder cancer to help plan treatment. However, qualitative assessment of MR images is prone to inaccuracies, adversely affecting patient outcomes. In this paper, T2-weighted MR image-based quantitative features were extracted from the bladder wall in 65 patients with bladder cancer to classify them into two primary tumor (T) stage groups: group 1 - T stage < T2, with primary tumor locally confined to the bladder, and group 2 - T stage < T2, with primary tumor locally extending beyond the bladder. The bladder was divided into 8 sectors in the axial plane, where each sector has a corresponding reference standard T stage that is based on expert radiology qualitative MR image review and histopathologic results. The performance of the classification for correct assignment of T stage grouping was then evaluated at both the patient level and the sector level. Each bladder sector was divided into 3 shells (inner, middle, and outer), and 15,834 features including intensity features and texture features from local binary pattern and gray-level co-occurrence matrix were extracted from the 3 shells of each sector. An optimal feature set was selected from all features using an optimal biomarker approach. Nine optimal biomarker features were derived based on texture properties from the middle shell, with an area under the ROC curve of AUC value at the sector and patient level of 0.813 and 0.806, respectively.

[Bladder stone caused by olive oil following TVT operation].

PubMed

Kato, Kumiko; Hirata, Tomohiko; Suzuki, Koichi; Yoshida, Kazuhiko; Suzuki, Shoji; Murase, Tatsuro

2005-07-01

Tension-free vaginal tape (TVT), a less-invasive variation of the suburethral sling, has been rapidly gaining popularity worldwide in the treatment of female stress urinary incontinence. We report on two cases of bladder stones composed of fatty acid calcium following TVT operations. Case 1: A 76-year-old woman with a history of hysterectomy due to cervical cancer was suffering from vault prolapse. The insertion of a ring pessary lead to the development of stress urinary incontinence, and she was referred to our hospital. As she was frail, sexually inactive, and elderly, she underwent partial colpocleisis (Le Fort operation) combined with a TVT operation. One-month postoperative videourodynamics and chain cystourethrography (CUG) using olive oil as the lubricant showed cure of incontinence and mild support of the urethra. Her maximum flow rate was 18.8 ml/s and no residual urine was observed. Six months postoperatively she developed postmiction pain and pyuria that were not improved by antibiotics. Cystoscopy showed a small bladder stone, whose removal cured cystitis. Case 2: A 49-year-old woman, with a history of abdominal hysterectomy due to myoma uteri, visited our hospital complaining of stress urinary incontinence. A periurethral collagen injection was only temporarily effective, and she underwent a TVT operation. A 1-month postoperative evaluation including chain CUG using olive oil as the lubricant showed cure of incontinence, mild support of the urethra, a maximum flow rate of 28.8 ml/s, and no residual urine. Two months postoperatively she developed miction pain and pyuria that were solved by removing a small bladder stone. Anti-incontinence surgery increases the risk of developing bladder stones due to either foreign bodies (bladder erosion) or obstruction. However, neither of our cases had these conditions; instead, both bladder stones were composed of fatty acid calcium that appeared to be related to the olive oil used as the lubricant in chain CUG. Only four cases (including ours) of bladder stones composed of fatty acid calcium have been documented, but they may indicate that care is necessary when using olive oil as a contrast medium or lubricant in the urinary tract. When a woman with a history of anti-incontinence surgery has persisting or recurrent cystitis, cystoscopy should be performed to exclude bladder erosion and stones.

A Real-Time Non-invasive Auto-bioluminescent Urinary Bladder Cancer Xenograft Model.

PubMed

John, Bincy Anu; Xu, Tingting; Ripp, Steven; Wang, Hwa-Chain Robert

2017-02-01

The study was to develop an auto-bioluminescent urinary bladder cancer (UBC) xenograft animal model for pre-clinical research. The study used a humanized, bacteria-originated lux reporter system consisting of six (luxCDABEfrp) genes to express components required for producing bioluminescent signals in human UBC J82, J82-Ras, and SW780 cells without exogenous substrates. Immune-deficient nude mice were inoculated with Lux-expressing UBC cells to develop auto-bioluminescent xenograft tumors that were monitored by imaging and physical examination. Lux-expressing auto-bioluminescent J82-Lux, J82-Ras-Lux, and SW780-Lux cell lines were established. Xenograft tumors derived from tumorigenic Lux-expressing auto-bioluminescent J82-Ras-Lux cells allowed a serial, non-invasive, real-time monitoring by imaging of tumor development prior to the presence of palpable tumors in animals. Using Lux-expressing auto-bioluminescent tumorigenic cells enabled us to monitor the entire course of xenograft tumor development through tumor cell implantation, adaptation, and growth to visible/palpable tumors in animals.

[Lower urinary tract dysfunction in normal pressure hydrocephalus: Review of the literature].

PubMed

Bey, E; Nicot, B; Casez, O; Le Normand, L

2016-12-01

Lower urinary tract dysfunction in normal pressure hydrocephalus has received little attention from the scientific community. The aim of this review article was to discuss diagnostic and therapeutic options for these patients. A literature review of MedLine publications on urinary incontinence in normal pressure hydrocephalus was conducted. The following keywords were used: "hydrocephalus, normal pressure" and "bladder dysfunction" or "urinary incontinence" or "overactive bladder" or "urinary bladder, neurogenic". Prospective and retrospective studies as well as previous reviews were analyzed. Urinary symptoms in normal pressure hydrocephalus are mainly represented by overactive bladder, which is a significant burden for the concerned patients. Isolated overactive bladder is more frequent (64%) than urinary incontinence (57%). Detrusor overactivity is seen in 95.2% of the cases. Neuro-surgery is efficient on urinary symptoms for 61.5% of the patients. Bladder recovery after surgery relates with increased mid-cingulate perfusion, probably linked with a functional restoration of the mid-cingulate that normally inhibits the micturition reflex. Medical options, added or not to surgery, include anticholinergic drugs unable to pass through the blood-brain barrier, Transcutaneous Electrical Nerve Stimulation and sacral neuromodulation. There is actually an insufficient concern about urinary symptoms in normal pressure hydrocephalus. This article highlights the importance of a harmonization of neuro-urological practices in the pre-therapeutic evaluation of patients suffering from normal pressure hydrocephalus. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A Very Long Foreign Body in the Bladder

PubMed Central

Imai, Atsushi; Suzuki, Yuichiro; Hashimoto, Yasuhiro; Sasaki, Atsushi; Saitoh, Hisao; Ohyama, Chikara

2011-01-01

In the urinary tract, foreign body is most commonly found in the urinary bladder. But it is anatomically very difficult for a man to self-insert a long object into the urinary bladder. Here we report a case of a 49-year-old Japanese man who has inserted a 140-cm vinyl tube in the bladder for masturbation. He could not retrieve it, and the bladder foreign body remained in this position for about two years. He was referred to our hospital and open surgery was performed. PMID:21687624

Longitudinal associations between mental health conditions and overactive bladder in women veterans.

PubMed

Bradley, Catherine S; Nygaard, Ingrid E; Hillis, Stephen L; Torner, James C; Sadler, Anne G

2017-10-01

One in 5 recently deployed US women veterans report overactive bladder symptoms. Mental health conditions such as depression and anxiety commonly co-occur in women with overactive bladder, but temporal relationships between these outcomes have not been well studied, and the mechanism behind this association is unknown. The Women Veterans Urinary Health Study, a nationwide longitudinal study in recently deployed women veterans, was designed to better understand relationships between overactive bladder and mental health conditions. We sought to estimate the 1-year incidence and remission of overactive bladder and to identify the impact of depression, anxiety, posttraumatic stress disorder, and prior sexual assault on 1-year overactive bladder incidence and remission rates. Participants of this 1-year prospective cohort study were female veterans separated from military service who had returned from Iraq or Afghanistan deployment within the previous 2 years. Eligible women were identified through the Defense Manpower Data Center and recruited by mail and telephone. Telephone screening confirmed participants were ambulatory, community-dwelling veterans and excluded those with urinary tract fistula, congenital abnormality, or cancer; pelvic radiation; spinal cord injury; multiple sclerosis; Parkinson disease; stroke; or current/recent pregnancy. Data collection included computer-assisted telephone interviews performed at enrollment and 1 year later. The interview assessed demographic and military service characteristics; urinary symptoms and treatment; depression, anxiety, and posttraumatic stress disorder symptoms and treatment; and a lifetime history of sexual assault. Overactive bladder was identified if at least moderately bothersome urgency urinary incontinence and/or urinary frequency symptoms were reported on Urogenital Distress Inventory items. Exposures included depression, anxiety, posttraumatic stress disorder, and lifetime sexual assault, assessed at baseline using validated questionnaires (including the Patient Health Questionnaire and Posttraumatic Stress Disorder Checklist). Associations between exposures and overactive bladder incidence and remission were estimated using propensity score adjusted logistic regression models. In all, 1107 (88.0%) of 1258 eligible participants completed 1-year interviews. Median age was 29 (range 20-67) years and 53% were nulliparous. Overactive bladder was identified at baseline in 242 (22%), and 102 (9.2%), 218 (19.7%), 188 (17.0%), and 287 (25.9%) met criteria for baseline depression, anxiety, posttraumatic stress disorder, and lifetime sexual assault, respectively. At 1 year, overactive bladder incidence was 10.5% (95% confidence interval, 8.6-12.8%), and remission of overactive bladder was 36.9% (95% confidence interval, 30.8-43.4%). New overactive bladder occurred more often in women with baseline anxiety (21% vs 9%), posttraumatic stress disorder (19% vs 9%) and lifetime sexual assault (16% vs 9%) (all: P < .01). After adjustment, anxiety (odds ratio, 2.4; 95% confidence interval, 1.4-4.1) and lifetime sexual assault (odds ratio, 1.7; 95% confidence interval, 1.0-2.8) predicted 1-year incident overactive bladder. Overactive bladder remission occurred less often in those with baseline depression (19% vs 41%, P < .01) and anxiety (29% vs 42%, P = .03). After adjustment, depression decreased 1-year overactive bladder remission risk (odds ratio, 0.37; 95% confidence interval, 0.16-0.83). Overactive bladder treatment was uncommon and not associated with remission. Anxiety, depression, and prior sexual assault-common postdeployment problems for women veterans-influence the natural history of overactive bladder. Providers should screen for mental health conditions and sexual assault in women with newly diagnosed or persistent overactive bladder. Copyright © 2017 Elsevier Inc. All rights reserved.

Benefits and limitations of animal models in partial bladder outlet obstruction for translational research.

PubMed

Kitta, Takeya; Kanno, Yukiko; Chiba, Hiroki; Higuchi, Madoka; Ouchi, Mifuka; Togo, Mio; Moriya, Kimihiko; Shinohara, Nobuo

2018-01-01

The functions of the lower urinary tract have been investigated for more than a century. Lower urinary tract symptoms, such as incomplete bladder emptying, weak urine stream, daytime urinary frequency, urgency, urge incontinence and nocturia after partial bladder outlet obstruction, is a frequent cause of benign prostatic hyperplasia in aging men. However, the pathophysiological mechanisms have not been fully elucidated. The use of animal models is absolutely imperative for understanding the pathophysiological processes involved in bladder dysfunction. Surgical induction has been used to study lower urinary tract functions of numerous animal species, such as pig, dog, rabbit, guinea pig, rat and mouse, of both sexes. Several morphological and functional modifications under partial bladder outlet obstruction have not only been observed in the bladder, but also in the central nervous system. Understanding the changes of the lower urinary tract functions induced by partial bladder outlet obstruction would also contribute to appropriate drug development for treating these pathophysiological conditions. In the present review, we discuss techniques for creating partial bladder outlet obstruction, the characteristics of several species, as well as issues of each model, and their translational value. © 2017 The Japanese Urological Association.

Air pollution and risk of urinary bladder cancer in a case-control study in Spain.

PubMed

Castaño-Vinyals, Gemma; Cantor, Kenneth P; Malats, Núria; Tardon, Adonina; Garcia-Closas, Reina; Serra, Consol; Carrato, Alfredo; Rothman, Nathaniel; Vermeulen, Roel; Silverman, Debra; Dosemeci, Mustafa; Kogevinas, Manolis

2008-01-01

Air pollution has been associated with an increased risk for lung cancer. We examined whether long-term air pollution is associated with bladder cancer risk. Information from a case-control study in Spain that included 1219 incident cases and 1271 hospital controls was used. Information on residential history including several indicators of exposure to air pollution and other potential risk factors was collected in a face-to-face computerised personal interview. Odds ratios (OR) and 95% confidence intervals (95% CI) were adjusted for age, gender, region, smoking, occupation, water contaminants and diet. Living more than 40 years in a city with a population of more than 100 000 was associated with an increased risk for bladder cancer overall (OR 1.30, 95% CI 1.04 to 1.63). Emissions of polycyclic aromatic hydrocarbons and diesel from industries near the residence, as evaluated by experts, were associated with an increased risk (OR 1.29, 95% CI 0.85 to 1.98), while lower or no excess risks were observed for other pollution-related variables. Odds ratios among never smokers tended to be higher than among smokers. The small to moderate positive associations found for several indices of air pollution and bladder cancer, while suggestive of excess risk, require further evaluation in other settings.

Technologic developments in the field of photonics for the detection of urinary bladder cancer.

PubMed

Palmer, Scott; Sokolovski, Sergei G; Rafailov, Edik; Nabi, Ghulam

2013-12-01

Bladder cancer is a common cause of morbidity and mortality worldwide in an aging population. Each year, thousands of people, mostly men, are diagnosed with this disease, but many of them present too late to receive optimal treatment. As with all cancers, early diagnosis of bladder cancer significantly improves the efficacy of therapy and increases survival and recurrence-free survival rates. Ongoing research has identified many limitations about the sensitivity of standard diagnostic procedures in detecting early-stage tumors and precancerous changes. The consequences of this are often tumor progression and increased tumor burden, leading to a decrease in patient quality of life and a vast increase in treatment costs. The necessity for improved early detection of bladder cancer has spurred on research into novel methods that use a wide range of biological and photonic phenomena. This review will broadly discuss standard detection methodologies and their major limitations before covering novel photonic techniques for early tumor detection and staging, assessing their diagnostic accuracy for flat and precancerous changes. We will do so in the context of both cystoscopic examination and the screening of voided urine and will also touch on the concept of using photonic technology as a surgical tool for tumor ablation. Copyright © 2013 Elsevier Inc. All rights reserved.

Decision curve analysis assessing the clinical benefit of NMP22 in the detection of bladder cancer: secondary analysis of a prospective trial.

PubMed

Barbieri, Christopher E; Cha, Eugene K; Chromecki, Thomas F; Dunning, Allison; Lotan, Yair; Svatek, Robert S; Scherr, Douglas S; Karakiewicz, Pierre I; Sun, Maxine; Mazumdar, Madhu; Shariat, Shahrokh F

2012-03-01

• To employ decision curve analysis to determine the impact of nuclear matrix protein 22 (NMP22) on clinical decision making in the detection of bladder cancer using data from a prospective trial. • The study included 1303 patients at risk for bladder cancer who underwent cystoscopy, urine cytology and measurement of urinary NMP22 levels. • We constructed several prediction models to estimate risk of bladder cancer. The base model was generated using patient characteristics (age, gender, race, smoking and haematuria); cytology and NMP22 were added to the base model to determine effects on predictive accuracy. • Clinical net benefit was calculated by summing the benefits and subtracting the harms and weighting these by the threshold probability at which a patient or clinician would opt for cystoscopy. • In all, 72 patients were found to have bladder cancer (5.5%). In univariate analyses, NMP22 was the strongest predictor of bladder cancer presence (predictive accuracy 71.3%), followed by age (67.5%) and cytology (64.3%). • In multivariable prediction models, NMP22 improved the predictive accuracy of the base model by 8.2% (area under the curve 70.2-78.4%) and of the base model plus cytology by 4.2% (area under the curve 75.9-80.1%). • Decision curve analysis revealed that adding NMP22 to other models increased clinical benefit, particularly at higher threshold probabilities. • NMP22 is a strong, independent predictor of bladder cancer. • Addition of NMP22 improves the accuracy of standard predictors by a statistically and clinically significant margin. • Decision curve analysis suggests that integration of NMP22 into clinical decision making helps avoid unnecessary cystoscopies, with minimal increased risk of missing a cancer. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Cancer incidence in Spain, 2015.

PubMed

Galceran, J; Ameijide, A; Carulla, M; Mateos, A; Quirós, J R; Rojas, D; Alemán, A; Torrella, A; Chico, M; Vicente, M; Díaz, J M; Larrañaga, N; Marcos-Gragera, R; Sánchez, M J; Perucha, J; Franch, P; Navarro, C; Ardanaz, E; Bigorra, J; Rodrigo, P; Bonet, R Peris

2017-07-01

Periodic cancer incidence estimates of Spain from all existing population-based cancer registries at any given time are required. The objective of this study was to present the current situation of cancer incidence in Spain. The Spanish Network of Cancer Registries (REDECAN) estimated the numbers of new cancer cases occurred in Spain in 2015 by applying the incidence-mortality ratios method. In the calculus, incidence data from population-based cancer registries and mortality data of all Spain were used. In 2015, nearly a quarter of a million new invasive cancer cases were diagnosed in Spain, almost 149,000 in men (60.0%) and 99,000 in women. Globally, the five most common cancers were those of colon-rectum, prostate, lung, breast and urinary bladder. By gender, the four most common cancers in men were those of prostate (22.4%), colon-rectum (16.6%), lung (15.1%) and urinary bladder (11.7%). In women, the most common ones were those of breast (28.0%), colon-rectum (16.9%), corpus uteri (6.2%) and lung (6.0%). In recent years, cancer incidence in men seems to have stabilized due to the fact that the decrease in tobacco-related cancers compensates for the increase in other types of cancer like those of colon and prostate. In women, despite the stabilization of breast cancer incidence, increased incidence is due, above all, to the rise of colorectal and tobacco-related cancers. To reduce these incident cancer cases, improvement of smoking control policies and extension of colorectal cancer screening should be the two priorities in cancer prevention for the next years.

Expression of cyclooxygenase-2 in transitional cell carcinoma of the urinary bladder in dogs.

PubMed

Khan, K N; Knapp, D W; Denicola, D B; Harris, R K

2000-05-01

To evaluate expression of cyclooxygenase (COX)-1 and COX-2 in the urinary bladder epithelium of clinically normal dogs and in transitional cell carcinoma cells of dogs. 21 dogs with transitional cell carcinoma of the urinary bladder and 8 dogs with clinically normal urinary bladders. COX-1 and COX-2 were evaluated by use of isoform-specific antibodies with standard immunohistochemical methods. COX-1, but not COX-2, was constitutively expressed in normal urinary bladder epithelium; however, COX-2 was expressed in neoplastic epithelium in primary tumors and in metastatic lesions of all 21 dogs and in new proliferating blood vessels in 3 dogs. Also, COX-1 was expressed in the neoplastic cells. Lack of expression of COX-2 in normal bladder epithelium and its substantial expression in transitional cell carcinoma cells suggest that this isoform may be involved in tumor cell growth. Inhibition of COX-2 is a likely mechanism of the antineoplastic effects of non steroidal antiinflammatory drugs.

Bovine papillomavirus type 2 infects the urinary bladder of water buffalo (Bubalus bubalis) and plays a crucial role in bubaline urothelial carcinogenesis.

PubMed

Roperto, Sante; Russo, Valeria; Ozkul, Ayhan; Sepici-Dincel, Aylin; Maiolino, Paola; Borzacchiello, Giuseppe; Marcus, Ioan; Esposito, Iolanda; Riccardi, Marita Georgia; Roperto, Franco

2013-02-01

Bovine papillomavirus type 2 (BPV-2) has been shown to infect and play a role in urinary bladder carcinogenesis of buffaloes grazed on pastures with ferns from the Marmara and Black Sea Regions of Turkey. BPV-2 DNA has been found in both neoplastic and non-neoplastic lesions of the urinary bladder. Furthermore, this virus may be a normal inhabitant of the urinary bladder since BPV-2 DNA has also been detected in clinically normal buffaloes. The viral activation by fern immunosuppressant or carcinogen may trigger the urothelial cell transformation. The E5 oncoprotein was solely detected in urothelial tumours and appeared to be co-localized with the overexpressed and phosphorylated platelet derived growth factor (PDGF) β receptor in a double-colour immunofluorescence assay. Our results indicate that the E5-PDGF β receptor interaction also occurs in spontaneous tumours of the bubaline urinary bladder, revealing an additional role of BPV-2 in bladder carcinogenesis of buffaloes.

Bladder stones

MedlinePlus

Stones - bladder; Urinary tract stones; Bladder calculi ... Benway BM, Bhayani SB. Lower urinary tract calculi. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology . 11th ed. Philadelphia, PA: Elsevier; 2016:chap 55. Sharma R, ...

Squamous cell carcinoma of the bladder mimicking interstitial cystitis and voiding dysfunction.

PubMed

Prudnick, Colton; Morley, Chad; Shapiro, Robert; Zaslau, Stanley

2013-01-01

Squamous cell carcinoma (SCC) of the bladder is a relatively uncommon cause of bladder cancer accounting for <5% of bladder tumors in the western countries. SCC has a slight male predominance and tends to occur in the seventh decade of life. The main presenting symptom of SCC is hematuria, and development of this tumor in the western world is associated most closely with chronic indwelling catheters and spinal cord injuries. A 39-year-old Caucasian female presented with bladder and lower abdominal pain, urinary frequency, and nocturia which was originally believed to be interstitial cystitis (IC) but was later diagnosed as SCC of the bladder. Presentation of SCC without hematuria is an uncommon presentation, but the absence of this symptom should not lead a practitioner to exclude the diagnosis of SCC. This case is being reported in an attempt to explain the delay and difficulty of diagnosis. Background on the risk factors for SCC of the bladder and the typical presenting symptoms of bladder SCC and IC are also reviewed.

Arsenate and dimethylarsinic acid in drinking water did not affect DNA damage repair in urinary bladder transitional cells or micronuclei in bone marrow

EPA Science Inventory

Arsenic is a recognized human skin, lung, and urinary bladder carcinogen, and may act as a cocarcinogen in the urinary bladder (with cigarette smoking) and skin (with UV light exposure). Possible modes of action of arsenic carcinogenesis/cocarcinogenesis include induction of DNA ...

Transcriptomic dose-and-time-course indicators of early key events in a cytotoxicity-mediated mode of action for rodent urinary bladder tumorigenesis

EPA Science Inventory

TRANSCRIPTOMIC DOSE- AND TIME-COURSE INDICATORS OF EARLY KEY EVENTS IN A CYTOTOXICITY-MEDIATED MODE OF ACTION FOR RODENT URINARY BLADDER TUMORIGENESISDiuron is a substituted urea compound used globally as an herbicide. Urinary bladder tumors were induced in rats after chronic die...

Is whole-body fluorine-18 fluorodeoxyglucose PET/CT plus additional pelvic images (oral hydration-voiding-refilling) useful for detecting recurrent bladder cancer?

PubMed

Yang, Zhongyi; Cheng, Jingyi; Pan, Lingling; Hu, Silong; Xu, Junyan; Zhang, Yongping; Wang, Mingwei; Zhang, Jianping; Ye, Dingwei; Zhang, Yingjian

2012-08-01

Because of the urinary excretion of fluorine-18 fluorodeoxyglucose ((18)F-FDG), FDG-PET or PET/CT is thought of little value in patients with bladder cancer. The purpose of our study was to investigate the value of (18)F-FDG PET/CT with additional pelvic images in detection of recurrent bladder cancers. From December 2006 to August 2010, 35 bladder cancer patients (median age 56 years old, ranging from 35 to 96) underwent routine (18)F-FDG PET/CT. To better detect bladder lesions, a new method called as oral hydration-voiding-refilling was introduced, which included that all the patients firstly received oral hydration, then were required to void frequently and finally were demanded to hold back urine when the additional pelvic images were scanned. Lesions were confirmed by either histopathology or clinical follow-up for at least 6 months. Finally, 12 recurrent cases of 35 patients were confirmed by cystoscope. PET/CT correctly detected 11 of them. Among these 11 true positive patients, 5 patients (45.5 %) were detected only after additional pelvic images. Lichenoid lesions on the bladder wall were missed, which caused 1 false negative result. All three false positive cases were testified to be inflammatory tissues by cystoscope. Therefore, the sensitivity, specificity and accuracy of PET/CT were 91.7 % (11/12), 87.0 % (20/23) and 88.6 % (31/35), respectively. PET/CT with additional pelvic images can highly detect recurrent lesions in residual bladder tissues. Our method with high accuracy and better endurance could be potentially applied.

Detection of Bladder Cancer Via Microfluidic Immunoassay and Single-Cell DNA Copy Number Alteration Analysis of Captured Urinary Exfoliated Tumor Cells.

PubMed

Chen, Anqi; Fu, Guanghou; Xu, Zhijie; Sun, Yukun; Chen, Xiaoyi; Cheng, Kok Suen; Neoh, Kuang Hong; Tang, Zhewen; Chen, Shifu; Liu, Ming; Huang, Tanxiao; Dai, Yun; Wang, Qibo; Jin, Jing; Jin, Baiye; Han, Ray P S

2018-05-22

The increasing incidence of bladder cancer (BC) and its high rate of recurrence over a 5-year period necessitate the need for diagnosis and surveillance amelioration. Cystoscopy and urinary cytology are the current tools, and molecular techniques such as BTA stat, NMP22, survivin mRNA, and urovysion FISH have attracted attention, however, they suf-fer from insufficient sensitivity or specificity. We developed a novel microfluidic approach for harvesting intact urinary-exfoliated tumor cells (UETCs), either individually or in clus-ters, in a clean and segregated environment, which is crucial to minimize cross-contamination and misreads. To reliably and accurately identify UETC, our quantitative immunoassay involved concurrent use of two oncoproteins CK20 and CD44v6 antigen. CK20 is an intermediate filament protein overexpressed in urothelial tumors, and CD44v6 is a membrane adhesion molecule closely associated with cell invasion, tumor progression and metastatic spread. Single-cell whole-genome sequencing on 12 captured UETCs and copy number alteration analysis showed that 11/12 (91.7%) of the immunofluorescence-identified UETCs possessed genomic instability. A total of 79 BC patients and 43 age-matched normal controls (NC) were enrolled in the study. We detected considerably high-er UETC counts in BC patients versus the NC group [53.3 (10.7-1001.9) vs. 0.0 (0-3.0) UETCs/10 mL; p < 0.0001]. For BC detection, a stratified 10-fold cross-validation of train-ing data reveals an overall predictive accuracy of 0.84 (95%CI: 0.76-0.93) with a 89.8% (95%CI: 71.5-86.4%) for sensitivity and 71.5% (95%CI: 59.7-83.3%) for specificity. Overall, the microfluidic immunoassay demonstrates increased sensitivity and specificity com-pared to other techniques for the detection of bladder cancer. Copyright ©2018, American Association for Cancer Research.

Pharmacologic evaluation of pressor and visceromotor reflex responses to bladder distension.

PubMed

Su, Xin; Riedel, Erin S; Leon, Lisa A; Laping, Nicholas J

2008-01-01

Several mechanisms that are involved in acute rat bladder nociception were examined. The nociceptive response was measured by analyzing both cardiovascular and visceromotor reflex responses to urinary bladder distension. The contributions of micro-opioid receptor, kappa-opioid receptor, sodium channels, muscarinic receptors, and cyclooxygenase, were explored with morphine, U50,488, mexiletine, oxybutynin, and naproxen, respectively. Female Sprague-Dawley rats were acutely instrumented with jugular venous, carotid arterial, and bladder cannulas. Needle electrodes were placed directly into the abdominal musculature to measure myoelectrical activity subsequent to repeated phasic urinary bladder distension (60 mmHg for 20 sec in 3 min intervals) under 1% isoflurane. Drugs were administered by i.v. bolus injection 2 min prior to distension. The analgesics morphine (ID50 0.69 mg/kg), U50,488 (1.34 mg/kg), and mexiletine (2.60 mg/kg) significantly inhibited the visceromotor reflex response to noxious urinary bladder distension. Oxybutynin also attenuated reflex responses to noxious urinary bladder distension to 41% of the maximal pressor response and 32% of the control visceromotor reflex response (3.01 and 5.05 mg/kg), respectively, indicating a role of muscarinic receptors in bladder nociception. Naproxen did not attenuate the pressor response, but moderately inhibited visceromotor reflex to 45% of control at 30 mg/kg (P < 0.05). Current results using the rat urinary bladder distension model are consistent with previous research demonstrating a role of the analgesics (morphine, U50,488, and mexiletine) in the inhibition of visceral nociceptive transmission. The utility of the reflex responses to urinary bladder distension may provide a method useful to examine mechanisms which target the bladder sensory pathway. (c) 2007 Wiley-Liss, Inc.

Cystocele (Prolapsed Bladder)

MedlinePlus

... Prostate Enlargement (Benign Prostatic Hyperplasia) Urinary Diversion Urinary Retention Urine Blockage in Newborns Vesicoureteral Reflux (VUR) The ... laughing, or physical activity, such as walking. Urinary retention —the inability to empty the bladder completely—may ...

Arsenic in drinking water and urinary tract cancers: a systematic review of 30 years of epidemiological evidence

PubMed Central

2014-01-01

Background Arsenic in drinking water is a public health issue affecting hundreds of millions of people worldwide. This review summarizes 30 years of epidemiological studies on arsenic exposure in drinking water and the risk of bladder or kidney cancer, quantifying these risks using a meta-analytical framework. Methods Forty studies met the selection criteria. Seventeen provided point estimates of arsenic concentrations in drinking water and were used in a meta-analysis of bladder cancer incidence (7 studies) and mortality (10 studies) and kidney cancer mortality (2 studies). Risk estimates for incidence and mortality were analyzed separately using Generalized Linear Models. Predicted risks for bladder cancer incidence were estimated at 10, 50 and 150 μg/L arsenic in drinking water. Bootstrap randomizations were used to assess robustness of effect size. Results Twenty-eight studies observed an association between arsenic in drinking water and bladder cancer. Ten studies showed an association with kidney cancer, although of lower magnitude than that for bladder cancer. The meta-analyses showed the predicted risks for bladder cancer incidence were 2.7 [1.2–4.1]; 4.2 [2.1–6.3] and; 5.8 [2.9–8.7] for drinking water arsenic levels of 10, 50, and 150 μg/L, respectively. Bootstrapped randomizations confirmed this increased risk, but, lowering the effect size to 1.4 [0.35–4.0], 2.3 [0.59–6.4], and 3.1 [0.80–8.9]. The latter suggests that with exposures to 50 μg/L, there was an 83% probability for elevated incidence of bladder cancer; and a 74% probability for elevated mortality. For both bladder and kidney cancers, mortality rates at 150 ug/L were about 30% greater than those at 10 μg/L. Conclusion Arsenic in drinking water is associated with an increased risk of bladder and kidney cancers, although at lower levels (<150 μg/L), there is uncertainty due to the increased likelihood of exposure misclassification at the lower end of the exposure curve. Meta-analyses suggest exposure to 10 μg/L of arsenic in drinking water may double the risk of bladder cancer, or at the very least, increase it by about 40%. With the large number of people exposed to these arsenic concentrations worldwide the public health consequences of arsenic in drinking water are substantial. PMID:24889821

DIETARY ARSENIC EXPOSURE ASSESSMENT USING ENZYMATIC BASED EXTRACTION CONDITIONS AND DETECTION OF URINARY THIO-ARSENICALS AS METABOLITES OF EXPOSURE - MCEARD2

EPA Science Inventory

Inorganic arsenic is classified as a carcinogen and has been linked to lung and bladder cancer as well as other non-cancerous health effects. Because of these health effects the U.S. EPA has set a Maximum Contaminant Level (MCL) at 10ppb based on a linear extrapolation of risk an...

[Urinary function after pelvic autonomic nerve preservation of laparoscopic radical resection for rectal cancer].

PubMed

Zheng, Zong-heng; Wei, Hong-bo; Chen, Tu-feng; Huang, Jiang-long; Wei, Bo; Hu, Bao-guang; Zheng, Feng; Guo, Wei-ping; Huang, Yong; Situ, Jie

2009-11-17

To evaluate the protection of urinary function after laparoscopic radical resection with pelvic autonomic nerve preservation (PANP) for rectal cancer. Prospectively 139 patients with middle or low rectal cancer receiving surgery during November 2005 to October 2007 were divided into two groups (L-PANP, n = 63; O-PANP, n = 76). The radicalism and safety of L-PANP surgery were analyzed and the effects upon urinary function between the two groups assessed by follow-ups and urodynamic study. Patients receiving subtypes I and II of L-PANP surgery had less decrease in contraction of bladder than those receiving the same subtype of O-PANP surgery at 10 days post-operation (Z = -2.358, P = 0.018; Z = -2.268, P = 0.033). And no difference was observed in patients receiving subtype III PANP surgery (Z = -1.302, P = 0.237). However, no matter which subtype of PANP surgery, patients of L-PANP group had a better contraction of bladder than those of O-PANP group at 1 month post-operation (P < 0.05). The 1-year survival rate was 98.0% (50/51) in L-PANP group and 96.6% (57/59) in O-PANP group. And no statistical difference was found between them (P = 0.898). Meanwhile, the 1-year relapse rate of pelvic cavity was 3.9% (2/52) in L-PANP group and 5.1% (3/59) in O-PANP group. And no statistical difference was found between them (P = 0.867). As compared with O-PANP surgery, L-PANP surgery shows a superiority in protection of urinary function.

[A case of vesicovaginal fistula repair with rectus abdominus myofascial interposition flap after radical hysterectomy and radiation therapy].

PubMed

Endo, Yuki; Iigaya, Shigeki; Nishimura, Taiji; Ishii, Naohiro; Kitaoka, Yoshihisa; Kawashima, Toshifumi; Ohara, Chiharu; Hamasaki, Tsutomu; Kondo, Yukihiro

2014-10-01

Vesicovaginal fistulas (VVFs) caused after radiation are difficult to repair and require interposition of non-irradiated, well-vascularized tissue between urinary bladder and vagina. A 48-year-old female suffered cervical cancer and underwent radical hysterectomy followed by radiation therapy which caused VVF. The initial surgical repair performed 3 months after development of VVF, was unsuccessful because of the absence of peritoneum or omentum to interpose between urinary bladder and vagina probably due to history of cesarean section and radical hysterectomy. The second surgical repair was performed 15 months after the first surgery utilizing a rectus abdominus myofascial (RAM) interposition flap. Fifteen months after the second operation, she remains free from incontinence. This case suggests that RAM is useful even for postradiation VVF.

Elevated urinary urea by high-protein diet could be one of the inducements of bladder disorders.

PubMed

Liu, Ming; Li, Min; Liu, Jiangfeng; Wang, Hongkai; Zhong, Dandan; Zhou, Hong; Yang, Baoxue

2016-02-16

Previous work found that urea accumulation in urothelial cells caused by urea transporter B knockout led to DNA damage and apoptosis that contributed to the carcinogenesis. The purpose of this study is to explore the potential connection between high urinary urea concentration and the bladder disorders. A high protein diet rat model was conducted by feeding with 40 % protein diet. In-silico modeling and algorithm, based on the results of microarray and proteomics from the bladder urothelium, were used for the reconstruction of accurate cellular networks and the identification of novel master regulators in the high-protein diet rat model. Pathway and biological process enrichment analysis were used to characterize predicted targets of candidate mRNAs/proteins. The expression pattern of the most significant master regulators was evaluated by qPCR and immunohistochemistry. Based on the analysis of different expressed mRNAs/proteins, 15 significant ones (CRP, MCPT2, MCPT9, EPXH2, SERPING1, SRGN, CDKN1C, CDK6, CCNB1, PCNA, BAX, MAGEB16, SERPINE1, HSPA2, FOS) were highly identified and verified by qPCR and immunohistochemistry. They were involved in immune and inflammatory response, cell cycle arrest, apoptosis and pathways in cancer. These abnormally activated processes caused the bladder interstitial congestion and inflammatory infiltrates under the thinner urothelium, cell desquamation, cytoplasm vacuolization, nucleus swelling and malformation in the high-protein diet group. We provided evidences that high urinary urea concentration caused by high-protein diet might be a potential carcinogenic factor in bladder.

Clinical experience with the Swiss lithoclast master in treatment of bladder calculi.

PubMed

Kingo, Pernille S; Ryhammer, Allan M; Fuglsig, Sven

2014-10-01

Bladder calculi account for 5% of urinary tract calculi in the Western world, and many different treatment modalities have been presented throughout the decades. We report our clinical experience using the Swiss LithoClast® Master (SLM). The SLM is a rigid, hand-held endourologic probe including a pneumatic lithotriptor and an ultrasonic lithotriptor. Attached to the ultrasonic modality is a suction system. The two lithotriptor modalities are controlled by a footswitch and can be activated separately or simultaneously. The SLM is used via a rigid endoscope. Indications for treatment were medical complaints such as hematuria, lower urinary tract symptoms, pain, recurrent urinary tract infections, recurrent bursts of balloon in indwelling catheters, and difficulties performing clean intermittent self-catheterization. From August 1, 2009, to August 1, 2011, 27 patients were treated for bladder calculi (24 men). Five had a neurogenic voiding dysfunction, 3 had prostate cancer, and 19 had benign prostatic enlargement or detrusor muscle insufficiency. Median age was 74 years (range 45-86 years). Stone clearance was obtained in 26 (96%) patients. Stone burden was one or multiple bladder calculi. Median stone size of the largest stone in each patient was 20 (5-40) mm. Under the same anesthesia, two patients underwent a transurethral resection of the prostate because of a very large prostate. Median lithotripsy time was 60 (range 20-144) minutes. All patients were discharged within 24 hours. The method described is a safe and quick method for endoscopic lithotripsy of bladder calculi rendering the patients stone free in the vast majority of cases. The procedure can be performed as day-case surgery.

Proteomic analysis of urine in patients with intestinal segments transposed into the urinary tract.

PubMed

Nabi, Ghulam; N'Dow, James; Hasan, Tahseen S; Booth, Ian R; Cash, Phil

2005-04-01

Intestinal segments are used to replace or reconstruct the urinary bladder when it has become dysfunctional or develops life-threatening disease such as cancer. The quality of life in patients with intestinal segments used to either enlarge or completely replace the native bladder is adversely affected by recurrent urinary tract infections, excessive mucus production and the occasional development of malignancy. At present, there is no reliable method of predicting or noninvasively monitoring these patients for the development of these complications. The characterisation of proteins secreted into urine from the transposed intestinal segments could serve as important indicators of these clinical complications. Urine is an ideal source of material in which to search for biomarkers, since it bathes the affected tissues and can be obtained relatively easily by noninvasive methods. The urinary proteome of patients with intestinal segments transposed into the urinary tract is unknown and we present the first global description of the urinary protein profile in these patients. Sample preparation is a critical step in achieving accurate and reliable data. We describe a method to prepare urinary proteins that was compatible with their subsequent analysis using two-dimensional polyacrylamide gel electrophoresis. This method helped to overcome some of the technical problems encountered in analysing urine from this patient cohort. The method was used to analyse urinary proteins recovered from five healthy controls and ten patients with intestinal segments transposed into the urinary tract. Four low molecular weight proteins were found to be present in nine out of ten for the patient group but for none of the healthy controls. The four proteins were identified as lithostathine-1 alpha precursor, pancreatitis associated protein-1 precursor, liver fatty acid binding protein and testis expressed protein-12. The role of these proteins as potential biomarkers of intestinal cell activity within the reconstructed bladder is discussed.

Causes and risk factors of urinary incontinence: Avicenna's point of view vs. contemporary findings.

PubMed

Nojavan, Fatemeh; Sharifi, Hossein; Ghanbari, Zinat; Kamalinejad, Mohammad; Mokaberinejad, Roshanak; Emami, Maryam

2015-02-22

To extract the causes and risk factors of urinary incontinence from an old medical text by Avicenna entitled "Canon of Medicine" and comparing it with contemporary studies. In this study, etiology and risk factors of urinary incontinence were extracted from Avicenna's "Canon of Medicine". Commentaries written on this book and other old reliable medical texts about bladder and its diseases were also studied. Then the achieved information was compared with contemporary findings of published articles. Urinary incontinence results from bladder dysfunction in reservoir phase. Bladder's involuntary muscles and voluntary external sphincter are two main components which are involved in this process. Urinary incontinence can exist without obvious structural and neuronal etiologies. According to Avicenna, distemperment of muscular tissue of bladder and external sphincter is the cause for urinary incontinence in such cases. Distemperment is the result of bothering qualities in tissue, i.e.: "wet" and "cold". They are the two bothering qualities which are caused by extracorporeal and intracorporeal factors. Interestingly, the positive associations of some of these factors with urinary incontinence have been shown in recent researches. "Cold" and "wet" distemperment of bladder and external sphincter can be independent etiologies of urinary incontinence which should be investigated. 

Pheochromocytoma of the Urinary Bladder - A Case Report of an Unusual Presentation.

PubMed

Nerli, Rajendra B; Magdum, Prasad V; Patil, Amey Y; Devraju, Shishir; Hiremath, M B

2015-09-01

Urinary bladder pheochromocytoma is rare. We report a case of bladder pheochromocytoma presenting with practically no obvious clinical symptoms in an adolescent who had undergone repair of mitral valve disease.

Characterization of dynamic physiology of the bladder by optical coherence tomography

NASA Astrophysics Data System (ADS)

Yuan, Zhijia; Keng, Kerri; Pan, Rubin; Ren, Hugang; Du, Congwu; Kim, Jason; Pan, Yingtian

2012-03-01

Because of its high spatial resolution and noninvasive imaging capabilities, optical coherence tomography has been used to characterize the morphological details of various biological tissues including urinary bladder and to diagnose their alternations (e.g., cancers). In addition to static morphology, the dynamic features of tissue morphology can provide important information that can be used to diagnose the physiological and functional characteristics of biological tissues. Here, we present the imaging studies based on optical coherence tomography to characterize motion related physiology and functions of rat bladder detrusor muscles and compared the results with traditional biomechanical measurements. Our results suggest that optical coherence tomography is capable of providing quantitative evaluation of contractile functions of intact bladder (without removing bladder epithelium and connective tissue), which is potentially of more clinical relevance for future clinical diagnosis - if incorporated with cystoscopic optical coherence tomography.

Radiation-induced cystitis following intracavitary irradiation for superficial bladder cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maatman, T.J.; Novick, A.C.; Montague, D.K.

Intracavitary irradiation is effective in the treatment of noninvasive papillary transitional cell carcinoma and carcinoma in situ of the bladder. Mortality has not been associated with this form of therapy. The morbidity associated with intracavitary irradiation consists of mild to severe radiation cystitis and we report 2 such cases. One patient is from a series of 65 patients with noninvasive bladder tumors treated with intracavitary irradiation at this clinic since 1965. The second patient had noninvasive bladder tumors and was treated with intracavitary irradiation elsewhere. In both patients severe radiation cystitis subsequently developed, requiring simple cystectomy and urinary diversion. Themore » potential for this serious side effect must be considered when choosing a form of therapy for patients with noninvasive papillary transitional cell carcinoma and carcinoma in situ of the bladder.« less

Expression and Function of Chemokines CXCL9-11 in Micturition Pathways in Cyclophosphamide (CYP)-Induced Cystitis and Somatic Sensitivity in Mice

PubMed Central

Guo, Michael; Chang, Phat; Hauke, Eric; Girard, Beatrice M.; Tooke, Katharine; Ojala, Jacqueline; Malley, Susan M.; Hsiang, Harrison; Vizzard, Margaret A.

2018-01-01

Changes in urinary bladder function and somatic sensation may be mediated, in part, by inflammatory changes in the urinary bladder including the expression of chemokines. Male and female C57BL/6 mice were treated with cyclophosphamide (CYP; 75 mg/kg, 200 mg/kg, i.p.) to induce bladder inflammation (4 h, 48 h, chronic). We characterized the expression of CXC chemokines (CXCL9, CXCL10 and CXCL11) in the urinary bladder and determined the effects of blockade of their common receptor, CXCR3, at the level urinary bladder on bladder function and somatic (hindpaw and pelvic) sensation. qRT-PCR and Enzyme-Linked Immunoassays (ELISAs) were used to determine mRNA and protein expression of CXCL9, CXCL10 and CXCL11 in urothelium and detrusor. In urothelium of female mice treated with CYP, CXCL9 and CXCL10 mRNA significantly (p ≤ 0.01) increased with CYP treatment whereas CXC mRNA expression in the detrusor exhibited both increases and decreases in expression with CYP treatment. CXC mRNA expression urothelium and detrusor of male mice was more variable with both significant (p ≤ 0.01) increases and decreases in expression depending on the specific CXC chemokine and CYP treatment. CXCL9 and CXCL10 protein expression was significantly (p ≤ 0.01) increased in the urinary bladder with 4 h CYP treatment in female mice whereas CXC protein expression in the urinary bladder of male mice did not exhibit an overall change in expression. CXCR3 blockade with intravesical instillation of AMG487 (5 mg/kg) significantly (p ≤ 0.01) increased bladder capacity, reduced voiding frequency and reduced non-voiding contractions in female mice treated with CYP (4 h, 48 h). CXCR3 blockade also reduced (p ≤ 0.01) hindpaw and pelvic sensitivity in female mice treated with CYP (4 h, 48 h). CXC chemokines may be novel targets for treating urinary bladder dysfunction and somatic sensitization resulting from urinary bladder inflammation. PMID:29681802

The Effects of Tempol on Cyclophosphamide-Induced Oxidative Stress in Rat Micturition Reflexes

PubMed Central

Gonzalez, Eric J.; Peterson, Abbey; Malley, Susan; Daniel, Mitchel; Lambert, Daniel; Kosofsky, Michael; Vizzard, Margaret A.

2015-01-01

We hypothesized that cyclophosphamide- (CYP-) induced cystitis results in oxidative stress and contributes to urinary bladder dysfunction. We determined (1) the expression of oxidative stress markers 3-nitrotyrosine (3-NT), reactive oxygen species (ROS)/reactive nitrogen species (RNS), inflammatory modulators, neuropeptides calcitonin gene-related peptide (CGRP), substance P (Sub P), and adenosine triphosphate (ATP) that contribute to the inflammatory process in the urinary tract and (2) the functional role of oxidative stress in urinary bladder dysfunction with an antioxidant, Tempol, (1 mM in drinking water) combined with conscious cystometry. In CYP-treated (4 hr or 48 hr; 150 mg/kg, i.p.) rats, ROS/RNS and 3-NT significantly (P ≤ 0.01) increased in urinary bladder. CYP treatment increased ATP, Sub P, and CGRP expression in the urinary bladder and cystometric fluid. In CYP-treated rats, Tempol significantly (P ≤ 0.01) increased bladder capacity and reduced voiding frequency compared to CYP-treated rats without Tempol. Tempol significantly (P ≤ 0.01) reduced ATP expression, 3-NT, and ROS/RNS expression in the urinary tract of CYP-treated rats. These studies demonstrate that reducing oxidative stress in CYP-induced cystitis improves urinary bladder function and reduces markers of oxidative stress and inflammation. PMID:25973443

Neural Mechanisms Underlying Lower Urinary Tract Dysfunction

PubMed Central

Ogawa, Teruyuki; Miyazato, Minoru; Kitta, Takeya; Furuta, Akira; Chancellor, Michael B.; Tyagi, Pradeep

2014-01-01

This article summarizes anatomical, neurophysiological, and pharmacological studies in humans and animals to provide insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract and alterations in these mechanisms in lower urinary tract dysfunction. The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra, and external urethral sphincter. During urine storage, the outlet is closed and the bladder smooth muscle is quiescent. When bladder volume reaches the micturition threshold, activation of a micturition center in the dorsolateral pons (the pontine micturition center) induces a bladder contraction and a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and purinergic) to the bladder and inhibitory input (nitrergic) to the urethra. These peripheral systems are integrated by excitatory and inhibitory regulation at the levels of the spinal cord and the brain. Therefore, injury or diseases of the nervous system, as well as disorders of the peripheral organs, can produce lower urinary tract dysfunction, leading to lower urinary tract symptoms, including both storage and voiding symptoms, and pelvic pain. Neuroplasticity underlying pathological changes in lower urinary tract function is discussed. PMID:24578802

[Develooment of the lower urinary tract and its functional disorders].

PubMed

Peco-Antić, Amira; Miloševski-Lomić, Gordana

2015-01-01

A normal development of lower urinary tract function control evolves from involuntary bladder empting (incontinence) during infancy to daytime urinary continence, and finally a successful day and night continence that is generally achieved by the 5th to 7th year of age.This gradual process primarily depends on the progressive maturation of the neural control of the lower urinary tract, but it is also influenced by behavioral training that evolves through social support. Functional voiding disorders (bladder dysfunction) are common problems during childhood. They are present in 5-15 % of general pediatric population, and in one-fifth of school-age children or in over one-third of patients of the pediatric urologist or nephrologist. More than half of children with bladder dysfunction have vesicoureteral reflux, and more than two-thirds have recurrent urinary tract infections. There is also a frequent association of bladder dysfunction with constipation and encopresis (dysfunctional elimination syndrome). Bladder dysfunction may cause a permanent damage to the upper urinary tract and kidneys. In addition, urinary incontinence, as the most common manifestation of bladder dysfunction can be the cause of major stress in school- age children and have a negative effect on the child's feeling of self-esteem. Thus, a timely detection and treatment of this group of disorders in children is highly significant.

Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer.

PubMed

Shahab, Uzma; Moinuddin; Ahmad, Saheem; Dixit, Kiran; Habib, Safia; Alam, Khursheed; Ali, Asif

2013-01-01

The interaction of environmental chemicals and their metabolites with biological macromolecules can result in cytotoxic and genotoxic effects. 4-Aminobiphenyl (4-ABP) and several other related arylamines have been shown to be causally involved in the induction of human urinary bladder cancers. The genotoxic and the carcinogenic effects of 4-ABP are exhibited only when it is metabolically converted to a reactive electrophile, the aryl nitrenium ions, which subsequently binds to DNA and induce lesions. Although several studies have reported the formation of 4-ABP-DNA adducts, no extensive work has been done to investigate the immunogenicity of 4-ABP-modified DNA and its possible involvement in the generation of antibodies in bladder cancer patients. Human DNA was modified by N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP), a reactive metabolite of 4-ABP. Structural perturbations in the N-OH-AABP modified DNA were assessed by ultraviolet, fluorescence, and circular dichroic spectroscopy as well as by agarose gel electrophoresis. Genotoxicity of N-OH-AABP modified DNA was ascertained by comet assay. High performance liquid chromatography (HPLC) analysis of native and modified DNA samples confirmed the formation of N-(deoxyguanosine-8-yl)-4-aminobiphenyl (dG-C8-4ABP) in the N-OH-AABP damaged DNA. The experimentally induced antibodies against N-OH-AABP-modified DNA exhibited much better recognition of the DNA isolated from bladder cancer patients as compared to the DNA obtained from healthy individuals in competitive binding ELISA. This work shows epitope sharing between the DNA isolated from bladder cancer patients and the N-OH-AABP-modified DNA implicating the role of 4-ABP metabolites in the DNA damage and neo-antigenic epitope generation that could lead to the induction of antibodies in bladder cancer patients.

Arctigenin anti-tumor activity in bladder cancer T24 cell line through induction of cell-cycle arrest and apoptosis.

PubMed

Yang, Shucai; Ma, Jing; Xiao, Jianbing; Lv, Xiaohong; Li, Xinlei; Yang, Huike; Liu, Ying; Feng, Sijia; Zhang, Yafang

2012-08-01

Bladder cancer is the most common neoplasm in the urinary system. This study assesses arctigenin anti-tumor activity in human bladder cancer T24 cells in vitro and the underlying molecular events. The flow cytometry analysis was used to detect cell-cycle distribution and apoptosis. Western blotting was used to detect changes in protein expression. The data showed that arctigenin treatment reduced viability of bladder cancer T24 cells in a dose- and time-dependent manner after treatment with arctigenin (10, 20, 40, 80, and 100 μmol/L) for 24 hr and 48 hr. Arctigenin treatment clearly arrested tumor cells in the G1 phase of the cell cycle. Apoptosis was detected by hoechst stain and flow cytometry after Annexin-V-FITC/PI double staining. Early and late apoptotic cells were accounted for 2.32-7.01% and 3.07-7.35%, respectively. At the molecular level, arctigenin treatment decreased cyclin D1 expression, whereas CDK4 and CDK6 expression levels were unaffected. Moreover, arctigenin selectively altered the phosphorylation of members of the MAPK superfamily, decreasing phosphorylation of ERK1/2 and activated phosphorylation of p38 significantly in a dose-dependent manner. These results suggest that arctigenin may inhibit cell viability and induce apoptosis by direct activation of the mitochondrial pathway, and the mitogen-activated protein kinase pathway may play an important role in the anti-tumor effect of arctigenin. The data from the current study demonstrate the usefulness of arctigenin in bladder cancer T24 cells, which should further be evaluated in vivo before translation into clinical trials for the chemoprevention of bladder cancer. Copyright © 2012 Wiley Periodicals, Inc.

Influence of gross specimen sampling on the incidence of incidental prostatic carcinoma in cystoprostatectomy specimens of patients with bladder carcinoma.

PubMed

Mlakar, J; Volavšek, M

2016-03-01

Reported prostate cancer incidence rates vary greatly among cystoprostatectomy samples. We investigated how the thoroughness of prostate sampling influences prostatic carcinoma incidence in bladder cancer patients. In a retrospective study, 313 cystoprostatectomy cases of urinary bladder carcinoma were analysed for the presence of concurrent prostatic carcinoma. Patients were divided into two groups: patients who had undergone the operation before and after 2007, when a policy of preferably complete prostate sampling in cystoprostatectomy specimens was introduced at our institution. Cases processed after the 2007 recommended sampling changes had a significantly higher rate of incidental prostatic carcinoma and clinically significant prostatic carcinoma than the pre-2007 group (p < 0.0001 and p = 0.003, respectively). Complete prostate processing in cystoprostatectomy specimens results in a higher incidence of incidental prostatic carcinoma than with partial processing. More patients with clinically significant prostate cancer are consequently discovered. In conclusion, we believe that complete prostate sampling should be mandatory.

Diesel exhaust exposure and bladder cancer risk.

PubMed

Iyer, V; Harris, R E; Wynder, E L

1990-03-01

A total of 136 cases of men with urinary bladder cancer and 272 matched hospital controls were examined for potential exposure to diesel exhaust. A lifetime occupational history was obtained for all subjects in the study and assessment of exposure to diesel exhaust was based on the job titles of the subject and self-reported exposure. The risk was assessed by odds ratios, with adjustment for confounding variables, in particular cigarette smoking. There was no evidence of elevated risk in occupations with possible or probable exposure (the ORs adjusted for smoking were 1.1. and 0.9 respectively). Truck driving alone was also not associated with elevated risk (adjusted OR = 0.5). There was a weak positive crude association with any exposure, including self-reports (OR = 1.4); however after adjustment for smoking, the estimate did not retain statistical significance (OR = 1.2, 95% CI = 0.8-2.0). This study provides little to support the hypothesis of an excess of bladder cancer risk from occupational exposure to diesel exhaust.

Tissue engineering of urinary bladder - current state of art and future perspectives.

PubMed

Adamowicz, Jan; Kowalczyk, Tomasz; Drewa, Tomasz

2013-01-01

Tissue engineering and biomaterials science currently offer the technology needed to replace the urinary tract wall. This review addresses current achievements and barriers for the regeneration of the urinary blad- der based on tissue engineering methods. Medline was search for urinary bladder tissue engineering regenerative medicine and stem cells. Numerous studies to develop a substitute for the native urinary bladder wall us- ing the tissue engineering approach are ongoing. Stem cells combined with biomaterials open new treatment methods, including even de novo urinary bladder construction. However, there are still many issues before advances in tissue engineering can be introduced for clinical application. Before tissue engineering techniques could be recognize as effective and safe for patients, more research stud- ies performed on large animal models and with long follow-up are needed to carry on in the future.

Cytological Diagnosis of Small Cell Carcinoma of Urinary Bladder in a Patient with CLL

PubMed Central

Şimşek, Gülçin Güler; Güreşçi, Servet; Oğuz, Ural; Ünsal, Ali

2014-01-01

Small cell carcinoma of the urinary bladder (SCCUB) is an extremely rare bladder malignancy characterized by an aggressive clinical behavior. So, it is important to diagnose this high grade disease by urinary cytology. We report a case of SCCUB in an old man with chronic lymphocytic leukemia (CLL) in remission, while bladder tumor was diagnosed by cytology. With this article, we aimed to review and to update the literature concerning this tumor. PMID:24518979

Development of Urinary Bladder Pre-Neoplasia by Schistosoma haematobium Eggs and Chemical Carcinogen in Mice

PubMed Central

Chala, Bayissa; Choi, Min-Ho; Moon, Kyung Chul; Kim, Hyung Suk; Kwak, Cheol; Hong, Sung-Tae

2017-01-01

Schistosoma haematobium is a biocarcinogen of human urinary bladder (UB). The present study investigated developing UB cancer mouse model by injecting S. haematobium eggs into the bladder wall and introduction of chemical carcinogens. Histopathological findings showed mild hyperplasia to epithelial vacuolar change, and high grade dysplasia. Squamous metaplasia was observed in the S. haematobium eggs+NDMA group at week 12 but not in other groups. Immunohistochemistry revealed significantly high expression of Ki-67 in urothelial epithelial cells of the S. haematobium eggs+BBN group at week 20. The qRT-PCR showed high expression of p53 gene in S. haematobium eggs group at week 4 and S. haematobium eggs+BBN group at week 20. E-cadherin and vimentin showed contrasting expression in S. haematobium eggs+BBN group. Such inverse expression of E-cadherin and vimentin may indicate epithelial mesenchymal transition in the UB tissue. In conclusion, S. haematobium eggs and nitrosamines may transform UB cells into squamous metaplasia and dysplasia in correlation with increased expression of Ki-67. Marked decrease in E-cadherin and increase in p53 and vimentin expressions may support the transformation. The present study introduces a promising modified animal model for UB cancer study using S. haematobium eggs. PMID:28285503

Sensory feedback from the urethra evokes state-dependent lower urinary tract reflexes in rat.

PubMed

Danziger, Zachary C; Grill, Warren M

2017-08-15

The lower urinary tract is regulated by reflexes responsible for maintaining continence and producing efficient voiding. It is unclear how sensory information from the bladder and urethra engages differential, state-dependent reflexes to either maintain continence or promote voiding. Using a new in vivo experimental approach, we quantified how sensory information from the bladder and urethra are integrated to switch reflex responses to urethral sensory feedback from maintaining continence to producing voiding. The results demonstrate how sensory information regulates state-dependent reflexes in the lower urinary tract and contribute to our understanding of the pathophysiology of urinary retention and incontinence where sensory feedback may engage these reflexes inappropriately. Lower urinary tract reflexes are mediated by peripheral afferents from the bladder (primarily in the pelvic nerve) and the urethra (in the pudendal and pelvic nerves) to maintain continence or initiate micturition. If fluid enters the urethra at low bladder volumes, reflexes relax the bladder and evoke external urethral sphincter (EUS) contraction (guarding reflex) to maintain continence. Conversely, urethral flow at high bladder volumes, excites the bladder (micturition reflex) and relaxes the EUS (augmenting reflex). We conducted measurements in a urethane-anaesthetized in vivo rat preparation to characterize systematically the reflexes evoked by fluid flow through the urethra. We used a novel preparation to manipulate sensory feedback from the bladder and urethra independently by controlling bladder volume and urethral flow. We found a distinct bladder volume threshold (74% of bladder capacity) above which flow-evoked bladder contractions were 252% larger and evoked phasic EUS activation 2.6 times as often as responses below threshold, clearly demonstrating a discrete transition between continence (guarding) and micturition (augmenting) reflexes. Below this threshold urethral flow evoked tonic EUS activity, indicative of the guarding reflex, that was proportional to the urethral flow rate. These results demonstrate the complementary roles of sensory feedback from the bladder and urethra in regulating reflexes in the lower urinary tract that depend on the state of the bladder. Understanding the neural control of functional reflexes and how they are mediated by sensory information in the bladder and urethra will open new opportunities, especially in neuromodulation, to treat pathologies of the lower urinary tract. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

An adaptive radiotherapy planning strategy for bladder cancer using deformation vector fields.

PubMed

Vestergaard, Anne; Kallehauge, Jesper Folsted; Petersen, Jørgen Breede Baltzer; Høyer, Morten; Søndergaard, Jimmi; Muren, Ludvig Paul

2014-09-01

Adaptive radiotherapy (ART) has considerable potential in treatment of bladder cancer due to large inter-fractional changes in shape and size of the target. The aim of this study was to compare our clinically applied method for plan library creation that involves manual bladder delineations (Clin-ART) with a method using the deformation vector fields (DVFs) resulting from intensity-based deformable image registrations (DVF-based ART). The study included thirteen patients with urinary bladder cancer who had daily cone beam CTs (CBCTs) acquired for set-up. In both ART strategies investigated, three plan selection volumes were generated using the CBCTs from the first four fractions; in Clin-ART boolean combinations of delineated bladders were used, while the DVF-based strategy applied combinations of the mean and standard deviation of patient-specific DVFs. The volume ratios (VRs) of the course-averaged PTV for the two ART strategies relative the non-adaptive PTV were calculated. Both Clin-ART and DVF-based ART considerably reduced the course-averaged PTV, compared to non-adaptive RT. The VR for DVF-based ART was lower than for Clin-ART (0.65 vs. 0.73; p<0.01). DVF-based ART for bladder irradiation has a considerable normal tissue sparing potential surpassing our already highly conformal clinically applied ART strategy. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The effect of multiple primary rules on cancer incidence rates and trends

PubMed Central

Weir, Hannah K.; Johnson, Christopher J.; Ward, Kevin C.; Coleman, Michel P.

2018-01-01

Purpose An examination of multiple primary cancers can provide insight into the etiologic role of genes, the environment, and prior cancer treatment on a cancer patient’s risk of developing a subsequent cancer. Different rules for registering multiple primary cancers (MP) are used by cancer registries throughout the world making data comparisons difficult. Methods We evaluated the effect of SEER and IARC/IACR rules on cancer incidence rates and trends using data from the SEER Program. We estimated age-standardized incidence rate (ASIR) and trends (1975–2011) for the top 26 cancer categories using joinpoint regression analysis. Results ASIRs were higher using SEER compared to IARC/IACR rules for all cancers combined (3 %) and, in rank order, melanoma (9 %), female breast (7 %), urinary bladder (6 %), colon (4 %), kidney and renal pelvis (4 %), oral cavity and pharynx (3 %), lung and bronchus (2 %), and non-Hodgkin lymphoma (2 %). ASIR differences were largest for patients aged 65+ years. Trends were similar using both MP rules with the exception of cancers of the urinary bladder, and kidney and renal pelvis. Conclusions The choice of multiple primary coding rules effects incidence rates and trends. Compared to SEER MP coding rules, IARC/IACR rules are less complex, have not changed over time, and report fewer multiple primary cancers, particularly cancers that occur in paired organs, at the same anatomic site and with the same or related histologic type. Cancer registries collecting incidence data using SEER rules may want to consider including incidence rates and trends using IARC/IACR rules to facilitate international data comparisons. PMID:26809509

Spatial and temporal profile of cisplatin delivery by ultrasound-assisted intravesical chemotherapy in a bladder cancer model.

PubMed

Sasaki, Noboru; Ishi, Kazuhiro; Kudo, Nobuki; Nakayama, Shouta M M; Nakamura, Kensuke; Morishita, Keitaro; Ohta, Hiroshi; Ishizuka, Mayumi; Takiguchi, Mitsuyoshi

2017-01-01

Non-muscle invasive bladder cancer is one of the most common tumors of the urinary tract. Despite the current multimodal therapy, recurrence and progression of disease have been challenging problems. We hereby introduced a new approach, ultrasound-assisted intravesical chemotherapy, intravesical instillation of chemotherapeutic agents and microbubbles followed by ultrasound exposure. We investigated the feasibility of the treatment for non-muscle invasive bladder cancer. In order to evaluate intracellular delivery and cytotoxic effect as a function to the thickness, we performed all experiments using a bladder cancer mimicking 3D culture model. Ultrasound-triggered microbubble cavitation increased both the intracellular platinum concentration and the cytotoxic effect of cisplatin at the thickness of 70 and 122 μm of the culture model. The duration of enhanced cytotoxic effect of cisplatin by ultrasound-triggered microbubble cavitation was approximately 1 hr. Based on the distance and duration of delivery, we further tested the feasibility of repetition of the treatment. Triple treatment increased the effective distance by 1.6-fold. Our results clearly showed spatial and temporal profile of delivery by ultrasound-triggered microbubble cavitation in a tumor-mimicking structure. Furthermore, we demonstrated that the increase in intracellular concentration results in the enhancement of the cytotoxic effect in a structure with the certain thickness. Repetition of ultrasound exposure would be treatment of choice in future clinical application. Our results suggest ultrasound-triggered microbubble cavitation can be repeatable and is promising for the local control of non-muscle invasive bladder cancer.

Effect of quercetin on tachykinin-induced plasma extravasation in rat urinary bladder.

PubMed

Wille, P R; Ribeiro-do-Valle, R M; Simões, C M; Gabilan, N H; Nicolau, M

2001-08-01

The effect of quercetin on substance P-induced plasma extravasation in rat urinary bladder and its modulation by endogenous peptidases in conscious rats was studied. Plasma protein extravasation (PE) was assayed by measurement of extravasated Evans blue dye (microg/g dry tissue). Intravenous injection of substance P (SP, 10 nmol/kg) significantly increased PE in the urinary bladder. PE evoked by SP was increased significantly by quercetin (20 mg/kg, p.o.) pretreatment in the urinary bladder (73.5 +/- 4.9 to 152.2 +/- 9.9). Pretreatment with captopril, an angiotensin-converting enzyme (ACE) inhibitor (10 nmol/kg, i.v.), or with phosphoramidon, a neutral endopeptidase (NEP) inhibitor (2.5 micromol/kg, i.v.) also potentiated the SP-induced PE in urinary bladder, 286.2 +/- 20.4 and 323.3 +/- 34.0, respectively. Quercetin did not show any effect on neurokinin-A (NKA, 10 nmol/kg, i.v.) -induced plasma extravasation. The present study demonstrates that quercetin potentiates the PE induced by substance P in the urinary bladder. These effects suggest that this flavonoid might cause inhibition of NEP and/or ACE. Copyright 2001 John Wiley & Sons, Ltd.

Proton beam therapy for invasive bladder cancer: A prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hata, Masaharu; Miyanaga, Naoto; Tokuuye, Koichi

Purpose: To present outcomes of bladder-preserving therapy with proton beam irradiation in patients with invasive bladder cancer. Methods and Materials: Twenty-five patients with transitional cell carcinoma of the urinary bladder, cT2-3N0M0, underwent transurethral resection of bladder tumor(s), followed by pelvic X-ray irradiation combined with intra-arterial chemotherapy with methotrexate and cisplatin. Upon completion of these treatments, patients were evaluated by transurethral resection biopsy. Patients with no residual tumor received proton irradiation boost to the primary sites, whereas patients demonstrating residual tumors underwent radical cystectomy. Results: Of 25 patients, 23 (92%) were free of residual tumor at the time of re-evaluation; consequently,more » proton beam therapy was applied. The remaining 2 patients presenting with residual tumors underwent radical cystectomy. Of the 23 patients treated with proton beam therapy, 9 experienced recurrence at the median follow-up time of 4.8 years: local recurrences and distant metastases in 6 and 2 patients, respectively, and both situations in 1. The 5-year overall, disease-free, and cause-specific survival rates were 60%, 50%, and 80%, respectively. The 5-year local control and bladder-preservation rates were 73% and 96%, respectively, in the patients treated with proton beam therapy. Therapy-related toxicities of Grade 3-4 were observed in 9 patients: hematologic toxicities in 6, pulmonary thrombosis in 1, and hemorrhagic cystitis in 2. Conclusions: The present bladder-preserving regimen for invasive bladder cancer was feasible and effective. Proton beam therapy might improve local control and facilitate bladder preservation.« less

Development of a Prosthesis for Urinary Control

NASA Technical Reports Server (NTRS)

Tenney, J. B.; Rabinowitz, R.; Tomkiewicz, Z.; Harrison, H. N.; Rogers, D. W.

1986-01-01

Report describes development and marketing of prosthetic sphincter for urinary control. With prosthetic device, patients void bladder every 3 to 4 hours. Periodic voiding keeps bladder muscles exercised and healthy and avoids bladder infections and kidney damage.

Don’t get caught out! A rare case of a calcified urachal remnant mimicking a bladder calculus

PubMed Central

Rodrigues, Jonathan Carl Luis; Gandhi, Sanjay

2013-01-01

Computer tomography through the kidneys, ureters and bladder (CT KUB) is the mainstay investigation of suspected renal tract calculi. However, several pathologies other than renal tract calculi can cause apparent urinary bladder calcification. We describe the case of a 45 year old man who presented with left sided renal colic. Prone CT KUB performed on admission revealed a calcified urachal remnant mimicking a urinary bladder calculus in the dependent portion of the urinary bladder, confirmed by reviewing the multi-planar reformatted images. This is the first reported case in the literature of this phenomenon. We discuss the importance of using multi-planar reformatted images (MPR) and maximum intensity projection images (MIP), as well as careful review of previous imaging, in making the correct diagnosis. We also discuss the differential diagnoses that should be considered when presented with urinary bladder calcification. PMID:23705044

The use of alteplase for the resolution of an intravesical clot in a neonate receiving extracorporeal membrane oxygenation.

PubMed

Olarte, J L; Glover, M L; Totapally, B R

2001-01-01

We present a case of the use of alteplase for the lysis of a large urinary bladder clot. A neonate presented with respiratory failure, secondary to a left diaphragmatic hernia necessitating the need for extracorporeal membrane oxygenation (ECMO) support. On day 3 of ECMO support, hematuria was noted, and a subsequent urinary bladder ultrasound revealed a significant urinary bladder clot. Alteplase (0.5-1 mg) was instilled into the urinary bladder via a 10 French Foley catheter (Sherwood Medical, St. Louis, MO). The catheter was clamped for 1 hour, followed by irrigation with normal saline. Multiple doses of alteplase were administered, resulting in complete resolution of the bladder clot. No adverse effects were attributed to the use of the intravesical alteplase. Alteplase seems to be safe and effective for the resolution of bladder clots, thereby potentially avoiding more invasive surgical procedures.

Bladder necrosis: 'A man without a bladder'.

PubMed

Bosschieter, Judith; Oudshoorn, Frederik H K; Meuleman, Eric J H; Nieuwenhuijzen, Jakko A

2018-02-17

Since the use of antibiotics, bladder necrosis has become a rare condition. We report a case of bladder necrosis in a 90-year-old man following urinary retention. After insertion of a transurethral catheter (TUC), 2 L of urine was evacuated. In the following days, the TUC became intermittently blocked. Adequate bladder drainage could not be obtained despite intensive rinsing and placement of a suprapubic catheter. On surgical exploration necrosis of almost the entire bladder wall, except for the trigone, was encountered. Surgical debridement of the non-viable bladder wall without opening the abdominal cavity was conducted, and a TUC was placed in the Retzius cavity to ensure evacuation of urine. Since the patient was haemodynamically unstable, construction of a urinary diversion was waived and urinary drainage of the Retzius cavity by the TUC was accepted, resulting in adequate urinary drainage without compromising renal function. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Steroid receptor coactivator-3 regulates glucose metabolism in bladder cancer cells through coactivation of hypoxia inducible factor 1α.

PubMed

Zhao, Wei; Chang, Cunjie; Cui, Yangyan; Zhao, Xiaozhi; Yang, Jun; Shen, Lan; Zhou, Ji; Hou, Zhibo; Zhang, Zhen; Ye, Changxiao; Hasenmayer, Donald; Perkins, Robert; Huang, Xiaojing; Yao, Xin; Yu, Like; Huang, Ruimin; Zhang, Dianzheng; Guo, Hongqian; Yan, Jun

2014-04-18

Cancer cell proliferation is a metabolically demanding process, requiring high glycolysis, which is known as "Warburg effect," to support anabolic growth. Steroid receptor coactivator-3 (SRC-3), a steroid receptor coactivator, is overexpressed and/or amplified in multiple cancer types, including non-steroid targeted cancers, such as urinary bladder cancer (UBC). However, whether SRC-3 regulates the metabolic reprogramming for cancer cell growth is unknown. Here, we reported that overexpression of SRC-3 accelerated UBC cell growth, accompanied by the increased expression of genes involved in glycolysis. Knockdown of SRC-3 reduced the UBC cell glycolytic rate under hypoxia, decreased tumor growth in nude mice, with reduction of proliferating cell nuclear antigen and lactate dehydrogenase expression levels. We further revealed that SRC-3 could interact with hypoxia inducible factor 1α (HIF1α), which is a key transcription factor required for glycolysis, and coactivate its transcriptional activity. SRC-3 was recruited to the promoters of HIF1α-target genes, such as glut1 and pgk1. The positive correlation of expression levels between SRC-3 and Glut1 proteins was demonstrated in human UBC patient samples. Inhibition of glycolysis through targeting HK2 or LDHA decelerated SRC-3 overexpression-induced cell growth. In summary, overexpression of SRC-3 promoted glycolysis in bladder cancer cells through HIF1α to facilitate tumorigenesis, which may be an intriguing drug target for bladder cancer therapy.

Molecular subtype classification of urothelial carcinoma in Lynch syndrome.

PubMed

Therkildsen, Christina; Eriksson, Pontus; Höglund, Mattias; Jönsson, Mats; Sjödahl, Gottfrid; Nilbert, Mef; Liedberg, Fredrik

2018-05-23

Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UCs of the upper urinary tract and the urinary bladder were identified in the Danish hereditary nonpolyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole-genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from patients with Lynch syndrome were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data were analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as urothelial-like tumors with only 20% being genomically unstable, basal/SCC-like, or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger datasets revealed that Lynch syndrome-associated UC shares molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset. © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Thermal dosimetry for bladder hyperthermia treatment. An overview.

PubMed

Schooneveldt, Gerben; Bakker, Akke; Balidemaj, Edmond; Chopra, Rajiv; Crezee, Johannes; Geijsen, Elisabeth D; Hartmann, Josefin; Hulshof, Maarten C C M; Kok, H Petra; Paulides, Margarethus M; Sousa-Escandon, Alejandro; Stauffer, Paul R; Maccarini, Paolo F

2016-06-01

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments.

Vitamin D Induction of the Human Antimicrobial Peptide Cathelicidin in the Urinary Bladder

PubMed Central

Hertting, Olof; Holm, Åsa; Lüthje, Petra; Brauner, Hanna; Dyrdak, Robert; Jonasson, Aino Fianu; Wiklund, Peter; Chromek, Milan; Brauner, Annelie

2010-01-01

The urinary tract is frequently being exposed to potential pathogens and rapid defence mechanisms are therefore needed. Cathelicidin, a human antimicrobial peptide is expressed and secreted by bladder epithelial cells and protects the urinary tract from infection. Here we show that vitamin D can induce cathelicidin in the urinary bladder. We analyzed bladder tissue from postmenopausal women for expression of cathelicidin, before and after a three-month period of supplementation with 25-hydroxyvitamin D3 (25D3). Cell culture experiments were performed to elucidate the mechanisms for cathelicidin induction. We observed that, vitamin D per se did not up-regulate cathelicidin in serum or in bladder tissue of the women in this study. However, when the bladder biopsies were infected with uropathogenic E. coli (UPEC), a significant increase in cathelicidin expression was observed after 25D3 supplementation. This observation was confirmed in human bladder cell lines, even though here, cathelicidin induction occurred irrespectively of infection. Vitamin D treated bladder cells exerted an increased antibacterial effect against UPEC and colocalization to cathelicidin indicated the relevance of this peptide. In the light of the rapidly growing problem of resistance to common urinary tract antibiotics, we suggest that vitamin D may be a potential complement in the prevention of UTI. PMID:21179490

GENE EXPRESSION PROFILING OF RESPONSES TO DIMETHYLARSINIC ACID IN FEMALE F344 RAT UROTHELIUM

EPA Science Inventory

Arsenic is a human carcinogen and epidemiologic evidence implicates it in the development of urinary bladder cancer. Even though several mechanisms have been proposed for arsenic carcinogenicity, the mode of action of inorganic arsenic (iAs) is confounded by the limited availabil...

PLASMID DNA DAMAGE CAUSED BY METHYLATED ARSENICALS, ASCORBIC ACID AND HUMAN LIVER FERRITIN

EPA Science Inventory

Plasmid DNA damage caused by methylated arsenicals, ascorbic acid and human liver ferritin.

Arsenic causes cancer in human skin, urinary bladder, lung, liver and kidney and is a significant world-wide public health problem. Although the metabolism of inorganic arsenic is ...

MEETING AT CAMBRIDGE, MA: GENE EXPRESSION IN NORMAL HUMAN KERATINOCYTES MODULATED BY TRIVALENT ARSENICALS

EPA Science Inventory

Arsenic exposure has been correlated with the development of several human cancers including those found in the skin, lung, liver, kidney and urinary bladder. Humans are generally exposed to inorganic forms of arsenic, which may be inhaled or ingested. Arsenic forms mono- and d...

MEETING AT SAN DIEGO, CA: GENE EXPRESSION IN NORMAL HUMAN KERATINOCYTES MODULATED BY TRIVALENT ARSENICALS

EPA Science Inventory

Arsenic exposure has been correlated with the development of several human cancers including those found in the skin, lung, liver, kidney and urinary bladder. Humans are generally exposed to inorganic forms of arsenic, which may be inhaled or ingested. Arsenic forms mono- and di-...

Functional, histological structure and mastocytes alterations in rat urinary bladders following acute and [corrected] chronic cyclophosphamide treatment.

PubMed

Juszczak, K; Gil, K; Wyczolkowski, M; Thor, P J

2010-08-01

Neurogenic inflammation is linked to urinary bladder overactivity development. Cyclophosphamide (CYP) damages all mucosal defence lines of urinary bladder and induces cystitis with overactivity. The aim of this study was to estimate the effect of CYP on rat urinary bladder function, histological structure and mastocytes numbers following acute and chronic CYP treatment. Fourty two female rats were divided into four groups: I (control), II (acute cystitis), III (chronic cystitis), IV (sham group). Acute and chronic cystitis were induced by CYP in single dose and four doses (1(st), 3(rd), 5(th), 7(th) day), respectively. In group I-III the cystometric evaluation was performed. Sections of the bladder were stained with HE and toluidine blue for the detection of mastocytes. The severity of inflammation was examined according to mucosal abrasion, haemorrhage, leukocyte infiltration and oedema. Acute and chronic CYP treatment caused inflammatory macroscopic and microscopic changes (mucosal abrasion, haemorrhage, oedema) and increased infiltration of inflammatory cells in urinary bladder. Acute treatment induced the infiltration of mastocytes within bladder wall contrary to chronic one decrement. Acute treatment caused more severe mucosal abrasion, whereas chronic one revealed more developed haemorrhage changes. Additionally, cystometric evaluation revealed urinary bladder overactivity development in both types of cystitis. Basal pressure and detrusor overactivity index after acute treatment increased considerably in comparison with the increase obtained after chronic one. Our results proved that acute model of CYP-induced cystitis in rats is more credible for further evaluation of neurogenic inflammation response in pathogenesis of overactive bladder as compared to chronic one.

Differences of response of human bladder cancer cells to photodynamic therapy (PDT) with Hypericum perforantum L extract and Photofrin

NASA Astrophysics Data System (ADS)

Nseyo, Unyime; Kim, Albert; Stavropoulos, Nikos E.; Skalkos, Dimitris; Nseyo, Unwana U.; Chung, Theodore D.

2005-04-01

Refractory carcinoma in situ and resistant multifocal transitional cell carcinoma (TCC) of the human urinary bladder respond modestly to PHOTOFRIN (PII) PDT. Hypericum perforatum L., (St. John"s wort /Epirus" Vasalmo, Greece), a medicinal plant used for many human ailments, is under investigation as a new photosensitizer. We have reported on the antiproliferative activity of the lipophilic extract of the Hypericum perforatum L. (HP) against cultured T-24, and NBT-11 bladder cancer cells. We investigated response of the polar methanolic fraction (PMF) of the HP extract versus PHOTOFRIN in photodynamic therapy (PDT) of human bladder cancer cells, RT-4 and T-24.The PMF was extracted from the dry herb with methanol, followed by liquid extraction with petroleum ether. RT-4/T-24, were plated (105 cells/well) and placed in the incubator (370 C, 5%CO) for 24 hours prior to addition of drugs. PII 2ug/ml, or PMF 60ug /ml was added and incubation continued. After 24 hours, the cells were treated with laser light (630nm) with 0,1,2,4 and 8 Joules. The cells were then washed and reincubated for another 24 hours. After this incubation cell survival was assessed by the MTT assay. PMF-PDT induced percent cell kill of 0%, 0%, 0%, 29% and 75%, in RT-4 cells (primary noninvasive urinary bladder TCC) versus 5%, 9%, 13%, 69% and 86%, in T-24 cells(metastatic TTC) at 0,1,2,4 and 8 Joules respectively. PII-PDT induced cell kill of 0 %, 0% ,0%,0% and 9 %, in RT-4 cells versus 0%,10%,0%,21% and 77%, in T-24 cells at 0,1,2,4 and 8 Joules respectively.RT-24 cells were relatively more resistant than T-24 cells to PMF and PII-PDT. Understanding mechanisms of such differential responses might prove useful

Quality of Life in Non-Muscle-Invasive Bladder Cancer Survivors: A Systematic Review.

PubMed

Jung, Ahrang; Nielsen, Matthew E; Crandell, Jamie L; Palmer, Mary H; Bryant, Ashley Leak; Smith, Sophia K; Mayer, Deborah K

2018-06-01

Non-muscle-invasive bladder cancer (NMIBC) represents approximately 75% of newly diagnosed patients with bladder cancer. Non-muscle-invasive bladder cancer survivors have unique chronic burdens including frequent recurrences, repeated surveillance cystoscopies and treatments, and the highest lifetime medical cost per person among all cancers. The purpose of this study was to summarize studies assessing quality of life (QOL) in NMIBC survivors. The literature from January 2005 to March 2017 found in PubMed, CINAHL, and PsycINFO databases was reviewed systematically. Inclusion criteria were as follows: (1) research about NMIBC survivors, (2) outcomes included QOL, (3) original research article published in peer-reviewed journals, and (4) published in English. A total of 15 studies were included: 14 quantitative studies and 1 mixed-methods study. Non-muscle-invasive bladder cancer survivors had significantly lower QOL compared with the general population, especially in fatigue, physical and role functioning, and mental health. Repeated transurethral resections and intravesical treatments were associated with impaired physical function and mental health. Most NMIBC survivors had concerns of urinary and bowel problems and sexual function. Despite a good prognosis, NMIBC and its treatment have a significant impact on QOL in survivors. The findings showed large burdens in NMIBC survivors and suggest that further research is needed to better understand potential opportunities to improve QOL in this population. Oncology nurses are in the critical position for assessing symptoms and concerns. Oncology nurses should pay special attention to NMIBC survivors who have unique symptoms and burden with the aim of improving survivors' QOL.

Afferent Nerve Regulation of Bladder Function in Health and Disease

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2012-01-01

The afferent innervation of the urinary bladder consists primarily of small myelinated (Aδ) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways, leading to urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain. Neurotrophic factors have been implicated in the pathophysiological mechanisms underlying the sensitization of bladder afferent nerves. Neurotoxins such as capsaicin, resiniferatoxin, and botulinum neurotoxin that target sensory nerves are useful in treating disorders of the lower urinary tract. PMID:19655106

Controversial roles played by toll like receptor 4 in urinary bladder cancer; A systematic review.

PubMed

Afsharimoghaddam, Amin; Soleimani, Mohammad; Lashay, Alireza; Dehghani, Mahdi; Sepehri, Zahra

2016-08-01

Urinary bladder cancer (UBC) is a prevalent human cancer. The main mechanisms which lead to eradication or progression the disease has yet to be clarified. Toll like receptor (TLR) 4 is a membrane receptor which is expressed either on immune cells or tumor cells. This review article was aimed to clear the main mechanisms played by TLR4 and its related intracellular pathways on outcome of UBC. PubMed, Scopus and Google scholar databases have been used for searching related research articles which have evaluated the roles played by TLR4 and its related intracellular pathways on outcome of UBC. Collected information from the related articles revealed that TLR4 either participates in induction of immune responses against UBC or development of the malignancy. There are limited investigations regarding the genetic variations of TLR4 in UBC. According to the results it seems that TLR4/ligands interaction outcome is dependent on several factors including TLR4 ligand doses, interaction of TLR4 with its ligands on immune cells or tumor cells, and other TLRs/ligand interaction simultaneously. Copyright © 2016 Elsevier Inc. All rights reserved.

Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer.

PubMed

Rafnar, Thorunn; Sulem, Patrick; Thorleifsson, Gudmar; Vermeulen, Sita H; Helgason, Hannes; Saemundsdottir, Jona; Gudjonsson, Sigurjon A; Sigurdsson, Asgeir; Stacey, Simon N; Gudmundsson, Julius; Johannsdottir, Hrefna; Alexiusdottir, Kristin; Petursdottir, Vigdis; Nikulasson, Sigfus; Geirsson, Gudmundur; Jonsson, Thorvaldur; Aben, Katja K H; Grotenhuis, Anne J; Verhaegh, Gerald W; Dudek, Aleksandra M; Witjes, J Alfred; van der Heijden, Antoine G; Vrieling, Alina; Galesloot, Tessel E; De Juan, Ana; Panadero, Angeles; Rivera, Fernando; Hurst, Carolyn; Bishop, D Timothy; Sak, Sei C; Choudhury, Ananya; Teo, Mark T W; Arici, Cecilia; Carta, Angela; Toninelli, Elena; de Verdier, Petra; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; van der Keur, Kirstin A; Lurkin, Irene; Goossens, Mieke; Kellen, Eliane; Guarrera, Simonetta; Russo, Alessia; Critelli, Rossana; Sacerdote, Carlotta; Vineis, Paolo; Krucker, Clémentine; Zeegers, Maurice P; Gerullis, Holger; Ovsiannikov, Daniel; Volkert, Frank; Hengstler, Jan G; Selinski, Silvia; Magnusson, Olafur T; Masson, Gisli; Kong, Augustine; Gudbjartsson, Daniel; Lindblom, Annika; Zwarthoff, Ellen; Porru, Stefano; Golka, Klaus; Buntinx, Frank; Matullo, Giuseppe; Kumar, Rajiv; Mayordomo, José I; Steineck, D Gunnar; Kiltie, Anne E; Jonsson, Eirikur; Radvanyi, François; Knowles, Margaret A; Thorsteinsdottir, Unnur; Kiemeney, Lambertus A; Stefansson, Kari

2014-10-15

Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC cases and 10 456 controls. We tested a dataset containing 34.2 million variants, generated by imputation based on whole-genome sequencing of 2230 Icelanders. Several correlated variants at 20p12, represented by rs62185668, show genome-wide significant association with UBC after combining discovery and replication results (OR = 1.19, P = 1.5 × 10(-11) for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately 300 kb upstream from the JAG1 gene, an important component of the Notch signaling pathways that may be oncogenic or tumor suppressive in several forms of cancer. Our results add to the growing number of UBC risk variants discovered through GWAS. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Accelerated Radiotherapy, Carbogen, and Nicotinamide (ARCON) in the Treatment of Advanced Bladder Cancer: Mature Results of a Phase II Nonrandomized Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoskin, Peter; Marie Curie Research Wing, Mount Vernon Hospital, Northwood, Middx; Rojas, Ana Ph.D.

2009-04-01

Purpose: We previously showed that accelerated radiotherapy combined with carbogen and nicotinamide (ARCON) was an effective approach to use in the radical treatment of patients with advanced bladder carcinoma. Interim analysis from this Phase II study showed that it achieved a high level of locoregional control and overall survival (OS) and an acceptable level of adverse events. Methods and Materials: From 1994 to 2000, a total of 105 consecutive patients with high-grade superficial or muscle-invasive bladder carcinoma were given accelerated radiotherapy (50-55 Gy in 4 weeks) with carbogen alone or ARCON. End points of the study were OS, disease-specific, andmore » local regional relapse-free survival, and for late adverse events, urinary (altered urination frequency, incontinence, hematuria, and urgency) and bowel dysfunction (stool frequency and blood loss). Results: At 5 and 10 years, local regional relapse-free survival rates were 44% after ARCON excluding the effect of salvage treatment and 62% after ARCON including the effect of salvage treatment (p = 0.04). Five- and 10-year rates were 35% and 27% for OS and 47% and 46% for disease-specific survival. The highest actuarial rate for Grade 3 or worse late urinary or bowel dysfunction was observed for altered urinary frequency (44% of patients had urinary events every 1 hour or less) and stool frequency of four or more events (26% at 5 years). Conclusions: Historic comparisons with other studies indicate no evidence of an increase in severe or worse adverse events and good permanent control of bladder disease after ARCON radiotherapy.« less

Portable bladder ultrasound: an evidence-based analysis.

PubMed

2006-01-01

The aim of this review was to assess the clinical utility of portable bladder ultrasound. TARGET POPULATION AND CONDITION Data from the National Population Health Survey indicate prevalence rates of urinary incontinence are 2.5% in women and 1.4 % in men in the general population. Prevalence of urinary incontinence is higher in women than men and prevalence increases with age. Identified risk factors for urinary incontinence include female gender, increasing age, urinary tract infections (UTI), poor mobility, dementia, smoking, obesity, consuming alcohol and caffeine beverages, physical activity, pregnancy, childbirth, forceps and vacuum-assisted births, episiotomy, abdominal resection for colorectal cancer, and hormone replacement therapy. For the purposes of this review, incontinence populations will be stratified into the following; the elderly, urology patients, postoperative patients, rehabilitation settings, and neurogenic bladder populations. Urinary incontinence is defined as any involuntary leakage of urine. Incontinence can be classified into diagnostic clinical types that are useful in planning evaluation and treatment. The major types of incontinence are stress (physical exertion), urge (overactive bladder), mixed (combined urge and stress urinary incontinence), reflex (neurological impairment of the central nervous system), overflow (leakage due to full bladder), continuous (urinary tract abnormalities), congenital incontinence, and transient incontinence (temporary incontinence). Postvoid residual (PVR) urine volume, which is the amount of urine in the bladder immediately after urination, represents an important component in continence assessment and bladder management to provide quantitative feedback to the patient and continence care team regarding the effectiveness of the voiding technique. Although there is no standardized definition of normal PVR urine volume, measurements greater than 100 mL to 150 mL are considered an indication for urinary retention, requiring intermittent catheterization, whereas a PVR urine volume of 100 mL to 150 mL or less is generally considered an acceptable result of bladder training. Urinary retention has been associated with poor outcomes including UTI, bladder overdistension, and higher hospital mortality rates. The standard method of determining PVR urine volumes is intermittent catheterization, which is associated with increased risk of UTI, urethral trauma and discomfort. Portable bladder ultrasound products are transportable ultrasound devices that use automated technology to register bladder volume digitally, including PVR volume, and provide three-dimensional images of the bladder. The main clinical use of portable bladder ultrasound is as a diagnostic aid. Health care professionals (primarily nurses) administer the device to measure PVR volume and prevent unnecessary catheterization. An adjunctive use of the bladder ultrasound device is to visualize the placement and removal of catheters. Also, portable bladder ultrasound products may improve the diagnosis and differentiation of urological problems and their management and treatment, including the establishment of voiding schedules, study of bladder biofeedback, fewer UTIs, and monitoring of potential urinary incontinence after surgery or trauma. To determine the effectiveness and clinical utility of portable bladder ultrasound as reported in the published literature, the Medical Advisory Secretariat used its standard search strategy to retrieve international health technology assessments and English-language journal articles from selected databases. Nonsystematic reviews, nonhuman studies, case reports, letters, editorials, and comments were excluded. Of the 4 included studies that examined the clinical utility of portable bladder ultrasound in the elderly population, all found the device to be acceptable. One study reported that the device underestimated catheterized bladder volume In patients with urology problems, 2 of the 3 studies concerning portable bladder ultrasound found the device acceptable to use. However, one study did not find the device as accurate for small PVR volume as for catheterization and another found that the device overestimated catheterized bladder volume. In the remaining study, the authors reported that when the device's hand-held ultrasound transducers (scanheads) were aimed improperly, bladders were missed, or lateral borders of bladders were missed resulting in partial bladder volume measurements and underestimation of PVR measurements. They concluded that caution should be used in interpreting PVR volume measured by portable bladder ultrasound machines and that catheterization may be the preferred assessment modality if an accurate PVR measurement is necessary. All 3 studies with post-operative populations found portable bladder ultrasound use to be reasonably acceptable. Two studies reported that the device overestimated catheter-derived bladder volumes, one by 7% and the other by 21 mL. The third study reported the opposite, that the device underestimated catheter bladder volume by 39 mL but that the results remained acceptable In rehabilitation settings, 2 studies found portable bladder ultrasound to underestimate catheter-derived bladder volumes; yet, both authors concluded that the mean errors were within acceptable limits. In patients with neurogenic bladder problems, 2 studies found portable bladder ultrasound to be an acceptable alternative to catheterization despite the fact that it was not as accurate as catheterization for obtaining bladder volumes. Lastly, examinations concerning avoidance of negative health outcomes showed that, after use of the portable bladder ultrasound, unnecessary catheterizations and UTIs were decreased. Unnecessary catheterizations avoided ranged from 16% to 47% in the selected articles. Reductions in UTI ranged from 38% to 72%. In sum, all but one study advocated the use of portable bladder ultrasound as an alternative to catheterization. An economic analysis estimating the budget-impact of BladderScan in complex continuing care facilities was completed. The analysis results indicated a $192,499 (Cdn) cost-savings per year per facility and a cost-savings of $2,887,485 (Cdn) for all 15 CCC facilities. No economic analysis was completed for long-term care and acute care facilities due to lack of data. Rapid diffusion of portable bladder ultrasound technology is expected. Recently, the IC5 project on improving continence care in Ontario's complex continuing care centres piloted portable bladder ultrasound at 12 sites. Preliminary results were promising. Many physicians and health care facilities already have portable bladder ultrasound devices. However, portable bladder ultrasound devices for PVR measurement are not in use at most health care facilities in Ontario and Canada. The Verathon Corporation (Bothell, Wisconsin, United States), which patents BladderScan, is the sole licensed manufacturer of the portable bladder ultrasound in Canada. Field monopoly may influence the rising costs of portable bladder ultrasound, particularly when faced with rapid expansion of the technology. Several thousand residents of Ontario would benefit from portable bladder ultrasound. The number of residents of Ontario that would benefit from the technology is difficult to quantify, because the incidence and prevalence of incontinence are grossly under-reported. However, long-term care and complex continuing care institutions would benefit greatly from portable bladder ultrasound, as would numerous rehabilitation units, postsurgical care units, and urology clinics. The cost of the portable bladder ultrasound devices ranges from $17,698.90 to $19,565.95 (Cdn) (total purchase price per unit as quoted by the manufacturer). Additional training packages, batteries and battery chargers, software, gel pads, and yearly warranties are additional costs. Studies indicate that portable bladder ultrasound is a cost-effective technology, because it avoids costs associated with catheterization equipment, saves nursing time, and reduces catheter-related complications and UTIs. The use of portable bladder ultrasound device will affect the patient directly in terms of health outcomes. Its use avoids the trauma related to the urinary tract that catheterization inflicts, and does not result in UTIs. In addition, patients prefer it, because it preserves dignity and reduces discomfort.

Portable Bladder Ultrasound

PubMed Central

2006-01-01

Executive Summary Objective The aim of this review was to assess the clinical utility of portable bladder ultrasound. Clinical Need: Target Population and Condition Data from the National Population Health Survey indicate prevalence rates of urinary incontinence are 2.5% in women and 1.4 % in men in the general population. Prevalence of urinary incontinence is higher in women than men and prevalence increases with age. Identified risk factors for urinary incontinence include female gender, increasing age, urinary tract infections (UTI), poor mobility, dementia, smoking, obesity, consuming alcohol and caffeine beverages, physical activity, pregnancy, childbirth, forceps and vacuum-assisted births, episiotomy, abdominal resection for colorectal cancer, and hormone replacement therapy. For the purposes of this review, incontinence populations will be stratified into the following; the elderly, urology patients, postoperative patients, rehabilitation settings, and neurogenic bladder populations. Urinary incontinence is defined as any involuntary leakage of urine. Incontinence can be classified into diagnostic clinical types that are useful in planning evaluation and treatment. The major types of incontinence are stress (physical exertion), urge (overactive bladder), mixed (combined urge and stress urinary incontinence), reflex (neurological impairment of the central nervous system), overflow (leakage due to full bladder), continuous (urinary tract abnormalities), congenital incontinence, and transient incontinence (temporary incontinence). Postvoid residual (PVR) urine volume, which is the amount of urine in the bladder immediately after urination, represents an important component in continence assessment and bladder management to provide quantitative feedback to the patient and continence care team regarding the effectiveness of the voiding technique. Although there is no standardized definition of normal PVR urine volume, measurements greater than 100 mL to 150 mL are considered an indication for urinary retention, requiring intermittent catheterization, whereas a PVR urine volume of 100 mL to 150 mL or less is generally considered an acceptable result of bladder training. Urinary retention has been associated with poor outcomes including UTI, bladder overdistension, and higher hospital mortality rates. The standard method of determining PVR urine volumes is intermittent catheterization, which is associated with increased risk of UTI, urethral trauma and discomfort. The Technology Being Reviewed Portable bladder ultrasound products are transportable ultrasound devices that use automated technology to register bladder volume digitally, including PVR volume, and provide three-dimensional images of the bladder. The main clinical use of portable bladder ultrasound is as a diagnostic aid. Health care professionals (primarily nurses) administer the device to measure PVR volume and prevent unnecessary catheterization. An adjunctive use of the bladder ultrasound device is to visualize the placement and removal of catheters. Also, portable bladder ultrasound products may improve the diagnosis and differentiation of urological problems and their management and treatment, including the establishment of voiding schedules, study of bladder biofeedback, fewer UTIs, and monitoring of potential urinary incontinence after surgery or trauma. Review Strategy To determine the effectiveness and clinical utility of portable bladder ultrasound as reported in the published literature, the Medical Advisory Secretariat used its standard search strategy to retrieve international health technology assessments and English-language journal articles from selected databases. Nonsystematic reviews, nonhuman studies, case reports, letters, editorials, and comments were excluded. Summary of Findings Of the 4 included studies that examined the clinical utility of portable bladder ultrasound in the elderly population, all found the device to be acceptable. One study reported that the device underestimated catheterized bladder volume In patients with urology problems, 2 of the 3 studies concerning portable bladder ultrasound found the device acceptable to use. However, one study did not find the device as accurate for small PVR volume as for catheterization and another found that the device overestimated catheterized bladder volume. In the remaining study, the authors reported that when the device’s hand-held ultrasound transducers (scanheads) were aimed improperly, bladders were missed, or lateral borders of bladders were missed resulting in partial bladder volume measurements and underestimation of PVR measurements. They concluded that caution should be used in interpreting PVR volume measured by portable bladder ultrasound machines and that catheterization may be the preferred assessment modality if an accurate PVR measurement is necessary. All 3 studies with post-operative populations found portable bladder ultrasound use to be reasonably acceptable. Two studies reported that the device overestimated catheter-derived bladder volumes, one by 7% and the other by 21 mL. The third study reported the opposite, that the device underestimated catheter bladder volume by 39 mL but that the results remained acceptable In rehabilitation settings, 2 studies found portable bladder ultrasound to underestimate catheter-derived bladder volumes; yet, both authors concluded that the mean errors were within acceptable limits. In patients with neurogenic bladder problems, 2 studies found portable bladder ultrasound to be an acceptable alternative to catheterization despite the fact that it was not as accurate as catheterization for obtaining bladder volumes. Lastly, examinations concerning avoidance of negative health outcomes showed that, after use of the portable bladder ultrasound, unnecessary catheterizations and UTIs were decreased. Unnecessary catheterizations avoided ranged from 16% to 47% in the selected articles. Reductions in UTI ranged from 38% to 72%. In sum, all but one study advocated the use of portable bladder ultrasound as an alternative to catheterization. Economic Analysis An economic analysis estimating the budget-impact of BladderScan in complex continuing care facilities was completed. The analysis results indicated a $192,499 (Cdn) cost-savings per year per facility and a cost-savings of $2,887,485 (Cdn) for all 15 CCC facilities. No economic analysis was completed for long-term care and acute care facilities due to lack of data. Considerations for Policy Development Rapid diffusion of portable bladder ultrasound technology is expected. Recently, the IC5 project on improving continence care in Ontario’s complex continuing care centres piloted portable bladder ultrasound at 12 sites. Preliminary results were promising. Many physicians and health care facilities already have portable bladder ultrasound devices. However, portable bladder ultrasound devices for PVR measurement are not in use at most health care facilities in Ontario and Canada. The Verathon Corporation (Bothell, Wisconsin, United States), which patents BladderScan, is the sole licensed manufacturer of the portable bladder ultrasound in Canada. Field monopoly may influence the rising costs of portable bladder ultrasound, particularly when faced with rapid expansion of the technology. Several thousand residents of Ontario would benefit from portable bladder ultrasound. The number of residents of Ontario that would benefit from the technology is difficult to quantify, because the incidence and prevalence of incontinence are grossly under-reported. However, long-term care and complex continuing care institutions would benefit greatly from portable bladder ultrasound, as would numerous rehabilitation units, postsurgical care units, and urology clinics. The cost of the portable bladder ultrasound devices ranges from $17,698.90 to $19,565.95 (Cdn) (total purchase price per unit as quoted by the manufacturer). Additional training packages, batteries and battery chargers, software, gel pads, and yearly warranties are additional costs. Studies indicate that portable bladder ultrasound is a cost-effective technology, because it avoids costs associated with catheterization equipment, saves nursing time, and reduces catheter-related complications and UTIs. The use of portable bladder ultrasound device will affect the patient directly in terms of health outcomes. Its use avoids the trauma related to the urinary tract that catheterization inflicts, and does not result in UTIs. In addition, patients prefer it, because it preserves dignity and reduces discomfort. PMID:23074481

Combined uterine and urinary bladder rupture: an unusual complication of obstructed labor in a primigravida

PubMed Central

Takai, Idris Usman; Abubakar, Abdulkadir

2016-01-01

Background Combined uterine and urinary bladder rupture following prolonged obstructed labor is indeed a momentous uro-obstetric emergency. The urinary bladder involvement is distinctly rare in the absence of factors that predispose the bladder to be adherent to the lower uterine segment and is quite unusual in a primigravida. Objective To report a rare case of uterine rupture involving urinary bladder secondary to a prolonged obstructed labor in a primigravida from a low resource setting. Case A 17-year-old married unbooked primigravida who presented with a 3-day history of spontaneous onset of labor at term that was initially managed at home and later in a primary health care center where she had fundal pressure and oxytocin augmentation, respectively. The labor was complicated by combined uterine and urinary bladder rupture with sepsis. She was resuscitated and had exploratory laparotomy with uterine and urinary bladder repair. The postoperative period was uneventful and she was followed-up at the gynecology and family planning clinics. Conclusion There is a need for community reawakening on the inherent risks of teenage pregnancy, bad obstetric practices, and unsupervised pregnancy, labor, and delivery, particularly in the rural settings as in the index patient. A high index of suspicion and prompt appropriate intervention will reduce the sequel of morbidity and occasional mortality from this predicament. PMID:27499647

Prognostic significance of epidermal growth factor receptor (EGFR) over expression in urothelial carcinoma of urinary bladder.

PubMed

Hashmi, Atif Ali; Hussain, Zubaida Fida; Irfan, Muhammad; Khan, Erum Yousuf; Faridi, Naveen; Naqvi, Hanna; Khan, Amir; Edhi, Muhammad Muzzammil

2018-06-07

Epidermal growth factor receptor (EGFR) has been shown to have abnormal expression in many human cancers and is considered as a marker of poor prognosis. Frequency of over expression in bladder cancer has not been studied in our population; therefore we aimed to evaluate the frequency and prognostic significance of EGFR immunohistochemical expression in locoregional population. We performed EGFR immunohistochemistry on 126 cases of bladder cancer and association of EGFR expression with tumor grade, lamina propria invasion, deep muscle invasion and recurrence of disease was evaluated. High EGFR expression was noted in 26.2% (33 cases), 15.1% (19 cases) and 58.7% (74 cases) revealed low and no EGFR expression respectively. Significant association of EGFR expression was noted with tumor grade, lamina propria invasion, deep muscle invasion and recurrence status while no significant association was seen with age, gender and overall survival. Kaplan- Meier curves revealed significant association of EGFR expression with recurrence while no significant association was seen with overall survival. Significant association of EGFR overexpression with tumor grade, muscularis propria invasion and recurrence signifies its prognostic value; therefore EGFR can be used as a prognostic biomarker in Urothelial bladder carcinoma.

Stem Cell Therapy in Bladder Dysfunction: Where Are We? And Where Do We Have to Go?

PubMed Central

Lee, Sang-Rae; Song, Yun Seob; Lee, Hong Jun

2013-01-01

To date, stem cell therapy for the bladder has been conducted mainly on an experimental basis in the areas of bladder dysfunction. The therapeutic efficacy of stem cells was originally thought to be derived from their ability to differentiate into various cell types. Studies about stem cell therapy for bladder dysfunction have been limited to an experimental basis and have been less focused than bladder regeneration. Bladder dysfunction was listed in MESH as “urinary bladder neck obstruction”, “urinary bladder, overactive”, and “urinary bladder, neurogenic”. Using those keywords, several articles were searched and studied. The bladder dysfunction model includes bladder outlet obstruction, cryoinjured, diabetes, ischemia, and spinal cord injury. Adipose derived stem cells (ADSCs), bone marrow stem cells (BMSCs), and skeletal muscle derived stem cells (SkMSCs) are used for transplantation to treat bladder dysfunction. The main mechanisms of stem cells to reconstitute or restore bladder dysfunction are migration, differentiation, and paracrine effects. The aim of this study is to review the stem cell therapy for bladder dysfunction and to provide the status of stem cell therapy for bladder dysfunction. PMID:24151627

Non-contrast magnetic resonance imaging for bladder cancer: fused high b value diffusion-weighted imaging and T2-weighted imaging helps evaluate depth of invasion.

PubMed

Lee, Minsu; Shin, Su-Jin; Oh, Young Taik; Jung, Dae Chul; Cho, Nam Hoon; Choi, Young Deuk; Park, Sung Yoon

2017-09-01

To investigate the utility of fused high b value diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) for evaluating depth of invasion in bladder cancer. We included 62 patients with magnetic resonance imaging (MRI) and surgically confirmed urothelial carcinoma in the urinary bladder. An experienced genitourinary radiologist analysed the depth of invasion (T stage <2 or ≥2) using T2WI, DWI, T2WI plus DWI, and fused DWI and T2WI (fusion MRI). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were investigated. Area under the curve (AUC) was analysed to identify T stage ≥2. The rate of patients with surgically confirmed T stage ≥2 was 41.9% (26/62). Sensitivity, specificity, PPV, NPV and accuracy were 50.0%, 55.6%, 44.8%, 60.6% and 53.2%, respectively, with T2WI; 57.7%, 77.8%, 65.2%, 71.8% and 69.4%, respectively, with DWI; 65.4%, 80.6%, 70.8%, 76.3% and 74.2%, respectively, with T2WI plus DWI and 80.8%, 77.8%, 72.4%, 84.9% and 79.0%, respectively, with fusion MRI. AUC was 0.528 with T2WI, 0.677 with DWI, 0.730 with T2WI plus DWI and 0.793 with fusion MRI for T stage ≥2. Fused high b value DWI and T2WI may be a promising non-contrast MRI technique for assessing depth of invasion in bladder cancer. • Accuracy of fusion MRI was 79.0% for T stage ≥2 in bladder cancer. • AUC of fusion MRI was 0.793 for T stage ≥2 in bladder cancer. • Diagnostic performance of fusion MRI was comparable with T2WI plus DWI. • As a non-contrast MRI technique, fusion MRI is useful for bladder cancer.

Effect of Dietary Treatment with Dimethylarsinous Acid (DMAIII) on the Urinary Bladder Epithelium of Arsenic (+3 Oxidation State) Methyltransferase (As3mt) Knockout and C57BL/6 Wild Type Female Mice

EPA Science Inventory

Abstract Chronic exposure to inorganic arsenic (iAs) is carcinogenic to the human urinary bladder. It produces urothelial cytotoxicity and proliferation in rats and mice. DMAv, a major methylated urinary metabolite of iAs, is a rat bladder carcinogen, but without effects on the...

Relevance of prostate cancer in patients with synchronous invasive bladder urothelial carcinoma: a monocentric retrospective analysis.

PubMed

Dell'Atti, Lucio

2015-03-31

We retrospectively reviewed data of patients with incidental prostate cancer (PCa) who underwent radical cystoprostatectomy (RCP) for invasive bladder cancer and we analyzed their features with regard to incidence, pathologic characteristics, clinical significance, and implications for management. Clinical data and pathological features of 64 patients who underwent standard RCP for bladder cancer were included in this study. Besides the urothelial carcinoma of the urinary bladder, the location and tumor volume of the PCa, prostate apex involvement, Gleason score, pathological staging and surgical margins were evaluated. Clinically significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, stage ≥ pT3, lymph node involvement, positive surgical margin or multifocality of three or more lesions. Postoperative follow-up was scheduled every 3 months in the first year, every 6 months in the second and third year, annually thereafter. 11 out of 64 patients (17.2%) who underwent RCP had incidentally diagnosed PCa. 3 cases (27.3%) were diagnosed as significant PCa, while 8 cases (72.7%) were clinically insignificant. The positive surgical margin of PCa was detected in 1 patient with significant disease. The prostate apex involvement was present in 1 patient of the significant PCa group. Median follow-up period was 47.8 ± 29.2 (range 4-79). During the follow-up, biochemical recurrence occurred in 1 patient (9%). Concerning the cancer specific survival there was no statistical significance (P = 0.326) between the clinically significant and clinical insignificant cancer group. In line with published studies, incidental PCa does not impact on the prognosis of bladder cancer of patients undergoing RCP.

Expression and function of CCL2/CCR2 in rat micturition reflexes and somatic sensitivity with urinary bladder inflammation

PubMed Central

Arms, Lauren; Girard, Beatrice M.; Malley, Susan E.

2013-01-01

Chemokines are proinflammatory mediators of the immune response, and there is growing evidence for chemokine/receptor signaling involvement in pronociception. Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic pain syndrome characterized by pain, pressure, or discomfort perceived to be bladder-related with at least one urinary symptom. We have explored the expression and functional roles of CCL2 (monocyte chemoattractant protein-1) and its high-affinity receptor, CCR2, in micturition reflex function and somatic sensitivity in rats with urinary bladder inflammation induced by cyclophosphamide (CYP) treatment of varying duration (4 h, 48 h, chronic). Real-time quantitative RT-PCR, ELISAs, and immunohistochemistry demonstrated significant (P ≤ 0.01) increases in CCL2 and CCR2 expression in the urothelium and in Fast Blue-labeled bladder afferent neurons in lumbosacral dorsal root ganglia with CYP-induced cystitis. Intravesical infusion of RS504393 (5 μM), a specific CCR2 antagonist, reduced voiding frequency and increased bladder capacity and void volume in rats with CYP-induced cystitis (4 h), as determined with open outlet, conscious cystometry. In addition, CCR2 blockade, at the level of the urinary bladder, reduced referred somatic sensitivity of the hindpaw and pelvic region in rats with CYP treatment, as determined with von Frey filament testing. We provide evidence of functional roles for CCL2/CCR2 signaling at the level of the urinary bladder in reducing voiding frequency and somatic sensitivity following CYP-induced cystitis (4 h). These studies suggest that chemokines/receptors may be novel targets with therapeutic potential in the context of urinary bladder inflammation. PMID:23594826

Bladder sensory physiology: neuroactive compounds and receptors, sensory transducers, and target-derived growth factors as targets to improve function

PubMed Central

Gonzalez, Eric J.; Merrill, Liana

2014-01-01

Urinary bladder dysfunction presents a major problem in the clinical management of patients suffering from pathological conditions and neurological injuries or disorders. Currently, the etiology underlying altered visceral sensations from the urinary bladder that accompany the chronic pain syndrome, bladder pain syndrome (BPS)/interstitial cystitis (IC), is not known. Bladder irritation and inflammation are histopathological features that may underlie BPS/IC that can change the properties of lower urinary tract sensory pathways (e.g., peripheral and central sensitization, neurochemical plasticity) and contribute to exaggerated responses of peripheral bladder sensory pathways. Among the potential mediators of peripheral nociceptor sensitization and urinary bladder dysfunction are neuroactive compounds (e.g., purinergic and neuropeptide and receptor pathways), sensory transducers (e.g., transient receptor potential channels) and target-derived growth factors (e.g., nerve growth factor). We review studies related to the organization of the afferent limb of the micturition reflex and discuss neuroplasticity in an animal model of urinary bladder inflammation to increase the understanding of functional bladder disorders and to identify potential novel targets for development of therapeutic interventions. Given the heterogeneity of BPS/IC and the lack of consistent treatment benefits, it is unlikely that a single treatment directed at a single target in micturition reflex pathways will have a mass benefit. Thus, the identification of multiple targets is a prudent approach, and use of cocktail treatments directed at multiple targets should be considered. PMID:24760999

No Promoting Effect of Ethyl Tertiary-butyl Ether (ETBE) on Rat Urinary Bladder Carcinogenesis Initiated with N-Butyl-N-(4-hydroxybutyl)nitrosamine

PubMed Central

Hagiwara, Akihiro; Imai, Norio; Doi, Yuko; Suguro, Mayuko; Kawabe, Mayumi; Furukawa, Fumio; Nagano, Kasuke; Fukushima, Shoji

2013-01-01

The effects of ethyl tertiary-butyl ether (ETBE) on two-stage urinary bladder carcinogenesis in male F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were investigated at various dose levels with regard to possible promoting activity. Groups of 30 rats were given drinking water containing 500 ppm BBN, as an initiator, for 4 weeks and starting one week thereafter received ETBE by gavage (daily, 7 days/week) at dose levels of 0 (control), 100, 300, 500 or 1000 mg/kg/day until experimental week 36. No statistically significant differences in incidences of preneoplastic lesions, papillomas, and carcinomas of the urinary bladder were evident in rats treated with 100–1000 mg/kg/day ETBE as compared with control values. Furthermore, the average numbers of preneoplastic or neoplastic lesions per unit length of basement membrane in rats given 100–1000 mg/kg/day ETBE were also comparable to control values. However, papillomatosis of the urinary bladder was found in 4 out of 30 rats (13%) in the group given 1000 mg/kg/day ETBE, and soft stones in the urinary bladder were found in 3 out of these 4 rats. The results thus demonstrated that ETBE did not exert promotional activity on urinary bladder carcinogenesis. However, papillomatosis of the urinary bladder developed in small numbers of the rats given ETBE at 1000 mg/kg/day but not in rats given 500 mg/kg/day or lower doses. PMID:24526807

Laboratory practical to study the differential innervation pathways of urinary tract smooth muscle.

PubMed

Rembetski, Benjamin E; Cobine, Caroline A; Drumm, Bernard T

2018-06-01

In the mammalian lower urinary tract, there is a reciprocal relationship between the contractile state of the bladder and urethra. As the bladder fills with urine, it remains relaxed to accommodate increases in volume, while the urethra remains contracted to prevent leakage of urine from the bladder to the exterior. Disruptions to the normal contractile state of the bladder and urethra can lead to abnormal micturition patterns and urinary incontinence. While both the bladder and urethra are smooth-muscle organs, they are differentially contracted by input from cholinergic and sympathetic nerves, respectively. The laboratory practical described here provides an experiential approach to understanding the anatomy of the lower urinary tract. Several key factors in urinary tract physiology are outlined, e.g., the bladder is contracted by activation of the parasympathetic pathway via cholinergic stimulation on muscarinic receptors, whereas the urethra is contracted by activation of the sympathetic pathway via adrenergic stimulation on α 1 -adrenoceptors. This is achieved by measuring the force generated by bladder and urethra smooth muscle to demonstrate that acetylcholine contracts the smooth muscle of the bladder, whereas adrenergic agonists contract the urethral smooth muscle. An inhibition of these effects is also demonstrated by application of the muscarinic receptor antagonist atropine and the α 1 -adrenergic receptor blocker phentolamine. A list of suggested techniques and exam questions to evaluate student understanding on this topic is also provided.

Intramembraneous Particle Cluster and Cytoplasmic Vesicles in Mice with Nephrogenic Defects of Urinary Concentration.

DTIC Science & Technology

1987-01-01

DiBona , D.R., M.M. Civan, and A. Leaf. The cellular specificity of the effect of vasopressin on toad urinary bladder. J. Membr. Biol. 1:79-91, 1969. 30...Chem. 240:4524-4526, 1965. 62. Hardy, M.A., and D.R. DiBona . Microfilaments and the hydrosmotic action of vasopressin in toad urinary bladder. Am. J... DiBona , D.R., M.M. Civan, and A. Leaf. The cellular specificity of the effect of vasopressin on toad urinary bladder. J. Membr. Biol. 1:79-91, 1969. 30

Comparison of essential and toxic elements in esophagus, lung, mouth and urinary bladder male cancer patients with related to controls.

PubMed

Kazi, Tasneem Gul; Wadhwa, Sham Kumar; Afridi, Hassan Imran; Talpur, Farah Naz; Tuzen, Mustafa; Baig, Jameel Ahmed

2015-05-01

There is a compelling evidence in support of negative associations between essential trace and toxic elements in different types of cancer. The aim of the present study was to investigate the relationship between carcinogenic (As, Cd, Ni) and anti-carcinogenic (Se, Zn) trace elements in scalp hair samples of different male cancerous patients (esophagus, lung, mouth, and urinary bladder). For comparative purposes, the scalp hair samples of healthy males of the same age group (ranged 35-65 years) as controls were analyzed. Both controls and patients have the same socioeconomic status, localities, dietary habits, and smoking locally made cigarette. The scalp hair samples were oxidized by 65% nitric acid: 30% hydrogen peroxide (2:1) ratio in microwave oven followed by atomic absorption spectrometry. The validity and accuracy of the methodology were checked using certified reference material of human hair BCR 397. The mean concentrations of As, Cd, and Ni were found to be significantly higher in scalp hair samples of patients having different cancers as compared to the controls, while reverse results were obtained in the case of Se and Zn levels (p < 0.01). The study revealed that the carcinogenic processes are significantly affecting the trace elements burden and mutual interaction of essential trace and toxic elements in the cancerous patients.

Bladder volume at onset of vesicoureteral reflux is an independent risk factor for breakthrough febrile urinary tract infection.

PubMed

Alexander, Siobhan E; Arlen, Angela M; Storm, Douglas W; Kieran, Kathleen; Cooper, Christopher S

2015-04-01

Improved identification of children with vesicoureteral reflux at risk for recurrent febrile urinary tract infection may impact management decisions. We hypothesized that reflux occurring earlier during bladder filling increases the duration of exposure of the kidneys to bacteria, and, therefore, increases the risk of pyelonephritis. Children with vesicoureteral reflux and detailed voiding cystourethrogram data were identified. Bladder volume at onset of reflux was normalized for age. Demographics, reflux grade, laterality, presence/absence of bladder-bowel dysfunction and breakthrough febrile urinary tract infections were assessed. Median followup was 24 months (IQR 12 to 52). A total of 208 girls and 47 boys were analyzed with a mean ± SD age at diagnosis of 3.1 ± 2.6 years. On univariate analysis history of febrile urinary tract infection (HR 2.17, 95% CI 1.33-2.85, p = 0.01), dilating vesicoureteral reflux (HR 1.6, 95% CI 1.05-2.42, p = 0.03) and bladder-bowel dysfunction (HR 1.66, 95% CI 0.99-2.75, p = 0.05) were associated with an increased risk of breakthrough febrile urinary tract infection. Median bladder volume at onset of reflux in children with breakthrough febrile urinary tract infection was significantly less (33.1%) than in those without infection (49.5%, p = 0.003). Reflux onset at 35% predicted bladder capacity or less was associated with a significantly increased risk of breakthrough febrile urinary tract infection on multivariate analysis (HR 1.58, 95% CI 1.05-2.38, p = 0.03). Children with early filling vesicoureteral reflux are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. Bladder volume at onset of reflux should be recorded during cystograms since it provides additional prognostic information about the risk of pyelonephritis and resolution, and may assist with counseling and clinical decision making. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Bladder inflammatory transcriptome in response to tachykinins: Neurokinin 1 receptor-dependent genes and transcription regulatory elements

PubMed Central

Saban, Ricardo; Simpson, Cindy; Vadigepalli, Rajanikanth; Memet, Sylvie; Dozmorov, Igor; Saban, Marcia R

2007-01-01

Background Tachykinins (TK), such as substance P, and their neurokinin receptors which are ubiquitously expressed in the human urinary tract, represent an endogenous system regulating bladder inflammatory, immune responses, and visceral hypersensitivity. Increasing evidence correlates alterations in the TK system with urinary tract diseases such as neurogenic bladders, outflow obstruction, idiopathic detrusor instability, and interstitial cystitis. However, despite promising effects in animal models, there seems to be no published clinical study showing that NK-receptor antagonists are an effective treatment of pain in general or urinary tract disorders, such as detrusor overactivity. In order to search for therapeutic targets that could block the tachykinin system, we set forth to determine the regulatory network downstream of NK1 receptor activation. First, NK1R-dependent transcripts were determined and used to query known databases for their respective transcription regulatory elements (TREs). Methods An expression analysis was performed using urinary bladders isolated from sensitized wild type (WT) and NK1R-/- mice that were stimulated with saline, LPS, or antigen to provoke inflammation. Based on cDNA array results, NK1R-dependent genes were selected. PAINT software was used to query TRANSFAC database and to retrieve upstream TREs that were confirmed by electrophoretic mobility shift assays. Results The regulatory network of TREs driving NK1R-dependent genes presented cRel in a central position driving 22% of all genes, followed by AP-1, NF-kappaB, v-Myb, CRE-BP1/c-Jun, USF, Pax-6, Efr-1, Egr-3, and AREB6. A comparison between NK1R-dependent and NK1R-independent genes revealed Nkx-2.5 as a unique discriminator. In the presence of NK1R, Nkx2-5 _01 was significantly correlated with 36 transcripts which included several candidates for mediating bladder development (FGF) and inflammation (PAR-3, IL-1R, IL-6, α-NGF, TSP2). In the absence of NK1R, the matrix Nkx2-5_02 had a predominant participation driving 8 transcripts, which includes those involved in cancer (EYA1, Trail, HSF1, and ELK-1), smooth-to-skeletal muscle trans-differentiation, and Z01, a tight-junction protein, expression. Electrophoretic mobility shift assays confirmed that, in the mouse urinary bladder, activation of NK1R by substance P (SP) induces both NKx-2.5 and NF-kappaB translocations. Conclusion This is the first report describing a role for Nkx2.5 in the urinary tract. As Nkx2.5 is the unique discriminator of NK1R-modulated inflammation, it can be imagined that in the near future, new based therapies selective for controlling Nkx2.5 activity in the urinary tract may be used in the treatment in a number of bladder disorders. PMID:17519035

Dose to the Bladder Neck Is the Most Important Predictor for Acute and Late Toxicity After Low-Dose-Rate Prostate Brachytherapy: Implications for Establishing New Dose Constraints for Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hathout, Lara; Folkert, Michael R.; Kollmeier, Marisa A.

2014-10-01

Purpose: To identify an anatomic structure predictive for acute (AUT) and late (LUT) urinary toxicity in patients with prostate cancer treated with low-dose-rate brachytherapy (LDR) with or without external beam radiation therapy (EBRT). Methods and Materials: From July 2002 to January 2013, 927 patients with prostate cancer (median age, 66 years) underwent LDR brachytherapy with Iodine 125 (n=753) or Palladium 103 (n=174) as definitive treatment (n=478) and as a boost (n=449) followed by supplemental EBRT (median dose, 50.4 Gy). Structures contoured on the computed tomographic (CT) scan on day 0 after implantation included prostate, urethra, bladder, and the bladder neck, defined asmore » 5 mm around the urethra between the catheter balloon and the prostatic urethra. AUT and LUT were assessed with the Common Terminology Criteria for Adverse Events, version4. Clinical and dosimetric factors associated with AUT and LUT were analyzed with Cox regression and receiver operating characteristic analysis to calculate area under the receiver operator curve (ROC) (AUC). Results: Grade ≥2 AUT and grade ≥2 LUT occurred in 520 patients (56%) and 154 patients (20%), respectively. No grade 4 toxicities were observed. Bladder neck D2cc retained a significant association with AUT (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.03-1.04; P<.0001) and LUT (HR, 1.01; 95% CI, 1.00-1.03; P=.014) on multivariable analysis. In a comparison of bladder neck with the standard dosimetric variables by use of ROC analysis (prostate V100 >90%, D90 >100%, V150 >60%, urethra D20 >130%), bladder neck D2cc >50% was shown to have the strongest prognostic power for AUT (AUC, 0.697; P<.0001) and LUT (AUC, 0.620; P<.001). Conclusions: Bladder neck D2cc >50% was the strongest predictor for grade ≥2 AUT and LUT in patients treated with LDR brachytherapy. These data support inclusion of bladder neck constraints into brachytherapy planning to decrease urinary toxicity.« less

Complications of bladder distension during retrograde urethrography.

PubMed

Barsanti, J A; Crowell, W; Losonsky, J; Talkington, F D

1981-05-01

A severe, ulcerative cystitis that resulted in macroscopic hematuria occurred in 8 of 20 healthy dogs undergoing a series of diagnostic tests. Four of the remaining 12 dogs had mild bladder lesions consisting of submucosal edema and hemorrhage. Nine of the 20 dogs developed urinary tract infection after the procedures. These complications seemed associated with the radiographic technique of retrograde urethrography performed when the urinary bladder was distended. To test this hypothesis, retrograde urethrography was performed on 5 additional dogs. With the bladder undistended, no complications occurred. However, distention of these same dogs' bladders for 1 minute or less with sterile lactated Ringer's solution administered through a Foley catheter in the penile urethra resulted in a macroscopic hematuria in all 5 dogs which persisted for 24 hours. A microscopic hematuria continued for 5 days. One dog developed a bacterial urinary tract infection. A severe fibrinopurulent cystitis was present at necropsy of 2 dogs 2 days after distention. The morphologic changes in the bladder gradually diminished over 7 days, but mild submucosal edema and hemorrhage were still present when 2 dogs were necropsied, 7 days after distention. These studies indicated that retrograde urethrography in dogs may be complicated by hemorrhagic cystitis and urinary tract infection if performed with urinary bladder distention.

Embryonal Rhabdomyosarcoma of the Adult Urinary Bladder: A Rare Case Report of Misclassification as Inflammatory Myofibroblastic Tumor

PubMed Central

Chen, Kelven Weijing; Wu, Fiona Mei Wen; Lee, Victor Kwan Min; Esuvaranathan, Kesavan

2015-01-01

Embryonal rhabdomyosarcoma (ERMS) of the adult urinary bladder is a rare malignant tumour. Inflammatory myofibroblastic tumour (IMT) of the bladder is a benign genitourinary tumour that may appear variable histologically but usually lacks unequivocal malignant traits. Techniques like flow cytometry and immunohistochemistry may be used to differentiate these two tumours. Our patient, a 46-year-old male, had rapidly recurring lower urinary tract symptoms after two transurethral resections of the prostate. He subsequently underwent a transvesical prostatectomy which showed IMT on histology. However, his symptoms did not resolve and an open resection done at our institution revealed a 6 cm tumour arising from the right bladder neck. This time, histology was ERMS with diffuse anaplasia of the bladder. Rapid recurrence of urinary symptoms with prostate regrowth after surgery is unusual. Differential diagnoses of uncommon bladder malignancies should be considered if there is an inconsistent clinical course as treatment approaches are different. PMID:25737794

Importance of contraction history on muscle force of porcine urinary bladder smooth muscle.

PubMed

Menzel, Robin; Böl, Markus; Siebert, Tobias

2017-02-01

The purpose of this study was to provide a comprehensive dataset of porcine urinary bladder smooth muscle properties. Particularly, the history dependence of force production, namely force depression (FD) following shortening and force enhancement (FE) following stretch, was analysed. During active micturition, the circumference of the urinary bladder changes enormously. Thus, FD might be an important phenomenon during smooth muscle contraction. Electrically stimulated, intact urinary bladder strips from pigs (n = 10) were suspended in an aerated-filled organ bath, and different isometric, isotonic, and isokinetic contraction protocols were performed to determine the force-length and the force-velocity relation. FD and FE were assessed in concentric and eccentric contractions with different ramp lengths and ramp velocities. Bladder smooth muscles exhibit considerable amounts of FD and FE. The amount of FD increased significantly with ramp length, while FE did not change. However, FE and FD were independent of ramp velocity. The results imply that smooth muscle bladder strips exhibit similar muscle properties and history-dependent behaviour compared to striated muscles. The provided dataset of muscle properties is important for bladder modelling as well as for the analyses and interpretation of dynamic bladder filling and voiding.

RECENT ADVANCES IN ARSENIC CARCINOGENESIS: MODES OF ACTION, ANIMAL MODEL SYSTEMS AND METHYLATED ARSENIC METABOLITES

EPA Science Inventory

Abstract:

Recent advances in our knowledge of arsenic carcinogenesis include the development of rat or mouse models for all human organs in which inorganic arsenic is known to cause cancer -skin, lung, urinary bladder, liver and kidney. Tumors can be produced from eit...

Impact of lifestage and duration of exposure on arsenic-induced proliferative lesions and neoplasia in C3H mice.

EPA Science Inventory

Epidemiological studies suggest that chronic exposure to inorganic arsenic is associated with cancer of the skin, urinary bladder and lung as well as the kidney and liver. Previous experimental studies have demonstrated increased incidence of liver, lung, ovary, and uterine tumo...

Inconsistency in the definition of urinary tract infection after intravesical botulinum toxin A injection: a systematic review.

PubMed

Stamm, Andrew W; Adelstein, Sarah A; Chen, Andrew; Lucioni, Alvaro; Kobashi, Kathleen C; Lee, Una J

2018-04-10

In order to more accurately examine the rate of urinary tract infection following onabotulinumtoxinA injection of the bladder, we systematically reviewed the literature for definitions of urinary tract infection utilized in series that reported on onabotulinumtoxinA injections and assessed them for consistency with guideline statements defining urinary tract infections. A systematic review of the literature was performed via query using MEDLINE and EMBASE. We included original studies that reported on adult idiopathic overactive bladder and/or neurogenic detrusor overactivity patients who underwent cystoscopy with injection of onabotulinumtoxinA and had urinary tract infection as a reported outcome. 299 publications were identified, of which 50 met the inclusion criteria. 27 studies (54%) defined their urinary tract infection diagnostic criteria, and 10 different definitions were noted amongst these studies. None of the OAB studies used a definition which met the European Association of Urology criteria for urinary tract infection. Only 2 of the 10 studies on neurogenic bladder patients used a urinary tract infection definition consistent with National Institute on Disability and Rehabilitation Research standards. Definitions for urinary tract infections are heterogeneous and frequently absent in the literature reporting on onabotulinumtoxinA for the treatment of overactive bladder and/or neurogenic bladder. Given the potential for post procedure urinary symptoms in this setting, explicit criteria are imperative to establish the true urinary tract infection rate following treatment with onabotulinumtoxinA. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Noninvasive Electromagnetic Detection of Bladder Cancer

PubMed Central

Cormio, Luigi; Vedruccio, Clarbruno; Leucci, Giorgio; Massenio, Paolo; Di Fino, Giuseppe; Cavaliere, Vincenzo; Carrieri, Giuseppe

2014-01-01

Objectives. Normal and neoplastic human tissues have different electromagnetic properties. This study aimed to determine the diagnostic accuracy of noninvasive electromagnetic detection of bladder cancer (BC) by the tissue-resonance interaction method (TRIM-prob). Patients and Methods. Consecutive patients were referred for cystoscopy because of (i) microscopic or gross hematuria and/or irritative voiding symptoms and (ii) bladder ultrasounds and urinary cytology findings negative or just suspicious of malignancy. Patients were first submitted to TRIM-prob bladder scanning by a single investigator and then to cystoscopy by another investigator blind to TRIM-prob data. Results. In 125 evaluated patients cystoscopy was positive for BC in 47 and negative in the remaining 78; conversely, TRIM-prob bladder scanning was positive for BC in 53 and negative in 72. In particular, TRIM-prob scanning yielded 7 false positives and only one false negative; therefore, its overall sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were 97.9%, 89.9%, 86.8%, 98.6%, and 93.6%, respectively. Conclusions. TRIM-prob bladder scanning was a simple and quite accurate method for non-invasive electromagnetic detection of BC. If the elevated positive and negative predictive values will be replicated in further well-designed studies, it could be used to screen asymptomatic patients at high risk of BC. PMID:24563795

Blind urethral catheterization in trauma patients suffering from lower urinary tract injuries.

PubMed

Shlamovitz, Gil Z; McCullough, Lynne

2007-02-01

The goals of our study were to review all cases of urethral and bladder trauma that presented to the University of California, Los Angeles (UCLA) Medical Center between January 1998 and August 2005 and determine (1) the clinical characteristics of patients with urethral and/or bladder injuries as well as the sensitivities of those clinical characteristics; (2) whether or not a blind attempt to insert a urethral catheter was performed; and (3) whether there is any evidence that a blind attempt to insert a urethral catheter worsened the initial urinary tract injury. This is a retrospective chart review. The study cohort comprised 46 patients with a mean age of 30 years, including 36 men (78.2%) and 10 women (21.8%). Bladder tears were found in 33 patients, 10 patients had urethral lacerations, and 3 patients had combined bladder and urethral lacerations. The most sensitive finding for urinary bladder or urethral injury was the presence of gross hematuria in the urethral catheter (100%, 95% confidence interval [CI] 0.63-0.89). Blinded insertion of a urethral catheter was attempted in 30 (90.9%, 95% CI 0.75-0.98) patients who suffered from urinary bladder injury, 6 (50%, 95% CI 0.26-0.87) patients who suffered from urethral injury and 1 (33%, 95% CI 0.0-0.9) patient who suffered from a combined urinary bladder and urethral injuries. We did not find evidence that a blind attempt to insert a urethral catheter worsened the initial urinary injury. Gross hematuria in the urethral catheter was the most sensitive sign for the presence of a urethral or urinary bladder injury in our study cohort, and often the only sign of such an injury. We found no evidence that a blind attempt to insert a urethral catheter in patients suffering from urethral and or urinary bladder injuries worsened the initial injury. Larger studies will be needed to determine the safety of blind urethral catheterization in patients that are suspected to suffer from a lower urological trauma. It is our opinion that the current guidelines should be revised to better reflect the current knowledge, technologies, and clinical practice.

Primary urinary bladder haemangiosarcoma in a captive saddleback tamarin (Saguinus fuscicollis).

PubMed

Gonzales-Viera, Omar; Quevedo, Tatiana; Chavera, Alfonso; Perales-Camacho, Rosa; Grandi, Fabrizio; Catão-Dias, José L

2014-08-01

A captive adult male saddleback tamarin, Saguinus fuscicollis, was lethargic, unresponsive to its surrounding and died before medical care. Necroscopic, histopathological and immunohistochemical examinations were performed. Neoplastic spindle cells of the urinary bladder were positive for antifactor VIII antibody. A primary urinary bladder haemangiosarcoma was diagnosed, and it has not been previously reported in non-human primates. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Unexpected complication after cystometry in the hypocompliant urinary bladder: formation of a knot in the double lumen urethral catheter--a case report.

PubMed

Ayyildiz, Ali; Huri, Emre; Nuhoğlu, Bariş; Germiyanoğlu, Cankon

2006-01-01

Urodynamic evaluation is frequently used in the follow-up of the treatment and diagnosis of incontinence, which develops in connection with a neurogenic or non-neurogenic reason. There is no identified serious complication during or after urodynamic evaluation, present in the literature up to date. Hematuria, due to the urethral catheter, the development of oedema in the urinary bladder wall and the development of urinary bladder spasm as a result of catheter irritation, are some of the complications, which may occur. In this paper, twist and knot formation in the double lumen urethral catheter after cystometry of a patient with a hypocompliant urinary bladder, has been presented.

Perivascular epithelioid cell neoplasm of the urinary bladder in an adolescent: a case report and review of the literature.

PubMed

Yin, Lijuan; Bu, Hong; Chen, Min; Yu, Jianqun; Zhuang, Hua; Chen, Jie; Zhang, Hongying

2012-12-31

Perivascular epithelioid cell neoplasms (PEComas) of the urinary bladder are extremely rare and the published cases were comprised predominantly of middle-aged patients. Herein, the authors present the first urinary bladder PEComa occurring in an adolescent. This 16-year-old Chinese girl present with a 3-year history of abdominal discomfort and a solid mass was documented in the urinary bladder by ultrasonography. Two years later, at the age of 18, the patient underwent transurethral resection of the bladder tumor. Microscopically, the tumor was composed of spindled cells mixed with epithelioid cells. Immunohistochemically, the tumor were strongly positive for HMB45, smooth muscle actin, muscle-specific actin, and H-caldesmon. Fluorescence in situ hybridization analysis revealed no evidence of EWSR1 gene rearrangement. The patient had been in a good status without evidence of recurrence 13 months after surgery. Urinary bladder PEComa is an extremely rare neoplasm and seems occur predominantly in middle-aged patients. However, this peculiar lesion can develop in pediatric population and therefore it should be rigorously distinguished from their mimickers. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1870004378817301.

Proteus mirabilis fimbriae- and urease-dependent clusters assemble in an extracellular niche to initiate bladder stone formation.

PubMed

Schaffer, Jessica N; Norsworthy, Allison N; Sun, Tung-Tien; Pearson, Melanie M

2016-04-19

The catheter-associated uropathogenProteus mirabilisfrequently causes urinary stones, but little has been known about the initial stages of bladder colonization and stone formation. We found thatP. mirabilisrapidly invades the bladder urothelium, but generally fails to establish an intracellular niche. Instead, it forms extracellular clusters in the bladder lumen, which form foci of mineral deposition consistent with development of urinary stones. These clusters elicit a robust neutrophil response, and we present evidence of neutrophil extracellular trap generation during experimental urinary tract infection. We identified two virulence factors required for cluster development: urease, which is required for urolithiasis, and mannose-resistantProteus-like fimbriae. The extracellular cluster formation byP. mirabilisstands in direct contrast to uropathogenicEscherichia coli, which readily formed intracellular bacterial communities but not luminal clusters or urinary stones. We propose that extracellular clusters are a key mechanism ofP. mirabilissurvival and virulence in the bladder.

Breast Cancer Metastases to the Gastrointestinal Tract Presenting with Anemia and Intra-abdominal Bleed.

PubMed

Khan, Idrees; Malik, Rehan; Khan, Amina; Assad, Salman; Zahid, Mehr; Sohail, Muhammad Saad; Yasin, Faizan; Qavi, Ahmed H

2017-07-06

Signet ring adenocarcinoma of the breast with synchronous metastasis to the gastrointestinal (GI) tract is a rare occurrence, typically presenting with abdominal pain, dyspepsia, or GI bleed. We report a case of metastatic breast cancer presenting with a complaint of anemia. A further diagnostic evaluation revealed generalized lymphadenopathy, nodular thickening of the urinary bladder wall, bone lesions, and enlarged pancreas. Biopsies from the lymph nodes, pancreatic biopsy, and bladder nodule all revealed a signet cell carcinoma. An upper and lower GI endoscopy revealed multiple ulcerated gastric mucosal nodules and polypoid folds in the cecum and proximal ascending colon; the biopsies from these lesions were also positive for signet ring cell adenocarcinoma.

[Carcinosarcoma of the bladder: a case report].

PubMed

Khabir, A; Boudawara, T; Jemel, S; Mhiri, M N; Jlidi, R

2000-02-01

Carcinosarcoma of the urinary bladder is a uncommon tumor with characteristic histopathologic and immunohistochemical findings; his histogenesis have still not been clear; the prognosis seems to be improved by radical cystectomy and adjuvants therapies. We report a case of 47 years old women suffering from suprapubic pains, dysuria and hematuria of five months duration and had a 10 cm suprapubic mass that was found on physical examination. Radiographically, the tumor invaded the dome of the urinary bladder and causes bilateral hydronephrosis. Microscopically it was an urinary bladder carcinosarcoma. Our objective is to discuss the histogenesis, the anatomoclinical and prognosis of these rare tumors.

Assessment of lower urinary tract symptoms in men by international prostate symptom score and core lower urinary tract symptom score.

PubMed

Fujimura, Tetsuya; Kume, Haruki; Nishimatsu, Hiroaki; Sugihara, Toru; Nomiya, Akira; Tsurumaki, Yuzuri; Miyazaki, Hideyo; Suzuki, Motofumi; Fukuhara, Hiroshi; Enomoto, Yutaka; Homma, Yukio

2012-05-01

Study Type - Therapy (symptom prevalence). Level of Evidence 2a. What's known on the subject? and What does the study add? The International Prostate Symptom Score (IPSS) has been most commonly used for the symptom assessment of men with lower urinary tract symptoms (LUTS). However, LUTS in men are so variable that they may not be fully captured by the IPSS questionnaire alone. This study has demonstrated that the Core Lower Urinary Tract Symptom Score (CLSS) questionnaire, which addresses 10 important symptoms, is an appropriate initial assessment tool for LUTS in men with various diseases/conditions. International Prostate Symptom Score (IPSS) has been commonly used to assess lower urinary tract symptoms (LUTS). We have recently developed Core Lower Urinary Tract Symptom Score (CLSS). The aim of this study is to compare IPSS and CLSS for assessing LUTS in men.  Consecutive 515 men fulfilled IPSS and CLSS questionnaires. IPSS QOL Index was used as the QOL surrogate. The clinical diagnoses were BPH (n = 116), BPH with OAB wet (n =80), prostate cancer (n = 128), prostatitis (n = 68), underactive bladder (n = 8), others (n = 72), and controls (e.g., occult blood) (n = 42). Simple statistics and predictability of poor QOL (QOL Index 4 or greater) were examined. All symptom scores were significantly increased in symptomatic men compared with controls. Scores of corresponding symptoms of two questionnaires were significantly correlated (r = 0.58-0.85, all P < 0.0001). A multivariate regression model to predict poor QOL indicated nine symptoms (daytime frequency, nocturia, urgency, urgency incontinence, slow stream, straining, incomplete emptying, bladder pain and urethral pain) as independent factors. The hazard ratios for bladder pain (2.2) and urgency incontinence (2.0) were among the highest. All the nine symptoms are addressed in CLSS, while three symptoms (urgency incontinence, bladder, and urethral pain) are dismissed in IPSS. CLSS questionnaire is more comprehensive than IPSS questionnaire for symptom assessment of men with various diseases/conditions, although both questionnaires can capture LUTS with possible negative impact on QOL. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

UTIs in patients with neurogenic bladder.

PubMed

Jahromi, Mona S; Mure, Amanda; Gomez, Christopher S

2014-09-01

Urinary tract infections (UTI) remain one of the most prevalent and frustrating morbidities for neurogenic bladder patients, and death attributed to urosepsis in the spinal cord injury (SCI) patient is higher when compared to the general population. Risk factors include urinary stasis, high bladder pressures, bladder stones, and catheter use. While classic symptoms of UTI include dysuria, increased frequency and urgency, neurogenic bladder patients present differently with increased spasticity, autonomic dysreflexia, urinary incontinence, and vague pains. Multiple modalities have been assessed for prevention including catheter type, oral supplements, bladder irrigation, detrusor injections and prophylactic antimicrobials. Of these, bladder inoculation with E. coli HU2117, irrigation with iAluRil(®), detrusor injections, and weekly prophylaxis with alternating antibiotics appear to have a positive reduction in UTI but require further study. Ultimately, treatment for symptomatic UTI should account for the varied flora and possible antibiotic resistances including relying on urine cultures to guide antibiotic therapy.

Different HER2 protein expression profiles aid in the histologic differential diagnosis between urothelial carcinoma in situ (CIS) and non-CIS conditions (dysplasia and reactive atypia) of the urinary bladder mucosa.

PubMed

Gunia, Sven; Koch, Stefan; Hakenberg, Oliver W; May, Matthias; Kakies, Christoph; Erbersdobler, Andreas

2011-12-01

We evaluated HER2 expression profiles in 32 carcinoma in situ (CIS) and 31 non-CIS conditions (5 dysplasia and 26 reactive atypia) of the urinary bladder mucosa by applying breast cancer scoring rules. In situ hybridization was performed on tissue microarrays to assess HER2 gene amplification status. Our immunoprofiling data disclosed moderate to strong HER2 expression in CIS, including the basal layer of the urothelium, and absent to weak HER2 expression in non-CIS conditions. From the histologic differential diagnostic standpoint, immunostaining for HER2 protein represents a useful adjunct to aid in the delineation between CIS and non-CIS conditions of the bladder mucosa. Pathogenically, aberrant HER2 protein expression in CIS seems to be more commonly associated with polysomy than with gene amplification. From a therapeutic viewpoint, prospective clinical studies should investigate the potential benefit of HER2-targeted therapies in CIS, particularly in cases unresponsive to conventional therapeutic regimens.

Urinary bladder organ hypertrophy is partially regulated by Akt1-mediated protein synthesis pathway.

PubMed

Qiao, Li-Ya; Xia, Chunmei; Shen, Shanwei; Lee, Seong Ho; Ratz, Paul H; Fraser, Matthew O; Miner, Amy; Speich, John E; Lysiak, Jeffrey J; Steers, William D

2018-05-15

The present study aims to investigate the role of Akt in the regulation of urinary bladder organ hypertrophy caused by partial bladder outlet obstruction (pBOO). Male rats were surgically induced for pBOO. Real-time PCR and western blot were used to examine the levels of mRNA and protein. A phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was used to inhibit the activity of endogenous Akt. The urinary bladder developed hypertrophy at 2 weeks of pBOO. The protein but not mRNA levels of type I collagen and α-smooth muscle actin (αSMA) were increased in pBOO bladder when compared to sham control. The phosphorylation (activation) levels of Akt1 (p-Ser 473 ), mammalian target of rapamycin (mTOR), p70S6 kinase (p70S6K), and 4E-BP1 were also increased in pBOO bladder. LY294002 treatment reduced the phosphorylation levels of Akt1 and 4E-BP1, and the protein levels of type I collagen and αSMA in pBOO bladder. The mRNA and protein levels of proliferating cell nuclear antigen (PCNA) were increased in pBOO bladder, and PCNA up-regulation occurred in urothelial not muscular layer. LY294002 treatment had no effect on the mRNA and protein levels of PCNA in pBOO bladder. LY294002 treatment partially reduced the bladder weight caused by pBOO. pBOO-induced urinary bladder hypertrophy is attributable to fibrosis, smooth muscle cellular hypertrophy, and urothelium cell hyper-proliferation. Akt1-mediated protein synthesis in pBOO bladder contributes to type I collagen and αSMA but not PCNA up-regulation. Target of Akt1 is necessary but not sufficient in treatment of urinary bladder hypertrophy following pBOO. Copyright © 2018 Elsevier Inc. All rights reserved.

Temperature measurement in intensive care patients: comparison of urinary bladder, oesophageal, rectal, axillary, and inguinal methods versus pulmonary artery core method.

PubMed

Lefrant, J-Y; Muller, L; de La Coussaye, J Emmanuel; Benbabaali, M; Lebris, C; Zeitoun, N; Mari, C; Saïssi, G; Ripart, J; Eledjam, J-J

2003-03-01

Comparisons of urinary bladder, oesophageal, rectal, axillary, and inguinal temperatures versus pulmonary artery temperature. Prospective cohort study. Intensive Care Unit of a University-Hospital. Forty-two intensive care patients requiring a pulmonary artery catheter (PAC). Patients requiring PAC and without oesophageal, urinary bladder, and/or rectal disease or recent surgery were included in the study. Temperature was simultaneously monitored with PAC, urinary, oesophageal, and rectal electronic thermometers and with axillary and inguinal gallium-in-glass thermometers. Comparisons used a Bland and Altman method. The pulmonary arterial temperature ranged from 33.7 degrees C to 40.2 degrees C. Urinary bladder temperature was assessed in the last 22 patients. A total of 529 temperature measurement comparisons were carried out (252 comparisons of esophageal, rectal, inguinal, axillary, and pulmonary artery temperature measurements in the first 20 patients, and 277 comparisons with overall methods in the last patients). Nine to 18 temperature measurement comparisons were carried out per patient (median = 13). The mean differences between pulmonary artery temperatures and those of the different methods studied were: oesophageal (0.11+/-0.30 degrees C), rectal (-0.07+/-0.40 degrees C), axillary (0.27+/-0.45 degrees C), inguinal (0.17+/-0.48 degrees C), urinary bladder (-0.21+/-0.20 degrees C). In critically ill patients, urinary bladder and oesophageal electronic thermometers are more reliable than the electronic rectal thermometer which is better than inguinal and axillary gallium-in-glass thermometers to measure core temperature.

Expression and function of transforming growth factor-β isoforms and cognate receptors in the rat urinary bladder following cyclophosphamide-induced cystitis

PubMed Central

Gonzalez, Eric J.; Girard, Beatrice M.

2013-01-01

Numerous proinflammatory cytokines have been implicated in the reorganization of lower urinary tract function following cyclophosphamide (CYP)-induced cystitis. The present study investigated the functional profile of three pleiotropic transforming growth factor-β (TGF-β) isoforms and receptor (TβR) variants in the normal and inflamed (CYP-induced cystitis) rat urinary bladder. Our findings indicate that TGF-β (1, 2, and 3) and TβR (1, 2, and 3) transcript and protein expression were regulated to varying degrees in the urothelium or detrusor smooth muscle following intermediate (48 h; 150 mg/kg ip) or chronic (75 mg/kg ip; once every 3 days for 10 days), but not acute (4 h; 150 mg/kg ip), CYP-induced cystitis. Conscious, open-outlet cystometry was performed to determine whether aberrant TGF-β signaling contributes to urinary bladder dysfunction following intermediate (48 h) CYP-induced cystitis. TβR-1 inhibition with SB505124 (5 μM) significantly (p ≤ 0.001) decreased voiding frequency and increased bladder capacity (2.5-fold), void volume (2.6-fold), and intercontraction intervals (2.5-fold) in CYP-treated (48 h) rats. Taken together, these results provide evidence for 1) the involvement of TGF-β in lower urinary tract neuroplasticity following urinary bladder inflammation, 2) a functional role of TGF-β signaling in the afferent limb of the micturition reflex, and 3) urinary bladder TβR-1 as a viable target to reduce voiding frequency with cystitis. PMID:23926183

Secondary signet-ring cell adenocarcinoma of urinary bladder from a gastric primary.

PubMed

Sharma, Pramod K; Vijay, Mukesh K; Das, Ranjit K; Chatterjee, Uttara

2011-05-01

Primary bladder tumor is a frequent urological malignancy, whereas the incidence of secondary bladder tumor from a distant organ is quite rare. Secondary bladder neoplasms represent 1% of all malignant bladder tumors, of which distant metastases from stomach account for about 4% of cases. We present the case of a 30-year-old male who underwent partial gastrectomy for Signet-ring cell carcinoma of the stomach and presented 2 years later with hematuria. On computerized tomography scan, a bladder tumor was found which was resected cystoscopically. The histopathological examination revealed secondary Signet-ring cell adenocarcinoma of the urinary bladder.

Nonkeratinised Squamous Metaplasia of the Urinary Bladder in Children: A Report of Case Experiences

PubMed Central

Jurkiewicz, Beata

2014-01-01

Background. Squamous metaplasia refers to the pathological transformation of the urothelium leading to nonkeratinised stratified squamous metaplasia (N-KSM). Objective. To present our experiences in the diagnosis and treatment of N-KSM of the urinary bladder in children. Materials and Methods. In this study, we present our experiences in the diagnosis and treatment of N-KSM of the urinary bladder in children aged from 5 to 17 years. From 2005 to 2013, metaplasia was diagnosed in 119 patients. The reasons behind visiting the hospital were nonspecific intense pain in the abdomen, recurrent urinary tract infections, and urination disorders. The most common symptoms of urinary bladder dysfunction were pollakiuria and difficulties in initiating micturition and retention of urine (reduced detrusor muscle activity). Results. In 20/119 patients (16.8%), metaplasia was incidentally diagnosed during cystoscopy performed for other causes. The changes characteristic for squamous metaplasia were diagnosed—in all these patients, a biopsy was performed. In all 119 patients, a squamous metaplasia was histopathologically diagnosed. Conclusions. Squamous metaplasia of the urinary bladder mucosa occurs in children and adolescents. Symptomatic treatment is administered mainly to improve the patients' quality of life and disease prognosis. PMID:24822222

Urinary tract infection associated with conditions causing urinary tract obstruction and stasis, excluding urolithiasis and neuropathic bladder.

PubMed

Heyns, C F

2012-02-01

The aim of this study was to examine urinary tract infection (UTI) associated with conditions causing urinary tract obstruction and stasis, excluding urolithiasis and neuropathic bladder dysfunction. An electronic literature search was performed using the key words urinary tract infection (UTI), benign prostatic hyperplasia (BPH), hydronephrosis, obstruction, reflux, diverticulum, urethra, and stricture. In total, 520 abstracts were reviewed, 210 articles were studied in detail, and 36 were included as references. It is one of the axioms of Urological practice that urinary tract obstruction and stasis predispose to UTI. Experimental studies indicate that, whereas transurethral inoculates of bacteria are rapidly eliminated from the normal bladder, urethral obstruction leads to cystitis, pyelonephritis, and bacteremia. BPH is, next to urolithiasis, the most common cause of urinary tract obstruction predisposing to UTI. Urethral stricture remains a common cause of UTI in many parts of the world. Urinary stasis in diverticula of the urethra or bladder predisposes to UTI. Experimental studies have shown that, whereas the normal kidney is relatively resistant to infection by organisms injected intravenously, ureteric obstruction predisposes to pyelonephritis. It also causes renal dysfunction which impairs the excretion of antibiotics in the urine, making eradication of bacteria difficult. In patients with UTI and urinary tract obstruction, targeted antibiotic treatment according to urine culture should be complemented with urgent drainage (bladder catheterization, percutaneous nephrostomy or ureteric stenting) followed by definitive surgery to remove the cause of obstruction or stasis once infection is under control.

Conservative treatment of concomitant extraperitoneal bladder rupture and intrabladder blood clot formation: Case report of application of ureteral catheterization.

PubMed

Fu, Chih-Yuan; Shih, Chun-Han; Chang, Po-Yen; Hsiao, Chi-Hao; Wang, Yu-Chun; Chen, Ray-Jade

2012-12-01

Most extraperitoneal bladder ruptures can be treated conservatively with catheter drainage only. However, in patients with concomitant intrabladder blood clot formation and extraperitoneal bladder rupture, surgery for blood clot evacuation and bladder repair are usually needed due to occlusion of the urinary catheter. In our patient, we used a ureteral catheter to bypass the clots in the bladder to provide adequate urinary drainage. This procedure serves as a valuable tool in the conservative treatment of extraperitoneal bladder injury.

Efficacy and safety of hexaminolevulinate fluorescence cystoscopy in the diagnosis of bladder cancer.

PubMed

Lee, Jae Seung; Lee, Seo Yeon; Kim, Woo Jung; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han Yong; Jeong, Byong Chang

2012-12-01

The aim of this study was to evaluate the efficacy and safety of hexaminolevulinate fluorescence cystoscopy in the diagnosis of bladder cancer. In a prospective design, we included patients who had a bladder lesion suggesting bladder cancer. Patients with massive hematuria, urethral Foley catheter insertion, chronic retention state, or urinary tract infection were excluded. After the bladder was emptied, hexaminolevulinate was gently administered into the bladder. One hour later, cystoscopy under white light and blue light was performed. After marking the lesions confirmed with white light or blue light, transurethral resection of the bladder lesion and pathologic confirmation were done. Transurethral resection of the lesions that were negative in both white and blue light was also performed. From April 2010 to September 2010, 30 patients were enrolled. From the total of 30 patients (25 men and 5 women; mean age, 60.4±9.22 years), 134 specimens were extracted. Among these, 101 specimens showed positive results by blue light cystoscopy (BLC). The sensitivity of BLC and white light cystoscopy (WLC) was 92.3% and 80.8%, respectively (p=0.021). The specificity of BLC and WLC was 48% and 49.1%, respectively (p>0.05). The positive and negative predictive values of BLC were 71.2% and 81.8%, respectively, whereas those of WLC were 72.0% and 68.6%, respectively. With WLC, 48 specimens showed negative findings, but of that group, 15 specimens (31.2%) were revealed to be malignant with BLC. There were no significant side effects in the 24 hours after the instillation of hexaminolevulinate. Photodynamic diagnosis with hexaminolevulinate helps to find tumors that could be missed by use of WLC only. Photodynamic diagnosis might be valuable in complete resection as well as for more accurate diagnosis of bladder tumor.

Downregulation of glutathione S-transferase M1 protein in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced mouse bladder carcinogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chuang, Jing-Jing; Dai, Yuan-Chang; Lin, Yung-Lun

2014-09-15

Bladder cancer is highly recurrent following specific transurethral resection and intravesical chemotherapy, which has prompted continuing efforts to develop novel therapeutic agents and early-stage diagnostic tools. Specific changes in protein expression can provide a diagnostic marker. In our present study, we investigated changes in protein expression during urothelial carcinogenesis. The carcinogen BBN was used to induce mouse bladder tumor formation. Mouse bladder mucosa proteins were collected and analyzed by 2D electrophoresis from 6 to 20 weeks after commencing continuous BBN treatment. By histological examination, the connective layer of the submucosa showed gradual thickening and the number of submucosal capillaries graduallymore » increased after BBN treatment. At 12-weeks after the start of BBN treatment, the urothelia became moderately dysplastic and tumors arose after 20-weeks of treatment. These induced bladder lesions included carcinoma in situ and connective tissue invasive cancer. In protein 2D analysis, the sequentially downregulated proteins from 6 to 20 weeks included GSTM1, L-lactate dehydrogenase B chain, keratin 8, keratin 18 and major urinary proteins 2 and 11/8. In contrast, the sequentially upregulated proteins identified were GSTO1, keratin 15 and myosin light polypeptide 6. Western blotting confirmed that GSTM1 and NQO-1 were decreased, while GSTO1 and Sp1 were increased, after BBN treatment. In human bladder cancer cells, 5-aza-2′-deoxycytidine increased the GSTM1 mRNA and protein expression. These data suggest that the downregulation of GSTM1 in the urothelia is a biomarker of bladder carcinogenesis and that this may be mediated by DNA CpG methylation. - Highlights: • GSTM1 and NQO-1 proteins decreased in the mouse bladder mucosa after BBN treatment. • BBN induced GSTO1 and Sp1 protein expression in the mouse bladder mucosa. • 5-Aza-2′-deoxycytidine increased GSTM1 mRNA and protein in human bladder cancer cell. • GSTM1 downregulation in the urothelia may be a biomarker of bladder carcinogenesis.« less

Occupational factors and the incidence of cancer of the bladder in Canada.

PubMed Central

Risch, H A; Burch, J D; Miller, A B; Hill, G B; Steele, R; Howe, G R

1988-01-01

During 1979-82, a case-control study of occupational factors and urinary bladder cancer was conducted in Edmonton, Calgary, Toronto, and Kingston, Canada. A total of 826 histologically verified cases of cancer were individually matched by sex, age, and area of residence to 792 randomly selected population controls. Subjects were specifically asked about employment in several industries thought relevant to risk of bladder cancer. Information was also obtained on lifelong occupational history, with special attention given regarding exposures to fumes, dusts, smoke, and chemicals. In addition, subjects provided data on past medical and residential history, on intake of certain dietary items, and on exposure to tobacco and other lifestyle factors. Conditional logistic regression methods were used for the analysis. Under adjustment for cumulative lifetime cigarette consumption, it appeared that for both men and women, most of the occupational factors examined were not associated with significant alteration in risk of bladder cancer. For exposures during the period eight to 28 years before diagnosis, however, raised risk was suggested for men employed at least six months in the chemicals industry (odds ratio = 2.37, p = 0.004), in dye manufacturing or the dyeing of cloth (OR = 3.62 and 4.63, p = 0.041 and 0.035, respectively), as tailors (OR = 3.85, p = 0.015), or in jobs in which contact with diesel or traffic fumes occurred (OR = 1.69, p = 0.0008). Increased risk was also seen for men occupationally exposed to tars or asphalt (OR = 3.11, p = 0.019). This study then, at least for men, supports perhaps a few of the suspect industries as related to risk of bladder cancer. PMID:3395572

A critical prognostic analysis of neutrophil-lymphocyte ratio for patients undergoing nephroureterectomy due to upper urinary tract urothelial carcinoma.

PubMed

Altan, Mesut; Haberal, Hakan Bahadır; Akdoğan, Bülent; Özen, Haluk

2017-10-01

To determine preoperative serum complete blood count parameters that affects survival of patients who underwent surgery for upper urinary tract urothelial cancer (UUT-UC). Since 1990, 150 patients underwent nephroureterectomy with bladder cuff excision for UUT-UC at Hacettepe University. Patients with a history of muscle-invasive bladder cancer, adjuvant chemotherapy or metastasis at the time of diagnosis were excluded. One hundred and thirteen patients without infective symptoms and with a full set of serum data were evaluated retrospectively. Effects of the neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), and leukocyte count on disease-free survival (DFS) and progression-free survival (PFS) were investigated. Threshold values for each parameter to predict PFS were calculated. The mean age and median follow-up were 63.7 ± 11.1 years and 34 (3-186) months, respectively. Male to female ratio was 86/27. The 5-years PFS (bladder recurrence was excluded) and DFS were 59.6 and 38.4%, respectively. In multivariate analysis, NLR was independent prognostic factor for PFS and DFS (p = 0.006 and p = 0.021, respectively) while LMR was prognostic only for PFS (p = 0.037). For UUT-UC, NLR is a prognostic factor for PFS and DFS, while LMR is a prognostic indicator for PFS in present series.

Positive association between hypertension and urinary bladder cancer: epidemiologic evidence involving 79,236 propensity score-matched individuals.

PubMed

Kok, Victor C; Zhang, Han-Wei; Lin, Chin-Teng; Huang, Shih-Chung; Wu, Ming-Feng

2018-06-18

We hypothesized that hypertensive patients harbor a higher risk of urinary bladder (UB) cancer. We performed a population-based cohort study on adults using a National Health Insurance Research Database (NHIRD) dataset. Hypertension and comparison non-hypertensive (COMP) groups comprising 39,618 patients each were propensity score-matched by age, sex, index date, and medical comorbidities. The outcome was incident UB cancer validated using procedure codes. We constructed multivariable Cox models to derive adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Cumulative incidence was compared using a log-rank test. During a total follow-up duration of 380,525 and 372,020 person-years in the hypertension and COMP groups, 248 and 186 patients developed UB cancer, respectively, representing a 32% increase in the risk (aHR, 1.32; 95% CI, 1.09-1.60). Hypertensive women harbored a significantly increased risk of UB cancer (aHR, 1.55; 95% CI, 1.12-2.13) compared with non-hypertensive women, whereas men with hypertension had a statistically non-significant increased risk (aHR, 1.22; 95% CI, 0.96-1.55). The sensitivity analysis demonstrated that the increased risk was sustained throughout different follow-up durations for the entire cohort; a statistical increase in the risk was also noted among hypertensive men. This nationwide population-based propensity score-matched cohort study supports a positive association between hypertension and subsequent UB cancer development.

Shale gas development and cancer incidence in southwest Pennsylvania.

PubMed

Finkel, M L

2016-12-01

To what extent does unconventional gas development lead to an increase in cancer incidence in heavily drilled Southwest Pennsylvania? Ecological study. Data for urinary bladder, thyroid and leukaemia were abstracted from the Pennsylvania Cancer Registry (PCR). Cancer incidence among counties with high, moderate and minimal number of producing wells is compared before drilling activity and thereafter. Observed vs expected cases, standardized incidence ratio and 95% confidence intervals are presented. Data are presented by county, diagnosis and sex for the years 2000-2004, 2004-2008 and 2008-2012. The percent difference between the observed cases from 2000 to 2004 and 2008-2012 was calculated. The observed number of urinary bladder cases was higher than expected in both sexes in counties with shale gas activity. In counties with the fewest number of producing wells, the increase was essentially non-existent. The number of observed cases of thyroid cancer increased substantially among both sexes over the time period in all counties regardless of the number of wells drilled. The pattern for leukaemia was mixed among males and females and among the counties regardless of the extent of shale gas development activities. Potential risk factors other than shale gas development must be taken into account to explain the higher than expected cancer cases in counties with and without shale gas wells before and during unconventional shale gas activity. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Variations of thickness of trigonal muscle layer in different age and sex.

PubMed

Sultana, J; Khalil, M; Sultana, S Z; Mannan, S; Choudhury, S; Ara, A; Sumi, M S; Farzana, T; Sultana, R; Tania, A H

2014-10-01

This cross sectional descriptive study was to measure the thickness of muscular layer in trigone of the urinary bladder and to establish the difference between sexes of different age groups in Bangladeshi cadaver. A total 60 human urinary bladders were collected by purposive sampling from May 2013 to October 2013. Among them from male 43 and from female 17 were collected from Bangladeshi cadavers of age ranging from 01 to 60 years, from autopsy laboratory of the Department of Forensic Medicine of Mymensingh Medical College, Mymensingh. The thickness of muscular layer in trigone of the urinary bladder was measured and significant differences of the value between age and sex groups were observed. The mean±SD thickness of muscular layer of trigone of the urinary bladder was 318.59±93.15μm in age Group A (01 to 20 years), 633.25±79.79μm in age Group B (21 to 40 years), and 352.50±116.15μm in age Group C (41 to 60 years). The mean difference of muscular layer of the trigone of the urinary bladder between age Groups A&B, B&C was statistically highly significant, where p=0.001. In statistical analysis, differences between age groups were calculated by using one way ANOVA test. The present study revealed that the value of thickness of muscular layer in trigone of the urinary bladder was increased with the increase of age and it was declined to a low level in the late age. The mean value of muscular layer of the trigone of the urinary bladder was higher in male than that of in female of Group A, B & C.

[Geomagnetic field variation in early ontogenesis as a risk factor for oncopathology].

PubMed

Iamshanov, V A

2003-01-01

The data on 534 cancer patients with tumors of 15 different sites were evaluated to elucidate the influence of geomagnetic field (GMF) in certain months of the pre- and early postnatal periods on future incidence of cancer. We identified neoplasms of the breast, lung, urinary bladder, hypophysis, ovary, prostate, liver, Hodgkin's disease, lymphoma and, possibly, gastric cancer as GMF-dependent. This relationship appeared to be idiosyncratic with every cancer variety. It was negligible in cases of esophagus, thyroid, uterine cervix and colorectal cancer. GMF variations as a carcinogenic factor in early ontogenesis can be assessed quantitatively.

Five-year prospective patient evaluation of bladder and bowel symptoms after dose-escalated radiotherapy for prostate cancer with the BeamCath (registered) technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fransson, Per; Bergstroem, Per; Loefroth, Per-Olov

2006-10-01

Purpose: Late side effects were prospectively evaluated up to 5 years after dose-escalated external beam radiotherapy (EBRT) and were compared with a previously treated series with conventional conformal technique. Methods and Materials: Bladder and bowel symptoms were prospectively evaluated with the Prostate Cancer Symptom Scale (PCSS) questionnaire up to 5 years posttreatment. In all, 257 patients completed the questionnaire 5 years posttreatment. A total of 168 patients were treated with the conformal technique at doses <71 Gy, and 195 were treated with the dose-escalated stereotactic BeamCath (registered) technique comprising three dose levels: 74 Gy (n = 68), 76 Gy (nmore » = 74), and 78 Gy (n = 53). Results: For all dose groups analyzed together, 5 years after treatment, urinary starting problems decreased and urinary incontinence increased in comparison to baseline values. No increase in other bladder symptoms or frequency was detected. When comparing dose groups after 5 years, both the 74-Gy and 78-Gy groups reported increased urinary starting problems compared with patients given the conventional dose (<71 Gy). No increased incontinence was seen in the 76-Gy or the 78-Gy groups. Bowel symptoms were slightly increased during the follow-up period in comparison to baseline. Dose escalation with stereotactic EBRT (74-78 Gy) did not increase gastrointestinal late side effects after 5 years in comparison to doses <71 Gy. Conclusion: Dose-escalated EBRT with the BeamCath (registered) technique with doses up to 78 Gy is tolerable, and the toxicity profile is similar to that observed with conventional doses <71 Gy.« less

Location-dependent correlation between tissue structure and the mechanical behaviour of the urinary bladder.

PubMed

Morales-Orcajo, Enrique; Siebert, Tobias; Böl, Markus

2018-05-25

The mechanical properties of the urinary bladder wall are important to understand its filling-voiding cycle in health and disease. However, much remains unknown about its mechanical properties, especially regarding regional heterogeneities and wall microstructure. The present study aimed to assess the regional differences in the mechanical properties and microstructure of the urinary bladder wall. Ninety (n=90) samples of porcine urinary bladder wall (ten samples from nine different locations) were mechanically and histologically analysed. Half of the samples (n=45) were equibiaxially tested within physiological conditions, and the other half, matching the sample location of the mechanical tests, was frozen, cryosectioned, and stained with Picro-Sirius red to differentiate smooth muscle cells, extracellular matrix, and fat. The bladder wall shows a non-linear stress-stretch relationship with hysteresis and softening effects. Regional differences were found in the mechanical response and in the microstructure. The trigone region presents higher peak stresses and thinner muscularis layer compared to the rest of the bladder. Furthermore, the ventral side of the bladder presents anisotropic characteristics, whereas the dorsal side features perfect isotropic behaviour. This response matches the smooth muscle fibre bundle orientation within the tunica muscularis. This layer, comprising approximately 78% of the wall thickness, is composed of two fibre bundle arrangements that are cross-oriented, one with respect to the other, varying the angle between them across the organ. That is, the ventral side presents a 60°/120° cross-orientation structure, while the muscle bundles were oriented perpendicular in the dorsal side. In the present study, we demonstrate that the mechanical properties and the microstructure of the urinary bladder wall are heterogeneous across the organ. The mechanical properties and the microstructure of the urinary bladder wall within nine specific locations matching explicitly the mechanical and structural variations have been examined. On the one hand, the results of this study contribute to the understanding of bladder mechanics and thus to their functional understanding of bladder filling and voiding. On the other hand, they are relevant to the fields of constitutive formulation of bladder tissue, whole bladder mechanics, and bladder-derived scaffolds i.e., tissue-engineering grafts. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Stricture of the afferent isoperistaltic tubular segment: a late and rare cause of bilateral dilation of the upper urinary tract after ileal bladder substitution.

PubMed

Kiss, Bernhard; Schöndorf, Daniel; Studer, Urs E; Roth, Beat

2013-08-01

To evaluate the etiology and treatment of bilateral hydronephrosis not responding to bladder substitute drainage after ileal bladder substitution using an afferent isoperistaltic tubular segment. A retrospective analysis was performed of a consecutive series of 739 patients who had undergone bladder substitution from April 1985 to August 2012. Of the 739 ileal bladder substitute patients, 10 (1.4%) developed bilateral hydronephrosis unresponsive to complete bladder substitute drainage. The etiology was stenosis of the afferent isoperistaltic tubular segment. The median interval to presentation was 131 months (range 45-192). The incidence of afferent tubular segment stenosis was significantly higher in the 61 ileal bladder substitute patients with recurrent urinary tract infection (9 [15%]) than in the 678 without recurrent urinary tract infection (1 [0.15%]; P <.001). Urine cultures revealed mixed infections (34%), Escherichia coli (18%), Staphylococcus aureus (13%), enterococci (11%), Candida (8%), Klebsiella (8%), and others (8%). Seven patients underwent 10 endourologic interventions, only 1 of which was successful (10%). After failed endourologic treatment, 7 open surgical revisions with resection of the stricture were performed, with all 7 (100%) successful. Bilateral dilation of the upper urinary tract after ileal orthotopic bladder substitution unresponsive to complete bladder substitute drainage is likely to be caused by stenosis of the afferent isoperistaltic tubular segment. The stenosis occurs almost exclusively in patients with long-lasting, recurrent urinary tract infection and can develop many years after the ileal bladder substitution. Minimally invasive endourologic treatment is usually unsuccessful; however, open surgical revision offers excellent results. Copyright © 2013 Elsevier Inc. All rights reserved.

Diagnosis and Management of Lower Urinary Tract Dysfunction.

PubMed

McDonough, Robert C; Ryan, Stephen T

2016-06-01

Lower urinary tract dysfunction is an umbrella diagnosis that covers difficulty evacuating urine from the bladder. In its most simple form, it is either an inability to store urine or an inability to empty the bladder of urine appropriately. The normal and the abnormal bladder, the role of urodynamics in evaluation of lower urinary tract dysfunction, and the medical and behavioral management of some of these disorders are reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

Urinary tract infection - children

MedlinePlus

UTI - children; Cystitis - children; Bladder infection - children; Kidney infection - children; Pyelonephritis - children ... Urinary tract infections (UTIs) can occur when bacteria get into the bladder or the kidneys. These bacteria are common ...

[Neuroendocrine carcinoma of the urinary bladder. A case report].

PubMed

Aragón-Tovar, Anel Rogelio; Pineda-Rodríguez, Marco Elí; Puente-Gallegos, Francisco Edgardo; Zavala-Pompa, Angel

2014-01-01

Small cell carcinoma of the urinary bladder is an infrequent lesion. We present the case of a 68-year-old male who arrived at the emergency room with a history of 24-h gross hematuria. Imaging studies show a urinary bladder tumor with a 218 cc volume that during a 20-day period increased to 426 cc. Histopathological images with hematoxylin-eosin show an infiltrating solid mass with uneven borders. It is composed of neoplastic cells with evident nuclei predominance and scant cytoplasm (small cells). Chromogranin immunohistochemical staining shows a diffusely positive cytoplasmic granular pattern on neoplastic cells. High molecular weight cytokeratin staining shows a negative pattern on neoplastic cells along with a positive pattern on reporsurrounding normal urothelium. Tumoral mass is positive for synaptophysin and CD-56 and negative for CK-7 and CK-20. Patient therapy was based on radiation plus chemotherapy. Small cell carcinoma of the urinary bladder represents 0.35-0.70% of urinary bladder tumors. Histological and immunohistochemical identification are key elements in the diagnosis. Treatment approach is based on cisplatin-based chemotherapy plus radical cystectomy, except when metastatic disease is present.

Urinary bladder stone extraction and instruments compared in textbooks of Abul-Qasim Khalaf Ibn Abbas Alzahrawi (Albucasis) (930-1013) and Serefeddin Sabuncuoglu (1385-1470).

PubMed

Elcioglu, Omur; Ozden, Hilmi; Guven, Gul; Kabay, Sahin

2010-09-01

We investigated urinary bladder stone, surgical tools, and procedures in urologic sections of textbooks of Abul-Qasim Khalaf Ibn Abbas Alzahrawi (Albucasis) and Serefeddin Sabuncuoglu. In addition, we compared the relation of their textbooks with urologic surgery. Al-Tasreef Liman Aajaz Aan Al-Taaleef (Al-Tasreef), a surgery textbook written by Alzahrawi (who lived in Endulus between 930 and 1013) and Cerrahiyyetu'l-Haniyye, written by Sabuncuoglu (who lived in Turkey between 1385 and 1470) were evaluated with regard to urinary bladder stone and surgical instruments. The textbooks give information about urinary bladder stones. They include definitions of diseases, etiologies, and surgical techniques, and describe surgical tools. Cerrahiyyetu'l Haniyye is a colorful miniaturized textbook. The urinary bladder stone section in Cerrahiyyetu'l Haniyye is the translation of Al-Tasreef with some additional information and illustrations. Surgical tools and procedures described by the two physicians have reached to our century. Tools and procedures invented by Alzahrawi come to the present day in similar or developed styles.

An unexpected resident in the ileum detected during robot-assisted laparoscopic radical cystoprostatectomy and intracorporeal Studer pouch formation: Taenia saginata parasite.

PubMed

Canda, Abdullah Erdem; Asil, Erem; Balbay, Mevlana Derya

2011-02-01

A case of moving ileal Taenia saginata parasites is presented with demonstrative images. We came across the parasites surprisingly while performing robot-assisted laparoscopic radical cystoprostatectomy with intracorporeal Studer pouch urinary diversion. We recommend stool sample evaluation in the preoperative period for possible presence of intestinal parasitic diseases, particularly in patients with bladder cancer who are admitted from areas with an increased incidence of intestinal parasitic diseases, before opening the bowel segments during surgery to perform radical cystectomy and urinary diversion.

Comprehensive Genomic Characterization of Upper Tract Urothelial Carcinoma.

PubMed

Moss, Tyler J; Qi, Yuan; Xi, Liu; Peng, Bo; Kim, Tae-Beom; Ezzedine, Nader E; Mosqueda, Maribel E; Guo, Charles C; Czerniak, Bogdan A; Ittmann, Michael; Wheeler, David A; Lerner, Seth P; Matin, Surena F

2017-10-01

Upper urinary tract urothelial cancer (UTUC) may have unique etiologic and genomic factors compared to bladder cancer. To characterize the genomic landscape of UTUC and provide insights into its biology using comprehensive integrated genomic analyses. We collected 31 untreated snap-frozen UTUC samples from two institutions and carried out whole-exome sequencing (WES) of DNA, RNA sequencing (RNAseq), and protein analysis. Adjusting for batch effects, consensus mutation calls from independent pipelines identified DNA mutations, gene expression clusters using unsupervised consensus hierarchical clustering (UCHC), and protein expression levels that were correlated with relevant clinical variables, The Cancer Genome Atlas, and other published data. WES identified mutations in FGFR3 (74.1%; 92% low-grade, 60% high-grade), KMT2D (44.4%), PIK3CA (25.9%), and TP53 (22.2%). APOBEC and CpG were the most common mutational signatures. UCHC of RNAseq data segregated samples into four molecular subtypes with the following characteristics. Cluster 1: no PIK3CA mutations, nonsmokers, high-grade

Follow-up imaging of the urinary tract in spinal injury patients: is a KUB necessary with every ultrasound?

PubMed

Tins, B; Teo, H-G; Popuri, R; Cassar-Pullicino, V; Tyrrell, P

2005-04-01

Prospective study of 100 consecutive patients. To evaluate the diagnostic usefulness of the urinary tract (KUB) radiograph routinely performed as part of spinal injury patient urinary tract screening with ultrasound (US) and the KUB radiograph. Orthopaedic and District General Hospital with spinal injuries unit, UK. Prospective study of the urinary tract of 100 consecutive routine follow-up spinal injury patients with KUB (kidneys, ureters, bladder) radiograph and US of the urinary tract. The percentage of the visualised area of kidneys and urinary bladder and relevant abnormal findings were recorded. Relevant patient history was recorded. In all, 80 men 20 women were examined (average age 46 years, average time since injury 11 years). A total of 199 kidneys and 99 urinary bladders were examined. On average, less than 50% of the renal area and about 70-75% of the urinary bladder area were visualised. Five patients had renal stones identified on the KUB radiograph, and of these two were seen on US. There were no stones seen on US only. The patient history was not helpful to identify patients with renal stones. Significant further renal abnormalities were identified with US in 14 patients, and with the KUB radiograph in 0 patients. Significant urinary bladder abnormalities were identified with US in 20 patients, and with the KUB radiograph in 0 patients. On average, less than 50% of the kidney area is visualised on the KUB due to overlying bowel markings making the KUB radiograph a poor tool to assess the kidneys. The KUB radiograph and US are poor tools to assess urinary tract stones. In the absence of a therapeutic consequence, the KUB radiograph does not seem justified in the routine follow-up of the urinary tract in spinal injury patients.

An attempt to diagnose cancer by PIXE

NASA Astrophysics Data System (ADS)

Uda, M.; Maeda, K.; Sasa, Y.; Kusuyama, H.; Yokode, Y.

1987-03-01

PIXE is suitable especially for trace elemental analysis for atoms with high atomic numbers, which are contained in matrices composed mainly of light elements such as biological materials. An attempt has been made to distinguish elemental concentrations of cancer tissues from those of normal ones. Kidney, testis and urinary bladder cancer tissues were examined by PIXE. Key elements to diagnose these cancers were Ca, Ti, Cr, Fe and Zn. Enrichment of Fe and Ti, and deficiency of Zn could be seen in the kidney cancer. An opposite tendency was observed in the testicular cancer. Imbalance of these elemental concentrations in characteristic organs might give us a possibility for cancer diagnosis.

Urinary tract injuries during cesarean section in patients with morbid placental adherence: retrospective cohort study.

PubMed

Alanwar, Ahmed; Al-Sayed, Helmy M; Ibrahim, Ahmed M; Elkotb, Ahmed M; Abdelshafy, Ahmed; Abdelhadi, Rasha; Abbas, Ahmed M; Abdelmenam, Hend S; Fares, Tamer; Nossair, Wael; Abdallah, Ameer A; Sabaa, Haitham; Nawara, Maii

2017-12-03

The purpose of this study is to evaluate the cases of lower urinary tract injuries during cesarean section with or without hysterectomy in cases with morbid placental adherence. This record based retrospective study was conducted at Ain Shams University Maternity Hospital in Cairo, Egypt during the period between January 2014 and December 2016. It included all patients who had urinary tract injuries during cesarean section with or without hysterectomy in the cases with morbid placental adherence and they were collected from files of pregnant women who were admitted at hospital planned for termination of pregnancy. Patients were enrolled in four groups, Group 1: cases without urinary tract injuries. Group 2: cases with injuries to the bladder. Group 3: cases with injuries of the ureter. Group 4: cases with injuries to the bladder and ureter. This study gave us new information about the incidence of urinary tract injuries during cesarean section with morbid adherence placenta was 21.7% (Bladder 11.7%, Ureter 4.7%, and bladder with ureter 5.3%). There were various types of repair of urinary tract injury, as the following, bladder repair 10.8%, ureteric catheterization 0.9%, ureterovesical repair or reimplantation 1.5%, bladder repair and ureterovesical 1.2%, bladder repair and ureteric catheterization 2.3%, ureteric catheterization and ureterovesical 1.5 and 6.4% of cases needed urologic consultations. There is a real relation between urinary tract injury and obesity (55.3%). Bladder invasion was found in only 26.9% of all cases according to sonography findings. Most of the cases were delivered by cesarean section in 67.5%, and the remainders were delivered by cesarean hysterectomy 32.5%. About 96.5% of cases needed a blood transfusion. The morbid adherent placenta is still a challenge, which faces us as obstetricians, due to high morbidity and mortality. A multidisciplinary team is mandatory to avoid complications.

p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma.

PubMed

Alexander, Riley E; Hu, Yingchuan; Kum, Jennifer B; Montironi, Rodolfo; Lopez-Beltran, Antonio; Maclennan, Gregory T; Idrees, Muhammad T; Emerson, Robert E; Ulbright, Thomas M; Grignon, David G; Eble, John N; Cheng, Liang

2012-11-01

Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

Receptors, channels, and signalling in the urothelial sensory system in the bladder

PubMed Central

Merrill, Liana; Gonzalez, Eric J.; Girard, Beatrice M.; Vizzard, Margaret A.

2017-01-01

The storage and periodic elimination of urine, termed micturition, requires a complex neural control system to coordinate the activities of the urinary bladder, urethra, and urethral sphincters. At the level of the lumbosacral spinal cord, lower urinary tract reflex mechanisms are modulated by supraspinal controls with mechanosensory input from the urothelium, resulting in regulation of bladder contractile activity. The specific identity of the mechanical sensor is not yet known, but considerable interest exists in the contribution of transient receptor potential (TRP) channels to the mechanosensory functions of the urothelium. The sensory, transduction, and signalling properties of the urothelium can influence adjacent urinary bladder tissues including the suburothelial nerve plexus, interstitial cells of Cajal, and detrusor smooth muscle cells. Diverse stimuli, including those that activate TRP channels expressed by the urothelium, can influence urothelial release of chemical mediators (such as ATP). Changes to the urothelium are associated with a number of bladder pathologies that underlie urinary bladder dysfunction. Urothelial receptor and/or ion channel expression and the release of signalling molecules (such as ATP and nitric oxide) can be altered with bladder disease, neural injury, target organ inflammation, or psychogenic stress. Urothelial receptors and channels represent novel targets for potential therapies that are intended to modulate micturition function or bladder sensation. PMID:26926246

Dietary factors associated with bladder cancer.

PubMed

Piyathilake, Chandrika

2016-06-01

It is biologically plausible for dietary factors to influence bladder cancer risk considering that beneficial as well as harmful components of a diet are excreted through the urinary tract and in direct contact with the epithelium of the bladder. However, studies that investigated the association between dietary factors and bladder cancer (BC) risk have largely reported inconsistent results. The macronutrient intake and risk of BC could have yield inconsistent results across studies because of lack of details on the type, source and the quantities of different dietary fatty acids consumed. There is evidence to suggest that consumption of processed meat may increase BC risk. Dietary carbohydrate intake does not appear to be directly associated with BC risk. Even though a large number of studies have investigated the association between fruit/vegetable consumption/micronutrients in those and BC risk, they have yielded inconsistent results. Gender-specific subgroup analysis, details of how fruits and vegetables are consumed (raw vs. cooked), adequate control for smoking status/aggressiveness of the cancer and consideration of genetic make-up may clarify these inconsistent results. There is no strong evidence to suggest that supplementation with any common micronutrient is effective in reducing BC risk. These limitations in published research however do not totally eclipse the observation that a diet rich in fruits and vegetables and low in processed meat along with especially smoking cessation may convey some protective effects against BC risk.

Inhibitors of peptidases: how they influence the biological activities of substance P, neurokinins, bradykinin and angiotensin in guinea pig, hamster and rat urinary bladders.

PubMed

Rouissi, N; Nantel, F; Drapeau, G; Rhaleb, N E; Dion, S; Regoli, D

1990-01-01

Neurokinins, bradykinin and angiotensins were tested in isolated urinary bladder of the guinea pig, the hamster and the rat, in the absence and in presence of a variety of peptidase inhibitors in order to establish if peptide degradation interferes with the bladder contractions elicited by the three types of peptides. Indeed, the effects of neurokinins, bradykinin and angiotensin I in the guinea pig bladder were significantly enhanced by captopril (4.6 x 10(-6) mol/l), chymostatin (1 mg/l), phosphoramidon (4.6 x 10(-6) mol/l) and thiorphan (1.0 x 10(-6) mol/l), while only captopril was found to potentiate the effects of the same peptides in the rat bladder. The four peptidase inhibitors, as well as bacitracin were found to modify the responses of the hamster urinary bladder to one or another or to all three groups of peptides and to DiMeC7. The present results suggest that the urinary bladders of various species have different types of active proteolytic enzymes: only the angiotensin-converting enzyme appears to be present in the rat bladder, while the same enzyme and possibly two additional endopeptidases interfere with the myotropic effects of neurokinins, kinins and angiotensins in the guinea pig and the hamster bladder.

Relationship among bacterial virulence, bladder dysfunction, vesicoureteral reflux and patterns of urinary tract infection in children.

PubMed

Storm, Douglas W; Patel, Ashay S; Horvath, Dennis J; Li, Birong; Koff, Stephen A; Justice, Sheryl S

2012-07-01

We hypothesized that virulence levels of Escherichia coli isolates causing pediatric urinary tract infections differ according to severity of infection and also among various uropathies known to contribute to pediatric urinary tract infections. We evaluated these relationships using in vitro cytokine interleukin-6 elicitation. E. coli isolates were cultured from children presenting with urinary tract infections. In vitro cytokine (interleukin-6) elicitation was quantified for each isolate and the bacteria were grouped according to type of infection and underlying uropathy (neurogenic bladder, nonneurogenic bowel and bladder dysfunction, primary vesicoureteral reflux, no underlying etiology). A total of 40 E. coli isolates were collected from children with a mean age of 61.5 months (range 1 to 204). Mean level of in vitro cytokine elicitation from febrile urinary tract infection producing E. coli was significantly lower than for nonfebrile strains (p = 0.01). The interleukin-6 response to E. coli in the neurogenic bladder group was also significantly higher than in the vesicoureteral reflux (p = 0.01) and no underlying etiology groups (p = 0.02). In vitro interleukin-6 elicitation, an established marker to determine bacterial virulence, correlates inversely with clinical urinary tract infection severity. Less virulent, high cytokine producing E. coli were more likely to cause cystitis and were more commonly found in patients with neurogenic bladder and nonneurogenic bowel and bladder dysfunction, whereas higher virulence isolates were more likely to produce febrile urinary tract infections and to affect children with primary vesicoureteral reflux and no underlying etiology. These findings suggest that bacteria of different virulence levels may be responsible for differences in severity of pediatric urinary tract infections and may vary among different underlying uropathies. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

[Intrarenal Bacillus Calmette-Guerin perfusion therapy was effective for carcinoma in situ of the upper urinary tract after ileal conduit replacement : a case report].

PubMed

Hayashi, Takuji; Yamanaka, Yohei; Kinjo, Takanori; Katayama, Kinzo; Kamoto, Akihito; Mori, Naoki; Yoshioka, Toshiaki

2014-04-01

A 63-year-old man who had undergone radical cystectomy and ileal conduit formation for invasive bladder cancer 3 years before presented with continuous positive urinary cytology in the ileal conduit. His diagnosis was carcinoma in situ (CIS) of the left upper urinary tract. He was treated with Bacillus Calmette-Guérin (BCG) perfusion therapy using a single-J ureteric stent. BCG (80 mg) in 100 ml saline was instilled in a one-hour period weekly for 6 weeks. Usage of another catheter was effective for continuing the therapy. Urinary cytology in the left upper urinary tract and the ileal conduit became negative after the therapy. There was no evidence of recurrence or metastasis of urothelial carcinoma 6 months after the therapy.

Optogenetic Modulation of Urinary Bladder Contraction for Lower Urinary Tract Dysfunction

NASA Astrophysics Data System (ADS)

Park, Jae Hong; Hong, Jin Ki; Jang, Ja Yun; An, Jieun; Lee, Kyu-Sung; Kang, Tong Mook; Shin, Hyun Joon; Suh, Jun-Kyo Francis

2017-01-01

As current clinical approaches for lower urinary tract (LUT) dysfunction such as pharmacological and electrical stimulation treatments lack target specificity, thus resulting in suboptimal outcomes with various side effects, a better treatment modality with spatial and temporal target-specificity is necessary. In this study, we delivered optogenetic membrane proteins, such as channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), to bladder smooth muscle cells (SMCs) of mice using either the Cre-loxp transgenic system or a viral transfection method. The results showed that depolarizing ChR2-SMCs with blue light induced bladder contraction, whereas hyperpolarizing NpHR-SMCs with yellow light suppressed PGE2-induced overactive contraction. We also confirmed that optogenetic contraction of bladder smooth muscles in this study is not neurogenic, but solely myogenic, and that optogenetic light stimulation can modulate the urination in vivo. This study thus demonstrated the utility of optogenetic modulation of smooth muscle as a means to actively control the urinary bladder contraction with spatial and temporal accuracy. These features would increase the efficacy of bladder control in LUT dysfunctions without the side effects of conventional clinical therapies.

Differentiation‐associated urothelial cytochrome P450 oxidoreductase predicates the xenobiotic‐metabolizing activity of “luminal” muscle‐invasive bladder cancers

PubMed Central

Arlt, Volker M.; Indra, Radek; Joel, Madeleine; Stiborová, Marie; Eardley, Ian; Ahmad, Niaz; Otto, Wolfgang; Burger, Maximilian; Rubenwolf, Peter; Phillips, David H.; Southgate, Jennifer

2018-01-01

Extra‐hepatic metabolism of xenobiotics by epithelial tissues has evolved as a self‐defence mechanism but has potential to contribute to the local activation of carcinogens. Bladder epithelium (urothelium) is bathed in excreted urinary toxicants and pro‐carcinogens. This study reveals how differentiation affects cytochrome P450 (CYP) activity and the role of NADPH:P450 oxidoreductase (POR). CYP1A1 and CYP1B1 transcripts were inducible in normal human urothelial (NHU) cells maintained in both undifferentiated and functional barrier‐forming differentiated states in vitro. However, ethoxyresorufin O‐deethylation (EROD) activity, the generation of reactive BaP metabolites and BaP‐DNA adducts, were predominantly detected in differentiated NHU cell cultures. This gain‐of‐function was attributable to the expression of POR, an essential electron donor for all CYPs, which was significantly upregulated as part of urothelial differentiation. Immunohistology of muscle‐invasive bladder cancer (MIBC) revealed significant overall suppression of POR expression. Stratification of MIBC biopsies into “luminal” and “basal” groups, based on GATA3 and cytokeratin 5/6 labeling, showed POR over‐expression by a subgroup of the differentiated luminal tumors. In bladder cancer cell lines, CYP1‐activity was undetectable/low in basal PORlo T24 and SCaBER cells and higher in the luminal POR over‐expressing RT4 and RT112 cells than in differentiated NHU cells, indicating that CYP‐function is related to differentiation status in bladder cancers. This study establishes POR as a predictive biomarker of metabolic potential. This has implications in bladder carcinogenesis for the hepatic versus local activation of carcinogens and as a functional predictor of the potential for MIBC to respond to prodrug therapies. PMID:29323757

COMPARISON OF IN VITRO AND IN VIVO RESPONSES TO ARSENIC: GENE EXPRESSION PROFILING IN NORMAL HUMAN EPIDERMAL KERATINOCYTES AND HYPERKERATOSES FROM ARSENIC-EXPOSED HUMANS

EPA Science Inventory

Chronic exposure to arsenic is positively associated with skin, urinary bladder, lung, liver and kidney cancer development in humans. Elucidating the mode of action of arsenic carcinogenesis is a complicated issue as target cells are exposed to different toxic species of arsenic....

Hospital-Acquired Urinary Tract Infections: Results of a Cohort Study Performed in an Internal Medicine Department.

PubMed

Lobão, Maria João; Sousa, Paulo

2017-09-29

Urinary tract infections are the most frequent healthcare associated infections, being related to both high costs and morbidity. Our intention was to carry out an epidemiological characterization of hospital acquired urinary tract infections that occurred in an internal medicine department of a Portuguese hospital. Retrospective cohort study (historic cohort). Data were analysed from a systematic random sample of 388 patients, representative of the 3492 admissions occurred in 2014 in that department. One in four patients underwent the placement of a bladder catheter [24.7% (n = 96); 95% CI: 20% - 29%], 36.5% (95% CI: 33% - 48%) of which in the absence of clinical criteria for that procedure. The global cumulative incidence rate for nosocomial urinary tract infections was 4.6% (95% CI: 2.5% - 6.7%). Most hospital acquired urinary tract infections (61.1%) were related to bladder catheter use. We quantified 3.06 infections / 1000 patient-days and 14.5 infections / 1000 catheter-days. Catheter associated urinary tract infection occurred at an early stage of hospitalization. The vast majority of patients (66.7%) that developed a catheter associated urinary tract infection were subjected to bladder catheter placement at emergency department. Seventy one per cent of catheter associated urinary tract infection occurred in patients that were subjected to bladder catheter placement without criteria. These results point to an excessive and inadequate use of urinary catheters, highlighting the need for judicious use taking into account the formal clinical indications. The incidence of catheter associated urinary tract infection is similar to what we found in other studies. Nevertheless we found a very high incidence density per catheter-days that may foresee a problem probably related to the absence of early withdrawal of the device, and to both bladder catheter placement and maintenance practices. A significant part of catheter associated urinary tract infection occurred in patients that had the bladder catheter placed in the emergency department, before the admission to the internal medicine ward, which highlights the need to assess the urinary catheterization practices in those departments. The high rate of catheter associated urinary tract infection that occurred in the absence of bladder placement indication reinforces the need to implement prevention strategies that contemplate the reduction of its use. Emergency departments should be part of quality improvement projects in this area. Causes for the early onset of catheter associated urinary tract infection in this cohort should be investigated.

Protocol of a prospective cohort study of the effect of different methods of drainage of neuropathic bladder on occurrence of symptomatic urinary infection, and adverse events related to the urinary drainage system in spinal cord injury patients

PubMed Central

Vaidyanathan, Subramanian; Soni, Bhakul M; Gurpreet, Singh; Mansour, Paul; Hughes, Peter L; Oo, Tun; Sett, Pradipkumar; Parsons, Keith F; Davies, John C

2001-01-01

Background To present a protocol of a prospective, cohort study in which four groups of spinal cord injury (SCI) patients will participate. (Patients with indwelling urethral catheter; patients who perform intermittent catheterisation without wearing a penile sheath; patients who perform intermittent catheterisation and wear penile sheath as well; and patients with penile sheath drainage). Objectives (1) What is the incidence of symptomatic urinary infection in men with spinal cord injury who use different types of bladder drainage? (2) Which are predisposing factors for the occurrence of symptomatic urinary infection in men with spinal cord injury who practise different methods of bladder drainage? (3) What is the incidence of catheter and urinary drainage system-related adverse events in the four groups of SCI patients? Patients The criteria for inclusion are as follow: (1) Male patients with neuropathic bladder due to spinal cord injury, who are registered with the Regional Spinal Injuries Centre, Southport, England. (2) Age: 18 years or above. (3) Patients who are willing to give informed consent for participation in the study. (4) Patients willing to be contacted every two weeks by a staff of the spinal unit for 36 months. (5) Patients who are willing to maintain an accurate record of adverse events related to urinary catheter and urinary drainage system and predisposing factors for the occurrence of symptomatic urinary infection. (6) Patients, who are stabilised in a particular method of bladder drainage, and therefore, unlikely to make a permanent change in the method of bladder drainage (e.g. from penile sheath drainage to the use of long-term indwelling catheter) during a foreseeable future. Methods The participants will be observed for a period of 36 months. A staff of the spinal injuries unit will contact the participants by telephone every two weeks on a mutually agreed day and time. The information obtained during this standardised telephonic interview conducted once in two weeks will be entered in a database. When a participant develops symptom(s) suggestive of urinary infection, he will undergo urine and blood tests, and imaging studies of the urinary tract. Conclusion This study will provide information regarding the occurrence of symptomatic urinary infection, predisposing factors for development of urinary infection, and adverse events related to urinary catheter and urinary drainage system in SCI patients using different methods of bladder drainage. PMID:11734072

Secondary signet-ring cell adenocarcinoma of urinary bladder from a gastric primary

PubMed Central

Sharma, Pramod K.; Vijay, Mukesh K.; Das, Ranjit K.; Chatterjee, Uttara

2011-01-01

Primary bladder tumor is a frequent urological malignancy, whereas the incidence of secondary bladder tumor from a distant organ is quite rare. Secondary bladder neoplasms represent 1% of all malignant bladder tumors, of which distant metastases from stomach account for about 4% of cases. We present the case of a 30-year-old male who underwent partial gastrectomy for Signet-ring cell carcinoma of the stomach and presented 2 years later with hematuria. On computerized tomography scan, a bladder tumor was found which was resected cystoscopically. The histopathological examination revealed secondary Signet-ring cell adenocarcinoma of the urinary bladder. PMID:21747602

Perivascular epithelioid cell neoplasm of the urinary bladder in an adolescent: a case report and review of the literature

PubMed Central

2012-01-01

Abstract Perivascular epithelioid cell neoplasms (PEComas) of the urinary bladder are extremely rare and the published cases were comprised predominantly of middle-aged patients. Herein, the authors present the first urinary bladder PEComa occurring in an adolescent. This 16-year-old Chinese girl present with a 3-year history of abdominal discomfort and a solid mass was documented in the urinary bladder by ultrasonography. Two years later, at the age of 18, the patient underwent transurethral resection of the bladder tumor. Microscopically, the tumor was composed of spindled cells mixed with epithelioid cells. Immunohistochemically, the tumor were strongly positive for HMB45, smooth muscle actin, muscle-specific actin, and H-caldesmon. Fluorescence in situ hybridization analysis revealed no evidence of EWSR1 gene rearrangement. The patient had been in a good status without evidence of recurrence 13 months after surgery. Urinary bladder PEComa is an extremely rare neoplasm and seems occur predominantly in middle-aged patients. However, this peculiar lesion can develop in pediatric population and therefore it should be rigorously distinguished from their mimickers. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1870004378817301 PMID:23276164

Carcinosarcoma of the Urinary Bladder: A Case Report

PubMed Central

Gupta, Limci; Elder, Jacqueline

2005-01-01

Carcinosarcomas are rare tumours containing both malignant mesenchymal and epithelial elements. This reports presents a 70-year-old man with carcinosarcoma of the urinary bladder, which is proven histologically. PMID:15962192

Lower urinary tract development and disease

PubMed Central

Rasouly, Hila Milo; Lu, Weining

2013-01-01

Congenital Anomalies of the Lower Urinary Tract (CALUT) are a family of birth defects of the ureter, the bladder and the urethra. CALUT includes ureteral anomalies such as congenital abnormalities of the ureteropelvic junction (UPJ) and ureterovesical junction (UVJ), and birth defects of the bladder and the urethra such as bladder-exstrophy-epispadias complex (BEEC), prune belly syndrome (PBS), and posterior urethral valves (PUV). CALUT is one of the most common birth defects and is often associated with antenatal hydronephrosis, vesicoureteral reflux (VUR), urinary tract obstruction, urinary tract infections (UTI), chronic kidney disease and renal failure in children. Here, we discuss the current genetic and molecular knowledge about lower urinary tract development and genetic basis of CALUT in both human and mouse models. We provide an overview of the developmental processes leading to the formation of the ureter, bladder, and urethra, and different genes and signaling pathways controlling these developmental processes. Human genetic disorders that affect the ureter, bladder and urethra and associated gene mutations are also presented. As we are entering the post-genomic era of personalized medicine, information in this article may provide useful interpretation for the genetic and genomic test results collected from patients with lower urinary tract birth defects. With evidence-based interpretations, clinicians may provide more effective personalized therapies to patients and genetic counseling for their families. PMID:23408557

Repeated variate stress in male rats induces increased voiding frequency, somatic sensitivity, and urinary bladder nerve growth factor expression

PubMed Central

Merrill, Liana; Malley, Susan

2013-01-01

Stress exacerbates symptoms of functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) in humans, but mechanisms contributing to symptom worsening are unknown. These studies address stress-induced changes in the structure and function of the micturition reflex using an animal model of stress in male rats. Rats were exposed to 7 days of repeated variate stress (RVS). Target organ (urinary bladder, thymus, adrenal gland) tissues were collected and weighed following RVS. Evans blue (EB) concentration and histamine, myeloperoxidase (MPO), nerve growth factor (NGF), brain-derived neurotropic factor (BDNF), and CXCL12 protein content (ELISA) were measured in the urinary bladder, and somatic sensitivity of the hindpaw and pelvic regions was determined following RVS. Bladder function was evaluated using continuous, open outlet intravesical infusion of saline in conscious rats. Increases in body weight gain were significantly (P ≤ 0.01) attenuated by day 5 of RVS, and adrenal weight was significantly (P ≤ 0.05) increased. Histamine, MPO, NGF, and CXCL12 protein expression was significantly (P ≤ 0.01) increased in the urinary bladder after RVS. Somatic sensitivity of the hindpaw and pelvic regions was significantly (P ≤ 0.01) increased at all monofilament forces tested (0.1–4 g) after RVS. Intercontraction interval, infused volume, and void volume were significantly (P ≤ 0.01) decreased after RVS. These studies demonstrate increased voiding frequency, histamine, MPO, NGF, and CXCL12 bladder content and somatic sensitivity after RVS suggesting an inflammatory component to stress-induced changes in bladder function and somatic sensitivity. PMID:23657640

The urinary bladder of spontaneously hypertensive rat demonstrates bladder hypertrophy, inflammation, and fibrosis but not hyperplasia

PubMed Central

Shen, Shanwei; Xia, Chun-mei; Qiao, Li-Ya

2014-01-01

The present study aims to systemically characterize the factors that are associated with urinary bladder organ enlargement in the spontaneously hypertensive rats (SHR). Material and Methods We compared the SHR to age-matched normotensive Wistar-Kyoto (WKY) control rats in the levels of bladder pro-inflammatory factors, collagen expression (type I), and detrusor smooth muscle growth. Key Findings Our results showed that enhanced inflammatory responses and fibrosis were key factors that were closely associated with bladder wall thickening in SHR. Specifically the mRNA levels of inflammatory factors interleukin (IL)-1α, IL-6 and TNFα were significantly higher in SHR than those in WKY. The SHR also had a higher number of mast cells in the suburothelium space. Type I collagen production was also significantly higher in SHR when compared to those in control rats. However, the smooth muscle content stayed the same in SHR and WKY rats. This was shown as that the ratio of α-smooth muscle actin (SMA) to the nuclear protein histone H3 showed no difference between these two rat strains. The mRNA and protein levels of proliferating cell nuclear antigen (PCNA) also showed no change in the urinary bladder of SHR and WKY. Further study showed that the phosphorylation level of Akt in the urinary bladder was not changed in SHR when compared to WKY. In contrast, the phosphorylation level of ERK1/2 was significantly higher in SHR bladder when compared to WKY. Significance These results suggest that inflammation and fibrosis are primary factors that may lead to urinary bladder hypertrophy in SHR. PMID:25445218

Proteus mirabilis fimbriae- and urease-dependent clusters assemble in an extracellular niche to initiate bladder stone formation

PubMed Central

Schaffer, Jessica N.; Norsworthy, Allison N.; Sun, Tung-Tien

2016-01-01

The catheter-associated uropathogen Proteus mirabilis frequently causes urinary stones, but little has been known about the initial stages of bladder colonization and stone formation. We found that P. mirabilis rapidly invades the bladder urothelium, but generally fails to establish an intracellular niche. Instead, it forms extracellular clusters in the bladder lumen, which form foci of mineral deposition consistent with development of urinary stones. These clusters elicit a robust neutrophil response, and we present evidence of neutrophil extracellular trap generation during experimental urinary tract infection. We identified two virulence factors required for cluster development: urease, which is required for urolithiasis, and mannose-resistant Proteus-like fimbriae. The extracellular cluster formation by P. mirabilis stands in direct contrast to uropathogenic Escherichia coli, which readily formed intracellular bacterial communities but not luminal clusters or urinary stones. We propose that extracellular clusters are a key mechanism of P. mirabilis survival and virulence in the bladder. PMID:27044107

Decursin inhibits growth of human bladder and colon cancer cells via apoptosis, G1-phase cell cycle arrest and extracellular signal-regulated kinase activation.

PubMed

Kim, Wun-Jae; Lee, Se-Jung; Choi, Young Deuk; Moon, Sung-Kwon

2010-04-01

Decursin, a pyranocoumarin isolated from the Korean Angelica gigas root, has demonstrated anti-cancer properties. In the present study, we found that decursin inhibited cell viability in cultured human urinary bladder cancer 235J cells and colon cancer HCT116 cells. The inhibited proliferation was due to apoptotic induction, because both cells treated with decursin dose-dependently showed a sub-G1 phase accumulation and an increased cytoplasmic DNA-histone complex. Cell death caused by decursin was also associated with the down-regulation of anti-apoptotic factor Bcl-2 and the up-regulation of pro-apoptotic molecules cytochrome c, caspase 3 and Bax. Treatment of both types of cancer cells with decursin resulted in G1-phase cell cycle arrest, as revealed by FACS analyses. In addition, decursin increased protein levels of p21WAF1 with a decrease in cyclins and cyclin dependent kinases (CDKs). Furthermore, decursin induced the activation of extracellular signal-regulated kinases (ERK) in both cancer cell lines, with the notable exceptions of c-Jun N-terminal kinase (JNK) and p38 mitogen activated protein (MAP) kinase. Finally, pretreatment with ERK-specific inhibitor PD98059 reversed decursin-induced p21WAF1 expression and decursin-inhibited cell growth. Thus, these findings suggest that decursin has potential therapeutic efficacy for the treatment of bladder and colon cancer.

Street ketamine-associated bladder dysfunction: an emerging health problem.

PubMed

Lee, Py; Ong, Ta; Chua, Cb; Lei, Ccm; Teh, Gc

2009-01-01

Ketamine is frequently abused nowadays as a recreational drug. Case reports are emerging since 2007 to describe a new clinical entity of severe bladder dysfunction associated with chronic abuse of street ketamine. Severe lower urinary tract symptoms of urinary frequency and urgency which are refractory to conventional treatment. Quality of life is adversely affected as a consequence. Chronic kidney disease will develop in advanced cases. Investigation findings: The urine is sterile on culture. Ultrasound will show reduced bladder capacity with thickened bladder wall. In advanced stage, hydronephrosis and renal impairment will develop. Patients should be advised to stop street ketamine use immediately. Anticholinergic medication could be tried to alleviate the symptoms. Refractory cases with dilatation of the upper urinary tract might need urinary diversion. Awareness of this new condition is essential in diagnosis. Early intervention offers better treatment outcome.

Myeloid sarcoma of the urinary bladder with cutaneous tumour seeding after percutaneous suprapubic catheterization.

PubMed

Geok Chin, Tan; Masir, Noraidah; Noor Hussin, Hamidah; Mohd Sidik, Shiran; Boon Cheok, Lee; Yean, Thean

2011-06-01

Myeloid sarcoma (MS) is a rare extramedullary myeloid tumour. It has been reported in various sites, including lymph node, bone, skin, soft tissue, various organs and the CNS. It may precede or occur concurrently with acute myeloid leukemia. Urinary bladder involvement is extremely uncommon. We report a 70-year-old female who had MS of the urinary bladder, presented with frank and persistent hematuria associated with lower abdominal pain. She subsequently had tumour seeding in the abdominal skin via percutaneous suprapubic catheter. Tumours from both the urinary bladder and skin showed immature cells that were immunoreactive toward LCA (focal), MPO (strong), CD99 (weak) and CD117 (weak). Summary of cases in the literature is presented. The potential of its misdiagnosis and the useful markers for the diagnosis of MS are discussed.

[Feasibility of using connective tissue prosthesis for autoplastic repair of urinary bladder wall defects (an experimental study)].

PubMed

Tyumentseva, N V; Yushkov, B G; Medvedeva, S Y; Kovalenko, R Y; Uzbekov, O K; Zhuravlev, V N

2016-12-01

Experiments on laboratory rats have shown the feasibility of autoplastic repair of urinary bladder wall defects using a connective-tissue capsule formed as the result of an inflammatory response to the presence of a foreign body. The formation of connective tissue prosthesis is characterized by developing fibrous connective tissue, ordering of collagen fibers, reducing the number of cells per unit area with a predominance of more mature cells - fibroblasts. With increasing time of observation, connective tissue prostheses were found to acquire a morphological structure similar to that of the urinary bladder wall. By month 12, the mucosa, the longitudinal and circular muscle layers were formed. The proposed method of partial autoplastic repair of urinary bladder wall is promising, has good long-term results, but requires further experimental studies.

PACAP/VIP and receptor characterization in micturition pathways in mice with overexpression of NGF in urothelium.

PubMed

Girard, Beatrice M; Malley, Susan E; Braas, Karen M; May, Victor; Vizzard, Margaret A

2010-11-01

Urothelium-specific overexpression of nerve growth factor (NGF) in the urinary bladder of transgenic mice stimulates neuronal sprouting or proliferation in the urinary bladder, produces urinary bladder hyperreflexia, and results in increased referred somatic hypersensitivity. Additional NGF-mediated changes might contribute to the urinary bladder hyperreflexia and pelvic hypersensitivity observed in these transgenic mice such as upregulation of neuropeptide/receptor systems. Chronic overexpression of NGF in the urothelium was achieved through the use of a highly urothelium-specific, uroplakin II promoter. In the present study, we examined pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal polypeptide (VIP), and associated receptor (PAC1, VPAC1, VPAC2) transcripts or protein expression in urothelium and detrusor smooth muscle and lumbosacral dorsal root ganglia in NGF-overexpressing and littermate wildtype mice using real-time quantitative reverse transcription-polymerase chain reaction and immunohistochemical approaches. Results demonstrate upregulation of PAC1 receptor transcript and PAC1-immunoreactivity in urothelium of NGF-OE mice whereas PACAP transcript and PACAP-immunoreactivity were decreased in urothelium of NGF-OE mice. In contrast, VPAC1 receptor transcript was decreased in both urothelium and detrusor smooth muscle of NGF-OE mice. VIP transcript expression and immunostaining was not altered in urinary bladder of NGF-OE mice. Changes in PACAP, VIP, and associated receptor transcripts and protein expression in micturition pathways resemble some, but not all, changes observed after induction of urinary bladder inflammation known to involve NGF production.

Selective binding of lectins to normal and neoplastic urothelium in rat and mouse bladder carcinogenesis models.

PubMed

Zupančič, Daša; Kreft, Mateja Erdani; Romih, Rok

2014-01-01

Bladder cancer adjuvant intravesical therapy could be optimized by more selective targeting of neoplastic tissue via specific binding of lectins to plasma membrane carbohydrates. Our aim was to establish rat and mouse models of bladder carcinogenesis to investigate in vivo and ex vivo binding of selected lectins to the luminal surface of normal and neoplastic urothelium. Male rats and mice were treated with 0.05 % N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water and used for ex vivo and in vivo lectin binding experiments. Urinary bladder samples were also used for paraffin embedding, scanning electron microscopy and immunofluorescence labelling of uroplakins. During carcinogenesis, the structure of the urinary bladder luminal surface changed from microridges to microvilli and ropy ridges and the expression of urothelial-specific glycoproteins uroplakins was decreased. Ex vivo and in vivo lectin binding experiments gave comparable results. Jacalin (lectin from Artocarpus integrifolia) exhibited the highest selectivity for neoplastic compared to normal urothelium of rats and mice. The binding of lectin from Amaranthus caudatus decreased in rat model and increased in mouse carcinogenesis model, indicating interspecies variations of plasma membrane glycosylation. Lectin from Datura stramonium showed higher affinity for neoplastic urothelium compared to the normal in rat and mouse model. The BBN-induced animal models of bladder carcinogenesis offer a promising approach for lectin binding experiments and further lectin-mediated targeted drug delivery research. Moreover, in vivo lectin binding experiments are comparable to ex vivo experiments, which should be considered when planning and optimizing future research.

Sacral neuromodulations for female lower urinary tract, pelvic floor, and bowel disorders.

PubMed

Wehbe, Salim A; Whitmore, Kristene; Ho, Mat H

2010-10-01

In recent years, sacral neuromodulation (SNM) has been investigated for the treatment of various types of lower urinary tract and bowel dysfunctions. This review discusses recently published data related to the therapeutic applications of SNM in female lower urinary tract, pelvic floor, and bowel disorders. SNM has been employed initially in the treatment of refractory idiopathic overactive bladder, urge urinary incontinence, and chronic nonobstructive urinary retention. Since then, several studies, including randomized and controlled trials, have confirmed the therapeutic effects of SNM in these disorders. The applications of SNM are now extended to the treatment of other female pelvic problems, such as fecal incontinence, chronic constipation, interstitial cystitis/painful bladder syndrome, sexual dysfunction, and neurogenic disorders, with similar promising results. SNM is approved by the Food and Drug Administration for the treatment of idiopathic overactive bladder, urge urinary incontinence, and chronic nonobstructive urinary retention. SNM is not yet an approved method for the treatment of other pelvic disorders, but data supporting its benefit are emerging. The major advantage of SNM lies in its potential to treat the bladder, urethral sphincter, anal sphincters, and pelvic floor muscles simultaneously, which might result in better therapeutic effects.

Heterotopic Prostate at Autopsy- An Unusual Mass at the Dome of the Urinary Bladder.

PubMed

Munde, Shital; Fernandes, Gwendolyn; Phadnis, Priyanka

2017-09-01

Heterotopic prostate in the dome of the urinary bladder is extremely rare and difficult to diagnose. It is often mistaken for neoplastic masses and histopathological examination is warranted for diagnosis. We report an autopsy case of an ectopic prostate at the dome of the bladder which mimicked a neoplasm on gross pathology.

Dysuria and fever in a young woman diagnosed as having inflammatory myofibroblastic tumour of the urinary bladder

PubMed Central

Patne, Shashikant Chandrakant Urmila; Katiyar, Richa; Chaudhary, Deepshikha; Trivedi, Sameer

2016-01-01

A 38-year-old woman presented with dysuria and fever. Her medical and family histories were unremarkable. CT scan of the abdomen revealed a polypoid mass of 4×2.6×2.2 cm. Her cystoscopy showed a 4×2 cm solid broad-based growth at trigone of the urinary bladder. She underwent transurethral resection of the urinary bladder tumour (TURBT). Histopathology revealed a poorly circumscribed proliferation of spindle cells arranged in a haphazard and fascicular manner along with many traversing blood vessels in a myxoid and hyalinised stroma. Immunohistochemistry was positive for anaplastic lymphoma kinase-1, smooth muscle actin, CD10, cytokeratin and desmin; and negative for CD34 and S-100 protein. Ki-67 proliferative index in the tumour was <1%. The patient was diagnosed as having inflammatory myofibroblastic tumour of the urinary bladder. After TURBT, her fever and urinary symptoms resolved. Her 1-month postoperative period was uneventful. She has been advised regular follow-up. PMID:26880824

Masked urinary bladder injury with a bullet expulsed spontaneously during voiding.

PubMed

Calışkan, Müjgan; Evren, Ismail; Kabak, Ismail; Atak, Ibrahim; Gökcan, Recai

2011-09-01

We report a case with gunshot to the pelvis. The injury site was the soft tissue between the rectum and urinary bladder. Several days later, the bullet was expulsed spontaneously during voiding. In the literature, only a few case reports have described spontaneous expulsion of an intravesical bullet. A 19-year-old male was wounded on the left hip by gunshot. Radiographic examinations showed a bullet in the pelvis, which was localized in the soft tissue between the rectum and urinary bladder, with no accompanying visceral injury on abdominopelvic computerized tomography. Macroscopic hematuria was noticed after urethral catheterization. Rectosigmoidoscopy and retrograde cystoscopic examinations were both negative. The patient was monitored closely and treated conservatively with no surgical intervention. The urinary catheter was removed on the fifth postoperative day, and the bullet was expulsed spontaneously via the urethra during normal voiding three hours after catheter removal. Thereafter, a retrograde urethrography was performed, which showed no evidence of urinary tract or bladder injury.

Effect of transcutaneous electrical stimulation treatment on lower urinary tract symptoms after class III radical hysterectomy in cervical cancer patients: study protocol for a multicentre, randomized controlled trial.

PubMed

Sun, Xiu-Li; Wang, Hai-Bo; Wang, Zhi-Qi; Cao, Ting-Ting; Yang, Xin; Han, Jing-Song; Wu, Yang-Feng; Reilly, Kathleen H; Wang, Jian-Liu

2017-06-15

Class III radical hysterectomy (RH III)_plus pelvic lymphadenectomy is the standard surgery for early stage cervical cancer (CC) patients, the 5 year survival rate is about 90%, but pelvic floor disorders especially bladder dysfunction are common due to damaged vessels and nerve fibers following surgery. Transcutaneous electrical stimulation (TENS) treatment has been used to treat bladder disorders for many years, but its effect on cervical cancer patients, the best treatment time point and stimulated protocol, had never been assessed. The aim of this study is to investigate the efficacy of TENS treatment on lower urinary tract symptoms (LUTS) after RH III in CC patients. The study will be conducted as a clinical, multicentre, randomised controlled trial with balanced randomisation (1:1). The planned sample size is 208 participants (at 1:1 ratio, 104 subjects in each group). At 5-7 days after RH III, patients are screened according to operative and pathological findings. Enrolled participants are randomised into an intervention group (TENS plus conventional clinical care) or control group (conventional clinical care), with stratification by menopausal status (menopause vs. non-menopause) and surgical modality (laparoscopic RH or abdominal RH). Participants in both groups will be followed up at 14 days, 21 days, 28 days, 3 months, 6 months, 12 months, 18 months and 24 months after surgery. The primary endpoint is improvement rate of urination function which is defined as recovery (residual urine ≤50 ml) or improvement (residual urine 50-100 ml). Secondary endpoints include urodynamic parameter, urinary incontinence, anorectal function, pelvic function, quality of life (QOL), disease-free survival and adverse events. Primary endpoint analyses will be carried out by Cochran-Mantel-Haenszel tests taking into center effect. To our knowledge this is the first trial to investigate the effect of TENS treatment on bladder function recovery after RH III among CC patients. This study will provide new information on TENS efficacy for bladder function recovery. Once confirmed, it may help to provide a new, non-invisive treatment for those postoperative CC patients with poor pelvic function, which would help improve their quality of life. The study is registered to Clinical Trials.gov ( NCT02492542 ) on June 25, 2015.

Leech in urinary bladder causing hematuria.

PubMed

Alam, Shadrul; Das Choudhary, Mrigen Kumar; Islam, Kabirul

2008-02-01

To estimate efficacy of normal saline in the management of hematuria caused by accidental entry of a leech per urethra into the urinary bladder. An intervention study was carried out in the Department of Pediatric Surgery of Sylhet MAG Osmani Medical College between January 1998 and December 2003. A total of 43 boys (mean age 8 years, SD+/-2.6) were enrolled. In all cases, a leech had entered the urinary bladder through the urethra causing hematuria. All patients were equipped with a self-retaining Foley catheter. They were managed by infusing 50ml of normal saline into the urinary bladder through the catheter that was then clamped for 3h. After removing the catheter, in all cases the whole leech was spontaneously expelled intact, dead or alive, within 2-24h during the subsequent act of micturition. Hematuria gradually diminished to a clear flow within the next 6h in 27 cases, 12h in 14 cases and 24h in two cases. All patients were followed up for 2 weeks, and none developed recurrent hematuria. Catheterization and irrigation of the urinary bladder with normal saline is a relatively simple, safe and inexpensive method of removing the leech and controlling hematuria.

Frailty and Lower Urinary Tract Symptoms.

PubMed

Suskind, Anne M

2017-09-01

The incidence of both frailty and lower urinary tract symptoms, including urinary incontinence, overactive bladder, underactive bladder, and benign prostatic hyperplasia, increases with age. However, our understanding of the relationship between frailty and lower urinary tract symptoms, both in terms of pathophysiology and in terms of the evaluation and management of such symptoms, is greatly lacking. This brief review will summarize definitions and measurement tools associated with frailty and will also review the existing state of the literature on frailty and lower urinary tract symptoms in older individuals.

Bladder leiomyoma presenting as dyspareunia: Case report and literature review.

PubMed

Xin, Jun; Lai, Hai-Ping; Lin, Shao-Kun; Zhang, Qing-Quan; Shao, Chu-Xiao; Jin, Lie; Lei, Wen-Hui

2016-07-01

Leiomyoma of the bladder is a rare tumor arising from the submucosa. Most patients with bladder leiomyoma may present with urinary frequency or obstructive urinary symptoms. However, there are a few cases of bladder leiomyoma coexisting with uterine leiomyoma presenting as dyspareunia. We herein report an unusual case of coexisting bladder leiomyoma and uterine leiomyoma presenting as dyspareunia. A 44-year-old Asian female presented to urologist and complained that she had experienced dyspareunia over the preceding several months. A pelvic ultrasonography revealed a mass lesion located in the trigone of urinary bladder. The mass lesion was confirmed on contrast-enhanced computed tomography (CT). The CT scan also revealed a lobulated and enlarged uterus consistent with uterine leiomyoma. Then, the biopsies were then taken with a transurethral resection (TUR) loop and these biopsies showed a benign proliferation of smooth muscle in a connective tissue stroma suggestive of bladder leiomyoma. An open local excision of bladder leiomyoma and hysteromyomectomy were performed successfully. Histological examination confirmed bladder leiomyoma coexisting with uterine leiomyoma. This case highlights a rare presentation of bladder leiomyoma, dyspareunia, as the chief symptom in a patient who had coexisting uterine leiomyoma. Bladder leiomyomas coexisting with uterine leiomyomas are rare and can present with a wide spectrum of complaints including without symptoms, irritative symptoms, obstructive symptoms, or even dyspareunia.

Surgical Outcomes of Urinary Tract Deep Infiltrating Endometriosis.

PubMed

Darwish, Basma; Stochino-Loi, Emanuela; Pasquier, Geoffroy; Dugardin, Fabrice; Defortescu, Guillaume; Abo, Carole; Roman, Horace

To report the outcomes of surgical management of urinary tract endometriosis. Retrospective study based on prospectively recorded data (NCT02294825) (Canadian Task Force classification II-3). University tertiary referral center. Eighty-one women treated for urinary tract endometriosis between July 2009 and December 2015 were included, including 39 with bladder endometriosis, 31 with ureteral endometriosis, and 11 with both ureteral and bladder endometriosis. Owing to bilateral ureteral localization in 8 women, 50 different ureteral procedures were recorded. Procedures performed included resection of bladder endometriosis nodules, advanced ureterolysis, ureteral resection followed by end-to-end anastomosis, and ureteroneocystostomy. The main outcome measure was the outcome of the surgical management of urinary tract endometriosis. Fifty women presented with deep infiltrating endometriosis (DIE) of the bladder and underwent either full-thickness excision of the nodule (70%) or excision of the bladder wall without opening of the bladder (30%). Ureteral lesions were treated by ureterolysis in 78% of the patients and by primary segmental resection in 22%. No patient required nephrectomy. Histological analysis revealed intrinsic ureteral endometriosis in 54.5% of cases. Clavien-Dindo grade III complications were present in 16% of the patients who underwent surgery for ureteral nodules and in 8% of those who underwent surgery for bladder endometriosis. Overall delayed postoperative outcomes were favorable regarding urinary symptoms and fertility. Patients were followed up for a minimum of 12 months and a maximum of 7 years postoperatively, with no recorded recurrences. Surgical outcomes of urinary tract endometriosis are generally satisfactory; however, the risk of postoperative complications should be taken into consideration. Therefore, all such procedures should be managed by an experienced multidisciplinary team. Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.

Paraganglioma of the Urinary Bladder: A Rare Cause of Hypertension and Urinary Tract Infections.

PubMed

Chaaya, Gerard; Morales, Jorge; Castiglioni, Analia; Subhani, Noman; Asmar, Abdo

2018-02-01

Pheochromocytoma is a neoplasm, which develops from cells of the chromaffin tissues that are derived from the ectodermic neural system and mostly situated within the adrenal medulla. Approximately 15% of pheochromocytoma cases arise from extra-adrenal chromaffin tissue. Pheochromocytoma of the bladder is rare and accounts for less than 0.06% of all bladder neoplasms and less than 1% of all pheochromocytomas. We report a case of a young woman who presented with uncontrolled hypertension, recurrent urinary tract infections and micturition attacks and was found to have a metastatic bladder paraganglioma. In addition, we provide a summary table of the clinical manifestations of paragangliomas based on anatomic locations. Published by Elsevier Inc.

Impact of complications and bladder cancer stage on quality of life in patients with different types of urinary diversions.

PubMed

Prcic, Alden; Aganovic, Damir; Hadziosmanovic, Osman

2013-12-01

Determine correlation between complications and stage of the disease and their impact on quality of life in patients with different types of ileal urinary derivation after radical cystectomy, and upon estimation of acquired results, to suggest the most acceptable type of urinary diversion. In five year period a prospective clinical study was performed on 106 patients, to whom a radical cystectomy was performed due to bladder cancer. Patients were divided into two groups, 66 patients with ileal conduit derivation and 40 patients with orthotopic derivation, whereby in each group a comparison between reflux and anti-reflux technique of orthotopic bladder was made. All patients from both groups filled the Sickness Impact Profile score six months after the operation. All patients had CT urography or Intravenous urography performed, as well as standard laboratory, vitamin B12 blood values, in order to evaluate early (ileus or subileus, wound dehiscence, bladder fistula, rupture of orthotopic bladder, urine extravazation) and late complications (VUR, urethral stricture, ureter stenosis, metabolic acidosis, mineral dis-balance, hypovitaminosis of vitamin B12, increased resorption of bone calcium, urinary infection, kidney damage, relapse of primary disease), so as disease stage and it's impact on quality of life. From gained results we observe that each category of SIP score correlates with different rate of correlation with the type of operation, group, T, N, and R grade, except work category. Average value of SIP score rises depending on the type of operation and T stage. It is notable that there is no difference in T1 stage, no matter the type of operation. So the average value of SIP score in T1 stage for conduit was 20.3, for Abol-Enein and Ghoneim 17.25 and Hautmann 18.75 respectively. Average value of SIP score in T2 stage for conduit was 31, for Abol-Enein and Ghoneim 19.1 and Hautmann 17.8. Average value of SIP score in T3 stage for conduit was 38.03, for Abol-Enein and Ghoneim 18.75 and Hautmann 19.5. SIP score for T4 was present only in patients with conduit performed and average value od SIP score was 40.42. There is a high level of correlation of late complications and psychosocial and physical dimension with their parameters, while for an independent dimension of correlation is not significant. Early complications have insignificant correlation in all categories of SIP score. Upon analyzing quality of life and morbidity, significant advantage is given to orthotopic derivations, especially Hautmann derivation with Chimney modification, unless there are no absolute contraindications for performing this type of operation. Factors which mostly influence quality of life are cancer stage, type of derivation, late complications and patient age. SIP score, as a well validated questionnaire, are applicable in this kind of research.

A pilot study of urinary microRNA as a biomarker for urothelial cancer

PubMed Central

Snowdon, Jaime; Boag, Sandy; Feilotter, Harriet; Izard, Jason; Siemens, D. Robert

2013-01-01

Objective: MicroRNAs (miRNAs) are part of a class of small ribonucleic acid (RNAs). They are important regulatory molecules, involved in several cell processes, such as developmental timing, stem cell division and apoptosis. Dysregulated miRNAs have been identified in several human malignancies, including bladder cancer tissue samples, and may confer a “tumour signature” that can be exploited for diagnostic purposes. We report on a prospective pilot study investigating the diagnostic capability of miRNAs in the urine of patients with urothelial cancer. Methods: Voided urine samples were collected from patients with urothelial carcinoma just prior to bladder tumour resection, as well as age-matched healthy control patients. Pathology demonstrated both low- and high-grade cancer. Total RNA was isolated and quantitative reverse transcriptase-polymerase chain reaction was performed on the RNA extracts using primers for 4 miRNAs shown previously to be dysregulated in solid urothelial carcinomas with RNU6B as the endogenous control. Standard urine cytology was performed on all samples in a blinded fashion. Results: Two miRNAs of interest were dysregulated in the urine from cancer patients with miR-125b showing an average 10.42-fold decrease (p < 0.01) and miR-126 showing an average 2.70-fold increase (p = 0.30) in the cancer samples compared to the normal controls. The sensitivity and specificity of the cytology on the same urine samples were 50% and 80%, respectively. Using these 2 miRNAs only, a decision-tree prediction model was generated for a validation cohort of patients yielding a specificity of 100% and a sensitivity of 80%. Discussion: This preliminary study of candidate urinary miRNA in patients with low- and high-grade urothelial cancer demonstrated a significantly improved diagnostic accuracy over cytology. These results provide rationale for further studies on discovery and validation of candidate miRNAs in voided urine and may potentially lead to the development of a non-invasive and sensitive test for bladder cancer diagnosis and prognosis. PMID:22630336

Novel Software-Assisted Hemodynamic Evaluation of Pelvic Flow During Chemoperfusion of Pelvic Arteries for Bladder Cancer: Double- Versus Single-Balloon Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamamoto, Kiyohito, E-mail: rad105@poh.osaka-med.ac.jp; Yamamoto, Kazuhiro, E-mail: rad043@poh.osaka-med.ac.jp; Nakai, Go, E-mail: rad091@poh.osaka-med.ac.jp

2016-06-15

PurposeApproximately 83 % of patients with bladder cancer have achieved a complete response after undergoing a novel bladder preservation therapy involving balloon-occluded intra-arterial infusion chemotherapy (BOAI) using a four-lumen double-balloon catheter, known as the Osaka Medical College regimen. This study aimed to show the quantitative difference in hemodynamics of the bladder arteries using syngo iFlow (Siemens Healthcare, Erlangen, Germany), which provides an automatic tool for quantitative blood flow analysis between double BOAI (D-BOAI) and conventional single BOAI (S-BOAI).Materials and MethodsFifty patients were included. The catheters were introduced into both posterior trunks of the internal iliac arteries via contralateral femoral artery access.more » A side hole between the distal and proximal balloons was placed at the origin of each bladder artery to allow clear visualization of angiographic flow of the injected agent into the urinary bladder. Digital subtraction angiography was used during analysis with the syngo iFlow to evaluate the hemodynamics of the contrast medium in the pelvic arteries during BOAI. The comparative change in the amount of contrast medium in the bladder arteries between D-BOAI and S-BOAI was assessed using syngo iFlow.ResultsOne-hundred pelvic sides were analyzed. The amount of contrast medium in the bladder arteries using D-BOAI was more than twice that using S-BOAI (right, 3.03-fold; left, 2.81-fold).ConclusionThe amount of contrast medium in the bladder arteries using D-BOAI was higher than that using conventional S-BOAI. This may increase the anticancer drug concentration in the affected bladder, leading to a good clinical response.« less

[Post-traumatic complication of trans-appendiceal cystostomy: urinary peritonitis].

PubMed

Landry, J L; Dubois, R; Chaffange, P; Pelizzo, G; Dodat, H

2001-04-01

Two children who had undergone a transappendicular urinary diversion (type Mitrofanoff) developed bladder rupture, one following abdominal trauma, 4 months after the operation and the other following traumatic self-catheterization at 4 years. The clinical history and standard radiological examinations (ultrasonography, cystography) confirmed the diagnosis of urinary peritonitis. Emergency surgical repair was possible in both cases with an uneventful postoperative course. This serious and rare complication requires emergency surgery and justifies rigorous selection of children suitable for this type of diversion giving preference to increased bladder neck resistance over bladder neck closure.

Clinical results from first use of prostate stent as fiducial for radiotherapy of prostate cancer.

PubMed

Carl, Jesper; Nielsen, Jane; Holmberg, Mats; Larsen, Erik Hoejkjaer; Fabrin, Knud; Fisker, Rune V

2011-05-01

A clinical feasibility study using a removable prostate stent as fiducial for image-guided radiotherapy (IGRT) of localized prostate cancer (PC). The study included patients with local or locally advanced PC. The clinical target volume (CTV) was outlined on magnetic resonance (MR) images co-registered to planning computer tomography (CT) images. Daily online IGRT was delivered using the stent as fiducial. Risk of migration was estimated using multiple MR. Acute urinary toxicity was scored using the international prostate symptom score (IPSS). Late gastro-intestinal (GI) and genito-urinary (GU) toxicity was scored using the Radio Therapy Oncology Group (RTOG) score, biochemical failure (BF) was defined as an elevation of prostate specific antigen (PSA) above nadir plus 2 ng/ml after radiotherapy. One hundred men were enrolled in the study. Ninety completed radiotherapy with the stent as fiducial. No migration of the stent was seen, but three cases of dislocation of the stent to the bladder were observed. Acute urinary toxicity based on IPSS was comparable to toxicity in patients who had gold markers (GM) as fiducials. Removal of the stent was associated with a high frequency of urinary retention. Late GI and GU toxicity and BF were comparable to those of other studies, but longer observation time is needed. This study reports the first clinical results of using a prostate stent as fiducial. No migration of the stent observed. Dislocation of the stent to the urinary bladder was observed in three cases, requiring removal of the stent and insertion of a new fiducial. Acute toxicity during radiotherapy evaluated from IPSS was comparable to toxicity in patients with GM. Removal of the stent was associated with a high frequency of post procedural urinary retention. Late toxicity and BF were comparable to those of other studies, though longer observation time is needed.

Large sliding inguino-scrotal hernia of the urinary bladder

PubMed Central

Wang, Ping; Huang, Yonggang; Ye, Jing; Gao, Guodong; Zhang, Fangjie; Wu, Hao

2018-01-01

Abstract Rationale: Sliding inguinal hernias of the urinary bladder are protrusions of the bladder through the internal inguinal ring, most of which are insignificant and diagnosed intra-operatively. Large inguino-scrotal bladder hernias commonly present with lower urinary tract symptoms and may cause severe complications, including bladder incarceration or necrosis, bladder hemorrhage, obstructive or neurogenic bladder dysfunction, and even renal failure. Patient concerns: We describe and discuss the clinical findings and management of a 59-year-old man who complained of a decrease in scrotal size after voiding and 2-stage voiding requiring pressure to the scrotum. Diagnoses: The patient was diagnosed preoperatively as massive, bilateral, inguinoscrotal hernias, and a large, left-sided, sliding bladder hernia. Interventions: The patient underwent a timely open re-peritoneal inguinal herniorrhaphy using a mesh. Outcomes: The surgical outcomes were good, and no surgical site infection, chronic postoperative inguinal pain or recurrence were recorded during the follow-up. Lessons: Better knowledge of this rare condition of large inguino-scrotal sliding bladder hernia could help in making a correct diagnosis preoperatively and provide proper surgical management timely, so as to reduce delay in treatment and avoid potential complications. PMID:29595706

Neuropeptides in Lower Urinary Tract (LUT) Function

PubMed Central

Arms, Lauren; Vizzard, Margaret A.

2014-01-01

Numerous neuropeptide/receptor systems including vasoactive intestinal polypeptide, pituitary adenylate cyclase-activating polypeptide, calcitonin gene-related peptide, substance P, neurokinin A, bradykinin, and endothelin-1 are expressed in the lower urinary tract (LUT) in both neural and non-neural (e.g., urothelium) components. LUT neuropeptide immunoreactivity is present in afferent and autonomic efferent neurons innervating the bladder and urethra and in the urothelium of the urinary bladder. Neuropeptides have tissue-specific distributions and functions in the LUT and exhibit neuroplastic changes in expression and function with LUT dysfunction following neural injury, inflammation and disease. LUT dysfunction with abnormal voiding including urinary urgency, increased voiding frequency, nocturia, urinary incontinence and pain may reflect a change in the balance of neuropeptides in bladder reflex pathways. LUT neuropeptide/receptor systems may represent potential targets for therapeutic intervention. PMID:21290237

Horseradish extract promotes urinary bladder carcinogenesis when administered to F344 rats in drinking water.

PubMed

Cho, Young-Man; Hasumura, Mai; Imai, Toshio; Takami, Shigeaki; Nishikawa, Akiyoshi; Ogawa, Kumiko

2017-07-01

Horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate and other isothiocyanates, has been used as a food additive. To evaluate the potential hazards of HRE, a 104-week chronic study, a 2-week analysis of cell proliferation in the urinary bladder and a medium-term promotion bioassay of HRE were conducted with administration at concentrations of up to 0.04% HRE in the drinking water to male F344 rats. In the 104-week chronic study with 32 male rats per group, no treatment-related increases in the incidences of neoplastic lesions in any organ, including urinary bladder, were observed, except for simple hyperplasia in the urinary bladder in rats treated with HRE at concentrations of more than 0.01% (5.0 mg kg -1 body weight day -1 ). In the promotion study, HRE treatment after N-butyl-N-(4-hydroxybutyl)nitrosamine initiation caused a clear increase in papillary or nodular hyperplasia, papilloma, and urothelial carcinoma of the urinary bladder in the groups given HRE for 13 weeks at doses higher than 0.005%, 0.01%, and 0.04% (2.7, 5.4 and 20.5 mg kg -1 body weight day -1 ), respectively. In the 2-week cell proliferation analysis, treatment with HRE at concentrations greater than 0.005% (3.9 mg kg -1 body weight day -1 ) caused transient increases in 5-bromo-2'-deoxyuridine labeling indices in the urothelium. Although clear tumor induction was not observed, administration of relatively low-dose HRE increased cell proliferation in the urothelium and exerted obvious promoting effects on rat urinary bladder carcinogenesis. Further studies are needed to elucidate the mode of action of HRE in the rat urinary bladder to facilitate data extrapolation from the present study and provide insights into risk assessment. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Heterotopic Prostate at Autopsy- An Unusual Mass at the Dome of the Urinary Bladder

PubMed Central

Munde, Shital; Phadnis, Priyanka

2017-01-01

Heterotopic prostate in the dome of the urinary bladder is extremely rare and difficult to diagnose. It is often mistaken for neoplastic masses and histopathological examination is warranted for diagnosis. We report an autopsy case of an ectopic prostate at the dome of the bladder which mimicked a neoplasm on gross pathology. PMID:29207717

Cystitis glandularis in a cat.

PubMed

Agut, Amalia; Carrillo, Juana D; Soler, Marta; García, Juan D; Belda, Eliseo; Gómez, Miguel A; Bernabe, Antonio

2014-04-01

An 8-year-old intact male Persian cat was presented for investigation of chronic haematuria. The cat had episodes of haematuria on several occasions that were non-responsive to antimicrobial therapy. Abdominal ultrasound examination revealed dilation of the renal pelvis and ureters of both kidneys. The urinary bladder wall was thickened, a mass of heterogeneous echogenicity filled the lumen of the bladder, and two parallel thin hyperechoic lines were identified within the lumen, which suggested a urethral catheter. Differential diagnoses for the urinary bladder mass included cystitis and neoplasia. The mass was surgically removed from the urinary bladder, and a urethral catheter was found embedded in the mass. Histopathological findings were consistent with cystitis glandularis of a typical type. Periodic bladder ultrasonographic studies were performed; at the time of writing, over 2 years later, recurrence had not been detected.

Vaginal prolapse with urinary bladder incarceration and consecutive irreducible rectal prolapse in a dog.

PubMed

Ober, Ciprian-Andrei; Peștean, Cosmin Petru; Bel, Lucia Victoria; Taulescu, Marian; Cătoi, Cornel; Bogdan, Sidonia; Milgram, Joshua; Schwarz, Guenter; Oana, Liviu Ioan

2016-09-22

True vaginal prolapse is a rare condition in dogs and it is occasionally observed in animals with constipation, dystocia, or forced separation during breeding. If a true prolapse occurs, the bladder, the uterine body and/or distal part of the colon, may be present in the prolapse. A 2-year-old intact non pregnant Central Asian Shepherd dog in moderate condition, was presented for a true vaginal and rectal prolapse. The prolapses were confirmed by physical examination and ultrasonography. Herniation of the urinary bladder was identified within the vaginal prolapse. The necrotic vaginal wall was resected, the urinary bladder was reduced surgically and fixed to the right abdominal wall to prevent recurrence. Rectal resection and anastomosis was necessary to correct the rectal prolapse. Recurrence of the prolapses was not observed and the dog recovered completely after the surgical treatment. In our opinion, extreme tenesmus arising from constipation may have predisposed to the vaginal prolapse with bladder incarceration and secondarily to rectal prolapse. In the young female dog, true vaginal prolapse with secondary involvement of the urinary bladder and irreducible rectal prolapse is an exceptionally rare condition.

Biomarkers in lower urinary tract symptoms/overactive bladder: a critical overview.

PubMed

Antunes-Lopes, Tiago; Cruz, Célia D; Cruz, Francisco; Sievert, Karl D

2014-07-01

Biomarkers constitute objectively measurable characteristics that can be evaluated as indicators of physiological and pathogenic processes and might be used as diagnostic, prognostic or predictive tools in clinical care. This review examines the availability of biomarkers to treat the dynamic and complex symptoms of overactive bladder (OAB). OAB biomarkers may contribute to reveal the origin of storage symptoms in otherwise healthy individuals. The research encompassing the changes that occur in the bladder or in the peripheral (and central) nervous system might be determined through blood or urinary molecules (neurotrophins, ATP, prostaglandins, C-reactive protein and cytokines) or the measurement of events occurring in the bladder wall (bladder wall or detrusor wall thickness, oxyhemoglobin and deoxyhemoglobin concentration). These biomarkers might contribute to a better understanding of the pathophysiologic mechanisms underlying OAB. The word biomarker to name all the parameters described above, from bladder wall thickness to urinary molecules, has been introduced to call the attention to a field wherein objective noninvasive parameters were nonexistent. OAB treatment based on a biomarker, in comparison to the treatment based on a diagnosis made from a careful history and exclusion of urinary tract infection, is not supported by current literature.

Sonographic findings in acute urinary retention secondary to retroverted gravid uterus: pathophysiology and preventive measures.

PubMed

Yang, J-M; Huang, W-C

2004-05-01

To explore the pathophysiology of acute urinary retention in women with a retroverted gravid uterus and to suggest measures to prevent its recurrence. In five women with a retroverted gravid uterus and acute urinary retention necessitating catheterization, the morphology of the genitourinary system was assessed by using transabdominal, transvaginal and introital sonography. In the supine resting position, the cervix was displaced superiorly and anteriorly by the impacted and retroverted uterus so that it compressed the lower bladder, leading to obstruction of the internal urethral orifice. The upper bladder extended superiorly and overlay the uterus. During straining, urethral motion was not limited and there was an average rotational angle of the bladder neck of 32 degrees, ranging from 21 degrees to 44 degrees. Increasing abdominal pressure further compressed the lower bladder. Measures suggested to the women for the prevention of urinary retention included limiting fluid intake before sleep, changing from the supine to the prone position before getting up and avoiding a Valsalva maneuver but performing a Credé maneuver during voiding. In all except one case these measures successfully prevented recurrence. Acute urinary retention secondary to a retroverted gravid uterus is caused by a displaced cervix compressing the lower bladder and interfering with drainage to the urethra. The urethra itself is not compressed or distorted. Understanding the pathophysiology of the lower urinary tract may allow maneuvers which prevent acute urinary retention. Copyright 2004 ISUOG. Published by John Wiley & Sons, Ltd.

[Recommendations for the urodynamic examination in the investigation of non-neurological female urinary incontinence].

PubMed

Hermieu, Jean François

2007-11-01

INDICATIONS FOR URODYNAMIC ASSESSMENT IN WOMEN: Urodynamic assessment is not useful for the diagnosis of female urinary incontinence which remains a clinical diagnosis. Before any form of surgery for pure stress urinary incontinence, evaluation of bladder emptying by determination of maximum flow rate and residual urine is recommended. In the presence of pure stress urinary incontinence with no other associated clinical symptoms, a complete urodynamic assessment is not mandatory, but can be helpful to define the prognosis and inform the patient about her vesicosphincteric function. On the other hand, a complete urodynamic assessment is recommended to investigate complex or complicated urinary incontinence, mainly in the case of: history of surgery for urinary incontinence. urgency with or without urine leakage, severe urinary incontinence, voiding abnormalities, negative cough test, decreased bladder capacity, suspected obstruction or decreased bladder contractility, failure of first-line treatment. PATIENT PREPARATION: The patient should be thoroughly informed about the examination procedure and its possible consequences. The patient should be advised to attend the examination with a normal desire to urinate. Urodynamic assessment must not be performed in the presence of untreated urinary tract infection. Antibiotic prophylaxis is not recommended. UROFLOWMETRY: The flowmeter must be regularly calibrated and must be installed in a quiet room. Whenever possible, uroflowmetry should be performed before cystometry with a normal desire to urinate. The patient should be advised to urinate normally without straining and by staying as relaxed as possible. During voiding, all of the stream must enter the flowmeter. The main parameters recorded are Qmax (expressed in ml/s), the voided volume (expressed in ml), and the appearance of the curve. The examination must be interpreted manually without taking into account the automated interpretation. GUIDELINES CONCERNING CYSTOMETRY EQUIPMENT: A three pressure line configuration is recommended. Bladder filling must be performed with a sterile liquid; filling with gas is no longer recommended. Bladder filling is ideally performed by a pump ensuring a sufficiently slow flow rate to avoid modifying bladder behaviour (< 50 ml/min). It is essential to determine and check the volume infused into the bladder. When a peristaltic pump is used, the bladder filling catheter must be adapted to the pump. Water or electronic transducers can be used to measure bladder pressure. Balloon catheters filled with air appear to be sufficiently precise to perform pressure measurements in a manometric chamber (during cystometry) but not in a virtual cavity such as the urethra (during the urethral pressure profile). Measurement of abdominal pressure is recommended, either via the infusion catheter or preferably by a rectal balloon catheter. GUIDELINES ON THE PRACTICAL CONDITIONS OF CYSTOMETRY: The equipment must be regularly calibrated. Make sure that the bladder is empty before starting cystometry. Transducers are zeroed at the superior extremity of the pubic symphysis for infused transducers and at atmospheric pressure for electronic and air transducers. Tubings must be correctly connected without kinks, bubbles or leaks. The catheter must be selected according to its technical characteristics, particularly its pressure loss. After filling for one or two minutes, the patient is asked to cough to ensure a similar increase in both abdominal pressure and bladder pressure. The following parameters are recorded: baseline detrusor pressure, first desire to void, detrusor activity, bladder capacity and bladder compliance. Measurement of bladder pressure during voiding is used to confirm whether or not the bladder is contractile, assess obstruction in the case of low urine flow rate with high bladder pressure, and detect abdominal straining. Good test conditions must be ensured in order to obtain good quality voiding. In the case of incoherent results, the bladder should be re-filled after checking the equipment. MEASUREMENT AND INTERPRETATION OF URETHRAL PRESSURE: To obtain a reliable measurement of urethral pressure, it is recommended to: Define the normal values used. Use a catheter smaller than 12 F. Perform a circumferential measurement. Use a catheter with an infusion rate of 2 ml/min. Remove the catheter at a rate of 1 mm/s. Perform the examination in the seating or supine position with a half-full bladder after reducing any prolapse. Repeat the measurements. THE FOLLOWING ELEMENTS MUST BE TAKEN INTO ACCOUNT WHEN INTERPRETING AN URETHRAL PRESSURE PROFILE: The functional urethral length is neither a diagnostic criterion nor a prognostic criterion of urinary incontinence. The urethral pressure profile cannot be considered to be a useful test for the diagnosis of female urinary incontinence. However, in combination with clinical criteria, it is predictive of the results of female stress urinary incontinence surgical repair techniques. The pressure transmission ratio is neither a diagnostic criterion nor a prognostic criterion of urinary incontinence.

Plasticity in reflex pathways to the lower urinary tract following spinal cord injury

PubMed Central

de Groat, William C.; Yoshimura, Naoki

2013-01-01

The lower urinary tract has two main functions, storage and periodic expulsion of urine, that are regulated by a complex neural control system in the brain and lumbosacral spinal cord. This neural system coordinates the activity of two functional units in the lower urinary tract: (1) a reservoir (the urinary bladder) and (2) an outlet (consisting of bladder neck, urethra and striated muscles of the external urethra sphincter). During urine storage the outlet is closed and the bladder is quiescent to maintain a low intravesical pressure. During micturition the outlet relaxes and the bladder contracts to promote efficient release of urine. This reciprocal relationship between bladder and outlet is generated by reflex circuits some of which are under voluntary control. Experimental studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through a coordination center (the pontine micturition center) located in the rostral brainstem. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary control of voiding as well as the normal reflex pathways that coordinate bladder and sphincter function. Following spinal cord injury the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. However the bladder does not empty efficiently because coordination between the bladder and urethral outlet is lost. Studies in animals indicate that dysfunction of the lower urinary tract after spinal cord injury is dependent in part on plasticity of bladder afferent pathways as well as reorganization of synaptic connections in the spinal cord. Reflex plasticity is associated with changes in the properties of ion channels and electrical excitability of afferent neurons and appears to be mediated in part by neurotrophic factors released in the spinal cord and/or the peripheral target organs. PMID:21596038

PACAP/Receptor System in Urinary Bladder Dysfunction and Pelvic Pain Following Urinary Bladder Inflammation or Stress

PubMed Central

Girard, Beatrice M.; Tooke, Katharine; Vizzard, Margaret A.

2017-01-01

Complex organization of CNS and PNS pathways is necessary for the coordinated and reciprocal functions of the urinary bladder, urethra and urethral sphincters. Injury, inflammation, psychogenic stress or diseases that affect these nerve pathways and target organs can produce lower urinary tract (LUT) dysfunction. Numerous neuropeptide/receptor systems are expressed in the neural pathways of the LUT and non-neural components of the LUT (e.g., urothelium) also express peptides. One such neuropeptide receptor system, pituitary adenylate cyclase-activating polypeptide (PACAP; Adcyap1) and its cognate receptor, PAC1 (Adcyap1r1), have tissue-specific distributions in the LUT. Mice with a genetic deletion of PACAP exhibit bladder dysfunction and altered somatic sensation. PACAP and associated receptors are expressed in the LUT and exhibit neuroplastic changes with neural injury, inflammation, and diseases of the LUT as well as psychogenic stress. Blockade of the PACAP/PAC1 receptor system reduces voiding frequency in preclinical animal models and transgenic mouse models that mirror some clinical symptoms of bladder dysfunction. A change in the balance of the expression and resulting function of the PACAP/receptor system in CNS and PNS bladder reflex pathways may underlie LUT dysfunction including symptoms of urinary urgency, increased voiding frequency, and visceral pain. The PACAP/receptor system in micturition pathways may represent a potential target for therapeutic intervention to reduce LUT dysfunction. PMID:29255407

Proteomics Analysis of Bladder Cancer Exosomes*

PubMed Central

Welton, Joanne L.; Khanna, Sanjay; Giles, Peter J.; Brennan, Paul; Brewis, Ian A.; Staffurth, John; Mason, Malcolm D.; Clayton, Aled

2010-01-01

Exosomes are nanometer-sized vesicles, secreted by various cell types, present in biological fluids that are particularly rich in membrane proteins. Ex vivo analysis of exosomes may provide biomarker discovery platforms and form non-invasive tools for disease diagnosis and monitoring. These vesicles have never before been studied in the context of bladder cancer, a major malignancy of the urological tract. We present the first proteomics analysis of bladder cancer cell exosomes. Using ultracentrifugation on a sucrose cushion, exosomes were highly purified from cultured HT1376 bladder cancer cells and verified as low in contaminants by Western blotting and flow cytometry of exosome-coated beads. Solubilization in a buffer containing SDS and DTT was essential for achieving proteomics analysis using an LC-MALDI-TOF/TOF MS approach. We report 353 high quality identifications with 72 proteins not previously identified by other human exosome proteomics studies. Overrepresentation analysis to compare this data set with previous exosome proteomics studies (using the ExoCarta database) revealed that the proteome was consistent with that of various exosomes with particular overlap with exosomes of carcinoma origin. Interrogating the Gene Ontology database highlighted a strong association of this proteome with carcinoma of bladder and other sites. The data also highlighted how homology among human leukocyte antigen haplotypes may confound MASCOT designation of major histocompatability complex Class I nomenclature, requiring data from PCR-based human leukocyte antigen haplotyping to clarify anomalous identifications. Validation of 18 MS protein identifications (including basigin, galectin-3, trophoblast glycoprotein (5T4), and others) was performed by a combination of Western blotting, flotation on linear sucrose gradients, and flow cytometry, confirming their exosomal expression. Some were confirmed positive on urinary exosomes from a bladder cancer patient. In summary, the exosome proteomics data set presented is of unrivaled quality. The data will aid in the development of urine exosome-based clinical tools for monitoring disease and will inform follow-up studies into varied aspects of exosome manufacture and function. PMID:20224111

The impact of obesity in urology.

PubMed

Mydlo, Jack H

2004-05-01

The incidence and progression of urologic diseases, as well as several urologic cancers.depend on many interrelated factors, such as obesity, diet, genetics, environment, age, and the immune system. Obesity is a risk factor for stress urinary incontinence, ED, infertility, and renal calculi. Numerous publications have demonstrated that a high dietary intake of fat increases prostate cancer risk, although the mechanisms are not clear. Although some reports may demonstrate an association between obesity and prostate cancer, it may be hard to establish because, in general, men with obesity have a high-fat diet. Obesity, recurrent urinary tract infections, increased intake of protein and fried foods, and female sex seem to increase the risk of renal cancer. Environmental toxins seem to be the major factors affecting the incidence of bladder cancers. Thus, dietary modification and other public health measures directed at reducing weight may reduce the incidence of urologic illnesses. More studies are necessary to determine the therapeutic effects of weight loss and dietary modification on the incidence and progression of urologic tumors.

Lymphoepithelioma-like carcinoma of the urinary bladder: A case report.

PubMed

Laforga, Juan B; Gasent, Joan M

We report a case of lymphoepithelioma-like carcinoma of the urinary bladder in an elderly female patient. A 97-year old woman presented with hematuria, and an ultrasonographic urinary study showed a localized tumor in the trigone region of the urinary bladder. A transurethral resection revealed a mixed tumor formed by high-grade transitional carcinoma and lymphoepithelioma-like carcinoma that had infiltrated into the muscular propria. We describe the clinicopathological, morphological and immunohistochemical features of this tumor and briefly discuss its differential diagnosis and biological behavior. Copyright © 2016 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.

Role for pAKT in rat urinary bladder with cyclophosphamide (CYP)-induced cystitis

PubMed Central

Arms, Lauren

2011-01-01

AKT phosphorylation following peripheral nerve injury or inflammation may play a role in somatic pain processes and visceral inflammation. To examine such a role in micturition reflexes with bladder inflammation, we induced bladder inflammation in adult female Wistar rats (200–300 g) by injecting cyclophosphamide (CYP) intraperitoneally at acute (150 mg/kg; 4 h), intermediate (150 mg/kg; 48 h), and chronic (75 mg/kg; every third day for 10 days) time points. Western blot analyses of whole urinary bladders showed significant increases (P ≤ 0.01) in phosphorylated (p) AKT at all time points; however, the magnitude of AKT phosphorylation varied with duration of CYP treatment. Immunohistochemical analyses of pAKT immunoreactivity (pAKT-IR) in cryostat bladder sections demonstrated duration-dependent, significant (P ≤ 0.01) increases in pAKT-IR in both the urothelium and detrusor smooth muscle of CYP-inflamed bladders. Additionally, a suburothelial population of pAKT-IR macrophages (CD68-, MAC2-, and F4/80-positive) was present in chronic CYP-treated bladders. The functional role of pAKT in micturition was evaluated using open, conscious cystometry with continuous instillation of saline in conjunction with administration of an inhibitor of AKT phosphorylation, deguelin (1.0 μg/10 μl), or vehicle (1% DMSO in saline) in control (no inflammation) and CYP (48 h)-treated rats. Bladder capacity, void volume, and intercontraction void interval increased significantly (P ≤ 0.05) following intravesical instillation of deguelin in CYP (48 h)-treated rats. These results demonstrate increased AKT phosphorylation in the urinary bladder with urinary bladder inflammation and that blockade of AKT phosphorylation in the urothelium improves overall bladder function. PMID:21632956

Incidence of abnormal imaging and recurrent pyelonephritis after first febrile urinary tract infection in children 2 to 24 months old.

PubMed

Juliano, Trisha M; Stephany, Heidi A; Clayton, Douglass B; Thomas, John C; Pope, John C; Adams, Mark C; Brock, John W; Tanaka, Stacy T

2013-10-01

The AAP (American Academy of Pediatrics) no longer recommends voiding cystourethrogram in children 2 to 24 months old who present with a first urinary tract infection if renal-bladder ultrasound is normal. We identified factors associated with abnormal imaging and recurrent pyelonephritis in this population. We retrospectively evaluated children diagnosed with a first episode of pyelonephritis at age 2 to 24 months using de-identified electronic medical record data from an institutional database. Data included age at first urinary tract infection, gender, race/ethnicity, need for hospitalization, intravenous antibiotic use, history of abnormal prenatal ultrasound, renal-bladder ultrasound and voiding cystourethrogram results, urinary tract infection recurrence and surgical intervention. Risk factors for abnormal imaging and urinary tract infection recurrence were analyzed by univariate logistic regression, the chi-square test and survival analysis. We identified 174 patients. Of the 154 renal-bladder ultrasounds performed 59 (38%) were abnormal. Abnormal prenatal ultrasound (p = 0.01) and the need for hospitalization (p = 0.02) predicted abnormal renal-bladder ultrasound. Of the 95 patients with normal renal-bladder ultrasound 84 underwent voiding cystourethrogram. Vesicoureteral reflux was more likely in patients who were white (p = 0.003), female (p = 0.02) and older (p = 0.04). Despite normal renal-bladder ultrasound, 23 of 84 patients (24%) had dilating vesicoureteral reflux. Of the 95 patients with normal renal-bladder ultrasound 14 (15%) had recurrent pyelonephritis and 7 (7%) went on to surgical intervention. Despite normal renal-bladder ultrasound after a first pyelonephritis episode, a child may still have vesicoureteral reflux, recurrent pyelonephritis and the need for surgical intervention. If voiding cystourethrogram is deferred, parents should be counseled on these risks. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Guillain-Barré Syndrome: Prevalence and Long-Term Factors Impacting Bladder Function in an Australian Community Cohort

PubMed Central

Khan, Fary; Whishaw, Michael; Pallant, Julie F.

2013-01-01

Background and Purpose Urinary dysfunction is associated with significant morbidity in persons with Guillain-Barré Syndrome (GBS). The aim of this study was to describe prevalence and long-term impact of bladder dysfunction on daily activities and quality of life (QoL) in persons in chronic phase of GBS and to examine the relationships between commonly used continence measures in this cohort. Methods Prospective cohort (n=66) following GBS treatment (1996-2009) was recruited from a tertiary hospital and assessed using standardised measures for bladder dysfunction: American Urological Association (AUA) Symptom Index, Incontinence Impact Questionnaire, Urogenital Distress Inventory. Results Sixty-six participants (64% male, mean age 56 years, median disease duration of 6.1 years) completed the study. Of these more than half reported nocturia and one-third reported urinary urgency and frequency. Urinary problems impacted on participants' daily activities: physical recreation (21%), emotional health and mood (17%), entertainment (14%), participation and mobility (>30 min) (12%), and performance of household chores (8%). Since GBS, 49% reported interference of urinary symptoms with daily life to some extent; and adverse impact on QoL (10.6%). Significant relationship between bladder symptoms; and the level of urogenital distress (p<0.001) and the impact of urinary problems (p<0.001), was noted. Higher scores on the bladder scales showed significant correlations with psychological, functional and participation scales. The single QoL item (AUA scale) correlated significantly with all other bladder scales (rho=0.63-0.86). This can be a potential 'screening tool' to identify patients for further assessment. Conclusions Bladder dysfunction in chronic phase of GBS is not well studied. More research in longer-term screening and outcomes for bladder intervention are needed for integrated care and to guide treating clinicians. PMID:23894237

Control over structure-specific flexibility improves anatomical accuracy for point-based deformable registration in bladder cancer radiotherapy.

PubMed

Wognum, S; Bondar, L; Zolnay, A G; Chai, X; Hulshof, M C C M; Hoogeman, M S; Bel, A

2013-02-01

Future developments in image guided adaptive radiotherapy (IGART) for bladder cancer require accurate deformable image registration techniques for the precise assessment of tumor and bladder motion and deformation that occur as a result of large bladder volume changes during the course of radiotherapy treatment. The aim was to employ an extended version of a point-based deformable registration algorithm that allows control over tissue-specific flexibility in combination with the authors' unique patient dataset, in order to overcome two major challenges of bladder cancer registration, i.e., the difficulty in accounting for the difference in flexibility between the bladder wall and tumor and the lack of visible anatomical landmarks for validation. The registration algorithm used in the current study is an extension of the symmetric-thin plate splines-robust point matching (S-TPS-RPM) algorithm, a symmetric feature-based registration method. The S-TPS-RPM algorithm has been previously extended to allow control over the degree of flexibility of different structures via a weight parameter. The extended weighted S-TPS-RPM algorithm was tested and validated on CT data (planning- and four to five repeat-CTs) of five urinary bladder cancer patients who received lipiodol injections before radiotherapy. The performance of the weighted S-TPS-RPM method, applied to bladder and tumor structures simultaneously, was compared with a previous version of the S-TPS-RPM algorithm applied to bladder wall structure alone and with a simultaneous nonweighted S-TPS-RPM registration of the bladder and tumor structures. Performance was assessed in terms of anatomical and geometric accuracy. The anatomical accuracy was calculated as the residual distance error (RDE) of the lipiodol markers and the geometric accuracy was determined by the surface distance, surface coverage, and inverse consistency errors. Optimal parameter values for the flexibility and bladder weight parameters were determined for the weighted S-TPS-RPM. The weighted S-TPS-RPM registration algorithm with optimal parameters significantly improved the anatomical accuracy as compared to S-TPS-RPM registration of the bladder alone and reduced the range of the anatomical errors by half as compared with the simultaneous nonweighted S-TPS-RPM registration of the bladder and tumor structures. The weighted algorithm reduced the RDE range of lipiodol markers from 0.9-14 mm after rigid bone match to 0.9-4.0 mm, compared to a range of 1.1-9.1 mm with S-TPS-RPM of bladder alone and 0.9-9.4 mm for simultaneous nonweighted registration. All registration methods resulted in good geometric accuracy on the bladder; average error values were all below 1.2 mm. The weighted S-TPS-RPM registration algorithm with additional weight parameter allowed indirect control over structure-specific flexibility in multistructure registrations of bladder and bladder tumor, enabling anatomically coherent registrations. The availability of an anatomically validated deformable registration method opens up the horizon for improvements in IGART for bladder cancer.

How should bladder sensation be measured? ICI-RS 2011.

PubMed

De Wachter, S; Smith, Philip P; Smith, P; Tannenbaum, C; Van Koeveringe, G; Drake, M; Wyndaele, J J; Chapple, C

2012-03-01

Disturbed bladder sensations, or in broader terms, sensory dysfunctions are increasingly recognized as key elements in the origin and manifestation of symptom syndromes of urinary dysfunction. Adequate assessment of bladder sensation is crucial to improve our understanding of the pathophysiology and treatment of urinary dysfunction. This manuscript summarizes the discussions of a think tank on "How to measure bladder sensation" held at the ICI-RS meeting in 2011. Based upon literature reviews on bladder sensation presented at the think tank in the ICI-RS meeting, discussions evolved which were summarized in the ICI-RS report. Different physicians/researchers further elaborated on this report, which is presented in this manuscript. Bladder sensations are not merely the result of bladder distension. Other factors inside the bladder or bladder wall: central processing and/or cognitive manipulation may play an important role. Current methods to measure sensations such as urodynamics, voiding diaries, forced diuresis, electrical stimulation and brain imaging are likely sub-optimal as they only consider part of these factors in isolation. Different methods to measure bladder sensations have been described and are used in clinical practice. Current methods only address part of the parameters responsible for the generation and perception of urinary sensations. Further focused research is required, and several recommendations are provided. Copyright © 2012 Wiley Periodicals, Inc.

Fitting NTCP models to bladder doses and acute urinary symptoms during post-prostatectomy radiotherapy.

PubMed

Mavroidis, Panayiotis; Pearlstein, Kevin A; Dooley, John; Sun, Jasmine; Saripalli, Srinivas; Das, Shiva K; Wang, Andrew Z; Chen, Ronald C

2018-02-02

To estimate the radiobiological parameters of three popular normal tissue complication probability (NTCP) models, which describe the dose-response relations of bladder regarding different acute urinary symptoms during post-prostatectomy radiotherapy (RT). To evaluate the goodness-of-fit and the correlation of those models with those symptoms. Ninety-three consecutive patients treated from 2010 to 2015 with post-prostatectomy image-guided intensity modulated radiotherapy (IMRT) were included in this study. Patient-reported urinary symptoms were collected pre-RT and weekly during treatment using the validated Prostate Cancer Symptom Indices (PCSI). The assessed symptoms were flow, dysuria, urgency, incontinence, frequency and nocturia using a Likert scale of 1 to 4 or 5. For this analysis, an increase by ≥2 levels in a symptom at any time during treatment compared to baseline was considered clinically significant. The dose volume histograms of the bladder were calculated. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS) and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC) and Odds Ratio methods. For the symptoms of urinary urgency, leakage, frequency and nocturia, the derived LKB model parameters were: 1) D 50  = 64.2Gy, m = 0.50, n = 1.0; 2) D 50  = 95.0Gy, m = 0.45, n = 0.50; 3) D 50  = 83.1Gy, m = 0.56, n = 1.00; and 4) D 50  = 85.4Gy, m = 0.60, n = 1.00, respectively. The AUC values for those symptoms were 0.66, 0.58, 0.64 and 0.64, respectively. The differences in AIC between the different models were less than 2 and ranged within 0.1 and 1.3. Different dose metrics were correlated with the symptoms of urgency, incontinence, frequency and nocturia. The symptoms of urinary flow and dysuria were poorly associated with dose. The values of the parameters of three NTCP models were determined for bladder regarding four acute urinary symptoms. All the models could fit the clinical data equally well. The NTCP predictions of urgency showed the best correlation with the patient reported outcomes.

Adenocarcinoma of urinary bladder: A report of two patients.

PubMed

Kumari, Nitu; Vasudeva, Pawan; Kumar, Anup; Agrawal, Usha

2015-01-01

Adenocarcinoma of the bladder is a rare tumor. Primary and metastatic adenocarcinomas of urinary bladder are morphologically similar, but histogenetically different. We present two cases, a signet ring cell adenocarcinoma with follow-up and another of glandular adenocarcinoma of urinary bladder. Pathological evaluation and immunohistochemical panel of eight markers (E-cadherin, CK20, CK7, CDX2, estrogen receptor (ER), gross cystic disease fluid protein 15 (GCDFP15), 34bE12, and prostate specific antigen (PSA) provides a diagnostic confirmation of primary adenocarcinoma with the positive expression of E-cadherin and CK20 in case 1 and metastatic adenocarcinoma of prostate with profile of E-cadherin+, CK20-, GCDFP15+, 34bE12+, and PSA+ in case 2.

Herpes zoster induced neuropathic bladder--a case report.

PubMed

Tsai, Hsiu-Nan; Wu, Wen-Jeng; Huang, Shu-Pin; Su, Chin-Ming; Chen, Chung-Chin; Wang, Chii-Jye; Chou, Yii-Her; Huang, Chun-Hsiung

2002-01-01

Herpes zoster infection involving the sacral dermatomes has been associated with bladder dysfunction and, although rarely, with acute urinary retention. Less than 150 cases have been reported in the literature. After reviewing our institute's chart records covering a period of time dating from 1991 to 2001, we found that three of our patients had developed acute urinary retention following herpes zoster skin lesions of the S2-4 dermatomes. Herein we report our findings. These three patients had previously been found to have normal voiding status. However, at the time of complaint urodynamic studies revealed detrusor areflexia or detrusor hyporeflexia with decreased sensation of bladder filling. After micturation recovery, repeat urodynamic studies revealed detrusor pressure and bladder sensation recovery. After one to six weeks of treatment, all three patients could void spontaneously without catheterization. We found that, when treated with antiviral medication, supportive analgesics, and temporary urinary drainage, which included urethral catheterization and suprapubic cystostomy, acute urinary retention associated with herpes zoster has a generally favorable prognosis. In other words, we found that in spite of its rarity, herpes zoster induced neuropathic bladder dysfunction is reversible when treated appropriately.

Urine Stasis Predisposes to Urinary Tract Infection by an Opportunistic Uropathogen in the Megabladder (Mgb) Mouse.

PubMed

Becknell, Brian; Mohamed, Ahmad Z; Li, Birong; Wilhide, Michael E; Ingraham, Susan E

2015-01-01

Urinary stasis is a risk factor for recurrent urinary tract infection (UTI). Homozygous mutant Megabladder (Mgb-/-) mice exhibit incomplete bladder emptying as a consequence of congenital detrusor aplasia. We hypothesize that this predisposes Mgb-/- mice to spontaneous and experimental UTI. Mgb-/-, Mgb+/-, and wild-type female mice underwent serial ultrasound and urine cultures at 4, 6, and 8 weeks to detect spontaneous UTI. Urine bacterial isolates were analyzed by Gram stain and speciated. Bladder stones were analyzed by x-ray diffractometry. Bladders and kidneys were subject to histologic analysis. The pathogenicity of coagulase-negative Staphylococcus (CONS) isolated from Mgb-/- urine was tested by transurethral administration to culture-negative Mgb-/- or wild-type animals. The contribution of urinary stasis to CONS susceptibility was evaluated by cutaneous vesicostomy in Mgb-/- mice. Mgb-/- mice develop spontaneous bacteriuria (42%) and struvite bladder stones (31%) by 8 weeks, findings absent in Mgb+/- and wild-type controls. CONS was cultured as a solitary isolate from Mgb-/- bladder stones. Bladders and kidneys from mice with struvite stones exhibit mucosal injury, inflammation, and fibrosis. These pathologic features of cystitis and pyelonephritis are replicated by transurethral inoculation of CONS in culture-negative Mgb-/- females, whereas wild-type animals are less susceptible to CONS colonization and organ injury. Cutaneous vesicostomy prior to CONS inoculation significantly reduces the quantity of CONS recovered from Mgb-/- urine, bladders, and kidneys. CONS is an opportunistic uropathogen in the setting of urinary stasis, leading to enhanced UTI incidence and severity in Mgb-/- mice.

Urine Stasis Predisposes to Urinary Tract Infection by an Opportunistic Uropathogen in the Megabladder (Mgb) Mouse

PubMed Central

Becknell, Brian; Mohamed, Ahmad Z.; Li, Birong; Wilhide, Michael E.; Ingraham, Susan E.

2015-01-01

Purpose Urinary stasis is a risk factor for recurrent urinary tract infection (UTI). Homozygous mutant Megabladder (Mgb-/-) mice exhibit incomplete bladder emptying as a consequence of congenital detrusor aplasia. We hypothesize that this predisposes Mgb-/- mice to spontaneous and experimental UTI. Methods Mgb-/-, Mgb+/-, and wild-type female mice underwent serial ultrasound and urine cultures at 4, 6, and 8 weeks to detect spontaneous UTI. Urine bacterial isolates were analyzed by Gram stain and speciated. Bladder stones were analyzed by x-ray diffractometry. Bladders and kidneys were subject to histologic analysis. The pathogenicity of coagulase-negative Staphylococcus (CONS) isolated from Mgb-/- urine was tested by transurethral administration to culture-negative Mgb-/- or wild-type animals. The contribution of urinary stasis to CONS susceptibility was evaluated by cutaneous vesicostomy in Mgb-/- mice. Results Mgb-/- mice develop spontaneous bacteriuria (42%) and struvite bladder stones (31%) by 8 weeks, findings absent in Mgb+/- and wild-type controls. CONS was cultured as a solitary isolate from Mgb-/- bladder stones. Bladders and kidneys from mice with struvite stones exhibit mucosal injury, inflammation, and fibrosis. These pathologic features of cystitis and pyelonephritis are replicated by transurethral inoculation of CONS in culture-negative Mgb-/- females, whereas wild-type animals are less susceptible to CONS colonization and organ injury. Cutaneous vesicostomy prior to CONS inoculation significantly reduces the quantity of CONS recovered from Mgb-/- urine, bladders, and kidneys. Conclusions CONS is an opportunistic uropathogen in the setting of urinary stasis, leading to enhanced UTI incidence and severity in Mgb-/- mice. PMID:26401845

The influence of botulinum toxin type A (BTX) on the immunohistochemical characteristics of noradrenergic and cholinergic nerve fibers supplying the porcine urinary bladder wall.

PubMed

Lepiarczyk, E; Bossowska, A; Kaleczyc, J; Majewski, M

2011-01-01

Botulinum toxin (BTX) belongs to a family of neurotoxins which strongly influence the function of autonomic neurons supplying the urinary bladder. Accordingly, BTX has been used as an effective drug in experimental therapies of a range of neurogenic bladder disorders. However, there is no detailed information dealing with the influence of BTX on the morphological and chemical properties of nerve fibres supplying the urinary bladder wall. Therefore, the present study investigated, using double-labeling immunohistochemistry, the distribution, relative frequency and chemical coding of cholinergic and noradrenergic nerve fibers supplying the wall of the urinary bladder in normal female pigs (n = 6) and in the pigs (n = 6) after intravesical BTX injections. In the pigs injected with BTX, the number of adrenergic (DbetaH-positive) nerve fibers distributed in the bladder wall (urothelium, submucosa and muscle coat) was distinctly higher while the number of cholinergic (VAChT-positive) nerve terminals was lower than that found in the control animals. Moreover, the injections of BTX resulted in some changes dealing with the chemical coding of the adrenergic nerve fibers. In contrast to the normal pigs, in BTX injected animals the number of DbetaH/NPY- or DbetaH/CGRP-positive axons was higher in the muscle coat, and some fibres distributed in the urothelium and submucosa expressed immunoreactivity to CGRP. The results obtained suggest that the therapeutic effects of BTX on the urinary bladder might be dependent on changes in the distribution and chemical coding of nerve fibers supplying this organ.

Construct validity of an instrument to measure neuropathic pain in women with bladder pain syndrome.

PubMed

Arya, Lily A; Harvie, Heidi S; Andy, Uduak U; Cory, Lori; Propert, Kathleen J; Whitmore, Kristene

2013-06-01

To determine the construct validity of an instrument to measure neuropathic pain in women with bladder pain syndrome (BPS). Our hypothesis is that neuropathic, bladder, and bowel pain represent different constructs in women with BPS. Secondary planned analysis of a prospective cross-sectional study of 150 women with BPS. The relationship between neuropathic pain, urinary, and bowel symptoms was assessed. The correlation of the total neuropathic pain score with total urinary and bowel symptom scores was low to moderate (r = 0.28-0.49). The correlation of specific neuropathic pain items with bladder and bowel pain was also low to moderate (r = 0.12-0.36). Women with neuropathic pain had significantly higher scores for urinary urgency, bladder pain, abdominal pain, diarrhea, and constipation than women with non-neuropathic pain (all P < 0.0001). Somatosensory neuropathic pain and "visceral" bladder and bowel pain represent separate but related constructs in women with BPS. Copyright © 2012 Wiley Periodicals, Inc.

Photoacoustic cystography using handheld dual modal clinical ultrasound photoacoustic imaging system

NASA Astrophysics Data System (ADS)

Sivasubramanian, Kathyayini; Periyasamy, Vijitha; Austria, Dienzo Rhonnie; Pramanik, Manojit

2018-02-01

Vesicoureteral reflux is the abnormal flow of urine from your bladder back up the tubes (ureters) that connect your kidneys to your bladder. Normally, urine flows only down from your kidneys to your bladder. Vesicoureteral reflux is usually diagnosed in infants and children. The disorder increases the risk of urinary tract infections, which, if left untreated, can lead to kidney damage. X-Ray cystography is used currently to diagnose this condition which uses ionising radiation, making it harmful for patients. In this work we demonstrate the feasibility of imaging the urinary bladder using a handheld clinical ultrasound and photoacoustic dual modal imaging system in small animals (rats). Additionally, we demonstrate imaging vesicoureteral reflux using bladder mimicking phantoms. Urinary bladder imaging is done with the help of contrast agents like black ink and gold nanoparticles which have high optical absorption at 1064 nm. Imaging up to 2 cm was demonstrated with this system. Imaging was done at a framerate of 5 frames per second.

[Investigation of urinary management after removal of indwelling urethral catheters in a general hospital: associations between bedridden state and impaired bladder emptying].

PubMed

Tsuchiyama, Katsuki; Ueki, Osamu; Minami, Hidero; Kawaguchi, Kouhei; Aoki, Yoshitaka; Yokoyama, Osamu

2010-06-01

In this study we investigated the influences of decreased levels of activities of daily living (ADL), especially in bedridden patients,on lower urinary tract dysfunction and urinary management during hospital care. All 1,106 non-urological inpatients (896 non-bedridden patients and 210 bedridden patients) with an indwelling urethral catheter treated at Noto General Hospital between April 2006 and October 2009 were retrospectively evaluated. Maximum bladder capacity and post-void residual urine volume (PVR) were evaluated with uroflowmetry or voiding cystourethrography at the time the catheter was removed. Clean intermittent catheterization (CIC) and drug administration were performed for patients who had a PVR of 100 ml or more. Bedridden patients required urinary interventions at a higher rate than did non-bedridden patients (bedridden : 29.0%,non-bedridden : 17.6%). Although indwelling urethral catheters were reinserted in 13 patients in the bedridden group and 16 patients in the non-bedridden group,many patients in both groups could be free from the catheter. Our results indicate that patients with low ADL are vulnerable to impaired bladder emptying,and early diagnosis of impaired bladder emptying and active urinary management are required to solve their urinary problems.

Intravesical TRPV4 blockade reduces repeated variate stress-induced bladder dysfunction by increasing bladder capacity and decreasing voiding frequency in male rats

PubMed Central

Merrill, Liana

2014-01-01

Individuals with functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) often report symptom (e.g., urinary frequency) worsening due to stress. One member of the transient receptor potential ion channel vanilloid family, TRPV4, has recently been implicated in urinary bladder dysfunction disorders including OAB and IC/BPS. These studies address the role of TRPV4 in stress-induced bladder dysfunction using an animal model of stress in male rats. To induce stress, rats were exposed to 7 days of repeated variate stress (RVS). Quantitative PCR data demonstrated significant (P ≤ 0.01) increases in TRPV4 transcript levels in urothelium but not detrusor smooth muscle. Western blot analyses of split urinary bladders (i.e., urothelium and detrusor) showed significant (P ≤ 0.01) increases in TRPV4 protein expression levels in urothelial tissues but not detrusor smooth muscle. We previously showed that RVS produces bladder dysfunction characterized by decreased bladder capacity and increased voiding frequency. The functional role of TRPV4 in RVS-induced bladder dysfunction was evaluated using continuous, open outlet intravesical infusion of saline in conjunction with administration of a TRPV4 agonist, GSK1016790A (3 μM), a TRPV4 antagonist, HC067047 (1 μM), or vehicle (0.1% DMSO in saline) in control and RVS-treated rats. Bladder capacity, void volume, and intercontraction interval significantly decreased following intravesical instillation of GSK1016790A in control rats and significantly (P ≤ 0.01) increased following administration of HC067047 in RVS-treated rats. These results demonstrate increased TRPV4 expression in the urothelium following RVS and that TRPV4 blockade ameliorates RVS-induced bladder dysfunction consistent with the role of TRPV4 as a promising target for bladder function disorders. PMID:24965792

Intraperitoneal Urinary Bladder Perforation with Pneumoperitoneum in Association with Indwelling Foley Catheter Diagnosed in Emergency Department.

PubMed

Zhan, Chenyang; Maria, Pedro P; Dym, R Joshua

2017-11-01

Indwelling Foley catheter is a rare cause of urinary bladder perforation, a serious injury with high mortality that demands accurate and prompt diagnosis. While the gold standard for diagnosis of bladder injury is computed tomography (CT) cystography, few bladder ruptures associated with Foley catheter have been reported to be diagnosed in the emergency department (ED). An 83-year-old man with indwelling Foley catheter presented to the ED for hematuria and altered mental status. He was diagnosed to have intraperitoneal rupture of the urinary bladder in the ED using abdominal and pelvic CT without contrast, which demonstrated bladder wall discontinuity, intraperitoneal free fluid, and pneumoperitoneum. The patient was treated successfully with medical management and bladder drainage. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: To our knowledge, this is the first report of intraperitoneal urinary bladder perforation associated with Foley catheter diagnosed in the ED by CT without contrast. Pneumoperitoneum found in this case was a clue to the diagnosis and is a benign finding that does not necessitate urgent surgical intervention. The early and accurate diagnosis in this case allowed for effective management with good clinical outcome. The use of indwelling Foley catheter has a high prevalence, especially in long-term care facility residents, who are frequent visitors in the ED. Therefore, emergency physicians and radiologists should be familiar with the presentation and imaging findings of this potential injury associated with Foley catheters. Copyright © 2017 Elsevier Inc. All rights reserved.

Experimental investigations on intracavity sonography. Part 2: Alteration of imaging by artificial alterations in the wall of isolated porcine urinary bladders.

PubMed

Jaeger, N; Vahlensieck, W

1986-01-01

Because the determination of the depth of urinary bladder tumors by means of intracavity sonography depends on several factors (tumor size, reflection behavior of the tumor etc.), we checked the imaging of this diagnostic technique in the isolated porcine urinary bladder under various experimental conditions. Different tissues of defined size were fixed on the inner or outer surface of the bladder wall; both the bladder mucosa and the foreign tissue were damaged thermally or by incision. The importance of a limited depth of sound penetration or of a sound shadow depending on the characteristics of the tissue under investigation was revealed; tissue types could not be distinguished unequivocally by the reflection pattern; above all, a sonographic diagnosis of the tumor was not possible in the presence of histo-pathologically detectable tissue changes due to thermal damage.

[Myofibroblasts and afferent signalling in the urinary bladder. A concept].

PubMed

Neuhaus, J; Scholler, U; Freick, K; Schwalenberg, T; Heinrich, M; Horn, L C; Stolzenburg, J U

2008-09-01

Afferent signal transduction in the urinary bladder is still not clearly understood. An increasing body of evidence supports the view of complex interactions between urothelium, suburothelial myofibroblasts, and sensory nerves. Bladder tissue from tumour patients was used in this study. Methods included confocal immunofluorescence, polymerase chain reaction, calcium imaging, and fluorescence recovery after photobleaching (FRAP).Myofibroblasts express muscarinic and purinergic receptors. They show constitutive spontaneous activity in calcium imaging, which completely depends on extracellular calcium. Stimulation with carbachol and ATP-evoked intracellular calcium transients also depend on extracellular calcium. The intensive coupling between the cells is significantly diminished by incubation with TGF-beta 1. Myofibroblasts form an important cellular element within the afferent signalling of the urinary bladder. They possess all features required to take part in the complex interactions with urothelial cells and sensory nerves. Modulation of their function by cytokines may provide a pathomechanism for bladder dysfunction.

Bladder Management

MedlinePlus

... Catheterization • Urinary Tract Infections: Indwelling (Foley) Catheter Bladder Management [ Download this pamphlet: "Bladder Management" - (PDF, 499KB) ] The ... and medication or surgery may be helpful. Bladder Management Foley or Suprapubic Catheter A tube is inserted ...

Incidentally Detected Penile Metastases in a Patient of Carcinoma Urinary Bladder on Follow-up FDG PET/CT.

PubMed

Parida, Girish Kumar; Tripathy, Sarthak; Roy, Shambo Guha; Singhal, Abhinav; Das, Chandanjyoti; Shamim, Shamim Ahmed

2017-05-01

Penis is an extremely uncommon site for metastases to occur and is often associated with very grave prognosis. Most of the secondary tumors originating in the penis have primaries from prostate, urinary bladder, and gastrointestinal tract. We hereby report a 65-year-old man, known case of carcinoma urinary bladder, who came for FDG PET/CT for metastatic workup. PET/CT study revealed FDG-avid mass lesion in the root and shaft of the penis, making it suggestive of metastases, which was confirmed later by MRI correlation.

Lack of Promoting Effects of α‐Linolenic, Linoleic or Palmitic Acid on Urinary Bladder Carcinogenesis in Rats

PubMed Central

Mori, Satoru; Chen, Tianxin; Murai, Takashi; Fukushima, Shoji

1995-01-01

Potential promoting effects of α‐linolenic, linoleic and palmitic acids were investigated in a two‐stage urinary bladder carcinogenesis model. In experiment 1, male F344 rats were given 0.05% N‐butyl‐N‐(4‐hydroxybutyl)nitrosainine (BBN) in their drinking water for 4 weeks and then basal diet containing 10%α‐linolenic, 10% linoleic or 10% palmitic acid along with 0.2% butylated hydroxyanisole (BHA) as an antioxidant for 24 weeks. The development of tumors in the urinary bladder was not increased by treatment with any of the fatty acids. In experiment 2, male F344 rats were given 10%α‐linolenic, 10% linoleic or 10% palmitic acid along with 0.2% BHA in their diet for 8 weeks without prior BBN treatment. The administration of fatty acids was not associated with any increase in the 5‐bromo‐2′‐deoxyuridine labeling index of the urinary bladder epithelium. Serum and/or urine fatty acid Ievels increased in the cases of α‐linolenic and linoleic acid treatments, but not with palmitic acid. Under the present experimental conditions neither the two polyunsaturated nor the one saturated fatty acid exerted any promoting effect on urinary bladder carcinogenesis. PMID:7622416

A Population-Based Study of Subsequent Primary Malignancies After Endometrial Cancer: Genetic, Environmental, and Treatment-Related Associations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Aaron P.; Neeley, E. Shannon; Werner, Theresa

2010-09-01

Purpose: To examine the risk of subsequent primary malignancies (SPMs) in women diagnosed with endometrial cancer. Methods and Materials: The National Cancer Institute's Survival, Epidemiology, and End Results database was used to determine the risk of SPM after endometrial cancer in 69,739 women diagnosed between 1973 and 2005. Standardized incidence ratios were calculated (observed/expected [O/E]) for SPM sites. Results: Median follow-up was 11.2 years, representing 757,567 person-years of follow-up. The risk of SPM was significantly increased for small intestine (O/E = 1.48; 99% confidence interval [CI], 1.03-2.05), colon (O/E = 1.16; CI, 1.09-1.24), vagina (O/E = 2.71; CI, 1.86-3.8), andmore » urinary bladder (O/E = 1.41; CI, 1.25-1.59) SPMs and decreased for oral cavity and pharynx (O/E = 0.75; CI, 0.6-0.93), lung and bronchus (O/E = 0.78; CI, 0.72-0.84), and esophagus (O/E = 0.58; CI, 0.37-0.86) SPMs. Patients receiving external-beam radiotherapy for endometrial cancer had an increased risk of colon (p < 0.001), bladder (p < 0.001), vagina (p = 0.04), and soft-tissue (p = 0.014) SPMs. Patients treated with brachytherapy had an increased risk of bladder SPM (p = 0.006). A positive bidirectional association with endometrial cancer was observed for colorectal cancer, with a negative bidirectional association for oropharyngeal and lung cancers. Conclusions: Genetic, environmental, and treatment-related factors influence SPM risk. Genetic factors may contribute to the increased risk of colorectal cancer. Smoking's negative effect on endometrial cancer risk factors might explain the decreased risk of lung and oropharyngeal cancer. Patients treated with radiotherapy likely have a small but significantly increased risk of bladder, vagina, colon, and soft-tissue SPM.« less

A population-based study of subsequent primary malignancies after endometrial cancer: genetic, environmental, and treatment-related associations.

PubMed

Brown, Aaron P; Neeley, E Shannon; Werner, Theresa; Soisson, Andrew Patrick; Burt, Randall W; Gaffney, David K

2010-09-01

To examine the risk of subsequent primary malignancies (SPMs) in women diagnosed with endometrial cancer. The National Cancer Institute's Survival, Epidemiology, and End Results database was used to determine the risk of SPM after endometrial cancer in 69,739 women diagnosed between 1973 and 2005. Standardized incidence ratios were calculated (observed/expected [O/E]) for SPM sites. Median follow-up was 11.2 years, representing 757,567 person-years of follow-up. The risk of SPM was significantly increased for small intestine (O/E = 1.48; 99% confidence interval [CI], 1.03-2.05), colon (O/E = 1.16; CI, 1.09-1.24), vagina (O/E = 2.71; CI, 1.86-3.8), and urinary bladder (O/E = 1.41; CI, 1.25-1.59) SPMs and decreased for oral cavity and pharynx (O/E = 0.75; CI, 0.6-0.93), lung and bronchus (O/E = 0.78; CI, 0.72-0.84), and esophagus (O/E = 0.58; CI, 0.37-0.86) SPMs. Patients receiving external-beam radiotherapy for endometrial cancer had an increased risk of colon (p < 0.001), bladder (p < 0.001), vagina (p = 0.04), and soft-tissue (p = 0.014) SPMs. Patients treated with brachytherapy had an increased risk of bladder SPM (p = 0.006). A positive bidirectional association with endometrial cancer was observed for colorectal cancer, with a negative bidirectional association for oropharyngeal and lung cancers. Genetic, environmental, and treatment-related factors influence SPM risk. Genetic factors may contribute to the increased risk of colorectal cancer. Smoking's negative effect on endometrial cancer risk factors might explain the decreased risk of lung and oropharyngeal cancer. Patients treated with radiotherapy likely have a small but significantly increased risk of bladder, vagina, colon, and soft-tissue SPM. Copyright (c) 2010 Elsevier Inc. All rights reserved.

High cumulative incidence of urinary tract transitional cell carcinoma after kidney transplantation in Taiwan.

PubMed

Wu, Ming-Ju; Lian, Jong-Da; Yang, Chi-Rei; Cheng, Chi-Hung; Chen, Cheng-Hsu; Lee, Wen-Chin; Shu, Kuo-Hsiung; Tang, Ming-Jer

2004-06-01

Cancer is a well-documented complication after kidney transplantation. Increased incidence of bladder cancer had been reported in long-term hemodialysis patients in Taiwan. Herein, the authors report a very high cumulative incidence of transitional cell carcinoma (TCC) of the urinary tract after kidney transplantation in Taiwan. The authors retrospectively reviewed the clinical data, medical records, and outcome of 730 kidney transplant (KT) recipients. The cumulative incidence of TCC was computed. The Cox regression method was used to analysis the role of potential risk factors. After a mean follow-up duration of 72.2 +/- 54.4 months, 69 cancers were diagnosed in 63 (8.6%) KT recipients. Of them, 30 cases (4.1%) were TCC. The cumulative incidence for TCC was 3.0% after 3 years of graft survival, increasing to 7.2% at 6 years and 17.5% at 10 years. Compared with the general population in Taiwan, the standardized mortality ratio was 398.4 (male, 192.6; female, 875.6). Painless gross hematuria was the cardinal initial symptom in 22 (73.3%) of the 30 KT recipients with TCC. Another 4 (13.3%) KT recipients with TCC presented with chronic urinary tract infection (UTI). Bilateral nephroureterectomy with removal of bladder cuffs was performed in 18 (60%) patients. Synchronous TCC in bilateral upper urinary tracts was confirmed in 11 (36.7%) of KT recipients with TCC. The age at the time of KT, female sex, compound analgesics usage, Chinese herb usage, and underground water intake had statistical significance as risk factors (P < 0.05). The KT recipients are at extremely high risk for TCC in Taiwan, with an incidence of 4.1%. This study indicates that hematuria and chronic UTI are the initial presentation of TCC in KT recipients. Carefully urologic screening is indicated for patients with high risk for TCC, including those with older age, compound analgesics usage, Chinese herbs usage, and underground water intake as well as women.

The association of benign prostatic hyperplasia with lower urinary tract stones in adult men: A retrospective multicenter study.

PubMed

Jung, Jae Hung; Park, Jinsung; Kim, Won Tae; Kim, Hong Wook; Kim, Hyung Joon; Hong, Sungwoo; Yang, Hee Jo; Chung, Hong

2018-04-01

To examine the relationship between benign prostatic hyperplasia (BPH) and the presence of lower urinary tract stones. We retrospectively reviewed the records of men with lower urinary tract stones who presented to three clinical centers in Korea over a 4-year period. We divided the patients into two groups based on the location of urinary stones: Group 1 (bladder calculi) and Group 2 (urethral calculi). We compared the characteristics of both groups and performed univariate and multivariate analyses with a logistic regression model to investigate the relationship between BPH and lower urinary tract stones. Of 221 patients, 194 (87.8%) had bladder calculi and 27 (12.2%) had urethral calculi. The mean age of Group 1 was higher than that of Group 2 (68.96 ± 12.11 years vs. 55.74 ± 14.20 years, p  < 0.001). The mean prostate volume of Group 1 was higher than that of Group 2 (44.47 ± 27.14 mL vs. 24.70 ± 6.41 mL, respectively, p  < 0.001). Multivariate logistic regression showed that age (OR = 1.075, 95%CI: 1.023-1.129) and prostate volume (OR = 1.069, 95%CI: 1.017-1.123) were independently associated with increased risk for bladder calculi. Upper urinary tract stones and/or hydronephrosis conferred a 3-fold risk for urethral calculi (OR = 3.468, 95%CI: 1.093-10.999). Age and prostate volume are independent risk factors for bladder calculi. In addition, men with upper urinary tract disease are at greater risk for urethral calculi, which may migrate from the upper urinary tract rather than from the bladder.

Acute Urinary Obstruction in a Tetraplegic Patient from Misplacement of Catheter in Urethra.

PubMed

Vaidyanathan, Subramanian; Singh, Gurpreet; Hughes, Peter L; Soni, Bakul M

2016-01-01

A male tetraplegic patient attended accident and emergency with a blocked catheter; on removing the catheter, he passed bloody urine. After three unsuccessful attempts were made to insert a catheter by nursing staff, a junior doctor inserted a three-way Foley catheter with a 30-mL balloon but inflated the balloon with 10 mL of water to commence the bladder irrigation. The creatinine level was mostly 19 µmol/L (range: 0-135 µmol/L) but increased to 46 µmol/L on day 7. Computerized tomography urogram revealed that the bilateral hydronephrosis with hydroureter was extended down to urinary bladder, the bladder was distended, prostatic urethra was dilated and filled with urine, and although the balloon of Foley catheter was not seen in the bladder, the tip of the catheter was seen lying in the urethra. Following the re-catheterization, the creatinine level decreased to 21 µmol/L. A follow-up ultrasound scan revealed no evidence of hydronephrosis in both kidneys. Flexible cystoscopy revealed inflamed bladder mucosa, catheter reaction, and tiny stones. There was no bladder tumor. This case report concludes that the cause of bilateral hydronephrosis, hydroureter, and distended bladder was inadequate drainage of urinary bladder as the Foley balloon that was under-filled slipped into the urethra resulting in an obstruction to urine flow. Urethral catheterization in tetraplegic patients should be performed by senior, experienced staff in order to avoid trauma and incorrect positioning. Tetraplegic subjects with decreased muscle mass have low creatinine level. Increase in creatinine level (>1.5 times the basal level) indicates acute kidney injury, although peak creatinine level may still be within laboratory reference range. While scanning the urinary tract of spinal cord injury patients with indwelling urinary catheter, if Foley balloon is not seen within the bladder, urethra should be scanned to locate the Foley balloon.

Topical and systemic immunoreaction triggered by intravesical chemotherapy in an N-butyl-N-(4-hydroxybutyl) nitorosamine induced bladder cancer mouse model

PubMed Central

Nakai, Yasushi; Tanaka, Nobumichi; Fujimoto, Kiyohide

2017-01-01

Intravesical bacillus Calmette-Guerin (BCG) treatment is the most common therapy to prevent progression and recurrence of non-muscle invasive bladder cancer (NMIBC). Although the immunoreaction elicited by BCG treatment is well documented, those induced by intravesical treatment with chemotherapeutic agents are much less known. We investigated the immunological profiles caused by mitomycin C, gemcitabine, adriamycin and docetaxel in the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced orthotopic bladder cancer mouse model. Ninety mice bearing orthotopic bladder cancer induced by BBN were randomly divided into six groups and treated with chemotherapeutic agents once a week for four weeks. After last treatment, bladder and serum samples were analyzed for cell surface and immunological markers (CD4, CD8, CD56, CD204, Foxp3, and PD-L1) using immunohistochemistry staining. Serum and urine cytokine levels were evaluated by ELISA. All chemotherapeutic agents presented anti-tumor properties similar to those of BCG. These included changes in immune cells that resulted in fewer M2 macrophages and regulatory T cells around tumors. This result was compatible with those in human samples. Intravesical chemotherapy also induced systemic changes in cytokines, especially urinary interleukin (IL)-17A and granulocyte colony stimulating factor (G-CSF), as well as in the distribution of blood neutrophils, lymphocytes, and monocytes. Our findings suggest that intravesical treatment with mitomycin C and adriamycin suppresses protumoral immunity while enhancing anti-tumor immunity, possibly through the action of specific cytokines. A better understanding of the immunoreaction induced by chemotherapeutic agents can lead to improved outcomes and fewer side effects in intravesical chemotherapy against NMIBC. PMID:28406993

Oncogenic Activation of Fibroblast Growth Factor Receptor-3 and RAS Genes as Non-Overlapping Mutual Exclusive Events in Urinary Bladder Cancer.

PubMed

Pandith, Arshad A; Hussain, Aashaq; Khan, Mosin S; Shah, Zafar A; Wani, M Saleem; Siddiqi, Mushtaq A

2016-01-01

Urinary bladder cancer is a common malignancy in the West and ranks as the 7th most common cancer in our region of Kashmir, India. FGFR3 mutations are frequent in superficial urothelial carcinoma (UC) differing from the RAS gene mutational pattern. The aim of this study was to analyze the frequency and association of FGFR3 and RAS gene mutations in UC cases. Paired tumor and adjacent normal tissue specimens of 65 consecutive UC patients were examined. DNA preparations were evaluated for the occurrence of FGFR3 and RAS gene mutations by PCR-SCCP and DNA sequencing. Somatic point mutations of FGFR3 were identified in 32.3% (21 of 65). The pattern and distribution were significantly associated with low grade/stage (<0.05). The overall mutations in exon 1 and 2 in all the forms of RAS genes aggregated to 21.5% and showed no association with any clinic-pathological parameters. In total, 53.8% (35 of 65) of the tumors studied had mutations in either a RAS or FGFR3 gene, but these were totally mutually exclusive in and none of the samples showed both the mutational events in mutually exclusive RAS and FGFR3. We conclude that RAS and FGFR3 mutations in UC are mutually exclusive and non-overlapping events which reflect activation of oncogenic pathways through different elements.

Impact of marital status in patients undergoing radical cystectomy for bladder cancer.

PubMed

Pruthi, Raj S; Lentz, Aaron C; Sand, Matthew; Kouba, Erik; Wallen, Eric M

2009-08-01

Married (vs. unmarried) individuals have improved health status and longer life expectancies in a variety of benign and malignant disease states, including prostate, breast, head/neck, and lung cancers. We sought to evaluate a cohort of patients undergoing cystectomy for bladder cancer to evaluate the impact of marital status on demographic, peri-operative, and pathological outcomes in order to better understand the factors which may contribute to the survival differences observed. Two-hundred and two patients underwent radical cystectomy and urinary diversion for bladder cancer. Patients were categorized based on marital status as either married or unmarried (widowed, divorced, never married). Correlations were made to demographic factors (age, race, gender, BMI, tobacco use, alcohol use), perioperative factors (pre-op renal function (creatinine), hematocrit, EBL, hospital stay, choice of diversion), and pathological outcomes (organ-confined status, LN positivity). Of the 202 patients, 74% were married. Married individuals (vs. unmarried) were more often male (84 vs. 62%) and had a higher BMI (28.1 vs. 25.9). Married persons had a significantly lower pre-op creatinine (1.1 vs. 1.4) and higher hematocrit (39 vs. 34). Hospital stay was shorter in married patients by a mean of 1.6 days. Regarding operative pathology, married patients had a higher rate of organ-confined disease (59 vs. 47%) (P = 0.05, 0.08 on multivariate) and trended towards a lower rate of LN positivity (15 vs. 21%; P = 0.10, 0.12 multivariate). In patients undergoing cystectomy for bladder cancer, married individuals appear to have improved pre-operative laboratory variables, shorter hospitalization, and improved pathological outcomes versus unmarried patients in our case series. These findings may support the evidence (observed in other tumor types and other disease states) that married persons present earlier than unmarried individuals, and this may help explain the improved survival outcomes that have been observed in married patients with bladder cancer.

Neurotrophin/receptor expression in urinary bladder of mice with overexpression of NGF in urothelium.

PubMed

Girard, Beatrice M; Malley, Susan E; Vizzard, Margaret A

2011-02-01

Urothelium-specific overexpression of nerve growth factor (NGF) in the urinary bladder of transgenic mice stimulates neuronal sprouting in the urinary bladder, produces increased voiding frequency, and results in increased referred somatic hypersensitivity. Additional NGF-mediated pleiotropic changes might contribute to the increased voiding frequency and pelvic hypersensitivity observed in these transgenic mice, such as modulation of other growth factor/receptor systems. Chronic overexpression of NGF in the urothelium was achieved through the use of a highly urothelium-specific uroplakin II promoter. In the present study, we examined NGF, brain-derived neurotrophic factor (BDNF), and associated receptor [p75(NTR), tyrosine kinase (Trk)A, TrkB] transcript and protein expression in urothelium and detrusor smooth muscle of NGF-overexpressing (OE) and littermate wild-type mice, using real-time quantitative reverse transcription-polymerase chain reaction, ELISAs, and semiquantitation of immunohistochemistry. We focused on these growth factor/receptors given the established roles of NGF/TrkA, NGF/p75(NTR), and BDNF/TrkB systems in bladder function. Increased voiding frequency in NGF-OE mice was confirmed by examining urination patterns. BDNF, TrkA, and TrkB protein expression was significantly (P ≤ 0.01) reduced and p75(NTR) protein expression was significantly (P ≤ 0.01) increased in urinary bladder of NGF-OE mice. The NGF-OE-induced changes in neurotrophic factor/receptor expression in urinary bladder may represent compensatory changes to reduce voiding frequency in the NGF-OE mouse.