Urinary bladder neoplasms

In the developed world, occupational exposures are a leading cause of bladder cancer. A few studies have suggested a link between pesticide exposures among agricultural populations and bladder cancer. We used data from the Agricultural Health Study, a prospective cohort study which includes 57 310 pesticide applicators with detailed information on pesticide use, to evaluate the association between pesticides and bladder cancer. We used Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) to estimate the association between each of 65 pesticides and 321 incident bladder cancer cases which accrued over the course of follow-up (1993-2011), adjusting for lifestyle and demographic and non-pesticide farm-related exposures, including those previously linked to bladder cancer. We conducted additional analyses stratified by smoking status (never, former, current). We observed associations with bladder cancer risk for two imidazolinone herbicides, imazethapyr a...

Intravesical BCG is a good treatment choice for vesical carcinomas. Nevertheless, it can also become a mortal toxin when applied in a wrong way. The application routes of the prescribed drug should be rigorously described to patients and detailed instructions regarding the ways of application such as intravesical application should be given to the persons taking this medicine (Ref. 9).

Enhanced recovery after surgery (ERAS) has played an important role in recovery management for radical cystectomy with ileal urinary diversion (RC-IUD). This study is to evaluate ERAS compared with the conventional recovery after surgery (CRAS) for RC-IUD. From October 2014 and July 2016, bladder cancer patients scheduled for curative treatment from 25 centers of Chinese Bladder Cancer Consortium were randomly assigned to either ERAS or CRAS group. Primary endpoint was the 30-day complication rate. Secondary endpoints included recovery of fluid and regular diet, flatus, bowel movement, ambulation, and length of stay (LOS) postoperatively. Follow-up period was 30-day postoperatively. There were 144 ERAS and 145 CRAS patients. Postoperative complications occurred in 25.7 and 30.3% of the ERAS and CRAS patients with 55 complications in each group, respectively (p = 0.40). There was no significant difference between groups in major complications (p = 0.82), or type of complications (p =...

Radical cystectomy involves a urinary diversion, the most used being the ileal conduit and the orthotopic neobladder. This review focuses on the complications associated with these procedures, dividing them into general and diversion related complications, as well as their management. We conducted a search on PubMed and Scopus to identify eligible articles on complications of urinary diversions. Randomized controlled trials and systematic reviews with meta-analysis were preferred when available. Early complications occur in the first 90 days after surgery. The most common is post-operative ileus, followed by urinary tract infections and urinary leakage. Most complications occur in the late post-operative setting, being related to the type of urinary diversion. Some of these complications are renal failure, metabolic abnormalities, infections, urolithiasis, and ureteroenteric strictures, each with particular management options. Specific ileal conduit complications are conduit deformities and parastomal hernias. Neobladder patients can have continence problems, like incontinence or urinary retention, but also fistulas and dehiscence. Standardization of complications’ definitions and time-dependent reporting are crucial to better understand and manage these complications. Complication rates are similar between open and robot-assisted procedures and between intracorporeal and extracorporeal diversion. Radical cystectomy with urinary diversion is the most difficult surgical procedure in urology with high early and late complication rates. There is an urgent need of standardizing complication reporting to better compare different procedures.

Intravesical BCG is a good treatment choice for vesical carcinomas. Nevertheless, it can also become a mortal toxin when applied in a wrong way. The application routes of the prescribed drug should be rigorously described to patients and detailed instructions regarding the ways of application such as intravesical application should be given to the persons taking this medicine (Ref. 9).

The modifying potential of ginger on the development of preneoplasia and tumors in the male Wistar rat urinary bladder was investigated in a 36-week-long initiation-promotion assay for chemical carcinogenesis. Groups G1 to G3 were given 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in drinking water for 5 weeks and a 3% uracil meal for the subsequent 3 weeks. Groups G4 and G5 were treated with 3% uracil only for the same period. After these steps, groups G2, and G3 and G4 were fed for 26 weeks a ginger extract mixed at 0.5 and 1.0% in a basal diet, respectively. Thirty six weeks after the beginning of the experiment all rats were killed. The multiplicity of urothelial lesions (hyperplasia and neoplasia) was significantly lower (P = 0.013) in group G3 than in groups G1 and G2. The results suggest that 1.0% ginger meal exerts a protective effect on the post-initiation stage of rat chemically-induced urothelial carcinogenesis.

Taxol is the most commonly used agent for salvage chemotherapy in transitional cell carcinoma of the urothelium. We examined mechanisms responsible for taxol resistance by using T24 human bladder carcinoma cells. We used an inhibitor and an activator of the phosphatidylinositol-3 kinase-Akt pathway in cell survival and caspase-3 assays, an HPLC method for determining released cytochrome c and immunoblotting for detecting protein phosphorylation. Activation of Akt increased paclitaxel resistance by increasing Bad phosphorylation, leading to decreased release of mitochondrial cytochrome c and caspase-3-mediated apoptosis. On the other hand, inhibition of Akt prevented paclitaxel resistance by enhancing the effects of paclitaxel on Bad phosphorylation, mitochondrial cytochrome c release and caspase-3-mediated apoptosis, besides diminishing or abolishing the opposing effects of Akt activation. Akt-mediated Bad phosphorylation plays an important role in preservation of mitochondrial memb...

Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio, 4.08; 95% confidence interval, 1.19-13.98; P = .025). Stage pTisN0 ...

Mortality from bladder cancer has shown downward trends over the last 2 decades in several western European countries (albeit 10-15 years later than similar trends in the US), but is still increasing in some eastern European countries. Tobacco smoking and occupational exposure to aromatic amines are the two major established environmental risk factors for bladder cancer. Controlling exposure to these factors has been an important contributor to the reduction in bladder cancer mortality, particularly among men. Diet could influence bladder carcinogenesis, as many compounds contained in foods--and their metabolites--are excreted through the urinary tract. Fruit and vegetable consumption was inversely related with bladder cancer in many studies, but no consistent association has emerged between intake of related micronutrients and reduced risk of bladder cancer. Other widely investigated lifestyle habits are probably not associated with risk of developing bladder cancer (e.g. coffee consumption, artificial sweetener use, hair dyes) or are difficult to assess (e.g. fluid intake). Infections and stones in the urinary tract might cause chronic irritation of the bladder epithelium, and thus increase bladder cancer risk. First-degree relatives of bladder cancer patients have a 50-100% increased relative risk of developing the disease, a risk that could be even higher when the proband is diagnosed at an early age.

Polypoid cystitis is a rare disease of the urinary bladder in dogs characterized by inflammation, epithelial proliferation, and development of a polypoid mass or masses without histopathologic evidence of neoplasia. Medical records of 17 dogs with polypoid cystitis ...

Muscle-invasive bladder cancer (MIBC) is an aggressive disease with limited therapeutic options. Although immunotherapies are approved for MIBC, the majority of patients fail to respond, suggesting existence of complementary immune evasion mechanisms. Here, we report that the PPARγ/RXRα pathway constitutes a tumor-intrinsic mechanism underlying immune evasion in MIBC. Recurrent mutations in RXRα at serine 427 (S427F/Y), through conformational activation of the PPARγ/RXRα heterodimer, and focal amplification/overexpression of PPARγ converge to modulate PPARγ/RXRα-dependent transcription programs. Immune cell-infiltration is controlled by activated PPARγ/RXRα that inhibits expression/secretion of inflammatory cytokines. Clinical data sets and an in vivo tumor model indicate that PPARγ(High)/RXRα(S427F/Y) impairs CD8(+) T-cell infiltration and confers partial resistance to immunotherapies. Knockdown of PPARγ or RXRα and pharmacological inhibition of PPARγ significantly increase cytokin...

Treatment of NIH 3T3 cells with interferon (IFN) after transfection with human bladder carcinoma EJ/T24 c-Ha-ras1 oncogene DNA caused inhibition of ras-induced cell transformation. Furthermore, the effect of IFN on oncogene expression in an established tumor line was studied. A tumor line of NIH 3T3 (RS485) was transformed by human c-Ha-ras1 activated by a viral long terminal repeat. Treatment of the tumor cells with IFN was associated with a progressive appearance of reverted, flat colonies which exhibited a normal phenotype with respect to morphology and growth. The revertants were well spread, contact inhibited cells; they did not grow in soft agar and were not tumorigenic in nude mice. Revertants retained their normal phenotype, although they contained transfecting human c-Ha-ras1 DNA; but, they produced significantly decreased levels of the onc-encoded protein p21 and c-Ha-ras1 mRNA as compared to RS485 cells.

This study describes the effects of a promising therapeutic alternative for non-muscle invasive bladder cancer (NMIBC) based on Bacillus Calmette-Guerin (BCG) intravesical immunotherapy combined with Platelet-rich plasma (PRP) in an animal model. Furthermore, this study describes the possible mechanisms of this therapeutic combination involving Toll-like Receptors (TLRs) 2 and 4 signaling pathways. NMIBC was induced by treating female Fischer 344 rats with N-methyl-N-nitrosourea (MNU). After treatment with MNU, the animals were distributed into four experimental groups: Control (without MNU) group, MNU (cancer) group, MNU + PRP group, MNU + BCG group and MNU + PRP + BCG group. Our results demonstrated that PRP treatment alone or associated with BCG triggered significant cytotoxicity in bladder carcinoma cells (HTB-9). Animals treated with PRP associated to BCG clearly showed better histopathological recovery from the cancer state and decrease of urothelial neoplastic lesions progres...

Comparative genomic hybridization (CGH) was applied for a comprehensive screening of chromosomal aberrations in 14 transitional cell carcinomas of the bladder of different grade and stage. The results were compared in a number of selected cases with those obtained by restriction fragment length polymorphism analyses and targeted fluorescence in situ hybridization. Distinct amplifications, found with CGH, were located on 3p22-24, 10p13-14, 12q13-15, 17q22-23, 18p11, and 22q11-13. These high copy number amplifications and the frequency of imbalances involving chromosome 5, occurring in 4 of 14 cases, have not yet been identified in transitional cell carcinomas. Apart from these new aberrations, imbalances were detected in 3 or more cases for chromosomes 9 and 11, as already described previously in the literature. In four tumors, the copy number of specific chromosomal regions was also analyzed by interphase cytogenetics. Although in most instances the CGH data were confirmed, in one t...

Human Papillomaviruses (HPVs) have been found in association with benign and malignant growth of epithelia. The cell cycle inhibitor p16(Ink4a) has been shown to be overexpressed in HPV-positive cervical pre-malignant and malignant lesions, probably as a result of pRB targeting by the viral E7 protein. Inverted papillomas of the urinary bladder are epithelial tumors considered to be of benign nature. In this report we analyze the expression of p16(Ink4a) and the presence of HPV sequences in inverted papillomas and in non-tumoral bladder controls. Our results show no association of HPV infection and inverted papillomas. Further, no correlation between p16 overexpression and HPV positivity was found. We conclude that HPV does not play an indispensable role in the development of urinary bladder inverted papillomas and that overexpression of p16(Ink4a) does not correlate with HPV infection in these tumors.

In this study, we investigated tissue levels of reduced glutathione (GSH) and carnitine as well as thiobarbituric acid reactive substances (TBARS, as a marker of lipid peroxidation) levels in bladder carcinoma and control group of patients. The average GSH, carnitine and TBARS levels for tumor group were respectively 7.11 +/- 3.3 micro g/mg protein, 1.81 +/- 0.39 nmol/mg protein, and 4.29 +/- 3.2 micro mol/mg protein, versus 14.45 +/- 4.11 micro g/mg protein, 2.14 +/- 0.66 nmol/mg protein, and 2.3 +/- 0.6 micro mol/mg protein for normal bladder tissues. Thus, tissue reduced glutathione levels (GSH) were significantly lower in patients as compared with the control group (p < 0.001) whereas average TBARS levels in the tumor group were found to be higher than those in control group. The average tissue carnitine levels in the patient group were found to be lower compared with the control group but the difference was not statistically significant (p > 0.05).

To identify the clinical variables associated with prevalence of lymph node metastasis in patients with bladder cancer treated by radical cystectomy and lymphadenectomy for primary bladder cancer. Review of records of Ninety-five patients who underwent radical cystectomy and pelvic lymph node (LN) dissection during the period of 1995-2008 from a prospectively maintained database. Eighteen patients were excluded due to lack of data on the nodal status, leaving 77 evaluable patients. Associations between LN metastasis and age, gender, duration of disease, number of transurethral resection (TUR) prior to cystectomy, pathological grade and tumour stage was analyzed. Data was analyzed using the SPSS software, version 15. Statistical tests applied were independent sample t test or the Mann Whitney U test, the chi-square test and the Fischer exact test. The median age of the patients was 58 years in lymph node negative group and 63 years in lymph node positive group. There were 87% males a...

Background/Aim. The therapy with intravesical instillation of bacillus Calmette-Gu?rin (BCG) after transurethral resection (TUR) of the tumor is the gold standard of treatment of non-muscle invasive bladder cancer (NMIBC). The aim of this study was to compare the frequencies of reccurence between a group of patients submitted to TUR + BCG therapy (group I) and a group of patients submitted only to TUR (group II). Methods. The patients with NMIBC, a total of 899, treated in our Institution from January 1, 2007 to March, 2013, were included in this study and divided into two groups: group I and group II. These two groups were divided into three subgroups: solitary first diagnosed tumor ? 3 cm (SFDGT), solitary first diagnosed tumor > 3 cm and multiple first diagnosed tumors (MFDGT), and recedive tumors (RCT). Statistical analysis was performed by using ?2-test and Kolmogorov-Smirnov test. Results: In the group I a total of 133 cases had reccurence contrary to 75 in the group II, ma...

We investigated the safety, efficacy and pharmacokinetics of the intravesical administration of 2000 mg gemcitabine once a week in the four weeks before transurethral resection of superficial bladder cancer (TUR), and in the four successive weeks. Nine patients with superficial transitional cell bladder carcinoma were studied. Two thousand mg of gemcitabine dissolved in 50 ml of distilled water were administered intravesically. The dwell time was 60 min. The pharmacokinetics of gemcitabine and its metabolite, 2',2'-difluorodeoxyuridine (dFdU), were studied in plasma and urine before and after TUR. Cystoscopy was repeated 30 days after completion of the TUR treatment and subsequently at time intervals of one or two months. No systemic toxicity was noted, and only three patients displayed modest signs of local toxicity. One patient had recurrence 1 month after TUR, three between 3 and 6 months, and another three after 8, 11 and 18 months, respectively; two were recurrence-free...

Small leucine-rich proteoglycans are components of extracellular matrix that regulates neoplastic transformation. Among small leucine rich proteoglycans, Decorin, Biglycan and Lumican are most commonly implicated markers, and their expression is well studied in various malignancies. In this novel study, we have collectively evaluated expression of these three molecules in urothelial carcinoma of bladder. Thirty patients of confirmed untreated bladder cancer, 30 healthy controls for blood and 30 controls for adjacent non-tumour tissue were enrolled. Blood was collected from all subjects and tumour/adjacent normal tissue was obtained from the patients. Circulatory levels were estimated by enzyme-linked immunosorbent assay, relative messenger RNA expression by quantitative polymerase chain reaction and protein expression by immunohistochemistry and western-blotting. Circulatory levels of Biglycan (p = 0.0038) and Lumican (p < 0.0001) were significantly elevated, and that of Decorin ...

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 etha...