Bladder Cancer

BACKGROUND: Urologic guidelines recommend perioperative instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) to decrease tumor recurrence, yet implementation of this recommendation is partial due to associated morbidity. Hypertonic saline destroys cells by osmotic dehydration and might present a safer alternative. OBJECTIVE: To evaluate the safety of 3% hypertonic saline (Hypersal) intravesical instillation following TURBT in rats and in humans. METHODS: In 8 rats whose bladders were electrically injured, intravesical blue-dyed Hypersal was administered. We measured serum sodium levels before and after instillation and pathologically evaluated their pelvic cavity for signs of inflammation or blue discoloration. Twenty-four patients were recruited to the human trial (NIH-NCT04147182), 15 comprised the interventional and 10 the control group (one patient crossed over). Hypersal was given postoperatively. Serum sodium was measured before, 1 hour and 12–24...

Background: Several prognostic models have been developed to stage hepatocellular carcinoma (HCC) but there is no general consensus on which is the most reliable. We compared three prognostic indices (Okuda, CLIP, and BCLC scoring systems) in a large series of cirrhotic patients with HCC undergoing nonsurgical treatment in terms of their ability to classify patients into different risk groups Methods: We retrospectively studied 268 Italian patients with HCC. A total of 146 patients were treated with ablation, 132 with percutaneous ethanol injection, and 14 with radiofrequency ablation; 103 underwent transcatheter arterial chemoembolisation and 19 had supportive care alone. Factors determining survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, CLIP, and BCLC scores evaluated before treatment were applied. Results: Median survival was 25.7 months. In a multivariate analysis, portal vein thrombosis, a fetoprotein, total bilirubin, and tumour size were significant predictors of survival. Okuda, CLIP, and BCLC scores were all able to predict survival (p,0.001). They identified two, four, and six risk groups, respectively, with a median survival ranging from 27 to 19 months for Okuda, 30 to 5 months for CLIP, and 43 to 7 months for BCLC. Conclusions: Both CLIP and BCLC scores were more effective than the Okuda score in stratifying patients into different risk groups with early-intermediate HCC. However, the BCLC scoring system gave a better prediction of prognosis in patients with disease diagnosis at a very early stage.

Carcinoma of the bladder is commonly treated for cure with external beam radiation. Whilst short-term results are associated with a good chance of disease control there is little information about the long-term results of such therapy. We present a retrospective review of the Princess Margaret Hospital experience in treating transitional cell carcinoma of the bladder and emphasis on the long-term follow-up of patients treated with radiotherapy (XRT). Between 1972 and 1980, 355 patients were treated with a radical course of external beam radiation. The overall survival was 20% at 10 years and the cause-specific survival was 32%. Radiation treatment resulted in a long-term bladder preservation in at least 25% of patients. The majority of long-term survivors without evidence of relapse were patients with T 1 (solitary tumours), T2 and T3a tumours. This subgroup represents patients with disease favourable for treatment with radiation. Factors affecting response to the XRT and survival included T stage and tumour bulk. Radiation complications were frequent and were usually associated with local disease recurrence.

Glutathione-S-transferases (GSTs) are active in the detoxification of wide variety of endogenous or exogenous carcinogens and genetic polymorphisms of CYP2E1 and GSTP1 genes have been studied extensively to evaluate the relative risk of various cancers. In the present study, we examined associations with CYP2E1 and GSTP1 gene polymorphisms in sporadic bladder cancers from North Indian patients. The subjects were 106 bladder cancer (Ca-B) cases and 162 age-matched controls. The GSTP1 313 A/G polymorphism was determined by the PCR/RFLP method using peripheral blood DNA. Binary Logistic Regression Model was used for assessing differences in genotype prevalence and their associations between patient and the control group. We observed a non-significant association in Pst1 polymorphism of the CYP2E1 gene; though the A/G genotype (OR = 2.69, 95% CI=1.57- 4.59, P= 0.000) and G/G genotype (OR = 7.68, 95% CI=2.77- 21.26, P= 0.000) of the GSTP1 gene polymorphism alone or in combination with to...

To assess the patterns of schistosomiasis-associated bladder cancer in Egypt from 2001 to 2010 in a retrospective study. Bilharzial bladder carcinoma is the most common cancer, particularly in Egyptian men. Classically, carcinoma in a bilharzial bladder is most commonly of the squamous cell type. During the past decade, certain changes have occurred in the features in Schistosomiasis-associated carcinoma in Egypt with a decline in the frequency of squamous cell carcinoma and increase in the frequency of transitional cell carcinoma.

Background: Coee consumption has been associated with an excess bladder cancer risk, but results from epidemiological studies are inconsistent. This association has been long debated, in part due to the potential confounding by smoking. We examined the risk associated with coee consumption in nonsmokers in a pooled analysis of ten European bladder cancer case±control studies. Methods: The pooled data set comprises 564 cases and 2929 hospital or population controls who had never smoked. They were enrolled in ten studies conducted in Denmark, Germany, Greece, France, Italy and Spain. Information on coee consumption and occupation was re-coded following standard criteria. Unconditional logistic regression was applied adjusting for age, study center, occupation and gender. Results: Seventy-nine percent of the study population reported having drunk coee, and 2.4% were heavy drinkers, reporting having drunk on average ten or more cups per day. There was no excess risk in ever coee drinkers (OR 1.0, 95% CI 0.8±1.3) compared to never drinkers. The risk did not increase monotonically with dose but a statistically signi®cant excess risk was seen for subjects having drunk ten or more cups per day (OR 1.8, 95% CI 1.0±3.3). This excess was seen in both men and women. There was no evidence of an association of the risk with duration or type of coee consumption. The pooled results were not dependent on the ®ndings of any speci®c study, but they depended on the type of controls with an overall excess risk observed only for studies using hospital controls. Conclusion: Nonsmokers who are heavy coee drinkers may have a small excess risk of bladder cancer. Although these results cannot be attributed to confounding by smoking, the possibility of bias in control selection cannot be discarded. On the basis of these results, only a very small proportion of cancers of the bladder among nonsmokers could be attributed to coee drinking.

The association between human papillomavirus (HPV) infection and development of bladder cancer is variable. Furthermore, the prevalence of HPV DNA in bladder carcinoma subtypes varies from study to study. To clarify the impact of HPV infection on the development of bladder carcinoma, we performed a retrospective study on Tunisian patients to determine the status of HPV infection in urothelial carcinoma, squamous cell carcinoma, and adenocarcinoma.

In tumour cells, alterations in cellular glycosylation may play a key role in their metastatic behaviour. This study used cell lines having very different behaviour in vivo: HCV29 non-malignant transitional epithelium and T24 bladder transitional cell carcinoma. These differences in behaviour might be due in part to differences in cellular glycosylation patterns. Glycan chain analysis of their glycoproteins was performed with the use of specific lectins. The functional role of carbohydrates was studied by treating these cells with swainsonine, an inhibitor of Golgi a-mannosidase II, and in vitro adhesion and migration assays. The adhesion of swainsonine-treated HCV29 and T24 cells was increased on fibronectin and type IV collagen by 1.5-and 2-fold, respectively, whereas adhesion on laminin was virtually unchanged after swainsoninetreatment in HCV29 cells and was increased in T24 cells. Swainsonine treatment reduced the rate of T24 cell migration by 20%. We concluded that b1-6 branched tri-and tetraantennary complex-type glycans have an important function in adhesion and migration in the studied cell lines. These data support the view that oligosaccharides are involved in several steps of the metastatic process.

Our aim is to apply image analysis on photosensitizer fluorescence and compare the relationship between histopathology and endoscopic fluorescence imaging. The correlation between hypericin fluorescence and histopathology of diseased tissue was explored in a clinical study involving 58 fluorescence cystoscopic images from 23 patients. Based on quantification of fluorescence colorimetric parameters extracted from the image analysis, diagnostic functions were developed to pathologically classify the bladder cancer. Our preliminary results show that the differences in fluorescence intensity ratios among the three different grades of bladder cancer are statistically significant. The results also show a decrease in macroscopic fluorescence intensity that correlated with higher cancer grades. By combining both the red-to-green and red-to-blue fluorescence intensity ratios into a 2-D scatter plot and defining diagnostic linear discrimination functions on the data points, this technique is able to yield an average sensitivity and specificity of around 68.6% and 86.1%, respectively, for pathological cancer grading of the three different grades of bladder cancer in our study. We conclude that our proposed approach in applying colorimetric intensity ratio analysis on hypericin fluorescence shows potential to optically grade bladder cancer in situ.

Background: The reorganisation of cancer services in England will result in the creation of specialist high volume cancer surgery centres. Studies have suggested a relationship between increasing surgical volume and improved outcomes in urological pelvic cancer surgery, although to date, they have pre-defined the definition of ''high'' and ''low'' volume surgeons. Aim: To derive the minimum caseload a surgeon requires to achieve optimum outcomes and to examine the effect of the operating centre size upon individual surgeon's outcomes. Methods: All cystectomies performed for bladder cancer in England over 5 years were analysed from Hospital Episode Statistics (HES) data. Statistical analysis was undertaken to describe the relationship between each surgeon's annual case volume and two outcome measures: in-hospital mortality rate, and hospital stay. The surgeon's outcomes were then analysed with respect to the overall level of activity in their operating centre. Results: A total of 6308 cystectomies were performed; the mean number of surgeons performing them annually was 327 with an overall mortality rate of 5.53%. A significant inverse correlation (20.968, p,0.01) was found between case volume and mortality rate. Applying 95% confidence interval estimation, the minimum caseload required to achieve the lowest mortality rate was eight procedures per year. Increasing caseload beyond eight operations per year did not produce a significant reduction in mortality rate. Conclusion: Analysis of HES data confirms an inverse relationship between surgeon's caseload and mortality for radical cystectomy. A caseload of eight operations per year is associated with the lowest mortality rate.

To determine the long-term results of a bladder-sparing approach in the treatment of muscle-invasive bladder cancer. Ninety-four patients with invasive transitional cell carcinoma of the bladder were treated by transurethral resection followed by 2 or 3 cycles of cisplatin-based chemotherapy. Patients were then treated with 6480 cGy of radiation in 49 patients, segmental cystectomy in 8, or surveillance only in 7. Patients who failed to respond to chemotherapy or radiation therapy, or who developed recurrent muscle-invasive disease in follow-up, underwent salvage cystectomy. Patients were then carefully followed for a median follow-up of more than 5 years. After initial therapy, 53 patients (56%) were alive with their bladder preserved. Thirty of those 53 (57%) developed a local recurrence in follow-up. After a median follow-up of more than 5 years, the ultimate relapse-free survival is 49% (Stage T2, 84%; T3, 53%; and T4, 11%; P < 0.01). Of all patients enrolled, 53% had bladder preservation; however, of the currently surviving patients, 16 of 39 (41%) have their bladders intact (T2, 50%; T3, 37%; T4, 0%). Only 18% of the initially enrolled population is alive with a preserved bladder. The 5-year survival of patients who had cystectomy at some point during the study, compared with those who have had their bladders preserved, was 65% versus 40%, respectively (P < 0.01). Our long-term results with multimodality therapy with attempted bladder preservation showed no definitive improvement in survival compared with modern series of cystectomy alone, and a disappointingly low rate of disease-free bladder preservation. We found a high rate of locally recurrent disease in the preserved bladders. We also noted a decrease in survival in our patients with bladder preservation compared with those without preservation. Bladder preservation, although possible, should be limited to a very select group of patients.

Background Firefighters are known to be exposed to recognized or probable carcinogens. Previous studies have found elevated risks of several types of cancers in firefighters. Methods Standardized morbidity odds ratio (SMORs) were used to evaluate the cancer risk in white, male firefighters compared to police and all other occupations in the Massachusetts Cancer Registry from 1986 to 2003. Firefighters and police were identified by text search of the usual occupation field. All other occupations included cases with identifiable usual occupations not police or firefighter. Control cancers were those not associated with firefighters in previous studies. Results Risks were moderately elevated among firefighters for colon cancer (SMOR ¼ 1.36, 95% CI: 1.04-1.79), and brain cancer (SMOR ¼ 1.90, 95% CI: 1.10-3.26). Weaker evidence of increased risk was observed for bladder cancer (SMOR ¼ 1.22, 95% CI: 0.89-1.69), kidney cancer (SMOR ¼ 1.34, 95% CI: 0.90-2.01), and Hodgkin's lymphoma (SMOR ¼ 1.81, 95% CI: 0.72-4.53). Conclusions These findings are compatible with previous reports, adding to the evidence that firefighters are at increased risk of a number of types of cancer. Am. J.

Background: Our experience with colovesical fistula (CVF) over a 12-year period was reviewed to clarify its clinical presentation and diagnostic confirmation. Methods: Twelve patients with CVF were identified. Presenting symptoms, etiologic factors, diagnostic investigations, and subsequent treatment were reviewed. Results: Underlying etiologies were diverticular disease (75%), colon cancer (16%), and bladder cancer (8%). Pneumaturia (77%) was the most common presentation, followed by urinary tract infections, dysuria and frequency (45%), fecaluria (36%), hematuria (22%), and orchitis (10%). The ability of various preoperative investigations to identify a CVF were: computed tomography (CT) (90%), barium enema (BE) (20%), and cystography (11%), whereas cystoscopy, intravenous pyelogram (IVP), and colonoscopy were nondiagnostic. All patients underwent single-or multiple-staged repair of the fistula. Conclusions: In patients with a suspected CVF, we recommend CT followed by a colonoscopy as a first-line investigation to rule out malignancy as a cause of CVF. Other modalities should only be used if the diagnosis is in doubt or additional information is needed to plan operative management. Published by Excerpta Medica Inc.

For other articles on a related topic see pages 741 and 749. Purpose: We compared 3 predictive models for survival after radical cystectomy, risk group stratification, nomogram and artificial neural networks, in terms of their accuracy, performance and level of complexity. Materials and Methods: Between 1996 and 2002, 1,133 patients were treated with single stage radical cystectomy as monotherapy for invasive bladder cancer. A randomly selected 776 cases (70%) were used as a reference series. The remaining 357 cases (test series) were used for external validation. Survival estimates were analyzed using univariate and then multivariate appraisal. The results of multivariate analysis were used for risk group stratification and construction of a nomogram, whereas all studied variables were entered directly into the artificial neural networks. Results: Overall 5-year disease-free survival was 64.5% with no statistical difference between the reference and test series. Comparisons of the 3 predictive models revealed that artificial neural networks outperformed the other 2 models in terms of the value of the area under the receiver operator characteristic curve, sensitivity and specificity, as well as positive and negative predictive values. Conclusions: In this study artificial neural networks outperformed the risk group stratification model and nomogram construction in predicting patient 5-year survival probability, and in terms of sensitivity and specificity.

DNA methylation is a key regulator of gene transcription. Alterations in DNA methylation patterns are common in most cancers, occur early in carcinogenesis and can be detected in body fluids. Reliable and sensitive quantitative assays are required to improve the diagnostic role of methylation in the management of cancer patients. Here we present an optimized procedure, based on differential-high resolution melting analysis (D-HRMA), for the rapid and accurate quantification of methylated DNA. Two sets of primers are used in a single tube for the simultaneous amplification of the methylated (M) and unmethylated (Um) DNA sequences in D-HRMA. After HRM, differential fluorescence was calculated at the specific melting temperature after automatic subtraction of UM-DNA fluorescence. Quantification was calculated by interpolation on an external standard curve generated by serial dilutions of M-DNA. To optimize the protocol, nine primer sets were accurately selected on the basis of the number of CpG on promoters of hTERT and Bcl2 genes. The use of optimized D-HRMA allowed us to detect up to 0.025% M-DNA. D-HRMA results of DNA from 85 bladder cancers were comparable to those obtained with real time quantitative methylation specific PCR. In addition, D-HRMA appears suitable for rapid and efficient measurements in 'in vitro' experiments on methylation patterns after treatment with demethylating drugs.

The complexes [Me 2 (Meclo)SnOSn(Meclo)Me 2 ] 2 (2) and [Ph 3 Sn(Meclo)] (3) where HMeclo is meclofenamic acid, N-(2,6-dichloro-m-tolylanthranilic acid)], have been prepared and structurally characterized by means of vibrational, 1 H and 13 C NMR spectroscopies. The crystal structure of complexes (2) and (3) have been determined by X-ray crystallography. Three distannoxane rings are present to the dimeric tetraorganodistannoxane of planar ladder arrangement of (2). The structure is centro symmetric and features a central rhombus Sn 2 O 2 unit two additional tin atoms linked at the oxygen atoms. Five-and six-coordinated tin centers are present in the dimer distannoxane. X-ray analysis of (3) revealed a penta-coordinated structure containing Ph 3 Sn coordinated to the chelated carboxylato group. The polar imino hydrogen atom participates in intra-molecular hydrogen bonds. Complexes and (3) are self-assembled via p ? p, C-H-p, stacking interactions and intra-molecular hydrogen bonds. Meclofenamic acid and [Ph 3 Sn(Meclo)] have been evaluated for antiproliferative activity in vitro against three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse L-929 (a fibroblast-like cell line cloned from strain L). The [Ph 3 Sn(Meclo)] complex exhibited high cytotoxic activity against all the cancer cell lines. Meclofenamic and [Ph 3 Sn(Meclo)]

Pagetoid urothelial carcinoma in situ (CIS) is a rare variant of bladder cancer that is characterized by an intraepithelial proliferation of large cells arranged singly or in clusters and randomly distributed. These neoplasms deserve recognition and attention, chiefly because they may be overlooked or misdiagnosed as urothelial dysplasia, then causing unsuspected tumor recurrence after surgery. We report on the clinicopathological features and immunohistochemical findings of 11 (14.86%) cases of pagetoid CIS in a retrospective study of 74 cases of conventional carcinoma in situ. Most patients were male (n=10). Their ages ranged from 31 years to 78 years. The lesion can be present with primary (n=2) or secondary (n=9) CIS. Pagetoid CIS is usually a focal lesion occurring in a clinical and histological setting of conventional CIS, and these patients essentially have the same progression and survival rates as patients without pagetoid changes and are treated in the same way. In cases with extensive urothelial denudation, pagetoid CIS may be focally present in otherwise normal-looking urothelium, thus alerting the pathologist to search for additional CIS elsewhere in the bladder. Given that primary extramammary Paget disease of the external genitalia and of the anal canal may extend to the bladder and, conversely, some bladder cases of pagetoid CIS may extend to the urethra, ureter, and beyond to the external genitalia, the differential diagnoses between these two entities represent an important therapeutic consideration. Our data suggest that a panel of immunostains including CK7+/CK20+/TM+ may assist in differentiating urothelial pagetoid CIS from extramammary Paget disease which is known to be CK7+/CK20-.

Tagetes erecta, Cosmos sulphureus, Antigonon leptopus and Bougainvillea glabra are edible flowers frequently used by the ethnic population of northern Thailand for preparation of salads and flower teas. The main constituents of ethanolic extracts of these flowers, identified with the help of a high-performance liquid chromatography (HPLC) method, were phenolic acids and flavonoids. T. erecta flowers contained the highest level of phenolic compounds, 1107.5 mg/100 g dry weight (DW), which was 3-to 4-fold the level of phenolic compounds in three other flowers evaluated in this study. Lyophilised aqueous extract of T. erecta had the highest Folin-Ciocalteu value (212 ± 9.0 mgGAE/g DW) and exhibited the highest total reducing capacity (Ferric Reducing Antioxidant Power, FRAP assay; 329.4 ± 21.8 μmol Fe 2+ /g DW) and cellular antioxidant activity (CAA assay; EC 50 = 413 μg/ml). However A. leptopus extract exhibited a superior oxygen free radical scavenging ability (oxygen radical absorbance capacity, ORAC-H assay). The extracts were evaluated for their abilities to suppress the proliferation of human cancer cells associated with the digestion system and to inhibit the activity of two enzymes, α-glucosidase and pancreatic lipase. A pronounced anti-proliferative activity against the colorectal adenocarcinoma (HT-29) cells exhibited T. erecta extract (IC 50 = 1.5 mg/ml), while A. leptopus was most active against the gastric adenocarcinoma (AGS) (IC 50 = 0.2 mg/ml) and bladder cancer cells (BL-13) (IC 50 = 0.9 mg/ml). T. erecta extract was identified as an efficient inhibitor of α-glucosidase enzyme (IC 50 = 0.06 mg/ml). T. erecta, C. sulphureus and B. glabra extracts equally inhibited the activity of pancreatic lipase (IC 50 : 4.82 and 4.60 mg/ml, respectively). The results obtained in this study for the first time identified a number of potential health-enhancing properties of aqueous extracts obtained from edible flowers consumed by the indigenous people of Thailand.

Cancer chemoprevention is a new approach in cancer prevention, in which chemical agents are used to prevent cancer in normal and/or high-risk populations. Although chemoprevention has shown promise in some epithelial cancers, currently available preventive agents are limited and the agents are costly, generally with side effects. Natural products, such as grape seed, green tea, and certain herbs have demonstrated anti-cancer effects. To find a natural product that can be used in chemoprevention of cancer, we tested Arizona cactus fruit solution, the aqueous extracts of cactus pear, for its anti-cancer effects in cultured cells and in an animal model. Aqueous extracts of cactus pear were used to treat immortalized ovarian and cervical epithelial cells, as well as ovarian, cervical, and bladder cancer cells. Aqueous extracts of cactus pear were used at six concentrations (0, 0.5, 1, 5, 10 or 25%) to treat cells for 1, 3, or 5 days. Growth inhibition, apoptosis induction, and cell cycl...

Disinfection by-products (DBPs) are formed when disinfectants (chlorine, ozone, chlorine dioxide, or chloramines) react with naturally occurring organic matter, anthropogenic contaminants, bromide, and iodide during the production of drinking water. Here we review 30 years of research on the occurrence, genotoxicity, and carcinogenicity of 85 DBPs, 11 of which are currently regulated by the U.S., and 74 of which are considered emerging DBPs due to their moderate occurrence levels and/or toxicological properties. These 74 include halonitromethanes, iodo-acids and other unregulated halo-acids, iodo-trihalomethanes (THMs), and other unregulated halomethanes, halofuranones (MX [3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone] and brominated MX DBPs), haloamides, haloacetonitriles, tribromopyrrole, aldehydes, and N-nitrosodimethylamine (NDMA) and other nitrosamines. Alternative disinfection practices result in drinking water from which extracted organic material is less mutagenic than extracts of chlorinated water. However, the levels of many emerging DBPs are increased by alternative disinfectants (primarily ozone or chloramines) compared to chlorination, and many emerging DBPs are more genotoxic than some of the regulated DBPs. Our analysis identified three categories of DBPs of particular interest. Category 1 contains eight DBPs with some or all of the toxicologic characteristics of human carcinogens: four regulated (bromodichloromethane, dichloroacetic acid, dibromoacetic acid, and bromate) and four unregulated DBPs (formaldehyde, acetaldehyde, MX, and NDMA). Categories 2 and 3 contain 43 emerging DBPs that are present at moderate levels (sub-to low-mg/L): category 2 contains 29 of these that are genotoxic (including chloral hydrate and chloroacetaldehyde, which are also a rodent carcinogens); category 3 contains the remaining 14 for which little or no toxicological data are available. In general, the brominated DBPs are both more genotoxic and carcinogenic than are chlorinated compounds, and iodinated DBPs were the most genotoxic of all but have not been tested for carcinogenicity. There were toxicological data gaps for even some of the 11 regulated DBPs, as well as for most of the 74 emerging DBPs. A systematic assessment of DBPs for genotoxicity has been performed for $60 DBPs for DNA damage in mammalian cells and 16 for mutagenicity in Salmonella. A recent epidemiologic study found that much of the risk for bladder cancer associated with drinking water was associated with three factors: THM levels, showering/bathing/swimming (i.e., dermal/inhalation exposure), and genotype (having the GSTT1-1 gene). This finding, along with mechanistic studies, highlights the emerging importance of dermal/ inhalation exposure to the THMs, or possibly other DBPs, and the role of genotype for risk for drinking-water-associated bladder cancer. More than 50% of the total organic halogen (TOX) formed by chlorination and more than 50% of the assimilable organic carbon (AOC) formed by ozonation has not been identified chemically. The potential interactions among the 600 identified DBPs in the complex mixture of drinking water to which we are exposed by various routes is not reflected in any of the toxicology studies of individual DBPs. The categories of DBPs described here, the identified data gaps, and the emerging role of dermal/inhalation exposure provide guidance for drinking water and public health research. #

Since DNA methylation is considered an important mechanism for silencing of retroelements in the mammalian genome, hypomethylation in human tumours may lead to their reactivation. The methylation status of LINE-1 retroposons was determined in 73 samples of urinary bladder cancers, 34 specimens of renal cell carcinoma and in the corresponding normal tissues by Southern blot analysis. LINE-1 sequences were strongly methylated in normal tissues and were significantly hypomethylated in 69 (95%) urothelial carcinomas, but in none of the renal carcinomas. Hypomethylation in bladder cancers was independent of stage and tended to increase with grade. The methylation status of HERV-K proviral DNA in normal and transformed urothelial cells paralleled that of LINE-1 sequences (r2 = 0.87). It was shown by ligation-mediated polymerase chain reaction that hypomethylation also extended to the LINE-1 promoter sequence located at the 5'-ends of full-length elements which is repressed by methylat...

Purpose: The usefulness of the expression of HERWneu oncoprotein and of p53 and Rb suppressor gene product as predictors of tumor recurrence was evaluated by using a bank of prospectively collected primary papillary bladder tumors treated initially only by transurethral resection.

Exponemos dos casos de reconversión de una derivación urinaria con asa ileal (Bricker) a neovejiga ortotópica. Exponemos dos casos de reconversión de una derivación urinaria con asa ileal (Bricker) a neovejiga ortotópica, uno mediante cirugía abierta y otro por laparoscopia. En ambos casos el postoperatorio transcurrió sin incidencias. Los dos pacientes se encuentran satisfechos con su nueva situación, continentes y sin presentar complicaciones metabólicas.

This review emphasizes the current knowledge related to optical coherence tomography (OCT) as a non-invasive diagnostic tool to perform ex vivo and showing great potential for in vivo structural imaging of features in the oral cavity. OCT technology can generate high-resolution cross-sectional and en-face images of the internal architecture of the investigated sample (2-3 mm in depth). To this goal, en-face time domain OCT (TD-OCT) and spectral domain OCT (SD-OCT) were employed. Topics included in this review refer to OCT non-destructive evaluations of: dental abfraction and attrition, material defects and micro-leakages at the tooth-filling interface, temporal-mandibular joint disc, quality of bracket bonding on dental hard tissue, prosthetic restorations and micro-leakages at prosthetic interfaces, root canals, presence or absence of apical micro-leakages, and osteo-integration of dental implants and of bone grafting materials. OCT revealed internal features of the material investigated with greater sensitivity than current diagnostic methods. We put our research in context with others' results but the review reflects primarily our joint group experience and it presents images collected with our OCT systems only. The studies demonstrate the viability of OCT as a useful tool in dental medicine practice, as well as in research. Being completely non-invasive, OCT can be extended to soft tissue. Both TD and SD implementations prove the unique capabilities of OCT. For handheld scanning devices it is expected that the swept source principle (as one of the SD possibilities) will prevail, due to its high speed that allows for the reduction of distorting effects caused by the involuntary movements of the hand and of the patient. For high transversal resolution investigations, especially in more research oriented studies, it is expected that en-face TD-OCT will continue to coexist with SD-OCT methods, offering additionally a low cost quick provision of en-face view and compatibility with dynamic focus. Dynamic focus, that is the simultaneous adjustment of focus and coherence gate in depth is incompatible with SD-OCT methods and require repetitions of acquisitions under different focus in order to improve the transversal resolution, or more complex heads with division of the optical path in the object arm along different focus adjustments. In this respect, en-face TD-OCT provides a lower cost alternative to high transversal resolution of static samples.

microRNAs (miRNA) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Here, we profiled the expression of 290 unique human miRNAs in 11 normal and 106 bladder tumor samples using spotted locked nucleic acid-based oligonucleotide microarrays. We identified several differentially expressed miRNAs between normal urothelium and cancer and between the different disease stages. miR-145 was found to be the most down-regulated in cancer compared with normal, and miR-21 was the most upregulated in cancer. Furthermore, we identified miRNAs that significantly correlated to the presence of concomitant carcinoma in situ. We identified several miRNAs with prognostic potential for predicting disease progression (e.g., miR-129, miR-133b, and miR-518c*). We localized the expression of miR-145, miR-21, and miR-129 to urothelium by in situ hybridization. We then focused on miR-129 that exerted significant growth inhibition and induced cell death upon transfection with a miR-129 precursor in bladder carcinoma cell lines T24 and SW780 cells. Microarray analysis of T24 cells after transfection showed significant miR-129 target downregulation (P = 0.0002) and pathway analysis indicated that targets were involved in cell death processes. By analyzing gene expression data from clinical tumor samples, we identified significant expression changes of target mRNA molecules related to the miRNA expression. Using luciferase assays, we documented a direct link between miR-129 and the two putative targets GALNT1 and SOX4. The findings reported here indicate that several miRNAs are differentially regulated in bladder cancer and may form a basis for clinical development of new biomarkers for bladder cancer. [Cancer Res 2009;69(11):4851-60]

We surveyed the extensive literature regarding the development, therapy and prevention of catheter-associated urinary tract infections (UTIs). We systematically searched for meta-analyses of randomised controlled trials available in Medline giving preference to the Cochrane Central Register of Controlled Trials and also considered other relevant publications, rating them on the basis of their quality. The studies' recommendations, rated according to a modification of the US Department of Health and Human Services (1992), give a close-to-evidencebased guideline for all medical disciplines, with special emphasis on urology where catheter care is an important issue. The survey found that the urinary tract is the commonest source of nosocomial infection, particularly when the bladder is catheterised (IIa). Most catheter-associated UTIs are derived from the patient's own colonic flora (IIb) and the catheter predisposes to UTI in several ways. The most important risk factor for the development of catheter-associated bacteriuria is the duration of catheterisation (IIa). Most episodes of short-term catheter-associated bacteriuria are asymptomatic and are caused by a single organism (IIa). Further organisms tend to be acquired by patients catheterised for more than 30 days. The clinician should be aware of two priorities: the catheter system should remain closed and the duration of catheterisation should be minimal (A). While the catheter is in place, systemic antimicrobial treatment of asymptomatic catheter-associated bacteriuria is not recommended (A), except for some special cases. Routine urine culture in an asymptomatic catheterised patient is also not recommended (C) because treatment is in general not necessary. Antibiotic treatment is recommended only for symptomatic infection (B). Long-term antibiotic suppressive therapy is not effective (A). Antibiotic irrigation of the catheter and bladder is of no advantage (A). Routine urine cultures are not recommended if the catheter is draining properly (C). A minority of patients can be managed with the use of the non-return (flip) valve catheter, avoiding the closed drainage bag. Such patients may exchange the convenience of on-demand drainage with an increased risk of infection. Patients with urethral catheters in place for 10 years or more should be screened annually for bladder cancer (C). Clinicians should always consider alternatives to indwelling urethral catheters that are less prone to causing symptomatic infection. In appropriate patients, suprapubic catheters, condom drainage systems and intermittent catheterisation are each preferable to indwelling urethral catheterisation (B). ଝ These guidelines based on the guidelines last published in 2006 by the European Association of Urology (ISBN-13:978-90-70244-59-0 ) were updated in cooperation with

Although several epidemiologic studies have been conducted on alcohol consumption and bladder cancer risk, the risk according to quantity and type of alcohol consumed is not clear. The authors investigated these associations in a large prospective cohort study on diet and cancer among 120,852 subjects in the Netherlands aged 55-69 years at baseline (1986). Subjects completed a questionnaire on risk factors for cancer, including alcohol consumption. Follow-up for incident cancer was established by record linkage to cancer registries. The case-cohort analysis was restricted to a follow-up period of 6.3 years and was based on 594 cases with bladder cancer and 3,170 subcohort members. The authors corrected for age and smoking in multivariable analyses. The incidence rate ratios for men who consumed <5, 5-<15, 15-<30, and ≥30 grams of alcohol per day were 1.49, 1.52, 1.16, and 1.63 compared with nondrinkers, respectively (p for trend = 0.13). Alcohol consumed from beer, wine, and liquor was associated with moderately elevated risks, although most were not statistically significant. The incidence rate ratios for women varied around unity. The results of this study do not suggest an important association between alcohol consumption and bladder cancer risk. Am J Epidemiol 2001;153:38-41. alcohol drinking; alcoholic beverages; bladder neoplasms; urologic neoplasms

This review emphasizes the current knowledge related to optical coherence tomography (OCT) as a non-invasive diagnostic tool to perform ex vivo and showing great potential for in vivo structural imaging of features in the oral cavity. OCT technology can generate high-resolution cross-sectional and en-face images of the internal architecture of the investigated sample (2-3 mm in depth). To this goal, en-face time domain OCT (TD-OCT) and spectral domain OCT (SD-OCT) were employed. Topics included in this review refer to OCT non-destructive evaluations of: dental abfraction and attrition, material defects and micro-leakages at the tooth-filling interface, temporal-mandibular joint disc, quality of bracket bonding on dental hard tissue, prosthetic restorations and micro-leakages at prosthetic interfaces, root canals, presence or absence of apical micro-leakages, and osteo-integration of dental implants and of bone grafting materials. OCT revealed internal features of the material investigated with greater sensitivity than current diagnostic methods. We put our research in context with others' results but the review reflects primarily our joint group experience and it presents images collected with our OCT systems only. The studies demonstrate the viability of OCT as a useful tool in dental medicine practice, as well as in research. Being completely non-invasive, OCT can be extended to soft tissue. Both TD and SD implementations prove the unique capabilities of OCT. For handheld scanning devices it is expected that the swept source principle (as one of the SD possibilities) will prevail, due to its high speed that allows for the reduction of distorting effects caused by the involuntary movements of the hand and of the patient. For high transversal resolution investigations, especially in more research oriented studies, it is expected that en-face TD-OCT will continue to coexist with SD-OCT methods, offering additionally a low cost quick provision of en-face view and compatibility with dynamic focus. Dynamic focus, that is the simultaneous adjustment of focus and coherence gate in depth is incompatible with SD-OCT methods and require repetitions of acquisitions under different focus in order to improve the transversal resolution, or more complex heads with division of the optical path in the object arm along different focus adjustments. In this respect, en-face TD-OCT provides a lower cost alternative to high transversal resolution of static samples.

Background In this work, we have conducted a case-control study in order to assess the effect of tobacco and three genetic polymorphisms in XPC, ERCC2 and ERCC5 genes (rs2228001, rs13181 and rs17655) in bladder cancer development in Tunisia. We have also tried to evaluate whether these variants affect the bladder tumor stage and grade. Methods The patients group was constituted of 193 newly diagnosed cases of bladder tumors. The controls group was constituted of non-related healthy subjects. The rs2228001, rs13181 and rs17655 polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism technique. Results Our data have reported that non smoker and light smoker patients (1-19PY) are protected against bladder cancer development. Moreover, light smokers have less risk for developing advanced tumors stage. When we investigated the effect of genetic polymorphisms in bladder cancer development we have found that ERCC2 and ERCC5 variants were not i...

Context: The incidence of bladder cancer increases with advancing age. Considering the increasing life expectancy and the increasing proportion of elderly people in the general population, radical cystectomy will be considered for a growing number of elderly patients who suffer from muscle-invasive or recurrent bladder cancer. Objective: This article reviews contemporary complication and mortality rates after radical cystectomy in elderly patients and the relationship between age and short-term outcome after this procedure. Evidence acquisition: A literature review was performed using the PubMed database with combinations of the following keywords cystectomy, elderly, complications, and comorbidity. English-language articles published in the year 2000 or later were reviewed. Papers were included in this review if the authors investigated any relationship between age and complication rates with radical cystectomy for bladder cancer or if they reported complication rates stratified by age groups. Evidence synthesis: Perioperative morbidity and mortality are increased and continence rates after orthotopic urinary diversion are impaired in elderly patients undergoing radical cystectomy. Complications are frequent in this population, particularly when an extended postoperative period (90 d instead of 30 d) is considered. Conclusions: Although age alone does not preclude radical cystectomy for muscleinvasive or recurrent bladder cancer or for certain types of urinary diversion, careful surveillance is required, even after the first 30 d after surgery. Excellent perioperative management may contribute to the prevention of morbidity and mortality of radical cystectomy, supplementary to the skills of the surgeon, and is probably a reason for the better perioperative results obtained in high-volume centers.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with risk of bladder cancer and with increased bulky DNA adduct levels in several studies, mainly in smokers. We investigated the relation between bulky PAH-DNA adducts in peripheral blood mononuclear cells and bladder cancer in nonsmoking subjects from a large hospital-based casecontrol study in Spain. Additionally, we examined the association between DNA adduct formation and several air pollution proxies. The study comprised 76 nonsmoking cases and 76 individually matched controls by sex, region of residence, age, and smoking status (never, former). To maximize the relevance of the DNA adduct measurement as a proxy of PAH exposure, subjects selected had not changed residence, occupation, and major lifestyle factors during the last 10 years. Bulky DNA adducts were measured using the 32 P-postlabeling technique, nuclease P1 treatment. The percentage of detectable adducts was higher in controls (41%) than in cases (32%) with an odds ratio of 0.75 (95% confidence interval, 0.36-1.58). In an analysis limited to controls, a higher percentage of DNA adducts was found among those whose last residence was in a big city (50%) compared with those living in villages (19%; P = 0.04). No consistent associations were found for other markers of air pollution. In this study, among nonsmokers with stable environmental and lifestyle factors, bulky DNA adducts were not associated with bladder cancer risk. Results do not support an association of bladder cancer risk with low-level exposure to PAHs as measured through the formation of bulky DNA adducts in peripheral mononuclear cells.

Objectives. Monti et al. recently described a technique for the construction of a continent catheterizable conduit using short segments of small bowel in a canine model. We review our experience with 25 adult and pediatric patients in whom the Monti procedure was used in their reconstructive efforts.Methods. Since October 1995, 25 patients (13 males and 12 females), aged 4 to 67 years (median 29), underwent the construction of 29 catheterizable stomas with a short (2.5 cm) segment of bowel following the Monti technique. Twenty-seven tubes were created as urinary stomas and two as part of the Malone antegrade continent enema procedure (MACE). Continence is based on the Mitrofanoff flap valve mechanism. Tubes were created when the appendix was unavailable as part of urinary reconstructive efforts or after exenterative oncologic surgery of the lower urinary tract. Tubes were created using ileum (24) and sigmoid colon (5). Ten tubes (34.5%) were done in combination with a simultaneous bowel patch in the same pedicle for bladder augmentation. Tubes were implanted in the ileum (13), bladder (9), sigmoid colon (3), stomach (1), and descending colon (1). The two tubes created to do a MACE procedure were anastomosed into the cecum. Double tubes were necessary in 7 adult patients for adequate length. The length of the tubes varied from 6 to 14 cm.Results. Follow-up ranged between 3 and 26 months (mean 13). One adult patient (4%) with bladder cancer died of myocardial infarction 14 days postoperatively. Three patients (12%) received a new Monti tube because of ischemic stenosis of the tube. All of them were continent at a follow-up of 1, 6, and 20 months, respectively. Two patients (8%) experienced leakage through the stoma, requiring additional procedures and pharmacologic manipulation to become continent. All patients used intermittent catheterization through the stoma without problems.Conclusions. Although the appendix remains the tissue of choice, the Monti procedure has substantial advantages over other efferent catheterizable tubes, including the need for a very short segment of bowel (2.5 cm), adequate lumen size (16F to 18F), length, reliable blood supply, and the versatility to combine with a simultaneous bowel patch in the same pedicle for bladder augmentation.

Genetic analysis of bladder cancer has revealed a number of frequently altered genes, including frequent alterations of the telomerase (TERT) gene promoter, although few altered genes have been functionally evaluated. Our objective is to characterize alterations observed by exome sequencing and sequencing of the TERT promoter, and to examine the functional relevance of histone lysine (K)-specific demethylase 6A (KDM6A/UTX), a frequently mutated histone demethylase, in bladder cancer. We analyzed bladder cancer samples from 54 U.S. patients by exome and targeted sequencing and confirmed somatic variants using normal tissue from the same patient. We examined the biologic function of KDM6A using in vivo and in vitro assays. We observed frequent somatic alterations in BRCA1 associated protein-1 (BAP1) in 15% of tumors, including deleterious alterations to the deubiquitinase active site and the nuclear localization signal. BAP1 mutations contribute to a high frequency of tumors with brea...

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cance...