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Transitional cell carcinoma is the most common cancer of the canine urinary tract. The inconsistent appearance of transitional cell carcinoma in patients introduces error if applying mathematic models for extrapolating total tumor volume from linear measurements. Reliable techniques to assess tumor size are important for monitoring treatment response. A method comparison study was performed comparing four techniques for calculating tumor volume were compared: (1 and 2) contoured tracing of tumor margins using serial computed tomography (CT) images using pre‐(1) and postintravenous (2) contrast medium studies, (3) longest three linear dimensions using CT, and (4) longest three linear dimensions on abdominal ultrasound. Volumes of the transitional cell carcinoma tumor calculated by CT tracing techniques were significantly smaller than volumes calculated with an ellipsoid mathematic model using the linear measurements (P < 0.01). Intravenous contrast medium did not significantly change the volumes calculated from tracing tumor margins on CT for observer B; however, volumes differed for observer A. The volumes extrapolated from linear measurements using CT and ultrasound did not differ significantly. The interobserver reliability was highest for the precontrast CT contoured technique and was lowest using the ultrasound linear technique. Tumor volumes differed significantly between techniques of contoured tracing of the tumor margins on serial CT images compared to calculation of tumor volume from linear dimensions. The calculated volume of a transitional cell carcinoma depends upon the technique used. Characterizing the response of urinary bladder transitional cell carcinoma tumor size to therapy differs based on the method and modality used. [ABSTRACT FROM AUTHOR]

Objective: To evaluate a potential association between Human Papillomavirus (H.P.V.) and squamous cell carcinoma (S.C.C.) urinary bladder cancer (B.C.). Furthermore, the relation between p16INK4a, H.P.V. and B.C. was examined. Patients and methods: Patients were included and divided into three groups based on the histological diagnosis of B.C. specimens. An extensive exclusion was performed, including accepted casual risk factors for S.C.C. B.C., such as long-term use of catheters, cystolithiasis and Schistosoma hematobium infection. A total of 100 patients were included: 50 with pure S.C.C., 25 with urothelial carcinomas (U.C.) and 25 with squamous differentiation of U.C. (Sq.D.). The patients were operated at one of four major Danish hospitals in the period January 2005 to December 2016. Clinical information was collected from the medical records. Presence of H.P.V. was analyzed using the INNO-LiPA H.P.V. Genotyping Extra II. p16INK4a was analyzed using immunohistochemical (I.H.C.) staining. A p-value <0.05 was considered statistically significant. Results: An overall H.P.V. prevalence of 12/100 (12%) was observed. H.P.V. was demonstrated in 9/50 (18%) of the S.C.C. patients. Overall, p16INK4a over-expression was observed in 52/100 (52%) patients. However, concomitant H.P.V. positivity and p16INK4a over-expression were observed in only 4/100 (4%) patients. Conclusion: The presence of H.P.V. in one fifth of patients with S.C.C. B.C. was demonstrated. H.P.V. infection could have a significant association with S.C.C. B.C. without other known casual risk factors for S.C.C. B.C. [ABSTRACT FROM AUTHOR]

Postoperative complications and readmission to hospital after major cancer surgery are common. Early mobilisation in hospital is thought to reduce complications, and patients are recommended to mobilise for at least 2 h on the day of surgery, and thereafter at least 6 h per day. Evidence for early mobilisation is limited and therefore also how early mobilisation may influence the development of postoperative complications. The aim of this study was to evaluate the association between early mobilisation after abdominal cancer surgery and readmission to hospital due to postoperative complications. Adult patients who had abdominal cancer surgery due to ovarian, colorectal, or urinary bladder cancer between January 2017 and May 2018 were included in the study. Exposure was set to the mean number of steps taken over the first three postoperative days, measured with an activity monitor. Primary outcome was readmission to hospital within 30 days after discharge, and secondary outcome was severity of complications. Data were obtained from medical records. Logistic regression was used to investigate the association between exposure and outcomes. Of 133 patients included in the study, 25 were readmitted to the hospital within 30 days after discharge. The analysis showed no association between early mobilisation and readmission or severity of complications. Early mobilisation does not seem to increase the odds of readmission, nor the severity of complications. This study contributes to the limited research on the association between early mobilisation and postoperative complications after abdominal cancer surgery. [ABSTRACT FROM AUTHOR]

Background: Exosomes are rich sources of biological material (proteins and nucleic acids) secreted by both tumor and normal cells, and found in urine of urinary bladder cancer patients. Objective: The objective of the study was to identify interacting exosomal proteins in bladder cancer for future use in targeted therapy. Methods: The Exocarta database (www.exocarta.org) was mined for urinary bladder cancer specific exosomal proteins. The urinary bladder cancer specific exosomal proteins (n = 248) were analyzed to identify enriched pathways by Onto-tool Pathway Express (http://vortex.cs.wayne.edu/ontoexpress). Results: Enriched pathways included cellular architecture, motility, cell to cell adhesion, tumorigenesis and metastasis. Proteins in the 9 top-ranked pathways included CTNNA1 (alpha-catenin), CTNNB1 (beta-catenin), VSAP, ITGA4, PAK1, DDR1, CDC42, RHOA, NRAS, RHO, PIK3AR1, MLC1, MMRN1, and CTTNBP2 and network analysis revealed 10 important hub proteins and identified inferred interactor NF2. Conclusions: The importance of identifying interactors is that that they can be used as targets for therapy, for example, using Bevacizumab (avastin – an angiogenesis inhibitor) against NF2 to inhibit protein–protein interactions will inhibit tumor growth and progression by hindering the exosome biogenesis.

This study aimed to evaluate the validity of the BTA STAT and BTA TRAK as biomarker tests in patients with suspected urinary bladder cancer (UBC) using histopathology as a reference method, and to clarify the relationship between the results of these tests and tumor grades. This is a cross sectional study that was carried out in Basrah, Southern of Iraq, from 1st of October 2010 to the 31st of March 2012. A total of 102 patients with signs and symptoms suggestive of UBC admitted to the urology ward in Basrah General Hospital were enrolled. A voided urine sample was obtained from each patient for analysis of BTA STAT and BTA TRAK prior to cystoscopy. The sensitivity and specificity of the BTA STAT test were 93.1% and 33.3% while for the BTA TRAK test were 97.7% and 33.3%, respectively. The sensitivity of the two studied urinary bladder cancer biomarkers rose with the increase in the grade of UBC and there was an elevation in the median and mean values of BTA TRAK test with the increase in the grade of UBC, although it was not significant. In conclusion, the sensitivity of both BTA STAT and BTA TRAK tests was very high; but their specificity was very low with high false positive results, however, they may be helpful in early detection and monitoring of recurrence of the disease in patients suffering from UBC.

Purpose: To evaluate the diagnostic performance of stalk morphology on diffusion-weighted imaging (DWI) in comparison with conventional MRI in predicting muscle invasion in urinary bladder cancer.Methods: The study was prospective and approved by the institutional ethics committee. A written informed consent was obtained from all the patients. The study included 56 patients who presented with bladder mass between January 2014 and November 2015. After excluding 16 patients, 40 patients with 92 tumors were assessed. All the 40 patients underwent MRI at 3.0 Tesla (Achieva, Philips) inclusive of DWI (b0, 500, 1000 and 1500). Two radiologists evaluated the images independently, and disparities were resolved through consensus. For predicting muscle invasion on T2-weighted images, tumor morphology (papillary versus non-papillary), distensibility of the underlying bladder wall, and perivesical fat infiltration were evaluated. On DWI, the criterion used in a previous study (Takeuchi et al.) was used along with tumor stalk morphology. Findings were compared with histopathology using Pearson’s χ2 test, and diagnostic performance indices were calculated.Results: All the evaluated features were present with significantly higher frequency in muscle-invasive tumors (p < 0.001). The finding of absent or distorted stalk on DWI had the highest sensitivity (87.5%) and specificity (97.6%). Conventional imaging features of non-papillary stalk morphology, restricted distension of underlying bladder wall, perivesical fat infiltration, as well as the previous DWI criterion were less sensitive (56.3%, 68.8%, 56.3% and 56.3%, respectively) in predicting muscle invasion.Conclusions: Assessment of the morphology of the reactive tumor stalk on DWI has better diagnostic performance in predicting muscle invasion than conventional MRI. [ABSTRACT FROM AUTHOR]

Genetic abnormalities and epigenetic alterations both play vital role in initiation as well as progression of cancer. Whereas genetic mutations cannot be reversed, epigenetic alterations such as DNA methylation can be reversed by the application of DNA methyltransferase inhibitor decitabine. Epigenetic silencing of RASSF1A and involvement of hippo pathway both have been shown to involve in chemo-resistance. Purpose of this study was to observe the effect of combination treatment of decitabine with cisplatin or doxorubicin on bladder cancer cells involving hippo pathway through RASSF1A. Bladder cancer cells (HT1376 & T24) were treated with decitabine and its effect on RASSF1A expression, hippo pathway molecules (MST & YAP), and its downstream targets (CTGF, CYR61 & CTGF) was observed. Effect of decitabine pretreatment on sensitivity of bladder cancer cells towards chemotherapeutic drugs was also studied. Decitabine treatment leads to restoration of RASSF1A, activation of hippo pathway followed by decreased expression of its oncogenic downstream targets (CTGF & CYR61). Further pretreatment of decitabine enhanced cytotoxicity of cisplatin and doxorubicin to bladder cancer cells. [ABSTRACT FROM AUTHOR]

Purpose: We prospectively evaluated the 90-day postoperative mortality and morbidity of open radical cystectomy by using a standardized reporting methodology. Additionally, we assessed the preoperative characteristics to determine risk factors for major complications.Methods: This multicenter prospective study included 185 consecutive patients undergoing open radical cystectomy from October 2010 through March 2014. Postoperative complications within 90 days were recorded and graded according to the modified Clavien-Dindo classification.Results: Totally, 328 postoperative complications were observed in 149 patients (80.5%). Of these events, 73 (22.2%) were high grade (≥ Grade III), and developed in 46 patients (24.9%). Three patients (1.6%) died postoperatively. Urinary tract infection, wound complications, and paralytic ileus were common complications that occurred in 55 (29.7%), 42 (22.7%) and 41 (22.2%) patients, respectively. Ureteroenteric stricture was diagnosed in 13 of the 151 patients (8.6%) undergoing intestinal urinary diversion. Emergency room visits were required for 13 patients (7.0%) and readmission after discharge was needed for 36 (19.5%). A body mass index ≥ 25 kg/m2, smoking history and Charlson Comorbidity Index ≥ 2 were independent risk factors for high-grade complications, and their odds ratios (95% confidence intervals) were 2.357 (1.123-4.948), 2.843 (1.225-6.596) and 3.025 (1.390-6.596), respectively.Conclusions: Open radical cystectomy is associated with a high incidence of postoperative complications. Most, however, are of low grade. Our results suggest that obesity, a smoking history, and increasing comorbidity are risk factors for major complications. [ABSTRACT FROM AUTHOR]

Urinary bladder cancer (UBC) is one of the most common malignancies worldwide. The etiology of UBC is multifactorial and includes both exogenous and endogenous factors. Exogenous risk factors include exposure to heavy metals, aromatic amines, and environmental pollutants including pesticides such as organochlorine pesticides (OCPs). Environmental factors alone are incapable of directly producing DNA damage and may require activation by phase I metabolizing enzymes like cytochrome P450 in order to become active carcinogen. The present study is designed to study CYP1A1 gene expression, OCP level in cases of UBC, as well as to explore the plausible role of gene--environment interaction in the etiology of UBC among North Indian population. A total of 60 cases with equal number of controls were enrolled under this study, the OCP levels were estimated using gas chromatography, CYP1A1 mRNA expression was quantified by real-time quantitative polymerase chain reaction, and fold change was calculated using the ΔΔCt method. In the present study, the levels of OCP were found to be significantly higher with the upregulation of CYP1A1 mRNA expression among UBC cases as compared to controls. While putting multiple linear regression, it has been observed that there is a significant interaction between the levels of OCPs and ΔCt value of CYP1A1 gene taken into account hematuria episodes as dependent variable. The study concludes that when there is predisposition of OCPs and upregulation of CYP1A1 gene, then the result will be an increment in hematuria episodes which indicates that gene--environment interaction plays a significant role in the causation of UBC among North Indian population. [ABSTRACT FROM AUTHOR]

Background: Urinary Bladder cancer is the second most common neoplasm of the urinary tract worldwide. It accounts for 6-8 % of malignancy in men and 2-3% in women with the highest incidence rates in North American and Europe as well as areas with endemic schistosomiasias in Africa and the middle east. Purpose: To show the staging accuracy of Dynamic MRI in urinary bladder carcinoma. Patients and Methods: This is a Prospective randomized clinical study, study setting: Radiology and Urology Departments, Faculty of Medicine, Ain Shams University, study period: 6 months from August 2017 till February 2018. Results: This study conducted on 20 patients (17 male and 3 females) with age ranged from 42 - 78 years and with mean±SD of 55.95±9.01 years. 4/20 patients (20.0%) were presented to TURT procedure while 16/20 patients (80.0%) were presented to radical cystectomy. Conclusion: In this study, despite small differences between the results of the MRI and pathology, Dynamic MRI was found to be an accurate modality for assessment of tumor staging, and its routine use in bladder cancer staging can lead to significant improvement of diagnostic accuracy of the staging and treatment planning and hence improvement of the prognosis of the patients and their survival rates. Furthermore, the use of Dynamic MRI systems with higher magnetic field and imaging techniques standardized with higher resolution could further enhance the accuracy of the method. Further studies with larger sample size may also help to validate the results of this study. [ABSTRACT FROM AUTHOR]

Introduction: We hypothesized that hypertensive patients harbor a higher risk of urinary bladder (UB) cancer. Material and methods: 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. Results: 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. Conclusion: This nationwide population-based propensity score-matched cohort study supports a positive association between hypertension and subsequent UB cancer development. [ABSTRACT FROM AUTHOR]

Aim of the study: to evaluate the role of diffusion weighted magnetic resonance imaging in urinary bladder cancer grading in comparison to histopathological grading. Patients and methods This prospective study included 50 patients; 30 males and 20 females with mean age 66.4 years. All patients were referred clinically for bladder cancer and hence all of them underwent MR imaging. T2 weighted images were acquired followed by diffusion study in the same plane, b value = 800 s/mm 2 . Results pathologic staging was between Tis and T1 (superficial) in 28% of tumors. More than T1 (Deep) in 72%. The mean ADC value was 1.203 × 10 –3 with a standard deviation of ±0.385 × 10 –3 . The mean ADC value for stages Tis to T1 tumors was 1.505 × 10 –3  ± 0.270 SD; and stages T2 to T4 tumors was 1.085 ± 0.385 SD; P < 0.001. Cutoff ADC value was 1.275 × 10 –3 as a useful indicator for differentiating stages Tis to T1 from T2 to T4; P < 0.005. Conclusion DW imaging is a noninvasive reliable modality for predicting histopathological aggressiveness of bladder cancer. [ABSTRACT FROM AUTHOR]

Involvement of matrix metalloproteinases (MMPs) in the pathogenesis of urothelial carcinoma elects them to be sensitive marker for clinical and prognostic implications. MMPs regulate tumor growth and invasion by inducing epithelial-to-mesenchymal transition (EMT) which is characterized by the complex reprogramming of epithelial cells and ultimately bring about major changes in the structural organization of bladder urothelium. The present study has been undertaken to evaluate the clinical relevance of MMPs in two distinct types of bladder cancer disease. Expression analysis of MMPs namely MMP-2, MMP-7, MMP-9 and EMT markers including epithelial marker, E-cadherin; mesenchymal markers, N-cadherin and Vimentin; and EMT-activating transcriptional factors (EMT-ATFs), Snail, Slug, Twist and Zeb was done in 64 cases of bladder tumor tissues [{Non-muscle invasive bladder cancer (NMIBC): 35 cases} and {Muscle invasive bladder cancer (MIBC): 29 cases}] by real-time quantitative polymerase chain reaction (RT-qPCR). Immunohistochemistry (IHC) staining was done in matched bladder tumor tissues to evaluate the protein expression and localization of E-cadherin, N-cadherin, Vimentin, Snail, and Slug. Our data showed overexpression of MMP-2, MMP-7 and MMP-9 at transcriptome level in 32.8%, 25% and 37.5% bladder tumor cases respectively. These tumor tissues were examined for higher expression of mesenchymal markers (N-cadherin and Vimentin) at mRNA and protein level and exhibited statistical association with tumor stage and tumor grade (p = 0.02, p = 0.04, Mann-Whitney test). Significant statistical correlation in tumor tissues with overexpressed MMPs has also been observed between gain of transcriptional factors and weak expression of E-cadherin with tumor stage, grade, gender, presence of hematuria and smoking history of the patients. Gene expression patterns of EMT markers in bladder tumors with overexpressed MMPs and their significant association with clinical profile validate the important role of MMPs in the pathogenesis of urothelial carcinoma of bladder (UCB). Increased expression of specific MMPs may affect several downstream EMT programs and thus may improve its diagnostic and prognostic utility in clinical setting. [ABSTRACT FROM AUTHOR]

N-acetyltransferase 1 (NAT1), a polymorphic Phase II enzyme, plays an essential role in metabolizing heterocyclic and aromatic amines, which are implicated in urinary bladder cancer (BCa). This systematic review investigates a possible association between the different NAT1 genetic polymorphisms and BCa risk. Medline, PubMed, EMBASE, Scopus, Web of Science, OpenGrey, and BASE databases were searched to identify eligible studies. The random-effect model was used to calculate pooled effects estimates. Statistical heterogeneity was tested with Chi-square and I2. Twenty case-control studies, including 5606 cases and 6620 controls, met the inclusion criteria. Pooled odds ratios (OR) analyses showed a statistically significant difference in NAT1*10 versus non-NAT1*10 acetylators in the total sample (OR: 0.87; 95% CI: 0.79-0.96) but was borderline among Caucasians (OR: 0.88 with 95% CI: 0.77-1.01). No statistically significant differences in BCa risk were found for: NAT1*10 versus NAT1*4 wild type (OR: 0.97; 95% CI: 0.78-1.19), NAT1 ‘Fast’ versus ‘Normal’ acetylators (OR: 1.03; 95% CI: 0.84-1.27), and NAT1 ‘Slow’ versus ‘Fast’ (OR: 2.32; 95% CI: 0.93-5.84) or ‘Slow’ versus ‘Normal’ acetylators (OR: 1.84; 95% CI: 0.92-3.68). When stratifying by smoking status, no statistically significant differences in BCa risk were found for NAT1*10 versus non-NAT1*10 acetylators among the different subgroups. Our study suggests a modest protective role for NAT1*10 and a possible risk contributory role for slow acetylation genotypes in BCa risk. Further research is recommended to confirm these associations. [ABSTRACT FROM AUTHOR]

Abstract: Alopecia areata (AA) is an organ‐specific autoimmune disorder. Defective immune system related disorders are prone to increase the risk of cancer formation. However, the association among AA and variety of cancer types had never been studied. A nationwide population‐based matched cohort study was conducted to evaluate the cancer risk in patients with AA. Records from Taiwan National Health Insurance Research Database were analyzed. Cases of AA from 1997 to 2013 and cancers registered in the catastrophic illness profile from the same time period were collected. The standard incidence ratio (SIR) of each cancer was calculated. In total, 2099 cancers among 162,499 patients with AA and without prior cancers were identified. The overall cancer risks in AA patients were slightly decreased, especially among male subjects (SIR: 0.89). Refer to individual cancer, the cancer risk of nonmelanoma skin cancer (NMSC) (SIR: 0.59), upper GI cancer (SIR: 0.70), liver cancer (SIR: 0.82), uterine, and cervix cancer (SIR: 0.84) were significantly lower in patients with AA. In contrast, AA patients were inclined to have lymphoma, breast cancer, kidney, and urinary bladder cancer with the SIR of 1.55, 2.93, and 2.95, respectively. Age stratified analyses revealed female AA patients younger than 50 years old have even higher risk of breast cancer (SIR: 3.37). Further sensitivity analysis showed similar results after excluding major autoimmune disorders. Cancer risk in AA patients is organ specific, and it is not associated with the underlying autoimmune disorders in patients with AA. [ABSTRACT FROM AUTHOR]

The association of dietary factors with urinary bladder cancer prognosis has scarcely been investigated, and results of studies conducted to date are inconsistent. We investigated whether empirically derived dietary patterns are associated with risks of recurrence and progression in non‐muscle‐invasive bladder cancer (NMIBC) patients. Data from 595 newly diagnosed NMIBC patients from an ongoing prospective cohort study were used to derive dietary patterns using exploratory factor analysis. Factor scores were calculated and then categorized in sex‐specific tertiles. Multivariable‐adjusted proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals for the associations between tertiles of adherence to the dietary patterns and risks of recurrence and progression. We identified four dietary patterns: “fruits and vegetables,” “Western,” “low‐fat,” and “Tex‐Mex.” Patients in the highest tertile of adherence to the Western pattern experienced a 1.48 times higher risk of recurrence (95% CI 1.06–2.06) compared to patients in the lowest tertile. No statistically significant associations of a Western diet with risk of progression or of the other dietary patterns with risk of recurrence and progression were found. Overall, we found that adherence to a Western diet was associated with a higher risk of recurrence but further studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to emphasize the critical importance of the clinician’s awareness of signet-ring cell carcinoma (SRCC) of the urinary bladder, a rare and aggressive disease entity. Materials and methods: A review of the current literature was conducted and a classic case of advanced SRCC of the urinary bladder is reported, clearly demonstrating the severity of this disease and the imperative need for standardized recommendations for the diagnostic work-up and management of urinary bladder SRCC. Results: The prognosis for patients with SRCC of the urinary bladder is poor, attributed to presentation at advanced stages following asymptomatic progression, inefficacy of multimodality therapy and possibly an aggressive underlying biological phenotype. Treatment options are limited and not well studied. Conclusion: Given the rarity of SRCC, multi-institutional clinical trials and international cooperation are mandatory to improve survival for patients with primary SRCC of the bladder. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Arylamine N -acetyltransferase 1 (NAT1) and 2 (NAT2) catalyze the acetylation of arylamine carcinogens. Single nucleotide polymorphisms in the NAT2 coding exon present in NAT2 haplotypes encode allozymes with reduced N -acetyltransferase activity towards the N -acetylation of arylamine carcinogens and the O -acetylation of their N -hydroxylated metabolites. NAT2 acetylator phenotype modifies urinary bladder cancer risk following exposures to arylamine carcinogens such as 4-aminobiphenyl. 4, 4′-methylene bis (2-chloroaniline) (MOCA) is a Group 1 carcinogen for which a role of the NAT2 acetylation polymorphism on cancer risk is unknown. We investigated the role of NAT2 and the genetic acetylation polymorphism on both MOCA N -acetylation and N -hydroxy-MOCA O -acetylation. MOCA N -acetylation exhibited a robust gene dose response in rabbit liver cytosol and in cryopreserved human hepatocytes derived from individuals of rapid, intermediate and slow acetylator NAT2 genotype. MOCA exhibited about 4-fold higher affinity for recombinant human NAT2 than NAT1. Recombinant human NAT2*4 (reference) and 15 variant recombinant human NAT2 allozymes catalyzed both the N -acetylation of MOCA and the O -acetylation of N -hydroxy-MOCA. Human NAT2 5, NAT2 6, NAT2 7 and NAT2 14 allozymes catalyzed MOCA N -acetylation and N -hydroxy- O -acetylation at rates much lower than the reference NAT2 4 allozyme. In conclusion, our results show that NAT2 acetylator genotype has an important role in MOCA metabolism and suggest that risk assessments related to MOCA exposures consider accounting for NAT2 acetylator phenotype in the analysis. [ABSTRACT FROM AUTHOR]

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Background Snail-1 actively participates in tumor progression, invasion, and migration. Targeting snail-1 expression can suppress the EMT process in cancer. The aim of this study was to investigate the effect of snail1 silencing on urinary bladder cancer. Methods Quantitative RT-PCR was used to detect snail-1 and other related metastatic genes expression following siRNA knockdown in urinary bladder cancer EJ-138 cells. The protein level of snail1 was assessed by Western blot. MTT and TUNEL assays were assessed to understand if snail-1 had survival effects on EJ-138 cells. Scratch wound healing assay measured cell motility effects after snail1 suppression. Results The significant silencing of snail-1 reached 60 pmol siRNA in a 48-h post-transfection. The result of scratch assay showed that snail-1 silencing significantly decreased Vimentin, MMPs, and CXCR4 expression; however, expression of E-cadherin was induced. The cell death assay indicated that snail-1 played the crucial role in bladder cancer survival rate. Conclusion These results propose that snail-1 plays a major role in the progression and migration of urinary bladder cancer, and can be a potential therapeutic target for target therapy of invasive urinary bladder cancer. [ABSTRACT FROM AUTHOR]

A 52-year-old Hispanic male presented with hematuria and was later diagnosed with a large invasive high-grade urothelial cell carcinoma (UCC) of the urinary bladder, but with ambiguous pT1/pT2 staging regarding musclaris propria invasion by UCC. The conventional treatment including radical cystoprostatectomy followed by neoadjuvant chemotherapy with or without radiation therapy was presented. The patient decided to delay the standard therapy until a later stage, but elected to go through transurethral resection of bladder tumor (TURBT) without Bacillus Calmette-Guérin instillation. Following TURBT, the patient started oral Boswellia sacra gum resin (aka frankincense or Ru Xiang in Chinese) hydrodistillates (BSGRH) administration at 3 mL daily with lifestyle changes, and continued this regimen in the last 25 months. Within the first year after diagnosis, the patient experienced 2 recurrences. Recurrent tumors were removed by TURBT alone and both tumors were far smaller than the original one. After the second recurrence, the patient has no detectible cancer in the bladder based on cystoscopy for 14 months and has an intact genitourinary system. His liver and kidney functions are considered to be normal based on blood chemistry tests. This index case suggests that BSGRH may have cancer chemopreventive effects on UCC. The use of Boswellia-derived products in the management of cancer has been well document in other published studies, and boswellic acids have been suggested to be the major component. However, BSGRH contains very little boswellic acids. Demonstration of cancer chemoprevention using BSGRH is one step forward in isolating the key components other than boswellic acids in frankincense. The critical question as to whether these components can simultaneously activate multiple pathways in cancer cells to execute cancer suppression/cytotoxicity or prevention effects remains to be addressed. More studies including identification of key molecules, pharmacokinetics of major compounds, as well as long-term benefits and possible adverse effects will be needed to meet the guidelines of the US Food and Drug Administration for botanical drug development. [ABSTRACT FROM AUTHOR]

With increasingly abundant spatial data in the form of case counts or rates combined over areal regions (eg, ZIP codes, census tracts, or counties), interest turns to formal identification of difference "boundaries," or barriers on the map, in addition to the estimated statistical map itself. "Boundary" refers to a border that describes vastly disparate outcomes in the adjacent areal units, perhaps caused by latent risk factors. This article focuses on developing a model-based statistical tool, equipped to identify difference boundaries in maps with a small number of areal units, also referred to as small-scale maps. This article proposes a novel and robust nonparametric boundary detection rule based on nonparametric Dirichlet processes, later referred to as Dirichlet process wombling (DPW) rule, by employing Dirichlet process-based mixture models for small-scale maps. Unlike the recently proposed nonparametric boundary detection rules based on false discovery rates, the DPW rule is free of ad hoc parameters, computationally simple, and readily implementable in freely available software for public health practitioners such as JAGS and OpenBUGS and yet provides statistically interpretable boundary detection in small-scale wombling. We offer a detailed simulation study and an application of our proposed approach to a urinary bladder cancer incidence rates dataset between 1990 and 2012 in the 8 counties in Connecticut. [ABSTRACT FROM AUTHOR]

The epithelium lining is defined as the mucosal surfaces of the renal collecting tubules, calyces and pelvis, as well as the ureter, bladder and urethra. The term 'urothelium' is used to refer to these surfaces. Upper tract urothelial carcinoma is a rare subset of urothelial cancers with a poor prognosis. Urinary bladder cancer is the most common malignancy involving the urinary system. Upper tract urothelial carcinoma is more common in men than in women, with a male-to-female ratio of 2:1. The incidence of urinary bladder cancer is also higher in men. Cigarette smoking and occupational exposure are the main upper tract urothelial carcinoma and urinary bladder cancer risk factors, while other factors are more specific to the carcinogenesis of upper tract urothelial carcinoma (i.e. Balkan endemic nephropathy, Chinese herb nephropathy). In Egypt until recent years, urinary bladder cancer was the most frequently diagnosed cancer due to Schistosoma haematobium. Substantial knowledge exists regarding the causes of upper tract urothelial carcinoma and urinary bladder cancer, and epidemiological studies have identified various chemical carcinogens that are believed to be responsible for most cases of urothelial carcinoma. In the era of precision medicine, genetic effects might play a direct role in the initiation and progression of urothelial carcinoma. [ABSTRACT FROM AUTHOR]

Altered signalling of human epidermal growth factor receptor-2 (HER-2/neu), insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF) have been shown to play important role in tumor development and progression in various cancers. Their serum levels may be reliable indicator for diagnosis and progression of cancer. To examine the serum levels of soluble HER-2/neu (sHER-2/neu), IGF1 and EGF in patients with urinary bladder cancer (UBC). Serum levels of sHER-2/neu, IGF1 and EGF were measured by enzyme-linked immune assay in newly diagnosed, untreated patients with UBC. In the patient group, sHER-2/neu level was found to be increased, IGF1 level was found to be decreased in comparison to those in the control group. Although serum level of sHER-2/neu was lower in the patients with Ta stage than that in the patients with T1 and T2 stages, this difference was not at a statistically significant level. Serum level of sHER-2/neu is increased in patients with UBC. Despite the lack of a significant association between sHER-2/neu level and pathological pT stage, sHER-2/neu may be a promising marker for UBC but IGF-1 and EGF have not such a potential. [ABSTRACT FROM AUTHOR]

Bladder cancer is among the most common and aggressive human malignant carcinomas, thus targeting and removal of bladder cancer cells is still a challenge. Although it is well known that chitosan hydrochloride (CH-HCl) causes desquamation of normal urothelial cells, its effect on cancer urothelial cells has not been recognized yet. In this in vitro study, we analyzed the cytotoxicity of 0.05% CH-HCl on three urothelial models: two cancer urothelial models, i.e. invasive and papillary urothelial neoplasms, and a normal urothelial model. The cytotoxicity of CH-HCl was evaluated with viability tests, transepithelial resistance (TER) measurements, and electron microscopy. TER measurements showed that 15-minute treatment with CH-HCl caused no reduction in TER of the cancer models, whereas the TER of the normal urothelial model significantly decreased. Furthermore, after CH-HCl treatment, the viability of cancer cells was reduced by only 5%, whereas the viability of normal cells was reduced by 30%. Ultrastructural analysis revealed necrotic cell death in all cases. We have demonstrated that although CH-HCl increases the mortality of cancer urothelial cells, it increases the mortality of normal urothelial cells even more so. However, shorter 2-minute CH-HCl treatment only temporarily increases the permeability of normal urothelial model, i.e. disrupts tight junctions and reduces TER without comprising cell viability, and enables the complete recovery of the permeability barrier after 24 h. Overall, our results suggest that CH-HCl cannot be used as a self-sufficient anticancer agent for urothelial bladder cancer treatment; nevertheless a possibility of its use as an enhancer of cytostatic treatment is discussed. [ABSTRACT FROM AUTHOR]

Introduction: More than 70,000 new cases of bladder cancer are diagnosed in the United States annually; with 75% being non‐muscle‐invasive (NMIBC). Research examining sexual dysfunction in bladder cancer survivors is limited, and previous studies have focused on cystectomy patients. Aims: To evaluate the impact of sexual dysfunction on NMIBC survivors. Methods: Mixed‐methods data collection integrated a quantitative survey (Study 1; n = 117) and semi‐structured qualitative interviews (Study 2; n = 26) from a non‐overlapping sample of NMIBC survivors. We performed descriptive and classification and regression tree (CART) analyses of survey data and qualitative analysis of interviews. Main Outcome Measures: Self‐reported sexual activity, interest in sex, and physiologic symptoms (e.g., male erectile/ejaculatory difficulties, female vaginal dryness) over the previous 4 weeks; partner communication about sexuality; contamination concerns; illness intrusiveness. Results: Participants in these studies averaged 65 years of age (mean and median) and were male (77%), white (91%), and married (75%). Survey (Study 1) results linked NMIBC treatment to sexual symptoms and relationship issues. Many participants reported sexual inactivity (38.8%). Sexually active participants reported erectile difficulties (60.0%), vaginal dryness (62.5%), and worry about contaminating partner with treatment agents (23.2%). While almost one‐half reported the usefulness of talking with partners about sexual function, only one‐fifth of participants reported sharing all concerns with their partners. CART analysis supported the importance of communication. One‐half of interviewees (Study 2) reported sexual dysfunction. Two‐thirds reported negative impacts on their relationships, including perceived loss of intimacy and divorce; over one‐third were sexually inactive for fear of contaminating their partner or spreading NMIBC. Conclusions: Survivors' sexual symptoms may result from NMIBC, comorbidities, or both. These results inform literature and practice by raising awareness about the frequency of symptoms and the impact on NMIBC survivors' intimate relationships. Further work is needed to design symptom management education programs to dispel misinformation about contamination post‐treatment and improve quality of life. Kowalkowski MA, Chandrashekar A, Amiel GE, Lerner SP, Wittmann DA, Latini DM, and Goltz HH. Examining sexual dysfunction in non‐muscle‐invasive bladder cancer: Results of cross‐sectional mixed‐methods research. Sex Med 2014;2:141–151.

Background: The primary and well established risk factor for urinary bladder cancer is cigarette smoking. ‎ Objective: The purpose of the present study was to evaluate the association between cigarette smoking and the ‎development of urinary bladder cancer in Basrah.‎ Methods: A case control study was conducted to examine the association between the risk of urinary bladder cancer and ‎various characteristics of smoking: the smoking status (current or ex-smoker), smoking intensity (cigarette per day), ‎duration, total exposure (pack-years), type of cigarette (filtered or unfiltered), inhalation, and environmental tobacco ‎smoke exposure. The study population composed of 87 patients with newly diagnosed bladder cancer cases and 357 ‎controls. Cases and controls were matched for age, sex, and residence.‎ Results: An increased risk of urinary bladder cancer was found for both current and ex-smoker (for current smoker OR ‎‎= 2.98; 95% CI = 1.68-5.28 and for ex-smoker OR = 4.05; 95% CI = 2.19-7.48). The study also revealed a significant ‎positive trend in urinary bladder cancer risk with smoking intensity, pack-years, and environmental tobacco smoke. ‎ Conclusion: The results of the present study are consistent with the findings of the previous epidemiological studies and ‎confirm that smoking is a major risk factor for urinary bladder cancer and preventive strategies should be directed ‎toward smoking as risk factor for urinary bladder cancer in Basrah. ‎

Objective(s):Green tea (GT) is one of the most popular beverages worldwide whose beneficial effects on health have been demonstrated. Recent studies suggest that GT may contribute to reduction of cancer risk and progression. The aim of this study was to evaluate the effects of whole GT on urinary bladder chemical carcinogenesis in male and female ICR mice. Materials and Methods: The GT characterization was performed using spectrophotometric methods. Urinary bladder lesions were induced using N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) by gavage during 10 weeks and whole GT (0.5%) was provided ad libitum during 20 weeks. Results:Animals from groups BBN+GT and BBN only developed preneoplastic lesions. Conclusion:We did not observe any effects by GT infusion administration on urinary bladder cancer development.