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Purpose: Patients with intermediate-risk non-muscle-invasive bladder cancer have traditionally been defined as those not included in the low- or high-risk groups. Therefore, the intermediate-risk group consists of heterogeneous patients.Materials and Methods: We reviewed 326 patients diagnosed with intermediate-risk tumors. We subclassified these patients into 3 groups according to their clinical courses. Group A included patients with initial and multiple low-grade tumors (N = 170). Group B consisted of patients with a low-grade tumor that recurred after a low-risk tumor (N = 97), and Group C consisted of patients with a low-grade tumor that recurred after a high-risk tumor (N = 59).Results: The 2-year recurrence-free survival rate was significantly lower in Group C (42%) than in Groups A (69%, P<0.01) and B (70%, P<0.01). Regarding progression-free survival, no significant differences were observed among the groups. In total, 167 patients received adjuvant bacillus Calmette-Guérin (BCG), and 39 received adjuvant chemotherapy instillations. In Groups A and B, there were no significant differences in efficiency against tumor recurrence between BCG and chemotherapy. In Group C, the 5-year recurrence-free survival rate was 65% in patients receiving BCG, which was significantly higher when compared with patients receiving chemotherapy (P = 0.01). Furthermore, Group C included 11 BCG refractory cases, 5 of whom later experienced stage progression during follow-up.Conclusion: Our subclassification analysis suggested that intermediate-risk tumors that recurred after a high-risk tumor (Group C) should be treated with adjuvant BCG therapy, owing to the high probability of subsequent recurrence. Furthermore, the definition of intermediate risk may include some BCG refractory cases. [ABSTRACT FROM AUTHOR]

Objective To evaluate risk factors for bladder cancer recurrence in a cohort of patients treated with radical nephroureterectomy (RNU). Patients and methods At 10 Canadian University Centers, we retrospectively evaluated data, between 1990 and 2010, from 743 patients who were free from bladder cancer and were previously treated with RNU for upper tract urothelial cancer. Results Of 743 patients, 167 (22.5%) developed bladder tumors after a median time of 17.2 months after RNU. Multivariable analysis detected age (hazard ratio [HR] = 1.028; 95% CI: 1.010-1.046; P = 0.0018), tumor location in both the renal pelvis and the ureter (HR = 2.205; 95% CI: 1.355-3.589; P = 0.0015), the use of adjuvant systemic chemotherapy (HR = 2.309; 95% CI: 1.439-3.705; P = 0.0005), and laparoscopic surgery (HR = 1.876; 95% CI: 1.226-2.87; P = 0.0037) as risk factors for bladder cancer recurrence. Open excision of a bladder cuff (HR = 0.661; 95% CI: 0.453-0.965; P = 0.0319) and transurethral resection of the intramural ureter (HR = 0.548; 95% CI: 0.306-0.981; P = 0.0429) on comparison with extravesical resection decreased the risk of bladder cancer recurrence significantly. Major limitations were the retrospective design and partially missing data, although the significance of variables did not change in the imputation analysis. Conclusion Older patients, those with tumor location in both the renal pelvis and the ureter, and those treated with adjuvant systemic chemotherapy were found at higher risk for intravesical recurrence, as were those having undergone extravesical ureterectomy or laparoscopic RNU. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To evaluate the risk factors and prognosis of muscle-invasive bladder cancer (MIBC) developing after nephroureterectomy for upper urinary tract urothelial cell carcinoma (UUT-UC). Materials and methods: We reviewed the medical records of 422 patients who underwent nephroureterectomy for UUT-UC between 1990 and 2010, and identified 173 (40.9%) with intravesical recurrence and 28 (6.6%) with MIBC. We evaluated the clinicopathologic features, risk factors, and cancer-specific survival (CSS) using the Kaplan-Meier method and the Cox proportional hazards regression models. Results: The median intervals from nephroureterectomy to intravesical recurrence and the development of MIBC were 8 and 17 months, respectively. On multivariate analysis, the pathologic stage (≥pT3 vs. Ta/T1, HR 5.03, P = 0.001) and ureteral tumor location (HR 2.79, P = 0.011) were independent risk factors for the development of MIBC, whereas a history of previous or concomitant bladder tumor was the only significant risk factor for intravesical recurrence. The probability of developing MIBC 5 years after nephroureterectomy was 12.6% in patients with 1 risk factor and 20.6% in patients with both risk factors. Patients with MIBC had significantly worse CSS than those without MIBC (P = 0.004), whereas CSS rates were similar in patients with and without intravesical recurrence (P = 0.593). However, stratification analysis for matching pathology revealed that CSS rates were not significantly different in patients with pT2 or higher stage of UUT-UC. Conclusions: Approximately 5% of the patients developed MIBC after nephroureterectomy with a median interval of 17 months. Patients with advanced pathologic stage (≥pT3) and a ureteral tumor location are at increased risk of developing MIBC after nephroureterectomy. [Copyright &y& Elsevier]

Abstract: Objectives: Prostate radiotherapy (RT) has been associated with an increased risk of bladder cancer (CaB). However it is unknown how prior RT affects the stage, grade, and histology of secondary CaB. While irradiated patients have adverse surgical outcomes, how RT affects survival is also unknown. We sought to determine how RT for prostate cancer (CaP) affects the characteristics and outcomes of secondary CaB. Materials and methods: A retrospective review of 275,200 cases of clinically localized CaP submitted to the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2007 was performed. CaP treatment was stratified by radical prostatectomy (RP) alone, RT, or RP + RT. Diagnosis of CaB at least 1 year after CaP, and CaB death were the primary outcomes. The stage, grade, and histology of CaB of patients exposed to RT or RP were compared. A competing risks multivariable survival analysis was performed to determine the effect of RT on CaB-specific mortality. Results: CaP patients treated with any RT were 1.70 times as likely to develop CaB (95% CI 1.57–1.86, P < 0.001) compared with RP alone. CaB in men who had RT were more likely non-urothelial (6.4% vs. 3.8%, P = 0.004), trigonal (6.9% vs. 5.4%, P = 0.012), and carcinoma in-situ (CIS) (9.2% vs. 7.0%, P < 0.001) compared with RP. RT increased CaB-specific mortality (HR = 1.30, P = 0.02), which remained significant when adjusted for CaB features (HR = 1.28, P = 0.05). Conclusions: Patients with localized CaP treated with RT have a higher risk of CaB. CaB after RT is more likely to be located at the trigone and contain CIS. Patients with CaB after RT have decreased cancer-specific survival compared with those undergoing RP alone. [Copyright &y& Elsevier]

Abstract: The glutathione-S-transferases (GSTs) comprise a class of enzymes that detoxify carcinogenic compounds by conjugating glutathione to facilitate their removal. Polymorphisms in GSTM1, GSTT1, and GSTP1 genes have been related to risk for bladder cancer. Studies focusing on GSTs gene variants relationship with the risk of bladder cancer have produced conflicting and inconsistent results. We examine the association between genetic polymorphism of glutathione S-transferase P1, GSTM1, GSTT1 genes and development of bladder transitional cell carcinoma (TCC). The study population consisted of 166 histologically confirmed male bladder TCC cases and 332 healthy male controls. Genotyping was done using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and also investigated combined gene interactions. The GSTP1 Val/Val genotype was significantly associated with bladder cancer (OR = 4.32, 95% CI: 2.64–6.34), whereas the association observed for GSTM1 null (OR = 1.32, 95% CI: 0.82–2.62; P = 0.67) and GSTT1 null genotype (OR = 1.18, 95% CI: 0.79–1.67; P = 0.74) did not reach statistical significance. There was a significant multiple interaction between GSTM1, GSTT1, and GSTP1 genotypes in risk of bladder cancer (P for interaction = 0.02). The risk associated with the concurrent presence of GSTM1 positive and GSTP1 Ile/Val or Val/Val (OR = 3.71, 95% CI: 2.34–5.54) and GSTT1 positive and GSTP1 Ile/Val or Val/Val (OR = 2.66, 95% CI: 1.54–4.72) was statistically significant. Patients carrying GSTP1 Val/Val genotype were at increased risk for developing high-grade (OR = 7.68, 95% CI: 4.73–19.25) and muscle invasive (OR = 10.67, 95% CI: 6.34–21.75) bladder cancer. High risk for bladder TCC also was observed with respect to combined GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 4.76, 95% CI: 2.68–18.72) and GSTM1 null/GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 6.42, 95% CI: 4.76–14.72) genotype variant. This study suggests that the GSTP1 polymorphism and its combination with GSTM1, and GSTT1 may be associated with bladder cancer susceptibility in the Iranian population. Further confirmation in large population-based studies is needed. [Copyright &y& Elsevier]

Abstract: Objective: We evaluated patients with history of previous malignancy to determine risk of an ensuing bladder cancer. Materials and methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results 9 registry database from 1973 to 1999 (SEER) was reviewed for patients with initial primary cancers in oral cavity and pharynx, colon and rectum, respiratory system, breast, prostate, testis, or penis. This group of patients was then examined to identify subsequent separate primary malignancies in the bladder. Comparison was made to the incidence of bladder cancer in the general population to determine a standardized incidence ratio (SIR). Additional analysis was performed based on age at diagnosis, stage, gender, race, and use of external beam radiation for treatment of initial cancer. Results: A total of 7,289 (0.5%) of patients had a bladder cancer following their initial malignancy. Patients with prostate cancer had the largest increase in risk of bladder cancer with a SIR of 8.24, and all initial cancer groups had an elevated risk of bladder cancer relative to the general population. External beam radiation and non-White gender were associated with an increased risk of bladder cancer. Older age at diagnosis of the initial cancer correlated with a lower risk of subsequent bladder cancer. Conclusions: This study suggests an increased risk of bladder cancer following a separate initial cancer. Lower threshold for working up those patients for bladder cancer may be warranted. [Copyright &y& Elsevier]

Abstract: Objective: Specific acquired HRAS mutations have been found to predominate in bladder cancer, and HRAS T81C polymorphism has been determined to contribute the risk of various cancers, including bladder cancer. Materials and methods: We screened the exon 1and 2 of HRAS and frequently detected polymorphism at nucleotide 81T to C (exon 1). A case-control study was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to test the genotype distribution of 140 bladder cancer patients in comparison with 160 cancer-free controls from a Kashmiri population. Results: In HRAS T81C SNP, frequencies of TT, TC, and CC genotypes among controls were 84.4%, 15.6%, and 0.0%, while in cases allele frequencies were 64.3%, 30%, and 5.7%, respectively. A significant differences was observed between the control and cases with odds ratio (OR) = 3.0 and 95% confidence interval (CI) = 1.74–5.20 (P = 0.000). Interestingly, combined TC and CC genotype abundantly presented in high grade (OR = 5.4 and 95% CI = 2.8–10.2; P < 0.00) and in advanced tumors (OR = 3.3, 95% CI = 1.71–6.30; P < 0.05). A significant association of the variant allele (TC+CC) was found with male subjects (≥50) and ever smokers (P = 0.001). Conclusion: It is evident from our study that HRAS T81C SNP moderately increases bladder cancer risk, and rare allele is a predictive marker of advanced bladder tumors. [Copyright &y& Elsevier]

Abstract: Objective: Matrix metalloproteinases (MMPs) are expressed in melanocytes and their overexpression has been linked to tumor development, progression, and metastasis. At the genetic level, following functional promoter polymorphisms are known to modify the gene transcription: −1306 C > T, −735 C > T in MMP2, and 799 C > T in MMP8 gene. Hence we hypothesize that functional polymorphisms in the 2 MMP SNPs in promoter region may modulate the risk for bladder cancer (BC) progression in North Indian population. Materials and methods: Genotyping for these polymorphisms were done in a group of 200 BC and 200 age matched, similar ethnicity unrelated healthy controls using PCR-based methods. Two-sided χ2, Cox-regression was utilized to evaluate the associations between genotype and various clinical and epidemiologic factors. Multivariate analyses were conducted using logistic regression, adjusting for known BC confounders such as age and gender. Survival analysis was done using the Kaplan-Meier method and differences in survival were assessed using the log rank test. Results: Individuals with MMP2 (−1306) TT genotype as well as T allele were at higher risk of BC (P, 0.042; OR, 2.85; P, 0.001; OR, 1.76). This effect was even more apparent in case of CT+TT (P < 0.001; OR, 2.61). In MMP2 (735), CT+TT demonstrated significant risk (P, 0.034; OR, 1.66). In MMP8 (799), reduced risk was observed with TT genotype (P, 0.006; OR, 0.27). Haplotype analysis showed that individuals with haplotype 735C-1306T and 735T-1306C were at 1.9- and 1.5-fold higher risk. MMP2 −1306CC in combination with MMP8 799CT genotype showed protective effect. The genotype CT and CT+TT of MMP2 1306C > T were associated with high risk of recurrence in BCG treated patients (HR, 4.32; P, 0.006 and HR, 2.06; P, 0.047) thus showing reduced recurrence free survival (CT+TT/CC = 34/45 months; log rank P, 0.039). Conclusion: Our data suggested that variant allele of MMP2 1306C > T was associated with high risk of tumor recurrence and reduced recurrence free survival in superficial BC patients. [Copyright &y& Elsevier]

Abstract: Objectives: To examine associations between urinary bladder cancer risk and polymorphisms of the gene encoding the catechol estrogen-metabolizing enzyme, catechol-O-methyltransferase (COMT), among Egyptian women and men. Materials and methods: We used questionnaire and genotype data from a case-control study in Egypt. This analysis focused on South Egypt cases with confirmed urothelial (UC) or squamous cell (SCC) carcinoma of the bladder, and controls frequency-matched on sex, 5-year age-group, and residence governorate. Real-time PCR on blood specimen DNA was used to determine COMT genotypes encoding for Val/Val, Val/Met, and Met/Met, the enzyme forms associated with high, intermediate, or low activity, respectively. Results: The study sample, which included 255 women and 666 men, consisted of 394 cases with histologically confirmed UC (225) or SCC (n = 169), and 527 controls. The odds of having either type of bladder cancer were lower among men with genotypes encoding Val/Met or Met/Met than among those with the genotype encoding Val/Val, even after adjustment for other factors, such as smoking and schistosomiasis history [adjusted odds ratio (AOR): 0.64; 95% confidence interval (CI): 0.43, 0.96]; however, the association was statistically significant for SCC (AOR 0.57; 95% CI: 0.34, 0.96) but marginal for UC (AOR: 0.64; 95% CI: 0.39, 1.02). No significant associations were detected between bladder cancer risk and COMT genotypes among postmenopausal women. Conclusions: These findings suggest that even after controlling for established risk factors, the involvement of COMT genotypes in bladder cancer risk differs among men compared with women in South Egypt. [Copyright &y& Elsevier]

Abstract: Objective: The present study was aimed at examining the local distribution of GSTM1, GSTT1, MDR1, and VEGF gene polymorphisms as possible risk factors contributing to the development of bladder cancer among the population from Canary Islands, Spain. Materials and methods: The genotypes were determined by PCR-based methods in a hospital-based case-control study consisting of 119 cases and 110 controls. The socio-demographic and clinicopathologic data were collected, including the smoking habits of the population covered in the study. Results: The observed allelic frequencies were (%): GSTM1-GSTT1, (positive) 54 and (null) 46 in cases, and 65 and 35, respectively, in controls (P = 0.144); MDR1 C3435T, (C) 57 and (T) 43 in cases, and 54 and 46, respectively, in controls (P = 0.633); VEGF A2578C, (A) 40 and (C) 60 in cases, and 51 and 49, respectively, in controls (P = 0.221). Among Canary Islands subjects, GSTT1-null genotype appeared as a significant risk factor for bladder cancer (odds ratio (OR) 2.0; 95% confidence interval (CI), 1.0–3.7; P = 0.041), in multivariate analysis adjusted by age and smoking habits. No statistical changes in genotype distribution of GSTM1, MDR1 C3435T, and VEGF A2578C gene polymorphisms were observed between cases and controls. The distribution of the initial clinical stage, clinical grade, or recurrence status was not significantly different among the polymorphic variants in the case group (P = NS). Conclusions: Subjects with the GSTT1-null genotype might be at an increased risk of bladder cancer in Canary Islands, Spain. However, extensive studies are required for accurate confirmation of these results. [Copyright &y& Elsevier]

Abstract: Several studies have investigated the association between TP53 Arg72Pro and an increased risk of developing bladder tumors, with controversial results. Taking advantage of the high admixture rates in the Brazilian population, we genotyped 94 bladder cancer patients (76 males and 18 females; aged 21–96 years old; 67 ± 13 years old; 79 smokers and 15 nonsmokers) carefully paired with 159 controls (104 males and 55 females; aged 20–100 years old; 65 ± 21 years old; 126 smokers and 33 nonsmokers) with respect to environmental exposure, diet routine, lifetime occupational history, smoking history, general health conditions, and previous diseases. Arg/Pro genotype was under-represented in the patient population, and conferred a 44% lower risk of bladder cancer. Univariate logistic regression analysis also identified male sex (OR = 6.87, 95% CI = 3.78–12.50; P < 0.001), age over 65 years (OR = 4.44, 95% CI = 2.56–7.71; P < 0.001), and smoking habits (OR = 18.61, 95% CI = 9.62–36.03; P < 0.001) as important risk factors for bladder cancer. However, the TP53Arg72Pro genotype disappeared as a susceptibility factor both in the multivariate regression analysis and in a univariate regression analysis adjusted for gender, age, and smoking, suggesting that it was connected with one of these factors in the predisposition to bladder cancer. Indeed, a further analysis demonstrated that both alleles and genotype variants of TP53Arg72Pro are less frequent in older patients (P = 0.029). We concluded that the effect of TP53Arg72Pro, described in some studies as an important risk factor, may not be an independent, but an age-related factor of susceptibility to bladder cancer. [Copyright &y& Elsevier]

Abstract: Objective: We evaluated the relationship between opium consumption and bladder cancer (BC) in a case-control study of an Iranian population. Materials and methods: In a hospital-based case-control study of 179 patients with BC and 179 cancer-free controls frequency-matched by age, sex, and smoking status, we investigated the relationship between opium consumption and BC. A comprehensive epidemiologic interview was conducted on all participants to collect personal information, such as demographics and smoking status. Results: Overall, we found significant age, sex, cigarette smoking adjusted association between BC risk and opium consumption, [odds ratio (OR) = 4.60; 95% confidence interval (CI) = 3.53–6.28]. The elevated risk was more evident in older individuals (OR = 5.42; 95% CI, 4.12–7.28) than younger individuals (OR = 3.65; 95% CI, 2.76–4.76) (P = 0.01). Heavy smokers with the opium consumption exhibited a 6-fold elevated risk for BC (OR = 6.16; 95% CI, 3.34–8.32) (P = 0.0001). When stratified according to different grades of BC, a 3.4-fold increased risk was associated with the opium consumption in grade III with an OR of 3.44 (95% CI, 2.82–8.28) (P = 0.001). A similar but slightly higher risk was also seen in case of grade IV tumors (OR = 3.86; 95% CI, 2.14–10.16) (P = 0.001). Invasive bladder tumors were more common among the opiates users (OR = 2.6; 95% CI, 1.44–5.42) (P = 0.01). Cumulative risk of BC in women with opium consumption (OR = 4.10 95% CI, 3.54–5.88) (P = 0.001) was slightly less than in men (OR = 5.10 95% CI, 3.54–5.88) (P = 0.0001). Based on Pearson correlations, the risk of BC significantly correlated with opium dependence duration (r = 0.74, P = 0.001), type of opiate used (r = 0.65, P = 0.001), and simultaneous cigarette smoking (r = 0.74, P = 0.0001). Conclusion: The results indicated that there is about 5-fold increase in risk of developing this cancer in the presence of opium consumption. Further research is needed to investigate the functional implications of the opium consumption in BC. [Copyright &y& Elsevier]

Objective: To compare preoperative predictors of nonorgan-confined (NOC) disease in patients with upper-tract urothelial carcinoma (UTUC) from the United States (US) and China.Methods: Clinicopathologic data of patients with UTUC treated surgically at tertiary care facilities in the US or China from 1998 to 2015 were, retrospectively, compiled. Patient characteristics, preoperative imaging, cytology, ureteroscopic findings, and serum markers (neutrophil-to-lymphocyte ratio, estimated glomerular filtration rate, hemoglobin, and albumin) were evaluated. After excluding patients who received neoadjuvant chemotherapy, rates of NOC disease at definitive surgery were tabulated. Logistic regression and receiver operating characteristic analyses were performed to determine predictors of NOC for each country using previously published nomograms, and the cohorts were compared.Results: Totally, 753 patients with UTUC were included for analysis (451 Chinese and 302 US). NOC rates were similar between the 2 countries (31% vs. 29%, P = 0.568). On multivariable analysis, cT3 stage (P = 0.001) and high-grade pathology on ureteroscopy (P = 0.011) were significant predictors for NOC in the US, while male gender (P = 0.034), tumor location on imaging (P = 0.009), tumor size on imaging (P = 0.044), neutrophil-to-lymphocyte (P = 0.043), and preoperative estimated glomerular filtration rate (P = 0.028) were significant in China. Areas under the curve differed by nomogram used (Western model: 0.750 in US, vs. 0.670 in China; Chinese model: 0.763 in US, vs. 0.828 in China).Conclusion: Predictors for NOC in UTUC differ between the US and China. There may be unique population-based markers that more profoundly influence the accuracy of nomograms in certain populations. Our findings highlight the importance of considering population differences when clinically applying predictive tools in UTUC. [ABSTRACT FROM AUTHOR]

Bladder cancer results from the combined effects of environmental and genetic factors, smoking being the strongest risk factor. Evaluating absolute risks resulting from the joint effects of smoking and genetic factors is critical to assess the public health relevance of genetic information. Analyses included up to 3,942 cases and 5,680 controls of European background in seven studies. We tested for multiplicative and additive interactions between smoking and 12 susceptibility loci, individually and combined as a polygenic risk score (PRS). Thirty-year absolute risks and risk differences by levels of the PRS were estimated for U.S. males aged 50 years. Six of 12 variants showed significant additive gene–environment interactions, most notably NAT2 (P = 7×10−4) and UGT1A6 (P = 8×10−4). The 30-year absolute risk of bladder cancer in U.S. males was 6.2% for all current smokers. This risk ranged from 2.9% for current smokers in the lowest quartile of the PRS to 9.9% for current smokers in the upper quartile. Risk difference estimates indicated that 8,200 cases would be prevented if elimination of smoking occurred in 100,000 men in the upper PRS quartile compared with 2,000 cases prevented by a similar effort in the lowest PRS quartile (P(additive) = 1×10−4). Thus, the potential impact of eliminating smoking on the number of bladder cancer cases prevented is larger for individuals at higher than lower genetic risk. Our findings could have implications for targeted prevention strategies. However, other smoking-related diseases, as well as practical and ethical considerations, need to be considered before any recommendations could be made. [ABSTRACT FROM AUTHOR]

Objective: The development of a ureteroenteric anastomotic (UEA) stricture has been reported in up to 15% of patients undergoing radical cystectomy (RC) with urinary diversion. Although benign strictures are thought to be the result of ischemia, the incidence, risk factors, and outcomes of patients with malignant UEA strictures have not been well described.Material and Methods: We reviewed 2,523 patients treated with RC for bladder cancer from 1980 to 2012 at Mayo Clinic. Patients diagnosed with a UEA stricture following the surgery were identified, and a subset with malignant UEA was then analyzed. Cox proportional hazard regression models were performed to evaluate factors associated with the diagnosis of malignant UEA. Survival was assessed using the Kaplan-Meier method.Results: At a median of 10.5 years of follow-up, 232 (9.2%) patients were diagnosed with UEA stricture, of which 38 (16.4%) had malignant strictures (MS). Median time from RC to the diagnosis of a malignant vs. benign UEA stricture was 32.4 months and 7.2 months, respectively (P = 0.004). Pathologic non-muscle-invasive disease stage at RC was more common among patients diagnosed with a MS compared with patients who did not develop a MS (71.1% vs. 45.9%; P = 0.002). The presence of carcinoma in situ on initial ureteral margin at RC was associated with a significantly increased risk of subsequent diagnosis (hazard ratio = 4.1; P<0.001). Following malignant stricture diagnosis, 2- and 5-year cancer-specific survival was 50% and 30%, respectively, whereas overall survival was 44% and 23%, respectively.Conclusions: MS are uncommon after RC, and present later than benign strictures. Ureteral margin involvement with carcinoma in situ was associated with a significantly increased risk of MS diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: The urinary bladder is the target of several toxic compounds, which makes the bladder more prone to cancer. Cytochrome P450 1B1 enzyme is present in tumor tissues and metabolizes the polyaromatic carcinogens and activates several procarcinogens that cause DNA damage. We examined the functional single-nucleotide polymorphisms in the CYP1B1 gene to study their association with the urinary bladder cancer.Methods: We recruited 234 cases of pure urothelial and 258 bladder cancer-free control samples from the individuals visiting the clinic for various investigations. We genotyped 4 CYP1B1 single-nucleotide polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism analysis. The genotype data were analyzed by the Chi-square test. Haplotypes were constructed to evaluate the joint effect of the 4 polymorphisms.Results: Overall, 3 polymorphisms-rs10012, rs150799650, and rs1056827 (odds ratio [OR] = 2.34, CI: 1.59-3.45, P<0.0001; OR = 2.59, CI: 1.78-3.77, P<0.0001; OR = 2.32, CI: 1.57-3.44, P<0.0001, respectively) were found to correlate with urinary bladder cancer. Haplotype analysis suggested GTTC, GTTG, and ATGC to be the risk factors for bladder cancer.Conclusions: Overall, 3 polymorphisms, rs10012, rs1056827, and rs150799650 in the CYP1B1 gene correlate with urinary bladder cancer significantly in the Indo-European population of Uttar Pradesh, India. Further investigations in other populations are advised. [ABSTRACT FROM AUTHOR]

Introduction Transurethral resection of bladder tumor (TURBT) is a common procedure used in the diagnosis and treatment of bladder cancer. Despite how often it is performed, not much is known about the risk factors for complications. Traditional surgery has an increase in morbidity and mortality with increasing operative duration. We assess the effect of operative duration on TURBT complications. Methods The years 2006 to 2012 of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) were queried for patients undergoing TURBT. We separated patients into 4 groups based on operative time: 0 to 30 minutes, 30.1 to 60 minutes, 60.1 to 90 minutes, and greater than 90 minutes. Standard statistical analysis including multivariate regression was performed to determine predictors of complications. Results A total of 10,599 TURBTs were included in our analysis. The overall complication rate for TURBT was 5.8% and there was an increase in the rate of complications seen as operative duration increased, which remained after controlling for age, comorbidities, tumor size, and American Society of Anesthesiology classification. Increased operative duration was associated with a greater risk of postoperative urinary tract infection, sepsis or septic shock, pulmonary embolism/deep venous thrombosis, reintubation or failure to wean, myocardial infarction, and death. Larger tumors were related to an increased odds of requiring blood transfusions. Conclusions Using a contemporary multicenter cohort of TURBTs from the ACS NSQIP database, we demonstrate that increased operative duration is associated with serious postoperative complications. This association was found to persist even after adjusting for patient age, comorbidities, tumor size, and functional status. [ABSTRACT FROM AUTHOR]

Purpose Bladder cancer (BC) screening is not accepted in part owing to low overall incidence. We used the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and National Lung Cancer Screening Trial (NLST) to identify optimal high-risk populations most likely to benefit from screening. Materials and methods Data were extracted from PLCO and NLST to stratify risk of BC by overall population, sex, race, age at inclusion, and smoking status. Incidence rates between groups were compared using chi-square test. Results BC was identified in 1,430/154,898 patients in PLCO and 439/53,173 patients in NLST. BCs were grade III/IV in 36.8% and 41.3%. Incidence rates were significantly higher in men than in women (PLCO: 1.4 vs. 0.31/1,000 person-years and NLST: 1.84 vs. 0.6/1,000 person-years, both P <0.0001). In proportional hazards models, male sex, higher age, and duration and intensity of smoking were associated with higher risk of BC (all P <0.0001). In men older than 70 years with smoking exposure of 30 pack-years (PY) and more, incidence rates were as high as 11.92 (PLCO) and 5.23 (NLST) (per 1,000 person-years). In current high-intensity smokers (≥50 PY), the sex disparity in incidence persists in both trials (0.78 vs. 2.99 per 1,000 person-years in PLCO and 1.12 vs. 2.65 per 1,000 person-years in NLST). Conclusions Men older than 60 years with a smoking history of>30 PY had incidence rates of more than 2/1,000 person-years, which could serve as an excellent population for screening trials. Sex differences in the incidence of BC cannot be readily explained by the differences in exposure to tobacco, as sex disparity persisted regardless of smoking intensity. [ABSTRACT FROM AUTHOR]

Objectives Cigarette smoking is the most important risk factor for urinary bladder cancer. The prognostic effect of cigarette smoking on disease recurrence and progression in patients with non–muscle-invasive bladder cancer (NMIBC), however, is still unclear. We evaluated the effect of smoking status and intensity, and timing of smoking cessation, on NMIBC prognosis. Methods and materials A population-based series of patients diagnosed with NMIBC from 1995 until 2010 was identified through the Netherlands Cancer Registry. Self-reported smoking history was obtained by a postal lifestyle questionnaire at study inclusion. Detailed clinical data concerning diagnosis, treatment, and disease course were collected retrospectively through a medical file survey. The association of smoking variables with recurrence- and progression-free survival of 963 patients with primary NMIBC was studied using cumulative incidence curves and competing risk regression analyses. Results The study population comprised 181 never smokers (18.8%), 490 former smokers (50.9%), and 292 current smokers (30.3%) at the time of diagnosis. No statistically significant difference or trend in risk of recurrence ( P trend = 0.47) or progression ( P trend = 0.23) across the 3 smoking status categories was found. Moreover, no dose-response association was observed across categories of smoking quantity, duration, or cumulative exposure in relation to NMIBC prognosis. The timing of smoking cessation (i.e., ceased smoking≥10 y before diagnosis,<10 y before diagnosis, vs. current smoker at diagnosis) did not significantly affect the risk of recurrence ( P trend = 0.31) and progression ( P trend = 0.19). Conclusions Based on our study, smoking status, smoking intensity, or cessation at any time before diagnosis does not seem to alter the risks of recurrence and progression among patients with NMIBC. Patients’ smoking history is not useful for the guidance of clinical management decisions. Patients should nevertheless be advised to quit considering the known beneficial effects on other non-NMIBC–related end points such as cardiovascular disease and second primary cancers. [ABSTRACT FROM AUTHOR]

Objective Coal tar ointments are used as treatment of various skin diseases, especially psoriasis and eczema. These ointments contain several carcinogenic polycyclic aromatic hydrocarbons. Metabolites of these polycyclic aromatic hydrocarbons are excreted in the urine and therefore, dermatological use of coal tar may be associated with an increased risk of bladder cancer. The objective of this study was to evaluate the association between dermatological use of coal tar ointments and bladder cancer. Material and methods A population-based case-control study was conducted including 1,387 cases diagnosed with bladder cancer and 5,182 population controls. Information on the use of coal tar, history of skin disease, and known risk factors for bladder cancer was obtained through postal questionnaires. Logistic regression analyses were performed to estimate the risk of bladder cancer after coal tar treatment, adjusted for age, gender, smoking status, duration of smoking, and intensity of smoking. Results The use of coal tar ointments was approximately equal among cases and controls (3.8% vs. 3.0%, respectively). Dermatological application of coal tar was not significantly associated with bladder cancer (adjusted odds ratio = 1.37, 95% CI: 0.93–2.01). An inverse association between bladder cancer and a history of skin disease was observed (adjusted odds ratio = 0.74, 95% CI: 0.61–0.90). Conclusion This is the first study with a specific aim to study the association between the use of coal tar preparations and bladder cancer. The results suggest that there is no reason for safety concerns with respect to the risk of bladder cancer after the use of coal tar preparations in dermatological practice. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the risk of prostate and bladder cancers in patients with spinal cord injury (SCI). Materials and methods: We used data obtained from the National Health Insurance system of Taiwan for this study. The SCI cohort contained 54,401 patients with SCI, and each patient was randomly frequency matched with 4 people from the general population (without SCI) based on age, sex, and index date. Incidence rates, SCI cohort to non-SCI cohort rate ratios, and hazard ratios were measured to evaluate the cancer risks. Results: Patients with SCI showed a significantly lower risk of developing prostate cancer compared with subjects without SCI (adjusted hazard ratio = 0.73; 95% confidence interval = 0.59, 0.90), after accounting for the competing risk of death. No significant difference in the risk of bladder cancer emerged between the SCI and control groups. Further analyses found a higher spinal level of SCI tended to predict a lower risk for prostate cancer. Conclusions: Patients with SCI incurred a lower risk for prostate cancer compared with people without SCI. The risk for bladder cancer did not differ between people with or without SCI. [Copyright &y& Elsevier]

Abstract: Objective: Noninvasive biomarkers are used routinely in the clinical management of several cancers but bladder cancer detection and surveillance remains dependent on invasive procedures such as cystoscopy. No validated biomarker currently exists in routine clinical practice other than cytology. Gene-based testing has shown great promise for biomarker profiling and this review addresses the current state of biomarker research in bladder cancer. Materials and methods: A comprehensive review of all published literature on urinary biomarkers from 1970 - 2012 was conducted in PubMed. Keywords used alone or in combination were bladder cancer, diagnosis, surveillance, urinary biomarker, molecular biomarkers, methylation, gene expression, single nucleotide polymorphism and microRNA. The cited references of the manuscripts included in the review were also screened. Results: We have reviewed various strategies currently used for gene-based biomarker profiling of bladder cancer. We have comprehensively summarized the performance of several biomarkers in the diagnosis and surveillance of bladder cancer. Finally we have identified biomarkers that have shown potential and now deserve the opportunity to be validated in the clinical setting. Conclusion: Several gene-based urinary biomarkers have demonstrated promise in initial studies, which now need to be rigorously validated in the clinical setting for them to be translated into clinically useful tests in diagnosis, surveillance or risk-stratification of bladder cancer. [Copyright &y& Elsevier]

Abstract: Background: Bladder cancer is the most prevalent form of cancer in men among Egyptians, for whom tobacco smoke exposure and Schistosoma haematobium (SH) infection are the major risk factors. We hypothesized that functional polymorphisms in NAD(P)H:quinone oxidoreductase 1 (NQO1) and superoxide dismutase 2 (SOD2), modulators of the effects of reactive oxidative species, can influence an individual's susceptibility to these carcinogenic exposures and hence the risk of bladder cancer. Methods: We assessed the effects of potential interactions between functional polymorphisms in the NQO1 and SOD2 genes and exposure to smoking and SH infection on bladder cancer risk among 902 cases and 804 population-based controls in Egypt. We used unconditional logistic regression to estimate the odds ratios (OR) and confidence intervals (CI) 95%. Results: Water pipe and cigarette smoking were more strongly associated with cancer risk among individuals with the TT genotype for SOD2 (OR [CI 95%] = 4.41 [1.86–10.42]) as compared with those with the CC genotype (OR [CI 95%] = 2.26 [0.97–6.74]). Conversely, the risk associated with SH infection was higher among the latter (OR [CI 95%] = 3.59 [2.21–5.84]) than among the former (OR [CI 95%] = 1.86 [1.33–2.60]). Polymorphisms in NQO1 genotype showed a similar pattern, but to a much lesser extent. The highest odds for having bladder cancer following SH infection were observed among individuals with the CC genotypes for both NQO1 and SOD2 (OR [CI 95%] = 4.41 [2.32–8.38]). Conclusion: Our findings suggest that genetic polymorphisms in NQO1 and SOD2 play important roles in the etiology of bladder cancer by modulating the effects of known contributing factors such as smoking and SH infection. [Copyright &y& Elsevier]

Abstract: Background: Most newly diagnosed bladder cancers present as non–muscle invasive bladder cancer (NMIBC). NMIBC is a heterogeneous disease with varying treatment options, follow-up schedules, and oncologic outcomes. We sought to review the role of active surveillance for low risk bladder cancer in the literature. Methods: A PubMed search was performed using the following keywords: active surveillance, low risk, bladder, transurethral resection of bladder tumor, cost, and quality of life. Relevant articles were reviewed and utilized. Results: Low-risk bladder cancer—defined as pTa low-grade papillary tumors—is the type of NMIBC with the most favorable oncologic outcome and which almost never progresses to muscle invasive disease or metastasizes. Bladder cancer has the highest per patient treatment costs of all cancers. One of the reasons is the high rate of recurrence. Patients with low-grade bladder tumors often experience a recurrence after primary transurethral resection. Many patients undergo multiple resections in the hospital. Conclusions: Appropriately selected patients with recurrent low-risk bladder cancer could be managed with either office fulguration or cystoscopic surveillance. Active surveillance for patients with low-risk bladder cancer avoids or delays the surgical and anesthetic risks of a TURBT, thus optimizing quality of life without compromising the patient's risk of cancer progression. [Copyright &y& Elsevier]

Abstract: Objectives: Cigarette smoking is a known risk factor for urothelial carcinoma (UC) of the bladder. However, the persistence of an increased risk for UC following smoking cessation is not well established. We assessed the risk of UC among former smokers using a recent, prospective cohort with a high proportion of former smokers. Materials and methods: Study participants were members of the VITamins And Lifestyle cohort (VITAL), a group of 77,719 men and women between the ages of 50 and 76 years from western Washington State. Smoking history and other risk factors were obtained at the time of recruitment. The primary outcome was a new diagnosis of UC (n =385), as determined through linkage to a population-based cancer registry. Results and limitations: The cohort included 8% current and 44% former smokers, and among the UC cases, 15% were current and 60% former smokers. Both the current and former smoker had an increased risk of UC compared with never smokers (hazard ratio [HRs]: 3.81; 95% confidence intervals [CI] 2.71–5.35 and 2.0; 95% CI 1.55–2.58, respectively). Among former smokers, the risk of UC increased with the pack-years smoked and decreased with the years since quitting. When both the measures of smoking were considered together, the risk of UC was similar for long-term quitters and recent quitters for a given level of pack-years. For example, for those with pack-years of 22.5–37.5, the HR of UC was 1.91 (95% CI 1.17–3.11) for the distant quitters (≥23.5y before baseline) and HR = 1.92 (95% CI 1.26–2.94) among the recent quitters. Limitations include the small number of cases at the extremes of smoking history and errors in self-reported smoking history. Conclusions: The risk of bladder cancer in former smokers remains elevated>32 years after quitting, even among those with moderate smoking histories. This argues that a history of smoking confers a lifelong increased risk of UC. [Copyright &y& Elsevier]