Association of Pro-Inflammatory Diet, Smoking, and Alcohol Consumption with Bladder Cancer: Evidence from Case-Control and NHANES Studies from 1999 to 2020.

BACKGROUND AND PURPOSE: Diet might be a modifiable factor in preventing cancer by modulating inflammation. This study aims to explore the association between the dietary inflammatory index (DII) score and the risk of bladder cancer (BC). METHODS: A total of 112 BC patients and 292 control subjects were enrolled in a case-control trial. Additionally, we tracked a total of 109 BC patients and 319 controls, whose propensity scores were obtained from the Nutrition Examination Survey (NHANES) database spanning from 1999 to 2020. The baseline index and dietary intake data were assessed using a food frequency questionnaire (FFQ). DII scores were calculated based on the dietary intake of 20 nutrients obtained from participants and categorized into four groups. The association between the inflammatory potential of the diet and BC risk was investigated using multivariate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: High DII scores were associated with a pro-inflammatory diet and a higher risk of BC, with higher DII scores positively associated with a higher risk of BC (quartiles 4 vs. 1, ORs 4.89, 95% CIs 2.09-11.25 p < 0.001). Specifically, this might promote BC development by inducing oxidative stress and affecting DNA repair mechanisms. This result was consistent with the NHANES findings (quartiles 4 vs. 1, ORs 2.69, 95% CIs 1.25-5.77, p = 0.006) and further supported the association of pro-inflammatory diet and lifestyle factors with the risk of BC. CONCLUSIONS: Diets with the highest pro-inflammatory potential were associated with an increased risk of BC. By adjusting lifestyle factors, individuals might effectively lower their DII, thereby reducing the risk of developing BC. The results are consistent with the NHANES cohort.

Ambient air pollution and urological cancer risk: A systematic review and meta-analysis of epidemiological evidence.

Exposure to ambient air pollution has significant adverse health effects; however, whether air pollution is associated with urological cancer is largely unknown. We conduct a systematic review and meta-analysis with epidemiological studies, showing that a 5 µg/m3 increase in PM2.5 exposure is associated with a 6%, 7%, and 9%, increased risk of overall urological, bladder, and kidney cancer, respectively; and a 10 µg/m3 increase in NO2 is linked to a 3%, 4%, and 4% higher risk of overall urological, bladder, and prostate cancer, respectively. Were these associations to reflect causal relationships, lowering PM2.5 levels to 5.8 µg/m3 could reduce the age-standardized rate of urological cancer by 1.5 ~ 27/100,000 across the 15 countries with the highest PM2.5 level from the top 30 countries with the highest urological cancer burden. Implementing global health policies that can improve air quality could potentially reduce the risk of urologic cancer and alleviate its burden.

[Does radiation therapy for prostate cancer increase the risk of second cancers?] / La radiothérapie du cancer de la prostate augmente-t-elle le risque de seconds cancers ?

PURPOSE: The increased risk of second cancer after prostate radiotherapy is a debated clinical concern. The objective of the study was to assess the risk of occurrence of second cancers after prostate radiation therapy based on the analysis the literature, and to identify potential factors explaining the discrepancies in results between studies. MATERIALS AND METHODS: A review of the literature was carried out, comparing the occurrence of second cancers in patients all presenting with prostate cancer, treated or not by radiation. RESULTS: This review included 30 studies reporting the occurrence of second cancers in 2,112,000 patients treated or monitored for localized prostate cancer, including 1,111,000 by external radiation therapy and 103,000 by brachytherapy. Regarding external radiation therapy, the average follow-up was 7.3years. The majority of studies (80%) involving external radiation therapy, compared to no external radiation therapy, showed an increased risk of second cancers with a hazard ratio ranging from 1.13 to 4.9, depending on the duration of the follow-up. The median time to the occurrence of these second cancers after external radiotherapy ranged from 4 to 6years. An increased risk of second rectal and bladder cancer was observed in 52% and 85% of the studies, respectively. Considering a censoring period of more than 10 years after irradiation, 57% and 100% of the studies found an increased risk of rectal and bladder cancer, without any impact in overall survival. Studies of brachytherapy did not show an increased risk of second cancer. However, these comparative studies, most often old and retrospective, had many methodological biases. CONCLUSION: Despite numerous methodological biases, prostate external radiation therapy appears associated with a moderate increase in the risk of second pelvic cancer, in particular bladder cancer, without impacting survival. Brachytherapy does not increase the risk of a second cancer.

Investigation of Knowledge, Attitudes, and Healthy Lifestyle Behaviors on Bladder Cancer in Turkey.

BACKGROUND: The prevalence of bladder cancer increases rapidly among individuals. The knowledge, attitude, and healthy lifestyle behaviors of individuals in Turkey regarding bladder cancer are unknown. The present study aim was to examine the knowledge and attitudes of the participants about bladder cancer and healthy lifestyle behaviors. Methods?:?This cross-sectional study was conducted with 400 participants from outpatient clinic at Erciyes University. Data were collected by using a socio-demographic form and Healthy Lifestyle Behaviors Scale. Results?:?Findings revealed that 55% of the participants were aware of bladder cancer risks?;?smoking 55.5%, older ages 67%, synthetic dyes and some chemicals 43.7%, and overweight 34.5% increases the risk of bladder cancer. The findings showed that economic status and education effect on the Healthy Lifestyle Behaviors Scale scores. The positive relationship was found between self-realization, exercise, and interpersonal subscale in those with high-income participants. It is found that exercise, nutrition, and stress management that have a positive attitude among non-smokers toward the risk factors of bladder cancer. Conclusion?:?The information obtained from the study can be used to inform patients about bladder cancer, risk factors, and cancer prevention. In this regard, healthcare professionals can increase patients f knowledge and create awareness by preparing informative brochures, giving information during the examination, or making presentations. J. Med. Invest. 71 : 40-46, February, 2024.

Migration of double-J ureteral stent in patients with ureteroileal anastomosis stricture undergoing radical cystectomy and orthotopic neobladder: Analysis risk factors of stent migration.

The objective was to evaluate the incidence and degree of double-J ureteral stent (DJUS) migration. Additionally, we aimed to investigate the risk factors associated with stent migration in the orthotopic neobladder group. In this retrospective study, 61 consecutive patients were included; 35 patients (45 DJUS placements) underwent radical cystectomy with orthotopic neobladder and 26 patients (35 DJUS placements) underwent urinary bladder without cystectomy between July 2021 and March 2023. All the patients were treated with a DJUS for ureteric strictures. The technical success rate was 100% in each group. The DJUS migration was significantly higher in the orthotopic neobladder group, with 22 of 45 cases (48.9%), compared to the urinary bladder group, which had 4 of 35 cases (11.4%) (P ≤ .001). Among the patients in the orthotopic neobladder group who experienced DJUS migration, stent dysfunction occurred in 18 cases (81.8%), which was statistically significant (P = .003). Multivariate logistic regression analysis revealed that only the size of the DJUS was significantly and positively associated with migration (odds ratio:10.214, P = .010). DJUS migration can easily occur in patients undergoing radical cystectomy and orthotopic neobladder, and smaller stent sizes are associated with a higher incidence of migration.

Assessing the Causal Relationship between Waterpipe Smoking and Bladder Cancer.

Rates of waterpipe use increase with very little data reporting any potential health consequences. The current study, a large case-control study, of 4,194 patients from Iran denotes an elevated risk of bladder cancer in exclusive waterpipe smokers compared with non-users. Additional studies are needed to further understand the risk waterpipe smoking has on bladder cancer. See related article by Hadji et al., p. 509.

A prospective study of smoking-related white blood cell DNA methylation markers and risk of bladder cancer.

Bladder cancer, a common neoplasm, is primarily caused by tobacco smoking. Epigenetic alterations including DNA methylation have the potential to be used as prospective markers of increased risk, particularly in at-risk populations such as smokers. We aimed to investigate the potential of smoking-related white blood cell (WBC) methylation markers to contribute to an increase in bladder cancer risk prediction over classical questionnaire-based smoking metrics (i.e., duration, intensity, packyears) in a nested case-control study within the prospective prostate, lung, colorectal, and ovarian (PLCO) Cancer Screening Trial and the alpha-tocopherol, beta-carotene cancer (ATBC) Prevention Study (789 cases; 849 controls). We identified 200 differentially methylated sites associated with smoking status and 28 significantly associated (after correction for multiple testing) with bladder cancer risk among 2670 previously reported smoking-related cytosine-phosphate-guanines sites (CpGs). Similar patterns were observed across cohorts. Receiver operating characteristic (ROC) analyses indicated that cg05575921 (AHHR), the strongest smoking-related association we identified for bladder cancer risk, alone yielded similar predictive performance (AUC: 0.60) than classical smoking metrics (AUC: 0.59-0.62). Best prediction was achieved by including the first principal component (PC1) from the 200 smoking-related CpGs alongside smoking metrics (AUC: 0.63-0.65). Further, PC1 remained significantly associated with elevated bladder cancer risk after adjusting for smoking metrics. These findings suggest DNA methylation profiles reflect aspects of tobacco smoke exposure in addition to those captured by smoking duration, intensity and packyears, and/or individual susceptibility relevant to bladder cancer etiology, warranting further investigation.

Functional and oncologic outcomes of prostate capsule-sparing radical cystectomy: A systematic review and meta-analysis.

Radical cystectomy (RC) is the gold standard treatment for patients with organ-confined bladder cancer. However, despite the success of this treatment, many men who undergo orthotopic neobladder substitution develop significant erectile dysfunction and urinary symptoms, including daytime and nighttime urinary incontinence. Prostate-capsule-sparing radical cystectomy (PCS-RC) with orthotopic neobladder (ONB) has been described in the literature as a surgical technique to improve functional outcomes in appropriately selected patients. We performed a systematic review and meta-analysis of manuscripts on PCS-RC with ONB published after 2000. We included retrospective and prospective studies with more than 25 patients and compared PCS-RC with nerve-sparing or conventional RC. Studies in which the entire prostate was spared (including the transitional zone) were excluded. Comparative studies were analyzed to assess rates of daytime continence, nighttime continence, and satisfactory erectile function in patients undergoing PCS-RC compared with those undergoing conventional RC. Fourteen reports were included in the final review. Our data identify high rates of daytime (83%-97%) and nighttime continence (60%-80%) in patients undergoing PCS-RC with ONB. In comparative studies, meta-analysis results demonstrate no difference in daytime continence (RR:1.12; 95% CI: 0.72-1.73) in those undergoing PCS-RC compared to those undergoing conventional RC. Similarly, nighttime continence was similar between the 2 groups (RR:1.85; 95% CI: 0.57-6.00. Erectile function was improved in those undergoing PCS-RC (RR 5.35; 95% CI: 1.82-15.74) in the PCS-RC series. Bladder cancer margin positivity and recurrence rates were similar to those reported in the literature with conventional RC with an average weighted follow-up of 52.2 months. While several studies utilized different prostate cancer (CaP) screening techniques, the rates of CaP were low (incidence 0.02; 95% CI:0.01-0.04), and oncologic outcomes were similar to standard RC. PCS-RC is associated with improved nighttime continence and erectile function compared to conventional RC techniques. Further work is needed to standardize CaP screening before surgery, but the data suggest low rates of CaP with similar oncologic outcomes when compared to RC.

Smoking characteristics and years since quitting smoking of US adults diagnosed with lung and bladder cancer: A national health and nutrition examination survey analysis.

PURPOSE: Smoking is a recognized risk factor for bladder BC and lung cancer LC. We investigated the enduring risk of BC after smoking cessation using U.S. national survey data. Our analysis focused on comparing characteristics of LC and BC patients, emphasizing smoking status and the latency period from smoking cessation to cancer diagnosis in former smokers. MATERIALS AND METHODS: We analyzed data from the National Health and Examination Survey (2003-2016), identifying adults with LC or BC history. Smoking status (never, active, former) and the interval between quitting smoking and cancer diagnosis for former smokers were assessed. We reported descriptive statistics using frequencies and percentages for categorical variables and median with interquartile ranges (IQR) for continuous variables. RESULTS: Among LC patients, 8.9% never smoked, 18.9% active smokers, and 72.2% former smokers. Former smokers had a median interval of 8 years (IQR 2-12) between quitting and LC diagnosis, with 88.3% quitting within 0-19 years before diagnosis. For BC patients, 26.8% never smoked, 22.4% were active smokers, and 50.8% former smokers. Former smokers had a median interval of 21 years (IQR 14-33) between quitting and BC diagnosis, with 49.3% quitting within 0-19 years before diagnosis. CONCLUSIONS: BC patients exhibit a prolonged latency period between smoking cessation and cancer diagnosis compared to LC patients. Despite smoking status evaluation in microhematuria, current risk stratification models for urothelial cancer do not incorporate it. Our findings emphasize the significance of long-term post-smoking cessation surveillance and advocate for integrating smoking history into future risk stratification guidelines.

One Size Fits Some: Approaching Rare Malignancies of the Urinary Tract.

OPINION STATEMENT: Urothelial carcinoma is the predominant cancer of the urinary tract but when divergent and subtype histology (non-urothelial) are identified at time of pathologic diagnosis, therapeutic and diagnostic challenges transpire. To this end, pathologic review to confirm any non-urothelial histology is key since these subtypes can often be overlooked. Few prospective trials are dedicated to understanding these non-urothelial histologic types; however, current, and past trials did allow patients with these non-urothelial histologic types to enroll, and inferences can be made about treatment efficacy and survival. Existing treatment regimens for non-urothelial bladder cancers are akin to standard urothelial cancer regimens using surgical approaches for localized disease and platinum-based chemotherapy for advanced disease. The reported clinical trials, that will be discussed, center on non-urothelial histologic types. These studies, albeit limited, provide critical insight into tumor biology and response to standard platinum-based chemotherapy, immune checkpoint inhibitors, and antibody drug conjugates. The inclusion of non-urothelial histologic types will be essential for clinical trials in development to provide further therapeutic advances and provide essential efficacy data.

Does intensity-modulated radiation therapy by helical tomotherapy for prostate cancer increase the subsequent risk of bladder cancer? A propensity score-matched analysis.

OBJECTIVES: This study aimed to evaluate the risk of bladder cancer after intensity-modulated radiation therapy (IMRT) using helical tomotherapy for prostate cancer in comparison to the risk post-radical prostatectomy (RP) using propensity score-matched analysis and to assess the risk factors for bladder cancer. METHODS: This retrospective study included 2067 patients with non-metastatic prostate cancer treated at our institution between June 2007 and December 2016. Of these, 1547 patients were treated with IMRT and 520 underwent RP. The propensity scores were calculated using age, National Comprehensive Cancer Network risk classification, prostate volume, Brinkman index, and follow-up time as matched covariates. A propensity score-matched patient cohort (n = 718; IMRT: 359, RP: 359) was created, and the risk of bladder cancer after treatment was compared. RESULTS: In total, bladder cancer was detected in 33 patients. Five patients in the IMRT group and one in the RP group died of bladder cancer. In the propensity score-matched analysis, the 5-year bladder cancer-free survival rate was significantly lower in the IMRT group than in the RP group (91.7% and 96.2%, respectively; p < 0.001). Multivariate analysis revealed that IMRT and the Brinkman index were the risk factors for bladder cancer in this cohort (odds ratio = 5.085, 95% confidence interval = 1.436-18.008, p = 0.012 and odds ratio = 1.001, 95% confidence interval = 1.000-1.001, p = 0.010, respectively). CONCLUSIONS: IMRT for prostate cancer using helical tomotherapy increases the subsequent risk of bladder cancer compared with RP and is an independent risk factor for bladder cancer similar to smoking.

Unveiling an Association between Waterpipe Smoking and Bladder Cancer Risk: A Multicenter Case-Control Study in Iran.

BACKGROUND: Limited data exist for the association between bladder cancers and waterpipe smoking, an emerging global public health concern. METHODS: We used the IROPICAN database in Iran and used multivariable logistic regression, adjusting for cigarette smoking, opium use, and other confounding factors. In addition, we studied the association between exclusive waterpipe smoking and bladder cancer. RESULTS: We analyzed 717 cases and 3,477 controls and a subset of 215 patients and 2,145 controls who did not use opium or cigarettes. Although the OR adjusted for opium, cigarettes, and other tobacco products was 0.92 [95% confidence interval (CI), 0.69-1.20], we observed a statistically significant elevated risk in exclusive waterpipe smokers (OR = 1.78; 95% CI, 1.16-2.72) compared with non-users of opium or any tobacco. Associations were strongest for smoking more than two heads/day (OR = 2.25; 95% CI, 1.21-4.18) and for initiating waterpipe smoking at an age less than 20 (OR = 2.73; 95% CI, 1.11-6.72). The OR for urothelial bladder cancer was higher in ex-smokers (OR = 2.35; 95% CI, 1.24-4.42) than in current smokers (OR = 1.52; 95% CI, 0.72-3.15). All observed associations were consistently higher for urothelial histology. CONCLUSIONS: Waterpipe smoking may be associated with an increased risk of bladder cancer, notably among individuals who are not exposed to cigarette smoking and opium. IMPACT: The study provides compelling evidence that waterpipe smoking is a confirmed human carcinogen, demanding action from policymakers. See related In the Spotlight, p. 461.

TAS0313 plus Pembrolizumab for Post-Chemotherapy Immune Checkpoint Inhibitor-Naïve Locally Advanced or Metastatic Urothelial Carcinoma.

We evaluated the efficacy and safety of TAS0313, a multi-epitope long peptide vaccine, plus pembrolizumab in post-chemotherapy immune checkpoint inhibitor-naïve patients with locally advanced/metastatic urothelial carcinoma (la/mUC). TAS0313 9 mg was administered subcutaneously followed by pembrolizumab 200 mg on Day 1, and as monotherapy on Day 8 and 15 of Cycles 1 and 2, and Day 1 of subsequent cycles in 21-day cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Biomarkers of response were assessed. In 36 patients enrolled, the ORR was 33.3% (complete response: 7 patients; partial response: 5 patients). Median PFS was 5.0 months; 6- and 12-month progression-free rates were 46.4% and 36.5%, respectively. Median OS was not reached; 6-, 12-, and 24-month OS rates were 83.3%, 72.2%, and 55.1%, respectively. In post hoc analysis, patients with a tumor infiltrating CD8+ lymphocyte (CD8+ TIL) count ≥99 and/or programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥50 and lymphocyte count >1,380 cells/µL had higher ORRs and prolonged PFS versus patients with a CD8+ TIL count <99, PD-L1 CPS <50, and lymphocyte count ≤1,380 cells/µL. Thirty-four (94.4%) patients receiving combination therapy experienced treatment-related adverse events (AE), with pyrexia (n = 15, 41.7%), injection-site reactions (n = 15, 41.7%), injection-site induration (n = 6, 16.7%), and malaise (n = 6, 16.7%) the most common. No grade ≥3 treatment-related AEs occurred in ≥10% of patients. TAS0313 plus pembrolizumab combination therapy showed promising efficacy and manageable safety in la/mUC. Clinical Trial Registration: JapicCTI-183824.

The Association between Dietary Inflammatory Potential and Urologic Cancers: A Meta-analysis.

A meta-analysis published in 2018 indicated a significant association between the dietary inflammatory index (DII) and risk of urologic cancers (UC). The number of included studies was limited, and more research has been published on this topic since then. The current study aimed to find a more precise estimate of the association between dietary inflammatory potential and risk of UC by updating the previous meta-analysis. The PubMed and Embase databases were searched between January 2015 and April 2023 to identify eligible articles. Combined relative risk (RR) and 95% confidence intervals (CI) were calculated by random-effects model to assess the association between dietary inflammatory potential and risk of UC by comparison of the highest versus the lowest category of the DII/empirical dietary inflammatory pattern (EDIP) or by using the continuous DII/EDIP score. The analysis, including 23 studies with 557,576 subjects, showed different results for UC. There was a significant association for prostate cancer among case-control studies (RR = 1.75, 95% CI: 1.34-2.28), whereas among cohort studies a null association was found (RR = 1.02, 95% CI: 0.96-1.08). For bladder cancer, a nonsignificant association was observed in both case-control (RR = 1.59, 95% CI: 0.95-2.64) and cohort studies (RR = 1.03, 95% CI: 0.86-1.24). Pooled RR from 3 case-control studies displayed a statistically significant association between the DII and risk of kidney cancer (RR = 1.27, 95% CI: 1.03-1.56). Although DII was positively associated with all types of UC, no association was found for EDIP. The present meta-analysis confirmed that an inflammatory diet has a direct effect on the development of prostate cancer and kidney cancer. Large-scale studies are needed to demonstrate the association between dietary inflammatory potential and risk of UC and provide effective nutritional advice for UC prevention. PROTOCOL REGISTRATION: The protocol was registered in the International Prospective Register of Systematic Reviews (CRD42023391204).

Physical Activity and Bladder Cancer Risk: Findings of the Japan Collaborative Cohort Study.

PURPOSE: The association of physical activity with the risk of bladder cancer remains inconsistent among Asian populations. We aimed to examine the association in a large Japanese cohort. MATERIALS AND METHODS: In a population-based prospective cohort study, a total of 50,374 Japanese adults aged 40-79 years without a history of cancer or cardiovascular disease who had information on physical activity from self-administrated questionnaires were used for analysis. We performed Cox proportional hazard models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident bladder cancer after adjusting for several potential confounders. RESULTS: During the median 17.5 years of follow-up, 153 incident bladder cancers (116 men and 37 women) were identified. After the multivariable adjustment, HRs (95% CI) of bladder cancer concerning those with recreational sports participation of 1-2 hr/wk, 3-4 hr/wk, and 5 hr/wk and more were 0.67 (0.38-1.20), 0.79 (0.36-1.74), and 0.28 (0.09-0.89), respectively (p for trend=0.017). Compared with mostly sitting at the workplace, occupational physical activity of standing and walking were associated with a lower risk of bladder cancer (HR, 0.53 [95% CI, 0.32 to 0.85]). Hours of daily walking were not associated with the risk. The lower risk of bladder cancer was more evident for recreational sports (HR, 0.33 [95% CI, 0.10 to 1.00]), and for occupational standing and walking activity at work (HR, 0.57 [95% CI, 0.33 to 0.98]) among men. CONCLUSION: Recreational sports participation and occupational physical activity were inversely associated with the risk of bladder cancer among Japanese, especially in men.

Association between cigarette smoke exposure and urinary bladder cancer in Scottish terriers in a cohort study.

Canine urothelial carcinoma (UC) initially responds favorably to treatment, but is ultimately lethal in most cases. Research to identify modifiable risk factors to prevent the cancer is essential. The high breed-associated risk for UC, e.g. 20-fold higher in Scottish terriers, can facilitate this research. The objective was to identify environmental and host factors associated with UC in a cohort of Scottish terriers. Information was obtained through dog owner questionnaires for 120 Scottish terriers ≥ 6 years old participating in a bladder cancer screening study, with comparisons made between dogs that did or did not develop UC during the 3 years of screening. Univariable models were constructed, and variables with P < 0.20 were included when building the multivariable model, and then removed using a backward stepwise procedure. P < 0.05 was considered statistically significant. Urine cotinine concentrations were measured by liquid chromatography-mass spectrometry to further investigate potential cigarette smoke exposure. Biopsy-confirmed UC which was found in 32 of 120 dogs, was significantly associated with the dogs living in a household with cigarette smokers (odds ratio [OR], 6.34; 95 % confidence intervals [CI], 1.16-34.69; P = 0.033), living within a mile of a marsh or wetland (OR, 21.23; 95 % CI, 3.64-123.69; P = 0.001), and history of previous bladder infections (OR, 3.87; 95 % CI, 1.0-14.98; P = 0.050). UC was diagnosed in 18 of 51 dogs (35.3 %) with quantifiable cotinine concentrations, and six of 40 dogs (15.0 %) without quantifiable cotinine concentrations in their urine (P = 0.0165). In conclusion, the main modifiable risk factor for UC in this cohort of dogs was exposure to second-hand tobacco smoke.

Microbial Trends in Infection-related Readmissions Following Radical Cystectomy for Bladder Cancer.

OBJECTIVE: To report microbial pathogens detected at infection-related readmissions, including their susceptibility to antimicrobials. MATERIALS AND METHODS: A retrospective review of 785 patients who underwent radical cystectomy for bladder cancer at a tertiary center in Denmark between 2009 and 2019. All patients received prophylactic cefuroxime preoperatively and pivmecillinam at stent- or catheter removal. Data were collected through the national medical records and microbiology database. The primary outcome was readmission rate and pathogens detected at infection-related readmissions. Univariable and multivariable regression analyses were carried out to identify risk factors of readmission. RESULTS: Within 90days of surgery, 225 (29%) patients experienced at least one infection-related readmission. The most common pathogen identified was Enterococcus spp (24% of all positive samples). In blood cultures, the most dominant species were Escherichia coli (29%) and Staphylococcus spp (26%). Due to the heterogeneity in microbial species identified, more than one-third of the bacteria where mecillinam was tested showed resistance. Most isolates were susceptible to piperacillin+tazobactam. Orthotopic neobladder and continent cutaneous reservoir were associated with the highest risk of infection-related readmission compared to ileal conduit (odds ratios 2.78 [95%CI 1.66;4.65] and 3.08 [95%CI 1.58;5.98], respectively). Patients with diabetes had an increased risk of infection-related readmission compared to patients without diabetes (odds ratio 1.67 [95%CI 1.02;2.73]). CONCLUSION: Nearly one-third of all patients experienced at least one postoperative infection-related readmission with a wide range of microbial etiologies. Generalizability of our results is uncertain, but the data can be used to plan interventional trials of antibiotic prophylaxis.

Evaluating interactions of polygenic risk scores and NAT2 genotypes with tobacco smoking in bladder cancer risk.

Tobacco smoking is the most important risk factor for bladder cancer. Previous studies have identified the N-acetyltransferase (NAT2) gene in association with bladder cancer risk. The NAT2 gene encodes an enzyme that metabolizes aromatic amines, carcinogens commonly found in tobacco smoke. In our study, we evaluated potential interactions of tobacco smoking with NAT2 genotypes and polygenic risk score (PRS) for bladder cancer, using data from the UK Biobank, a large prospective cohort study. We used Cox proportional hazards models to measure the strength of the association. The PRS was derived using genetic risk variants identified by genome-wide association studies for bladder cancer. With an average of 10.1 years of follow-up of 390 678 eligible participants of European descent, 769 incident bladder cancer cases were identified. Current smokers with a PRS in the highest tertile had a higher risk of developing bladder cancer (HR: 6.45, 95% CI: 4.51-9.24) than current smokers with a PRS in the lowest tertile (HR: 2.41, 95% CI: 1.52-3.84; P for additive interaction = <.001). A similar interaction was found for genetically predicted metabolizing NAT2 phenotype and tobacco smoking where current smokers with the slow NAT2 phenotype had an increased risk of developing bladder cancer (HR: 5.70, 95% CI: 2.64-12.30) than current smokers with the fast NAT2 phenotype (HR: 3.61, 95% CI: 1.14-11.37; P for additive interaction = .100). Our study provides support for considering both genetic and lifestyle risk factors in developing prevention measures for bladder cancer.

Precision Medicine in Urothelial Carcinoma: Current Markers to Guide Treatment and Promising Future Directions.

OPINION STATEMENT: The treatment landscape for urothelial cancer has changed dramatically in the last 10 years, with the approval of several new treatments. At the same time, profiling of individual tumors has become more commonplace with widespread availability of molecular testing and immunohistochemistry. For urothelial cancer, this has led to current guidelines recommending that molecular testing be obtained in the metastatic setting, and that it be considered in the setting of locally advanced disease. Between molecular testing and immunohistochemistry testing of tumors, the only current guideline-directed application of these tests is in the identification of FGFR3 or FGFR2 alterations for use of FGFR inhibitors. While additional recurrent molecular alterations linked to the pathogenesis of urothelial cancer have been identified, the ability to successfully "drug" the pathways association with such alterations remains limited. There has been extensive research into whether expression of particular proteins might inform specific treatment approaches such as the use of PD-L1 testing to guide immune checkpoint blockade. With the integration of antibody-drug conjugates into the treatment armamentarium for urothelial cancer, ongoing research is seeking to determine whether expression of the targets of these therapies, such as Nectin 4, Trop-2, or HER2, could help to guide treatment.