Adiposity, Weight Change, and Urinary Melatonin Levels among Men in the Multiethnic Cohort.

BACKGROUND: Low levels of 6-sulfatoxymelatonin, the primary urinary metabolite of melatonin, have been linked to cancer and cardiometabolic outcomes in White and female populations. METHODS: We examined the association between adulthood adiposity and 6-sulfatoxymelatonin levels in a racially and ethnically diverse population. Our study included 4,078 men in the Multiethnic Cohort with adiposity measurements at enrollment (1993-1996) and biomarkers measured in urines collected in 1995 and 2005. Multivariable linear regression models were used to estimate the percent change in 6-sulfatoxymelatonin levels and 95% confidence intervals (CI). Associations were examined separately by racial/ethnic group. RESULTS: The prevalence of obesity varied by race and ethnicity, from 10% for Japanese American men to 34% for Native Hawaiian men. Compared with men with normal body mass index (BMI), men who were overweight (-7.8%; 95% CI, -11.9 to -3.5%) and obese (-18.1%; 95% CI, -23.2 to -12.6%) had significantly lower 6-sulfatoxymelatonin levels adjusting for potential confounding factors. Increasing weight gain in adulthood was also associated with lower 6-sulfatoxymelatonin (Ptrend < 0.0001). The inverse associations for BMI and weight change were qualitatively similar across racial and ethnic groups. CONCLUSIONS: Obesity is inversely associated with melatonin in a racially diverse population. This finding is relevant given higher rates of obesity among Black, Native Hawaiian, and Latino men, as well as potential racial and ethnic differences in circadian function. IMPACT: Melatonin may be a relevant biomarker among obesity-associated malignancies and could shed light on a potential mechanism of cancer disparities.

SLCO1B3 and SLCO2B1 genotypes, androgen deprivation therapy, and prostate cancer outcomes: a prospective cohort study and meta-analysis.

Solute carrier organic anion (SLCO) transporters (OATP transporters) are involved in cellular uptake of drugs and hormones. Germline variants in SLCO1B3 and SLCO2B1 have been implicated in prostate cancer progression and therapy response, including to androgen deprivation and statin medications, but results have appeared heterogeneous. We conducted a cohort study of five single-nucleotide polymorphisms (SNPs) in SLCO1B3 and SLCO2B1 with prior evidence among 3208 men with prostate cancer who participated in the Health Professionals Follow-up Study or the Physicians' Health Study, following participants prospectively after diagnosis over 32 years (median, 14 years) for development of metastases and cancer-specific death (lethal disease, 382 events). Results were suggestive of, but not conclusive for, associations between some SNPs and lethal disease and differences by androgen deprivation and statin use. All candidate SNPs were associated with SLCO mRNA expression in tumor-adjacent prostate tissue. We also conducted a systematic review and harmonized estimates for a dose-response meta-analysis of all available data, including 9 further studies, for a total of 5598 patients and 1473 clinical events. The A allele of the exonic SNP rs12422149 (14% prevalence), which leads to lower cellular testosterone precursor uptake via SLCO2B1, was associated with lower rates of prostate cancer progression (hazard ratio per A allele, 0.80; 95% confidence interval, 0.69-0.93), with little heterogeneity between studies (I2, 0.27). Collectively, the totality of evidence suggests a strong association between inherited genetic variation in SLCO2B1 and prostate cancer prognosis, with potential clinical use in risk stratification related to androgen deprivation therapy.

Individual-level home values and cancer mortality in a statewide registry.

BACKGROUND: Prior work assessing disparities in cancer outcomes has relied on regional socioeconomic metrics. These metrics average data across many individuals, resulting in a loss of granularity and confounding with other regional factors. METHODS: Using patients' addresses at the time of diagnosis from the Ohio Cancer Incidence Surveillance System, we retrieved individual home price estimates from an online real estate marketplace. This individual-level estimate was compared with the Area Deprivation Index (ADI) at the census block group level. Multivariable Cox proportional hazards models were used to determine the relationship between home price estimates and all-cause and cancer-specific mortality. RESULTS: A total of 667 277 patients in Ohio Cancer Incidence Surveillance System were linked to individual home prices across 16 cancers. Increasing home prices, adjusted for age, stage at diagnosis, and ADI, were associated with a decrease in the hazard of all-cause and cancer-specific mortality (hazard ratio [HR] = 0.92, 95% confidence interval [CI] = 0.92 to 0.93, and HR = 0.95, 95% CI = 0.94 to 0.95, respectively). Following a cancer diagnosis, individuals with home prices 2 standard deviations above the mean had an estimated 10-year survival probability (7.8%, 95% CI = 7.2% to 8.3%) higher than those with home prices 2 standard deviations below the mean. The association between home price and mortality was substantially more prominent for patients living in less deprived census block groups (Pinteraction < .001) than for those living in more deprived census block groups. CONCLUSION: Higher individual home prices were associated with improved all-cause and cancer-specific mortality, even after accounting for regional measures of deprivation.

Association between Outdoor Light at Night and Prostate Cancer in the Health Professionals Follow-up Study.

BACKGROUND: Circadian disruption is a potential risk factor for advanced prostate cancer, and light at night (LAN) exposure may disrupt circadian rhythms. We evaluated whether outdoor LAN increases the risk of prostate cancer. METHODS: We prospectively followed 49,148 participants in the Health Professionals Follow-up Study from 1986 through 2016. We estimated baseline and cumulative time-varying outdoor LAN with ∼1 km2 resolution using data from the US Defense Meteorological Satellite Program's Operational Linescan System, which was assigned to participants' geocoded addresses. Participants reside in all 50 U.S. states and reported a work or home address. We used multivariable Cox models to estimate HRs and 95% confidence intervals (CI) for the association between outdoor LAN and risk of overall (7,175 cases) and fatal (915 cases) prostate cancer adjusting for individual and contextual factors. RESULTS: There was no association between the interquartile range increase in cumulative LAN and total (HR, 1.02; 95% CI, 0.98-1.06) or fatal (HR, 1.05; 95% CI, 0.96-1.15) prostate cancer in adjusted models. However, there was a positive association between baseline LAN and total prostate cancer among non-movers (HR, 1.06; 95% CI, 1.00-1.14) including among highly screened participants (HR, 1.11; 95% CI, 1.01-1.23). CONCLUSIONS: There was a suggestive positive association between baseline outdoor LAN and total prostate cancer. Additional studies with different measures of outdoor LAN and in more diverse populations are necessary. IMPACT: To our knowledge, this is the first longitudinal cohort study exploring the relationship between outdoor LAN and prostate cancer.

Variation in KRAS/NRAS/BRAF-Mutation Status by Age, Sex, and Race/Ethnicity Among a Large Cohort of Patients with Metastatic Colorectal Cancer (mCRC).

BACKGROUND: Racial/ethnic disparities in metastatic colorectal cancer (mCRC) survival are well documented as is the impact that tumor mutation of KRAS and BRAF has on prognosis. It has been suggested that frequency differences of KRAS- and BRAF-mutated tumors may partially explain this disparity. Demographic differences in mutation frequency are not well established nor whether mutation and microsatellite instability (MSI) differentially impact survival among groups. METHODS: Using data for 11,117 patients diagnosed with de-novo mCRC from an electronic health record-derived database we estimated adjusted odds ratios (aOR) to characterize the association between demographics and MSI and KRAS/NRAS/BRAF-mutation status. Stratified Cox models were used to identify differences in overall survival (OS), adjusting for treatment and demographics. RESULTS: Being female, compared to male, (aORKRAS:1.33 (1.23-1.44); aORBRAF:1.84 (1.56-2.16)), and non-Hispanic Black race (NHB), compared to non-Hispanic White (NHW) (aORKRAS:1.62 (1.42-1.85); aORBRAF: 0.55 (0.38-0.77)) were associated with KRAS- or BRAF-mutant tumors. MSI prevalence was similar across race/ethnicity but higher in women. BRAF-mutant tumors were associated with poorer prognosis overall, especially among non-white patients. Among patients who had KRAS/NRAS/BRAF-WT tumors we observed no difference in OS by race or MSI. Among patients with KRAS-mutant tumors, Hispanic patients had more favorable prognosis adjusted hazards ratio (aHR) = 0.76 (0.65-0.89)) than their NHW counterparts. Among those with BRAF-mutant tumors, NHB patients had poorer prognosis than NHW patients (aHR:1.78 (1.08-2.93)). CONCLUSION: MSI and frequency of KRAS and BRAF mutations differed by demographics. Racial/ethnic disparities in OS differed by mutation. Future studies should explore biological and/or social determinants underlying these differences.

Cancer burden in women with HIV on Medicaid: A nationwide analysis.

BACKGROUND: Cancer is the leading cause of death in people living with HIV. In the United States, nearly 1 in 4 people living with HIV are women, more than half of whom rely on Medicaid for healthcare coverage. OBJECTIVE: The objective of this study is to evaluate the cancer burden of women living with HIV on Medicaid. DESIGN: We conducted a cross-sectional study of women 18-64 years of age enrolled in Medicaid during 2012, using data from Medicaid Analytic eXtract files. METHODS: Using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes, we identified women living with HIV (n = 72,508) and women without HIV (n = 17,353,963), flagging the presence of 15 types of cancer and differentiating between AIDS-defining cancers and non-AIDS-defining cancers. We obtained adjusted prevalence ratios and 95% confidence intervals for each cancer and for all cancers combined, using multivariable log-binomial models, and additionally stratifying by age and race/ethnicity. RESULTS: The highest adjusted prevalence ratios were observed for Kaposi's sarcoma (81.79 (95% confidence interval: 57.11-117.22)) and non-Hodgkin's lymphoma (27.69 (21.67-35.39)). The adjusted prevalence ratios for anal and cervical cancer, both of which were human papillomavirus-associated cancers, were 19.31 (17.33-21.51) and 4.20 (3.90-4.52), respectively. Among women living with HIV, the adjusted prevalence ratio for all cancer types combined was about two-fold higher (1.99 (1.86-2.14)) in women 45-64 years of age than in women 18-44 years of age. For non-AIDS-defining cancers but not for AIDS-defining cancers, the adjusted prevalence ratios were higher in older than in younger women. There was no significant difference in the adjusted prevalence ratios for all cancer types combined in the race/ethnicity-stratified analyses of the women living with HIV cohort. However, in cancer type-specific sub-analyses, differences in adjusted prevalence ratios between Hispanic versus non-Hispanic women were observed. For example, the adjusted prevalence ratio for Hispanic women for non-Hodgkin's lymphoma was 2.00 (1.30-3.07) and 0.73 (0.58-0.92), respectively, for breast cancer. CONCLUSION: Compared to their counterparts without HIV, women living with HIV on Medicaid have excess prevalence of cervical and anal cancers, both of which are human papillomavirus related, as well as Kaposi's sarcoma and lymphoma. Older age is also associated with increased burden of non-AIDS-defining cancers in women living with HIV. Our findings emphasize the need for not only cancer screening among women living with HIV but also for efforts to increase human papillomavirus vaccination among all eligible individuals.

Bladder and Kidney Cancer Diagnosis and Survival Increase With Medicare Eligibility at Age 65.

INTRODUCTION: Medicare eligibility at 65 has been associated with increased diagnosis and survival for certain cancers due to greater health care utilization. We aim to assess for a similar "Medicare effect" for bladder and kidney cancers, which has not been previously established. METHODS: Patients diagnosed with bladder or kidney cancer from 2000-2018 at ages 60-69 years were identified with the Surveillance, Epidemiology, and End Results database. We used age-over-age percent change calculations to characterize trends in cancer diagnoses focusing on patients aged 65. Multivariable Cox models were used to compare cancer-specific mortality across ages at diagnosis. RESULTS: We identified 63,960 patients diagnosed with bladder cancer and 52,316 diagnosed with kidney cancer. Age-over-age change in diagnosis was highest for patients aged 65 compared to all other ages for both cancers (P < .01 for both). Stratified by stage, patients aged 65 had a higher age-over-age change than those aged 61-64 or 66-69 for in situ (P = .01, P < .01, respectively), localized (P = .03, P = .01), and regional (P = .02, P = .02) bladder cancer and localized (P = .01, P = .01) kidney cancer. Bladder cancer patients aged 65 had lower cancer-specific mortality than patients aged 66 (HR = 1.17, P = .01) and 69 (HR = 1.18, P = .01), while kidney cancer patients aged 65 had lower mortality than patients aged 64 (HR = 1.18, P < .01) and 66-69. CONCLUSIONS: The age of 65, marking the onset of Medicare eligibility, is associated with more diagnoses of bladder and kidney cancer. Patients diagnosed at age 65 demonstrate decreased bladder and kidney cancer-specific mortality.

Disparities in cause-specific mortality by race and sex among bladder cancer patients from the SEER database.

PURPOSE: Previous literature shows that more bladder cancer patients overall die from causes other than the primary malignancy. Given known disparities in bladder cancer outcomes by race and sex, we aimed to characterize differences in cause-specific mortality for bladder cancer patients by these demographics. METHODS: We identified 215,252 bladder cancer patients diagnosed with bladder cancer from 2000 to 2017 in the SEER 18 database. We calculated cumulative incidence of death from seven causes (bladder cancer, COPD, diabetes, heart disease, external, other cancer, other) to assess differences in cause-specific mortality between race and sex subgroups. We used multivariable Cox proportional hazards regression and Fine-Gray competing risk models to compare risk of bladder cancer-specific mortality between race and sex subgroups overall and stratified by cancer stage. RESULTS: 17% of patients died from bladder cancer (n = 36,923), 30% died from other causes (n = 65,076), and 53% were alive (n = 113,253). Among those who died, the most common cause of death was bladder cancer, followed by other cancer and diseases of the heart. All race-sex subgroups were more likely than white men to die from bladder cancer. Compared to white men, white women (HR: 1.20, 95% CI: 1.17-1.23) and Black women (HR: 1.57, 95% CI: 1.49-1.66) had a higher risk of dying from bladder cancer, overall and stratified by stage. CONCLUSION: Among bladder cancer patients, death from other causes especially other cancer and heart disease contributed a large proportion of mortality. We found differences in cause-specific mortality by race-sex subgroups, with Black women having a particularly high risk of dying from bladder cancer.

Global Meta-analysis of Urine Microbiome: Colonization of Polycyclic Aromatic Hydrocarbon-degrading Bacteria Among Bladder Cancer Patients.

BACKGROUND: The application of next-generation sequencing techniques has enabled characterization of urinary tract microbiome. Although many studies have demonstrated associations between the human microbiome and bladder cancer (BC), these have not always reported consistent results, thereby necessitating cross-study comparisons. Thus, the fundamental questions remain how we can utilize this knowledge. OBJECTIVE: The aim of our study was to examine the disease-associated changes in urine microbiome communities globally utilizing a machine learning algorithm. DESIGN, SETTING, AND PARTICIPANTS: Raw FASTQ files were downloaded for the three published studies in urinary microbiome in BC patients, in addition to our own prospectively collected cohort. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Demultiplexing and classification were performed using the QIIME 2020.8 platform. De novo operational taxonomic units were clustered using the uCLUST algorithm and defined by 97% sequence similarity and classified at the phylum level against the Silva RNA sequence database. The metadata available from the three studies included were used to evaluate the differential abundance between BC patients and controls via a random-effect meta-analysis using the metagen R function. A machine learning analysis was performed using the SIAMCAT R package. RESULTS AND LIMITATIONS: Our study includes 129 BC urine and 60 healthy control samples across four different countries. We identified a total of 97/548 genera to be differentially abundant in the BC urine microbiome compared with that of healthy patients. Overall, while the differences in diversity metrics were clustered around the country of origin (Kruskal-Wallis, p < 0.001), collection methodology was a driver of microbiome composition. When assessing dataset from China, Hungary, and Croatia, data demonstrated no discrimination capacity to distinguish between BC patients and healthy adults (area under the curve [AUC] 0.577). However, inclusion of samples with catheterized urine improved the diagnostic accuracy of prediction for BC to AUC 0.995, with precision-recall AUC = 0.994. Through elimination of contaminants associated with the collection methodology among all cohorts, our study identified increased abundance of polycyclic aromatic hydrocarbon (PAH)-degrading bacteria Sphingomonas, Acinetobacter, Micrococcus, Pseudomonas, and Ralstonia to be consistently present in BC patients. CONCLUSIONS: The microbiota of the BC population may be a reflection of PAH exposure from smoking, environmental pollutants, and ingestion. Presence of PAHs in the urine of BC patients may allow for a unique metabolic niche and provide necessary metabolic resources where other bacteria are not able to flourish. Furthermore, we found that while compositional differences are associated with geography more than with disease, many are driven by the collection methodology. PATIENT SUMMARY: The goal of our study was to compare the urine microbiome of bladder cancer patients with that of healthy controls and evaluate any potential bacteria that may be more likely to be found in patients with bladder cancer. Our study is unique as it evaluates this across multiple countries, to find a common pattern. After we removed some of the contamination, we were able to localize several key bacteria that are more likely to be found in the urine of bladder cancer patients. These bacteria all share their ability to break down tobacco carcinogens.

Rotating Night Shift Work and Bladder Cancer Risk in Women: Results of Two Prospective Cohort Studies.

Bladder cancer is the sixth most common cancer in the United States. Night shift work has previously been linked with cancer risk. Whether there is an association between rotating night shift work and bladder cancer in women has not been studied previously. Eligible participants in the Nurses' Health Study (NHS, n = 82,147, 1988-2016) and Nurses' Health Study II (NHSII, n = 113,630, 1989-2015) were prospectively followed and a total of 620 and 122 incident bladder cancer cases were documented during the follow-up of NHS and NHSII, respectively. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for bladder cancer incidence. We observed a significantly increased risk of bladder cancer among women with >5 years of night shift work history compared with women who never worked rotating night shifts in NHS (HR = 1.24; 95%CI = 1.01-1.54, p for trend = 0.06), but not in the pooled NHS and NHS II (HR = 1.18; 95%CI = 0.97-1.43, p for trend = 0.08). Secondary analyses stratified by smoking status showed no significant interaction (p = 0.89) between the duration of rotating night shift work and smoking status. In conclusion, our results did not provide strong evidence for an association between rotating night shift work and bladder cancer risk.

Receipt of Targeted Therapy and Survival Outcomes in Patients With Metastatic Colorectal Cancer.

Importance: Professional society guidelines recommend treating patients with metastatic colorectal cancer with targeted therapies, including epithelial growth factor receptor (EGFR) inhibitors and vascular endothelial growth factor (VEGF) inhibitors, depending on the presence or absence of certain mutations. Since most studies of first-line targeted therapies have been limited by sample size, there is a need for larger studies using data from routine clinical care. Objectives: To identify factors associated with receipt of first-line targeted therapies among patients with metastatic colorectal cancer for whom RAS or BRAF mutation data in the tumor were available and investigate whether targeted therapy is associated with survival. Design, Setting, and Participants: This cohort study used deidentified data from an electronic health record-derived database to include patients from 800 sites of patient care across the US who were diagnosed with de novo metastatic colorectal cancer between January 1, 2013, and March 31, 2020 (n = 9134). Main Outcomes and Measures: Receipt of first-line targeted therapy, categorized as ever having received EGFR inhibitors, VEGF inhibitors, or neither. The secondary outcome was overall survival. Results: The study population included 9134 patients. The median age at diagnosis was 62 years (IQR, 53-71 years), 5019 (54.9%) were male, and 5692 (62.3%) were White. The median follow-up period was 15 months. Overall, 713 patients (7.8%) received EGFR inhibitors and 5081 patients (55.6%) received VEGF inhibitors as part of their first-line treatment. Among patients with RAS wild-type (RAS-WT) tumors, 625 patients (15.5%) received EGFR inhibitors and 2053 patients (50.9%) received VEGF inhibitors. In patients with RAS mutant (RAS-Mut) tumors, 50 patients (1.1%) received EGFR inhibitors and 2682 patients (59.7%) received VEGF inhibitors; among those with BRAF-mutant (BRAF-Mut) tumors, 38 patients (6.3%) received EGFR inhibitors and 346 patients (57.2%) received VEGF inhibitors. More than one-third of the patients (36.6%) received neither EGFR inhibitors nor VEGF inhibitors. Compared with patients younger than age 40 years, those aged 80 years or older had significantly lower odds to receive targeted therapies (EGFR or VEGF inhibitors in patients with RAS-WT tumors: adjusted odds ratio [aOR], 0.53; 95% CI, 0.36-0.79; and VEGF inhibitors in patients with RAS-Mut tumors: aOR, 0.62; 95% CI, 0.42-0.90). Improved survival was associated with EGFR inhibitor therapy in patients with RAS-WT tumors (adjusted hazard ratio [aHR], 0.85; 95% CI, 0.74-0.98). Unlike in clinical trials, however, no survival benefit was noted with use of VEGF inhibitors among patients with RAS-WT (aHR, 1.00; 95% CI, 0.91-1.11) or RAS-Mut (aHR, 1.01; 95% CI, 0.93-1.10) tumors. Conclusions and Relevance: The findings of this study showed mixed results on survival benefits associated with targeted therapy. In addition, given that some of the results differed from those of randomized clinical trials, this study highlights the importance of using data originating from routine clinical care.

Evaluating Factors Associated With Continuous Glucose Monitoring Utilization With the Type 1 Diabetes Exchange Registry.

BACKGROUND: The 2022 American Diabetes Association (ADA) Standards of Care recommends considering use of continuous glucose monitoring (CGM) for insulin-managed diabetes mellitus (DM), but equitable access remains challenging. This study evaluates socioeconomic and demographic metrics associated with CGM use. METHODS: RStudio 2021.09.1+372 was utilized to perform uni- and bivariable analysis, as well as binomial logistic regression modeling for categorical CGM use (yes/no) on the most recent cross-section from the Type 1 Diabetes Exchange (T1DX) Registry 2016-2018 cohort (n = 22 418). RESULTS: Compared with White Non-Hispanic participants, Black Non-Hispanic (OR = 0.45, CI = 0.36-0.57, P < 0.001) and American Indian/Alaskan Native individuals (OR = 0.33, CI = 0.14-0.70, P = 0.008) had lower odds of CGM use. Compared with private insurance, government insurance had reduced odds of CGM use (OR = 0.59, CI = 0.52-0.66, P < 0.001). Individuals earning $100,000 or more were twice as likely to use CGMs (OR = 2.06, CI = 1.75-2.45, P < 0.001) compared with those earning <$25,000 annually. Subgroup analysis based on income bracket demonstrated that government insured individuals earning <$25,000 annually were the least likely to use CGMs (OR = 0.44, CI = 0.32-0.61, P < 0.001), as compared with private insurance. CONCLUSIONS: T1DX Registry data demonstrate that CGM use follows the inverse care law, with health technology utilization inversely related to disease burden. Federal policies promoting CGM use in Medicare and Medicaid populations can facilitate the ADA's recommendation for patients with insulin-managed diabetes mellitus.

Sociodemographic and clinical factors associated with receipt of biomarker testing in patients with metastatic colorectal cancer.

BACKGROUND: Standard clinical practice and national guidelines dictate somatic testing of metastatic colorectal cancer (mCRC) tumors to guide appropriate therapy; however, previous studies suggest that not all patients are tested. The objective of this study was to investigate potential differences in testing for mCRC by demographic and clinical factors. METHODS: We performed a retrospective review of de-identified patient data derived from electronic health records (EHRs) of 25,469 patients diagnosed with mCRC between the years 2013 and 2020. Our outcome was a receipt of the following tests: (a) biomarker testing (BRAF, KRAS, NRAS, MMR/MSI) and (b) next-generation sequencing (NGS). We interrogated our data using the machine-learning algorithm Classification and Regression Tree (CART), a unique approach to identifying combinations of, rather than individual demographic and clinical characteristics associated with receipt of testing. RESULTS: A total of 25,469 patients were identified with mCRC. Of these, 21,133 (83%) received either biomarker testing only (n = 12,485) or any testing (biomarker + NGS) (n = 8648). The proportion of patients who received any testing increased over calendar time for all age, race, and sex categories. Receipt of any testing was highest (90%) among younger and patients with better performance status, and there was no difference in receipt of any testing by race. The highest percentage of NGS testing was among those with better performance status, <70 years old, commercial or other governmental program payers, and low comorbidity burden; however, those who were Black or Hispanic had a lower prevalence of NGS testing than those who were White. CONCLUSIONS AND RELEVANCE: Considerable variations exist in somatic biomarker testing across subgroups of the population. Identification of genomic alterations can aid in determining targeted treatment and improving clinical outcomes; therefore, equitable use of these testing strategies, particularly NGS, is necessary.

A systematic review and in silico study of potential genetic markers implicated in cases of overactive bladder.

OBJECTIVE: The contribution of genetic factors to the presence of an overactive bladder is recognized. This study aimed to (1) assemble and synthesize available data from studies assessing differential gene expression in patients with overactive bladder vs controls without overactive bladder and (2) determine possible correlations and functional pathways between genes. DATA SOURCES: We searched PubMed, Ovid or Medline, and Wiley Cochrane Central Register of Controlled Trials databases between January 1, 2000, and December 15, 2021. STUDY ELIGIBILITY CRITERIA: Studies were included if gene expression was detected and quantified using molecular approaches performed on human bladder tissue specimens directly and excluded if the gene expression analysis was carried out from blood and urine specimens alone. METHODS: A systematic review was completed to identify publications that reported differently expressed gene candidates among patients with overactive bladder vs healthy individuals. Gene networking connections and pathway analysis were performed employing Metascape software, where inputs were identified from our systematic review of differentially expressed genes in overactive bladder. RESULTS: A total of 9 studies were included in the final analysis and 11 genes were identified as being up-regulated (purinergic receptor P2X 2 [P2RX2], smoothelin [SMTN], growth-associated protein 43 [GAP43], transient receptor potential cation channel subfamily M member 8 [TRPM8], cadherin 11 [CDH1], gap junction protein gamma 1 [GJC1], cholinergic receptor muscarinic 2 [CHRM2], cholinergic receptor muscarinic 3 [CHRM3], and transient receptor potential cation channel subfamily V member 4 [TRPV4]) or down-regulated (purinergic receptor P2X 2 [P2RX3] and purinergic receptor P2X 5 [P2RX5]) in patients with overactive bladder. Gene network analysis showed that genes are involved in chemical synaptic transmission, smooth muscle contraction, blood circulation, and response to temperature stimulus. Network analysis demonstrated a significant genetic interaction between TRPV4, TRPM8, P2RX3, and PR2X2 genes. CONCLUSION: Outcomes of this systematic review highlighted potential biomarkers for treatment efficacy and have laid the groundwork for developing future gene therapies for overactive bladder in clinical settings.

Risk factors for postoperative Clostridium difficile infection after radical cystectomy for bladder cancer: a NSQIP database analysis.

INTRODUCTION: Patients undergoing cystectomy for bladder cancer are at an increased risk for Clostridium difficile infection (CDI) due to prolonged antibiotics and underlying comorbidities. We aim to evaluate CDI risk factors in cystectomy patients. MATERIALS AND METHODS: Utilizing National Surgical Quality Improvement Program (NSQIP), patients undergoing cystectomy with diagnosis of bladder cancer between 2015-2017 were included. Baseline demographics including age, sex, comorbidities, and preoperative labs were collected. Univariate and multivariable logistic regression were used to evaluate risk factors for and complications of CDI during the index hospitalization. RESULTS: There were a total of 6,432 patients included in the analysis, with 6,242 (96%) and 190 (4%) in the non-CDI vs. CDI groups, respectively. Patients with a diagnosis of postoperative CDI were more likely to be female [4.09% vs. 2.71%, p = 0.001] and have lower preoperative albumin [3.78 g/dL (0.52) vs. 3.92 g/dL (0.48), p = 0.003]. Patients with a history of female sex (OR 1.46, p = 0.03), neobladder (OR 1.57, p = 0.01), and low preoperative albumin (OR 1.45, p = 0.04) were at the highest risk for development of CDI postoperatively. Patients with a diagnosis of CDI were more likely to experience readmission within 30 days (31.1% vs. 19.2%, p < 0.001). CONCLUSION: Utilizing the NSQIP database, we identified predictors for development of CDI in cystectomy patients. Female sex, continent diversion, and low preoperative albumin all significantly increased the rate of CDI. While our findings are retrospective, they are compelling enough to warrant further prospective investigation.

Harm-to-Benefit of Three Decades of Prostate Cancer Screening in Black Men.

BACKGROUND: Prostate-specific antigen screening has profoundly affected the epidemiology of prostate cancer in the United States. Persistent racial disparities in outcomes for Black men warrant re-examination of the harms of screening relative to its cancer-specific mortality benefits in this population. METHODS: We estimated overdiagnoses and overtreatment of prostate cancer for men of all races and for Black men 50 to 84 years of age until 2016, the most recent year with treatment data available, using excess incidence relative to 1986 based on the Surveillance, Epidemiology, and End Results registry and U.S. Census data as well as an established microsimulation model of prostate cancer natural history. Combining estimates with plausible mortality benefit, we calculated numbers needed to diagnose (NND) and treat (NNT) to prevent one prostate cancer death. RESULTS: For men of all races, we estimated 1.5 to 1.9 million (range between estimation approaches) overdiagnosed and 0.9 to 1.5 million overtreated prostate cancers by 2016. Assuming that half of the 270,000 prostate cancer deaths avoided by 2016 were attributable to screening, the NND and the NNT would be 11 to 14 and 7 to 11 for men of all races and 8 to 12 and 5 to 9 for Black men, respectively. Alternative estimates incorporating a lag between incidence and mortality resulted in a NND and a NNT for Black men that reached well into the low single digits. CONCLUSIONS: Complementary approaches to quantifying overdiagnosis indicate a harm-benefit tradeoff of prostate-specific antigen screening that is more favorable for Black men than for men of all races considered together. Our findings highlight the need to account for the increased value of screening in Black men in clinical guidelines. (Funded by the Patient-Centered Outcomes Research Institute, the National Cancer Institute, the Bristol Myers Squibb Foundation, and the Damon Runyon Cancer Research Foundation.).

Racial Disparities in Prostate Cancer: Evaluation of Diet, Lifestyle, Family History, and Screening Patterns.

BACKGROUND: Racial disparities in prostate cancer incidence and mortality rates are considerable. We previously found in the Health Professionals Follow-up Study (HPFS) that African-American men had an 80% higher prostate cancer risk than White men. With 21 additional years of follow-up and four-fold increase in cases, we undertook a contemporary analysis of racial differences in prostate cancer incidence and mortality in HPFS. METHODS: For 47,679 men, we estimated HRs and 95% confidence intervals (CI) for the association between race and risk of prostate cancer through 2016 using Cox proportional hazards regression. Multivariable models (mHR) were adjusted for lifestyle, diet, family history, and PSA screening collected on biennial questionnaires. RESULTS: 6,909 prostate cancer cases were diagnosed in White, 89 in African-American, and 90 in Asian-American men. African-Americans had higher prostate cancer incidence (mHR = 1.31; 95% CI, 1.06-1.62) and mortality (mHR = 1.67; 95% CI, 1.00-2.78), and lower PSA screening prevalence than White men. The excess risk was greater in the pre-PSA screening era (HR = 1.68; 95% CI, 1.14-2.48) than the PSA screening era (HR = 1.20; 95% CI, 0.93-1.56). Asian-Americans had lower prostate cancer risk (mHR = 0.74; 95% CI, 0.60-0.92), but similar risk of fatal disease compared with white men. CONCLUSIONS: Racial differences in prostate cancer incidence and mortality in HPFS are not fully explained by differences in lifestyle, diet, family history, or PSA screening. IMPACT: Additional research is necessary to address the disproportionately higher rates of prostate cancer in African-American men.

Excess cancer prevalence in men with HIV: A nationwide analysis of Medicaid data.

BACKGROUND: Cancer is one of the most common comorbidities in men living with HIV (MLWH). However, little is known about the MLWH subgroups with the highest cancer burden to which cancer prevention efforts should be targeted. Because Medicaid is the most important source of insurance for MLWH, we evaluated the excess cancer prevalence in MLWH on Medicaid relative to their non-HIV counterparts. METHODS: In this cross-sectional study using 2012 Medicaid Analytic eXtract data nationwide, we flagged the presence of HIV, 13 types of cancer, symptomatic HIV, and viral coinfections using codes from the International Classification of Diseases, Ninth Revision, Clinical Modification. The study population included individuals administratively noted to be of male sex (men), aged 18 to 64 years, with (n = 82,495) or without (n = 7,302,523) HIV. We developed log-binomial models with cancer as the outcome stratified by symptomatic status, age, and race/ethnicity. RESULTS: Cancer prevalence was higher in MLWH than in men without HIV (adjusted prevalence ratio [APR], 1.84; 95% confidence interval [CI], 1.78-1.90) and was higher among those with symptomatic HIV (APR, 2.74; 95% CI, 2.52-2.97) than among those with asymptomatic HIV (APR, 1.73; 95% CI, 1.67-1.79). The highest APRs were observed for anal cancer in younger men, both in the symptomatic and asymptomatic groups: APR, 312.97; 95% CI, 210.27-465.84, and APR, 482.26; 95% CI, 390.67-595.32, respectively. In race/ethnicity strata, the highest APRs were among Hispanic men for anal cancer (APR, 198.53; 95% CI, 144.54-272.68) and for lymphoma (APR, 9.10; 95% CI, 7.80-10.63). CONCLUSIONS: Given the Medicaid program's role in insuring MLWH, the current findings highlight the importance of the program's efforts to promote healthy behaviors and vaccination against human papillomavirus in all children and adolescents and to provide individualized cancer screening for MLWH.

Weight Tracking as a Novel Prognostic Marker After Pancreatectomy.

BACKGROUND: Objective measures of post-pancreatectomy weight change for pancreatic ductal adenocarcinoma (PDAC) have not been extensively studied for long-term outcomes. We used weight measurements in our institutional medical record to analyze trends in post-pancreatectomy weight and determine the association with disease status. METHODS: Pancreatectomies for PDAC (n = 315) and benign indications (n = 111) were identified. Preoperative baseline, minimum postoperative (Min #1), and subsequent postoperative maximum (Max) weights were abstracted. Multivariable Cox hazards regression was conducted to analyze the association between weight change and survival. RESULTS: Median weight loss postoperatively in each group was > 20 lbs. PDAC patients gained 10 lbs after Min #1 compared to 15 lbs in the benign cohort (p < 0.001). Few patients returned to their preoperative weight (29.8% PDAC vs. 40.5% benign, p = 0.04). Patients with early PDAC recurrence (< 13 months) lost more weight (18.0% vs. 13.3% vs. 10.9%, p < 0.001) and gained less weight (2.1% vs. 12.0% vs. 7.9%, p < 0.001) compared with those with late cancer recurrence (≥ 13 months) or no evidence of active disease, respectively. PDAC patients lost 11.2 lbs in the year preceding recurrence diagnosis. Weight loss was not associated with survival; however, weight gain was associated with improved survival. CONCLUSIONS: Resections for PDAC are complicated by a similar degree of weight loss as patients with benign disease, and there is no association with survival. However, failure to gain weight is especially ominous. Weight loss after weight recovery foreshadows disease recurrence. These data suggest that rigorous weight tracking is an untapped surveillance strategy in patients with PDAC.