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Assessment of the size and function of a functional single ventricle (FSV) is a key element in the management of patients after the Fontan procedure. Measurement variability of ventricular mass, volume, and ejection fraction (EF) among observers by echocardiography and cardiac magnetic resonance imaging (CMR) and their reproducibility among readers in these patients have not been described. From the 546 patients enrolled in the Pediatric Heart Network Fontan Cross-Sectional Study (mean age 11.9 +/- 3.4 years), 100 echocardiograms and 50 CMR studies were assessed for measurement reproducibility; 124 subjects with paired studies were selected for comparison between modalities. Interobserver agreement for qualitative grading of ventricular function by echocardiography was modest for left ventricular (LV) morphology (kappa = 0.42) and weak for right ventricular (RV) morphology (kappa = 0.12). For quantitative assessment, high intraclass correlation coefficients were found for echocardiographic interobserver agreement (LV 0.87 to 0.92, RV 0.82 to 0.85) of systolic and diastolic volumes, respectively. In contrast, intraclass correlation coefficients for LV and RV mass were moderate (LV 0.78, RV 0.72). The corresponding intraclass correlation coefficients by CMR were high (LV 0.96, RV 0.85). Volumes by echocardiography averaged 70% of CMR values. Interobserver reproducibility for the EF was similar for the 2 modalities. Although the absolute mean difference between modalities for the EF was small (<2%), 95% limits of agreement were wide. In conclusion, agreement between observers of qualitative FSV function by echocardiography is modest. Measurements of FSV volume by 2-dimensional echocardiography underestimate CMR measurements, but their reproducibility is high. Echocardiographic and CMR measurements of FSV EF demonstrate similar interobserver reproducibility, whereas measurements of FSV mass and LV diastolic volume are more reproducible by CMR. [ABSTRACT FROM AUTHOR]

Background: Pollutants including metals/metalloids, nitrate, disinfection byproducts, and volatile organic compounds contaminate federally regulated community water systems (CWS) and unregulated domestic wells across the United States. Exposures and associated health effects, particularly at levels below regulatory limits, are understudied., Objective: We described drinking water sources and exposures for the California Teachers Study (CTS), a prospective cohort of female California teachers and administrators., Methods: Participants' geocoded addresses at enrollment (1995-1996) were linked to CWS service area boundaries and monitoring data (N = 115,206, 92%); we computed average (1990-2015) concentrations of arsenic, uranium, nitrate, gross alpha (GA), five haloacetic acids (HAA5), total trihalomethanes (TTHM), trichloroethylene (TCE), and tetrachloroethylene (PCE). We used generalized linear regression to estimate geometric mean ratios of CWS exposures across demographic subgroups and neighborhood characteristics. Self-reported drinking water source and consumption at follow-up (2017-2019) were also described., Results: Medians (interquartile ranges) of average concentrations of all contaminants were below regulatory limits: arsenic: 1.03 (0.54,1.71) µg/L, uranium: 3.48 (1.01,6.18) µg/L, GA: 2.21 (1.32,3.67) pCi/L, nitrate: 0.54 (0.20,1.97) mg/L, HAA5: 8.67 (2.98,14.70) µg/L, and TTHM: 12.86 (4.58,21.95) µg/L. Among those who lived within a CWS boundary and self-reported drinking water information (2017-2019), approximately 74% self-reported their water source as municipal, 15% bottled, 2% private well, 4% other, and 5% did not know/missing. Spatially linked water source was largely consistent with self-reported source at follow-up (2017-2019). Relative to non-Hispanic white participants, average arsenic, uranium, GA, and nitrate concentrations were higher for Black, Hispanic and Native American participants. Relative to participants living in census block groups in the lowest socioeconomic status (SES) quartile, participants in higher SES quartiles had lower arsenic/uranium/GA/nitrate, and higher HAA5/TTHM. Non-metropolitan participants had higher arsenic/uranium/nitrate, and metropolitan participants had higher HAA5/TTHM., Impact: Though average water contaminant levels were mostly below regulatory limits in this large cohort of California women, we observed heterogeneity in exposures across sociodemographic subgroups and neighborhood characteristics. These data will be used to support future assessments of drinking water exposures and disease risk., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Atrazine is a common agricultural herbicide in the United States. Few epidemiologic studies have evaluated cancer risks. Previous analyses within the Agricultural Health Study (AHS) have found some evidence of associations with cancer at some sites., Objective: We updated exposure information, incident cases, and follow-up time to assess the associations between atrazine use and cancer at specific sites in the AHS., Methods: Information about lifetime pesticide use was reported at enrollment (1993-1997) and follow-up (1999-2005). Among 53,562 pesticide applicators in North Carolina and Iowa, we identified 8,915 incident cases through cancer registry linkages through 2014 (North Carolina)/2017 (Iowa). We used Poisson regression to evaluate the association between ever/never and intensity-weighted lifetime days of atrazine use and incident cancer risk controlling for several confounders. We also evaluated lagged exposures and age-stratified risk., Results: Approximately 71.2% of applicators reported ever using atrazine, which was associated with lung cancer [ rate ratios  ( RR ) = 1.24 ; 95% confidence interval (CI): 1.04, 1.46]. Aggressive prostate cancer risk was increased in the highest quartile ( RR Q 4 = 1.20 ; 95% CI: 0.95, 1.52; p -trend = 0.19 ), particularly among those < 60 years old ( RR Q 4 = 3.04 ; 95% CI: 1.61, 5.75; p -trend < 0.001 ; p -interaction = 0.04 ). Among applicators < 50 years of age, ever-atrazine use was associated with non-Hodgkin lymphoma (NHL) ( RR = 2.43 ; 95% CI: 1.10, 5.38; p -interaction = 0.60 ). For soft tissue sarcoma, there was an elevated risk in the highest tertile of exposure ( RR T 3 : 2.54; 95% CI: 0.97, 6.62; p -trend = 0.31 ). In analyses with exposure lagged by 25 years, there was an elevated risk of pharyngeal ( RR T 3 = 3.04 ; 95% CI: 1.45, 6.36; p -trend = 0.07 ) and kidney ( RR Q 4 = 1.62 ; 95% CI: 1.15, 2.29; p -trend < 0.005 ) cancers., Discussion: We observed suggestive associations with some malignancies in overall, age-specific, and lagged analyses. Associations with aggressive prostate cancer and NHL were apparent among those diagnosed at younger ages and with cancers of the pharynx and kidney, and soft tissue sarcomas were observed in lagged analyses. Further work is needed to confirm these observed associations and elucidate potential underlying mechanisms. https://doi.org/10.1289/EHP13684.

Background: Though obesity, measured by body mass index (BMI), is an established risk factor for several cancer sites, there is conflicting evidence on whether obesity increases prostate cancer risk or mortality and, if it does, whether it increases risk directly or indirectly by affecting prostate cancer screening efficacy., Methods: We examined associations between BMI and prostate cancer screening outcomes, incidence, and mortality in men randomly assigned to the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (n = 36 756) between 1993 and 2001. Participants received annual screening with the prostate-specific antigen test and digital rectal exam. Associations between baseline BMI and screening outcomes were assessed via multinomial logistic regression, and associations with prostate cancer incidence and mortality were assessed via Cox proportional hazards regression., Results: Individuals with higher BMI were less likely to screen positive via the prostate-specific antigen test and/or digital rectal exam and more likely to have an inadequate screen (all Ptrend < .01). Higher BMI was inversely associated with prostate cancer incidence (per 5 kg/m2 BMI increase: hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.91 to 0.97), including incidence of early stage (HR = 0.94, 95% CI = 0.90 to 0.97) and advanced-stage (HR = 0.91, 95% CI = 0.82 to 1.02) disease, but positively associated with prostate cancer mortality (HR = 1.21, 95% CI = 1.06 to 1.37). The association with mortality was not modified by screening outcome (Pinteraction = .13)., Conclusions: Within this screened population, individuals with higher BMI had lower risk of prostate cancer diagnosis but higher risk of prostate cancer mortality. As higher BMI was not positively associated with advanced-stage prostate cancer risk, the increased mortality is unlikely to be due to delayed prostate cancer detection., (Published by Oxford University Press 2023.)

More than 200 genetic variants have been independently associated with prostate cancer risk. Studies among farmers have also observed increased prostate cancer risk associated with exposure to specific organophosphate (fonofos, terbufos, malathion, dimethoate) and organochlorine (aldrin, chlordane) insecticides. We examined the joint associations between these pesticides, established prostate cancer loci, and prostate cancer risk among 1,162 cases (588 aggressive) and 2,206 frequency-matched controls nested in the Agricultural Health Study cohort. History of lifetime pesticide use was combined with a polygenic risk score (PRS) generated using 256 established prostate cancer risk variants. Logistic regression models estimated the joint associations of the pesticides, the PRS, and the 256 individual genetic variants with risk of total and aggressive prostate cancer. Likelihood ratio tests assessed multiplicative interaction. We observed interaction between ever use of fonofos and the PRS in relation to total and aggressive prostate cancer risk. Compared to the reference group (never use, PRS < median), men with ever use of fonofos and PRS > median had elevated risks of total (OR 1.35 [1.06-1.73], p-interaction = 0.03) and aggressive (OR 1.49 [1.09-2.04], p-interaction = 0.19) prostate cancer. There was also suggestion of interaction between pesticides and individual genetic variants occurring in regions associated with DNA damage response (CDH3, EMSY genes) and with variants related to altered androgen receptor-driven transcriptional programs critical for prostate cancer. Our study provides evidence that men with greater genetic susceptibility to prostate cancer may be at higher risk if they are also exposed to pesticides and suggests potential mechanisms by which pesticides may increase prostate cancer risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer., Methods: Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium., Results: In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I., Conclusions: These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease., (© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Importance: Frequent aspirin use is associated with reduced ovarian cancer risk, but it is unknown whether genetic factors modify this association. Understanding effect modifiers is important given that any use of aspirin for ovarian cancer chemoprevention will likely need to focus on specific higher-risk subgroups., Objective: To evaluate whether the association between frequent aspirin use and ovarian cancer is modified by a polygenic score (PGS) for nonmucinous ovarian cancer., Design, Setting, and Participants: We pooled individual-level data from 8 population-based case-control studies from the Ovarian Cancer Association Consortium conducted in the US, UK, and Australia between 1995 and 2009. We included case patients and control participants with both genetic data and data on frequent aspirin use. Case patients with mucinous ovarian cancer were excluded. Data were analyzed between November 1, 2021, and July 31, 2022., Exposures: Frequent aspirin use, defined as daily or almost daily use for 6 months or longer., Main Outcomes and Measures: The main outcome was nonmucinous epithelial ovarian cancer. We used logistic regression to estimate odds ratios (ORs) and 95% CIs and likelihood ratio tests to investigate effect modification by the PGS., Results: There were 4476 case patients with nonmucinous ovarian cancer and 6659 control participants included in this analysis. At study enrollment, the median (IQR) age was 58 (50-66) years for case patients and 57 (49-65) years for control participants. Case patients and control participants self-reported that they were Black (122 [3%] vs 218 [3%]), White (3995 [89%] vs 5851 [88%]), or of other race and ethnicity (348 [8%] vs 580 [9%]; race and ethnicity were unknown for 11 [0%] vs 10 [0%]). There were 575 case patients (13%) and 1030 control participants (15%) who reported frequent aspirin use. The 13% reduction in ovarian cancer risk associated with frequent aspirin use (OR, 0.87 [95% CI, 0.76-0.99]) was not modified by the PGS. Consistent ORs were observed among individuals with a PGS less than (0.85 [0.70-1.02]) and greater than (0.86 [0.74-1.01]) the median. Results were similar by histotype., Conclusions and Relevance: The findings of this study suggest that genetic susceptibility to ovarian cancer based on currently identified common genetic variants does not appear to modify the protective association between frequent aspirin use and ovarian cancer risk. Future work should continue to explore the role of aspirin use for ovarian cancer prevention among individuals who are at higher risk for ovarian cancer.

Background: The Prostate Cancer Cohort Consortium (PC3) Working Group proposed a definition for aggressive prostate cancer (PC) for aetiologic epidemiologic research. We aimed to validate this definition as well as a second approach utilising only information on stage at diagnosis., Methods: First primary PCs diagnosed 2004 - 2009 in the population-based Janus Serum Bank (JSB) cohort were identified by linkage to the population-based Cancer Registry of Norway (CRN) ( n  = 3568). The CRN and Norwegian Prostate Cancer Registry provided clinicopathological data for these cases. Approach 1 classified PC as aggressive if it was clinically T4, or N1, or M1, or had a Gleason score ≥8 at diagnosis (as proposed). Approach 2 classified PC as aggressive if CRN stage at diagnosis was 'regional spread' or 'distant metastases'. Both approaches were validated by calculating the sensitivity and positive predictive value (PPV) against PC-death within 10 years of diagnosis., Results: Overall, 555 died from PC within 10 years. Approach 1 classified 24.7% of cases as aggressive and 13.6% were unclassified due to missing information. Approach 2 classified 19.6% as aggressive and 29% were unclassified. Sensitivity was highest for Approach 1 (0.76, 95% CI: 0.72 - 0.80 vs 0.69, 95% CI: 0.64 - 0.73), while PPVs were similar for both approaches (0.43, 95% CI: 0.40 - 0.46 and 0.40, 95% CI: 0.36 - 0.44). We observed similarly high sensitivity and higher PPVs than those reported by the PC3 Working Group., Conclusions: The proposed definition of aggressive PC was applicable and valid in the JSB cohort. Stage at diagnosis can be useful if data on cTNM or Gleason score is unavailable.

Purpose: Frequent aspirin use has been associated with reduced ovarian cancer risk, but no study has comprehensively assessed for effect modification. We leveraged harmonized, individual-level data from 17 studies to examine the association between frequent aspirin use and ovarian cancer risk, overall and across subgroups of women with other ovarian cancer risk factors., Methods: Nine cohort studies from the Ovarian Cancer Cohort Consortium (n = 2,600 cases) and eight case-control studies from the Ovarian Cancer Association Consortium (n = 5,726 cases) were included. We used Cox regression and logistic regression to assess study-specific associations between frequent aspirin use (≥ 6 days/week) and ovarian cancer risk and combined study-specific estimates using random-effects meta-analysis. We conducted analyses within subgroups defined by individual ovarian cancer risk factors (endometriosis, obesity, family history of breast/ovarian cancer, nulliparity, oral contraceptive use, and tubal ligation) and by number of risk factors (0, 1, and ≥ 2)., Results: Overall, frequent aspirin use was associated with a 13% reduction in ovarian cancer risk (95% CI, 6 to 20), with no significant heterogeneity by study design ( P = .48) or histotype ( P = .60). Although no association was observed among women with endometriosis, consistent risk reductions were observed among all other subgroups defined by ovarian cancer risk factors (relative risks ranging from 0.79 to 0.93, all P -heterogeneity > .05), including women with ≥ 2 risk factors (relative risk, 0.81; 95% CI, 0.73 to 0.90)., Conclusion: This study, the largest to-date on aspirin use and ovarian cancer, provides evidence that frequent aspirin use is associated with lower ovarian cancer risk regardless of the presence of most other ovarian cancer risk factors. Risk reductions were also observed among women with multiple risk factors, providing proof of principle that chemoprevention programs with frequent aspirin use could target higher-risk subgroups.

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; P het  = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Though studies have observed inverse associations between use of analgesics (aspirin, NSAIDs, and acetaminophen) and the risk of several cancers, the potential biological mechanisms underlying these associations are unclear. We investigated the relationship between analgesic use and serum concentrations of estrogens, androgens, and their metabolites among postmenopausal women to provide insights on whether analgesic use might influence endogenous hormone levels, which could in turn influence hormone-related cancer risk. The study included 1,860 postmenopausal women from two case-control studies nested within the Women's Health Initiative Observational Study. Analgesic use was reported at study baseline. Fifteen estrogens and estrogen metabolites and 12 androgens and androgen metabolites were quantified in baseline serum by LC/MS-MS. Linear regression with inverse probability weighting, stratified by menopausal hormone therapy (MHT) use, was used to estimate adjusted geometric mean concentrations of each hormone by analgesic use. Among women not currently using MHT (n = 951), low-dose aspirin (<100 mg) use was associated with a higher serum concentration of estrone, estradiol, and 2, 4, and 16 hydroxylated metabolites. Use of regular-dose aspirin (≥100 mg), non-aspirin NSAIDs, and acetaminophen was not associated with serum concentrations of estrogens, androgens, or their metabolites. This study highlights the importance of examining aspirin use by dose and suggests that low-dose aspirin may influence endogenous estrogen concentrations., Prevention Relevance: This study explores a potential pathway by which analgesic medications such as aspirin may prevent hormone-related cancers. The findings support a positive association between low-dose aspirin use and endogenous estrogens, indicating that further elucidation of the interplay between low-dose aspirin, estrogen concentrations, and cancer risk is needed., (©2021 American Association for Cancer Research.)

Background: In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on the outcome of aggressive prostate cancer, but studies have defined this outcome differently. We aimed to develop an evidence-based consensus definition of aggressive prostate cancer using clinical features at diagnosis for etiologic epidemiologic research., Methods: Among prostate cancer cases diagnosed in 2007 in the National Cancer Institute's Surveillance, Epidemiology, and End Results-18 database with follow-up through 2017, we compared the performance of categorizations of aggressive prostate cancer in discriminating fatal prostate cancer within 10 years of diagnosis, placing the most emphasis on sensitivity and positive predictive value (PPV)., Results: In our case population (n = 55 900), 3073 men died of prostate cancer within 10 years. Among 12 definitions that included TNM staging and Gleason score, sensitivities ranged from 0.64 to 0.89 and PPVs ranged from 0.09 to 0.23. We propose defining aggressive prostate cancer as diagnosis of category T4 or N1 or M1 or Gleason score of 8 or greater prostate cancer, because this definition had one of the higher PPVs (0.23, 95% confidence interval = 0.22 to 0.24) and reasonable sensitivity (0.66, 95% confidence interval = 0.64 to 0.67) for prostate cancer death within 10 years. Results were similar across sensitivity analyses., Conclusions: We recommend that etiologic epidemiologic studies of prostate cancer report results for this definition of aggressive prostate cancer. We also recommend that studies separately report results for advanced category (T4 or N1 or M1), high-grade (Gleason score ≥8), and fatal prostate cancer. Use of this comprehensive set of endpoints will facilitate comparison of results from different studies and help elucidate prostate cancer etiology., (Published by Oxford University Press 2020.)

Background: The association of aspirin use with prostate cancer has been investigated, but few studies included African-American men. Here, we analyzed the relationship of aspirin intake with prostate cancer risk and mortality among African-American men in the Southern Community Cohort Study (SCCS)., Methods: SCCS recruited 22,426 African-American men between 2002 and 2009. Aspirin use was assessed at enrollment. Our exposures of interest were any aspirin use (regular strength, low-dose or baby aspirin, or half tablets of aspirin) and regular strength aspirin. Each exposure variable was compared with nonusers. Associations between aspirin use and prostate cancer risk and mortality were examined with Cox proportional hazards models., Results: At enrollment, 5,486 men (25.1%) reported taking any aspirin and 2,634 men (12.1%) reported regular strength aspirin use. During follow-up (median, 13 years), 1,058 men developed prostate cancer, including 103 prostate cancer-specific deaths. Aspirin use was not associated with prostate cancer development [adjusted HR, 1.07; 95% confidence interval (CI), 0.92-1.25 for any aspirin use and HR, 0.97; 95% CI, 0.78-1.19 for regular strength aspirin], but was suggestively associated with reduced prostate cancer mortality (HR, 0.66; 95% CI, 0.39-1.14 for any aspirin use and HR, 0.41; 95% CI, 0.17-1.00 for regular strength aspirin)., Conclusions: Aspirin use at enrollment was tentatively associated with reduced prostate cancer mortality, but not risk, among African-American men in SCCS., Impact: Prospective SCCS data suggest that aspirin use may help prevent lethal prostate cancer among this high-risk group of men., (©2020 American Association for Cancer Research.)

Purpose: Daily aspirin use has been shown to reduce risk of colorectal, and possibly other, cancers, but it is unknown if these benefits are consistent across subgroups of people with differing cancer risk factors. We investigated whether age, body mass index (BMI), smoking status, physical inactivity, and family history of cancer modify the effect of daily aspirin use on colorectal, ovarian, breast, endometrial and aggressive prostate cancer risk., Methods: We pooled 423,495 individuals from two prospective, U.S.-based studies: the NIH-AARP Diet and Health Study (1995-2011) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2009). Using Cox proportional hazards regression, we examined associations between daily aspirin use (≥ 5 days/week) and risk of colorectal, ovarian, breast, endometrial, and aggressive prostate cancer, overall and across strata of risk factors., Results: Daily aspirin use was associated with a 15% reduction in colorectal cancer risk (hazard ratio [HR]: 0.85, 95% confidence interval [CI] 0.80-0.89). Risk reductions were generally consistent across strata of risk factors but attenuated with increasing BMI (p-interaction = 0.16). For ovarian cancer, there was no significant association overall (HR: 0.93, 95% CI 0.80-1.08) but reduced risk among obese women (HR: 0.73, 95% CI 0.52-0.98, p-interaction = 0.12). Weak or null associations were observed for breast, endometrial, and aggressive prostate cancer, with no strong effect modification observed., Conclusions: Daily aspirin use appears to reduce colorectal cancer risk regardless of other risk factors, though the potential modifying effect of BMI warrants further investigation and may need to be considered in risk-benefit calculations for aspirin use.

Background: In the USA, it is unknown whether metastatic prostate cancer incidence has continued to increase and whether racial differences have persisted., Objective: Combining multiple imputation with age and delay adjustment, we provide an up-to-date, comprehensive assessment of US prostate cancer incidence trends by stage and race., Design, Setting, and Participants: From Surveillance Epidemiology and End Results (SEER)-18, 774 240 prostate cancer cases were diagnosed during 2004-2017., Outcome Measurements and Statistical Analysis: Multiple imputation assigned prostate cancer stage to the 4.7% of cases with missing stage, which varied by year and race-ethnicity. SEER delay factors adjusted case counts to anticipated future data corrections. Twenty datasets were imputed, and Rubin's rules were used for summary estimation. Overall and stage-specific rates were estimated and stratified by race and age group. Joinpoint software identified significant temporal changes and estimated annual percentage changes. We compared these estimates without multiple imputation and delay adjustment., Results and Limitations: Metastatic prostate cancer incidence increased during 2011-2017, with an annual percentage change of 5.5. This was followed by increases in localized and regional disease since 2014. Non-Hispanic black men continued to have the highest incidence, especially for metastatic disease. The increasing rate of metastatic prostate cancer in non-Hispanic white men aged 50-74 yr accelerated recently, and the incidence was 56% higher in 2017 than in 2004. Rates without multiple imputation and delay adjustment were quantitatively and qualitatively different. This observational study is unable to assign causes to observed changes in prostate cancer incidence., Conclusions: Multiple imputation and delay adjustment are essential for portraying accurately stage- and race-specific prostate cancer incidence as clinical practice evolves., Patient Summary: In the USA, diagnosis of prostate cancer that has spread to distant sites (metastatic disease) continues to increase. Black men continue to have higher risks of being diagnosed with metastatic prostate cancer than other race-ethnicities., (Published by Elsevier B.V.)

Obesity has been associated with an increased risk of advanced prostate cancer. However, most studies have been conducted among North American and European populations. Prostate cancer mortality appears elevated in West Africa, yet risk factors for prostate cancer in this region are unknown. We thus examined the relationship between obesity and prostate cancer using a case-control study conducted in Accra, Ghana in 2004 to 2012. Cases and controls were drawn from a population-based sample of 1037 men screened for prostate cancer, yielding 73 cases and 964 controls. An additional 493 incident cases were recruited from the Korle-Bu Teaching Hospital. Anthropometric measurements were taken at enrollment. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR) and prostate cancer, adjusting for potential confounders. The mean BMI was 25.1 kg/m 2 for cases and 24.3 kg/m 2 for controls. After adjustment, men with BMI ≥ 30 kg/m 2 had an increased risk of prostate cancer relative to men with BMI < 25 kg/m 2 (OR 1.86, 95% CI 1.11-3.13). Elevated WC (OR 1.76, 95% CI 1.24-2.51) and WHR (OR 1.46, 95% CI 0.99-2.16) were also associated with prostate cancer. Associations were not modified by smoking status and were evident for low- and high-grade disease. These findings indicate that overall and abdominal obesity are positively associated with prostate cancer among men in Ghana, implicating obesity as a potentially modifiable risk factor for prostate cancer in this region., (© 2020 UICC.)

Objective: Frequent use of aspirin has been associated with reduced ovarian cancer risk in observational studies, but it is unclear if only daily, low-dose aspirin confers a protective benefit. We examined associations between patterns of aspirin use and ovarian cancer risk among postmenopausal women in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial., Methods: Participants were enrolled in PLCO between 1993 and 2001 and followed for cancer outcomes through 2014. Detailed data on aspirin use (e.g., dose, frequency and duration) were ascertained via the supplemental questionnaire (SQX) administered in 2006-2007. We used Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between aspirin use (defined as use ≥once/week) and incident ovarian cancer. We conducted analyses among all women in the study sample and stratified by age at the time of the SQX., Results: There were 41,633 women included in this analysis, of whom 223 developed incident ovarian cancer. Overall, aspirin use was not significantly associated with ovarian cancer risk (HR: 0.93, 95% CI: 0.72-1.21). Among women <70 years, there was suggestion of an inverse association for daily use of aspirin (HR: 0.65, 95% CI: 0.40-1.05), low-dose aspirin (HR: 0.79, 95% CI: 0.51-1.24) and daily use of low-dose aspirin (HR: 0.64, 95% CI: 0.38-1.09)., Conclusions: These findings suggest a potential modest effect of daily, low-dose aspirin in reducing ovarian cancer risk. However, effect estimates were imprecise given the small number of events, and further research will be needed to confirm and extend these findings., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to report., (Published by Elsevier Inc.)

Introduction: Combined radiotherapy and hormonal treatment are recommended for intermediate- and high-risk prostate cancer (CaP). This study compared the long-term effects on health-related quality of life (HRQoL) of intermediate- and high-risk CaP patients managed with radiation therapy (RT) with vs. without hormone therapy (HT)., Methods: Patients with intermediate- and high-risk CaP enrolled in the Center for Prostate Disease Research diagnosed from 2007 to 2017 were included. EPIC and SF-36 questionnaires were completed and HRQoL scores were compared for patients receiving RT vs. RT + HT at baseline (pretreatment), 6, 12, 24, 36, 48, and 60 months after CaP diagnosis. Longitudinal patterns of change in HRQoL were modeled using linear regression models, adjusting for baseline HRQoL, age at CaP diagnosis, race, comorbidities, National Comprehensive Cancer Network (NCCN) risk stratum, time to treatment, and follow-up time., Results: Of 164 patients, 93 (56.7%) received RT alone and 71 (43.3%) received RT + HT. Both groups reported comparable baseline HRQoL. Patients receiving RT+HT were more likely to be NCCN high risk as compared to those receiving only RT. The RT + HT patients experienced worse sexual function, hormonal function, and hormonal bother than those who only received RT; however, HRQoL recovered over time for the RT + HT group. No significant differences were observed between groups in urinary and bowel domains or SF-36 mental and physical scores., Conclusion: Combined RT + HT treatment was associated with temporary lower scores in sexual and hormonal HRQoL compared with RT only. Intermediate- and high-risk CaP patients should be counseled about the possible declines in HRQoL associated with HT., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aspirin and statin use may lower the risk of advanced/fatal prostate cancer, possibly by reducing intraprostatic inflammation. To test this hypothesis, we investigated the association of aspirin and statin use with the presence and extent of intraprostatic inflammation, and the abundance of specific immune cell types, in benign prostate tissue from a subset of men from the placebo arm of the Prostate Cancer Prevention Trial. Men were classified as aspirin or statin users if they reported use at baseline or during the 7-year trial. Presence and extent of inflammation were assessed, and markers of specific immune cell types (CD4, CD8, FoxP3, CD68, and c-KIT) were scored, in slides from end-of-study prostate biopsies taken irrespective of clinical indication, per trial protocol. Logistic regression was used to estimate associations between medication use and inflammation measures, adjusted for potential confounders. Of 357 men included, 61% reported aspirin use and 32% reported statin use. Prevalence and extent of inflammation were not associated with medication use. However, aspirin users were more likely to have low FoxP3, a T regulatory cell marker [OR, 5.60; 95% confidence interval (CI), 1.16-27.07], and statin users were more likely to have low CD68, a macrophage marker (OR, 1.63; 95% CI, 0.81-3.27). If confirmed, these results suggest that these medications may alter the immune milieu of the prostate, which could potentially mediate effects of these medications on advanced/fatal prostate cancer risk., (©2020 American Association for Cancer Research.)

Purpose: Assess image quality of dual-energy (DE) and single-energy (SE) cardiac multi-detector computed tomographic (MDCT) post aortic valve replacement (AVR) on a dual source MDCT scanner., Methods: Eighty patients with cardiac MDCT acquisitions (ECG gated, dual-source) post-surgical and transcatheter AVR were retrospectively identified. Forty DE (cohort 1) and 40 SE acquisitions (cohort 2; 100 or 120 kVp) were reviewed. Metal artefact at valve coaptation (VC) and valve insertion site (VIS), and contrast enhancement were assessed. Valve leaflet edge definition was graded on a 4-point scale by three radiologists., Results: The mean percentage valve area obscured by metal artifact differed between the cohorts; cohort 1 DE blended, high keV and low keV: 14.8 %, 11.1 % and 17.8 % at VC and 16.4 %, 13 %, 20.4 % at VIS respectively. Cohort 2: 25.8 % and 33.6 % (VC and VIS); each DE reconstruction vs SE: P < 0.0001. Average contrast opacification and coefficient of variance for cohort 1: 562.9 ± 144.7, 281.1 ± 60.3 and 1132.7 ± 300.8 Hounsfield Units (HU) and 9.6 %, 10 % and 8.9 %. For cohort 2: 437.2 ± 119.2 HU and 10.8 % (P < 0.01). Average leaflet edge definition cohort 1: 2.3 ± 0.4, 2.7 ± 0.2 and 2.3 ± 0.2, and cohort 2: 2.9 ± 0.2., Conclusion: DE high keV renderings can result in up to 17.2 % less metal artefact compared to standard SE acquisition for cardiac CT. Contrast opacification and homogeneity is higher for DE blended and low keV renderings compared to SE acquisition with leaflet visibility preferred for low keV and blended DE renderings., Competing Interests: Declaration of Competing Interest No conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

OBJECTIVE. The purpose of this study was to quantify temporal variability in vascular and parenchymal enhancement within the same patient and to determine technique-related factors contributing to this variability. MATERIALS AND METHODS. We identified 100 patients who underwent four CT scans within 12 months with identical acquisition and contrast injection parameters. Enhancement was recorded in the abdominal aorta, main portal vein, liver parenchyma, and subcutaneous fat. Patient demographic and body habitus data were recorded. Injection-related factors were recorded including delay time from contrast injection to image acquisition. All pairwise differences in enhancement within each patient were evaluated for absolute and percentage change. RESULTS. Based on predetermined thresholds, we observed clinically relevant variability in 34% of patients for the abdominal aorta, 38% for the portal vein, and 33% for the liver parenchyma. A highly significant association was observed between higher variability in delay time and variability in the abdominal aorta ( p = 0.009) and between female sex and variability in liver parenchyma ( p = 0.008). A marginally significant association was seen between increasing age ( p = 0.025) and female sex ( p = 0.039) with variability in the abdominal aorta. No statistically significant association was found between all recorded variables and variability in the portal vein. CONCLUSION. Approximately one-third of patients may show clinically relevant variability in enhancement of the abdominal aorta, portal vein, and liver parenchyma even when using identical scanning and injection parameters. Delay time was the only controllable factor associated with variability in enhancement of the abdominal aorta; no other controllable factor is associated with variability in the portal vein or liver parenchyma.

Introduction: To assess the impact of primary and secondary therapies for high- and intermediate-risk prostate cancer on health-related quality of life (HRQoL)., Materials and Methods: A prospective study was initiated in 2007 at Center for Prostate Disease Research Multicenter National Database sites. Longitudinal patterns in HRQoL from baseline (pre-treatment) to 5 years post-diagnosis were examined for patients with high- and intermediate-risk prostate cancer, treated by radical prostatectomy (RP) or external beam radiation therapy (EBRT). Change in HRQoL was modeled using linear regression models fit with generalized estimating equations. The probability of maintaining HRQoL was compared between patients receiving RP only versus RP with secondary treatment., Results: Of 445 men with high- and intermediate-risk prostate cancer, 228 underwent RP and 143 had EBRT± androgen deprivation therapy (ADT). Fifty received secondary therapy (EBRT and/or ADT or chemotherapy) after RP. RP patients showed a greater decline over time in sexual function and bother and urinary function compared to EBRT±ADT patients. Patients who had secondary therapy after RP were less likely to maintain their HRQoL compared to those who had RP alone. These differences were most pronounced for sexual and hormonal function., Conclusions: Prostate cancer patients experience significant declines in HRQoL after primary therapy. Additional secondary therapy after RP, in the form of EBRT and/or ADT, appears to be responsible for further deterioration in HRQoL outcomes.

Purpose: The aim of this study was to identify the effects of subsequent prostate needle biopsies after the baseline biopsy on health related quality of life with time. We compared men with and without prostate cancer, and men who did and did not undergo followup prostate needle biopsy., Materials and Methods: Included in analysis were patients enrolled in the Center for Prostate Disease Research Multicenter National Database between 2007 and 2015 who had low or favorable intermediate risk prostate cancer, were on active surveillance and underwent prostate needle biopsy for suspicion of prostate cancer. Patients completed the EPIC (Expanded Prostate Cancer Index Composite) and the RAND SF-36 (36-Item Short Form Health Survey) after baseline biopsy and at regular followup intervals. Mean health related quality of life was compared with time between patients who did and did not undergo subsequent prostate needle biopsies following baseline., Results: Of the 637 patients included in study 129 (20.3%) with prostate cancer were on active surveillance and 508 (79.7%) were in the noncancer group. In the cancer and noncancer groups mean ± SD followup was 34.7 ± 16.9 and 31.6 ± 14.6 months, respectively. Of the patients with prostate cancer 54 (60.7%) underwent subsequent prostate needle biopsies compared with 114 (27.1%) without cancer. No significant impact on health related quality of life was observed in men who underwent subsequent prostate needle biopsies during a 5-year period., Conclusions: A subsequent prostate needle biopsy is required in most active surveillance protocols and in men with persistent suspicion of prostate cancer. Our analysis shows that subsequent prostate needle biopsies do not significantly impact health related quality of life.

Background: NSAIDs appear to moderately reduce prostate cancer risk. However, evidence is limited on whether NSAIDs protect against prostate cancer mortality (death from prostate cancer among men without a cancer history) and case fatality (death from prostate cancer among men with prostate cancer), and whether benefits are consistent in white and black men. This study investigated associations of aspirin and non-aspirin (NA) NSAID use with prostate cancer incidence, mortality, and case fatality in a population-based cohort of white and black men., Methods: We included 6,594 men (5,060 white and 1,534 black) from the Atherosclerosis Risk in Communities study without a cancer history at enrollment from 1987 to 1989. NSAID use was assessed at four study visits (1987-1998). Cancer outcomes were ascertained through 2012. Cox proportional hazards regression was used to estimate adjusted HRs, overall and by race., Results: Aspirin use was not associated with prostate cancer incidence. However, aspirin use was inversely associated with prostate cancer mortality [HR, 0.59; 95% confidence interval (CI), 0.36-0.96]. This association was consistent among white and black men and appeared restricted to men using aspirin daily and/or for cardiovascular disease prevention. Aspirin use was inversely associated with case fatality (HR, 0.45; 95% CI, 0.22-0.94). NA-NSAID use was not associated with these endpoints., Conclusions: Aspirin use was inversely associated with prostate cancer mortality and case fatality among white and black men., Impact: If confirmed by additional studies, benefits of aspirin for preventing prostate cancer mortality may need to be factored into risk-benefit calculations of men considering an aspirin regimen., (©2018 American Association for Cancer Research.)

Chronic chest pain (CCP) of a cardiac etiology is a common clinical problem. The diagnosis and classification of the case of chest pain has rapidly evolved providing the clinician with multiple cardiac imaging strategies. Though scintigraphy and rest echocardiography remain as appropriate imaging tools in the diagnostic evaluation, new technology is available. Current evidence supports the use of alternative imaging tests such as coronary computed tomography angiography (CCTA), cardiac MRI (CMRI), or Rb-82 PET/CT. Since multiple imaging modalities are available to the clinician, the most appropriate noninvasive imaging strategy will be based upon the patient's clinical presentation and clinical status. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

While there is no single diagnostic test for heart failure (HF), imaging plays a supportive role beginning with confirmation of HF, especially by detecting ventricular dysfunction (Variant 1). Ejection fraction (EF) is important in HF classification, and imaging plays a subsequent role in differentiation between HF with reduced EF (HFrEF) versus preserved EF (HFpEF) (Variant 2). Once HFrEF is identified, distinction between ischemic and nonischemic etiologies with imaging support (Variant 3) facilitates further planning. Imaging approaches which are usually appropriate include: both resting transthoracic echocardiography (TTE) and chest radiography for Variant 1; resting TTE and/or MRI (including functional, without absolute need for contrast) for Variant 2; and for Variant 3, a. Coronary CTA or coronary arteriography (if high pretest probability/symptoms for ischemic disease) for coronary assessment; b. Rest/vasodilator stress SPECT/CT, PET/CT, or MRI for myocardial perfusion assessment; c. Rest/exercise or inotropic stress TTE for myocardial contraction assessment; or d. MRI (including morphologic with contrast) for myocardial characterization. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2018 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to assess the noninferiority of dual-source high-pitch CT angiography (CTA) performed with high-concentration (iopamidol 370) low-volume (60 mL) iodinated contrast material at low voltage (100 kVp) in comparison with dual-source high-pitch CTA with standard-of-care low-concentration (iopamidol 300) standard-volume (75 mL) iodinated contrast material at high voltage (120 kVp) to determine whether use of the high-concentration low-volume method would afford a reduction in radiation dose and contrast volume without negatively affecting vascular opacification., Subjects and Methods: This study had three arms. A phantom was used to assess vascular contrast enhancement at different iodine and saline solution dilutions with iopamidol 300 or 370 to compare lower-iodination (iopamidol 300) high-voltage (120 kVp) high-pitch (120 kVp, 250 mAs) imaging with higher-iodination (iopamidol 370) low-voltage (100 kVp) high-pitch (100 kVp, 100-240 mAs) acquisition. Metal-oxide-semiconductor field-effect transistors were placed in an anthropomorphic phantom to extract organ-based radiation profiles, and ANOVA was performed. The study prospectively enrolled 150 patients: 50 patients received 75 mL iopamidol 300, and image acquisition was performed at 120 kVp and 250 mAs; 50 patients received 75 mL iopamidol 370, and acquisition was performed at 100 kVp and 240 mAs; and 50 patients received 60 mL iopamidol, and acquisition was performed at 370 at 100 kVp and 240 mAs. Vascular signal-to-noise ratio was evaluated at 18 anatomic locations. Longitudinal signal-to-noise ratio was used to assess homogeneity of contrast enhancement. Size-specific dose estimates were calculated. Statistical analyses were performed by ANOVA., Results: Noninferiority of high-concentration (iopamidol 370) low-voltage (100 kVp) high-pitch acquisitions compared with low-concentration (iopamidol 300) high-voltage (120 kVp) high-pitch acquisition was achieved at 170 mAs in vitro. Radiation assessment showed significant decreases in radiation dose for the 100-kVp 240-mAs protocol (p < 0.0001). Noninferior vascular contrast (p > 0.280) and luminal homogeneity (p > 0.191) were found for all high-pitch protocols. Significantly decreased radiation dose was observed for the two groups that received 60 and 75 mL of iopamidol 370 at 100 kVp and 240 mAs (p < 0.0001)., Conclusion: Dual-source high-pitch CTA with high-concentration (iopamidol 370) low-volume (60 mL) iodinated contrast medium and low-voltage acquisition (100 kVp) is noninferior to dual-source high-pitch CTA with low-concentration (iopamidol 300) standard-volume (75 mL) iodinated contrast material at high voltage (120 kVp) and affords simultaneous reduction in radiation dose and contrast volume without negatively affecting vascular contrast enhancement.

Aortic stenosis is a common valvular condition with increasing prevalence in aging populations. When severe and symptomatic, the downstream prognosis is poor without surgical or transcatheter aortic valve replacement. Transcatheter aortic valve replacement is now considered a viable alternative to surgical aortic valve replacement in patients considered high and intermediate risk for surgery. Pre-intervention imaging with echocardiography and CT are essential for procedure planning and device selection to help optimize clinical outcomes with MR angiography playing largely a complementary role. Modern 3-D cross-sectional imaging has consistently shown to help reduce procedural complications from vascular access injury to paravalvular regurgitation and coronary obstruction. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Prostate cancer patients diagnosed with low- and intermediate-risk disease have several treatment options. Decisional regret after treatment is a concern, especially when poor oncologic outcomes or declines in health-related quality of life (HRQoL) occur. This study assessed determinants of longitudinal decisional regret in prostate cancer patients attending a multidisciplinary clinic and treated with radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy (BT), or active surveillance (AS)., Methods: Patients newly diagnosed with prostate cancer at the Walter Reed National Military Medical Center who attended a multidisciplinary clinic were enrolled into a prospective study from 2006 to 2014. The Decision Regret Scale was administered at 6, 12, 24, and 36 months posttreatment. HRQoL was also assessed at regular intervals using the Expanded Prostate Cancer Index Composite and 36-item RAND Medical Outcomes Study Short Form questionnaires. Adjusted probabilities of reporting regret were estimated via multivariable logistic regression fitted with generalized estimating equations., Results: A total of 652 patients met the inclusion criteria (395 RP, 141 EBRT, 41 BT, 75 AS). Decisional regret was consistently low after all of these treatments. In multivariable models, only African American race (odds ratio, 1.67; 95% confidence interval, 1.12-2.47) was associated with greater regret across time. Age and control preference were marginally associated with regret. Regret scores were similar between RP patients who did and did not experience biochemical recurrence. Declines in HRQoL were weakly correlated with greater decisional regret., Conclusion: In the context of a multidisciplinary clinic, decisional regret did not differ significantly between treatment groups but was greater in African Americans and those reporting poorer HRQoL. Cancer 2017;123:4252-4258. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Magnetic resonance imaging is increasingly being used to evaluate the lymphatic system. Advances in magnetic resonance (MR) software and hardware allow improved visualization of lymph nodes and lymphatic vessels. We describe how MR lymphangiography can be used to diagnose central lymphatic system anatomy and pathology, which can be used for diagnostic purposes or for pre-procedural planning.

While imaging of the central venous system has traditionally been performed with conventional venography, MR venography (MRV) has emerged as an important modality as techniques and validation studies have evolved over time. While magnetic resonance angiography has a very robust representation in the literature, the proportion representing MRV is relatively sparse. The purpose of this article is to review the indications, techniques, and dedicated studies validating MRV of the central veins of the thorax.

Purpose To develop, in a phantom environment, a method to obtain multidetector computed tomographic (CT) data sets at multiple radiation exposure levels within the same patient and to validate its use for potential dose reduction by using different image reconstruction algorithms for the detection of liver metastases. Materials and Methods The American College of Radiology CT accreditation phantom was scanned by using a dual-source multidetector CT platform. By adjusting the radiation output of each tube, data sets at six radiation exposure levels (100%, 75%, 50%, 37.5%, 25%, and 12.5%) were reconstructed from two consecutive dual-source single-energy (DSSE) acquisitions, as well as a conventional single-source acquisition. A prospective, HIPAA-compliant, institutional review board-approved study was performed by using the same DSSE strategy in 19 patients who underwent multidetector CT of the liver for metastatic colorectal cancer. All images were reconstructed by using conventional weighted filtered back projection (FBP) and sinogram-affirmed iterative reconstruction with strength level of 3 (SAFIRE-3). Objective image quality metrics were compared in the phantom experiment by using multiple linear regression analysis. Generalized linear mixed-effects models were used to analyze image quality metrics and diagnostic performance for lesion detection by readers. Results The phantom experiment showed comparable image quality between DSSE and conventional single-source acquisition. In the patient study, the mean size-specific dose estimates for the six radiation exposure levels were 13.0, 9.8, 5.8, 4.4, 3.2, and 1.4 mGy. For each radiation exposure level, readers' perception of image quality and lesion conspicuity was consistently ranked superior with SAFIRE-3 when compared with FBP (P ≤ .05 for all comparisons). Reduction of up to 62.5% in radiation exposure by using SAFIRE-3 yielded similar reader rankings of image quality and lesion conspicuity when compared with routine-dose FBP. Conclusion A method was developed and validated to synthesize multidetector CT data sets at multiple radiation exposure levels within the same patient. This technique may provide a foundation for future clinical trials aimed at estimating potential radiation dose reduction by using iterative reconstructions. © RSNA, 2016 Online supplemental material is available for this article.

Introduction: Patients with low-risk prostate cancer (PCa) often have excellent oncologic outcomes. However, treatment with curative intent can lead to decrements in health-related quality of life (HRQoL). Patients treated with radical prostatectomy have been shown to suffer declines in urinary and sexual HRQoL as compared to those managed with active surveillance (AS). Similarly, patients treated with external-beam radiation therapy (EBRT) are hypothesized to experience greater declines in bowel HRQoL. As health-related quality-of-life (HRQoL) concerns are paramount when selecting among treatment options for low-risk PCa, this study examined HRQoL outcomes in men undergoing EBRT as compared to AS in a prospective, racially diverse cohort., Methods: A prospective study of HRQoL in patients with PCa enrolled in the Center for Prostate Disease Research (CPDR) Multicenter National Database was initiated in 2007. The current study included patients diagnosed through April 2014. HRQoL was assessed with the Expanded Prostate Cancer Index Composite (EPIC) and the Medical Outcomes Study Short Form (SF-36). Temporal changes in HRQoL were compared for patients with low-risk PCa managed on AS vs. EBRT at baseline, 1-, 2-, and 3 years post-PCa diagnosis. Longitudinal patterns were modeled using linear regression models fitted with generalized estimating equations (GEE), adjusting for baseline HRQoL, demographic, and clinical patient characteristics., Results: Of the 499 eligible patients with low-risk PCa, 103 (21%) selected AS and 60 (12%) were treated with EBRT. Demographic characteristics of the treatment groups were similar, though a greater proportion of patients in the EBRT group were African American (P = 0.0003). At baseline, both treatment groups reported comparable HRQoL. EBRT patients experienced significantly worse bowel function and bother at 1 year (adjusted mean score: 87 vs. 95, P = 0.001 and 89 vs. 95, P = 0.008, respectively) and 2 years (87 vs. 93, P = 0.007 and 87 vs. 96, P = 0.002, respectively) compared to patients managed on AS. In contrast to those on AS, more than half the number of patients who received EBRT experienced a decline in bowel function (52% vs. 17%, p=0.003) and bother (52% vs. 15%, P = 0.002) from baseline to 1 year. Patients who received EBRT were significantly more likely to experience a decrease in more than one functional domain (urinary, sexual, bowel, or hormonal) at 1 year when compared with those on AS (60% vs. 28%, P = 0.004)., Conclusions: Patients receiving EBRT for low-risk prostate cancer suffer declines in bowel HRQoL. These declines are not experienced by patients on AS, suggesting that management of low-risk prostate cancer with AS may offer a means for preserving HRQoL following prostate cancer diagnosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This article discusses imaging guidelines for five dyspnea variants: (1) dyspnea due to heart failure, ischemia not excluded; (2) dyspnea due to suspected nonischemic heart failure, ischemia excluded; (3) dyspnea due to suspected valvular heart disease, ischemia excluded; (4) dyspnea due to suspected cardiac arrhythmia, ischemia excluded; and (5) dyspnea due to suspected pericardial disease, ischemia excluded. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment., (Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Objective: Five percent of cardiac implantable electric devices (CIEDs) are removed each year. Percutaneous extraction is preferred but can be complicated if the leads adhere to the vasculature or perforate. The goal of this study is to assess the frequency of findings on dedicated MDCT that alter preprocedural planning for percutaneous CIED extraction., Materials and Methods: One hundred patients with CIEDs who underwent MDCT before percutaneous lead extraction were analyzed. Major findings that could preclude percutaneous removal, including lead course and termination, were distinguished from moderately significant findings that could alter but not preclude percutaneous removal, including endofibrosis of leads to the vasculature, lead termination abnormalities, central vein stenosis, or thrombus. Incidental findings were characterized separately. Findings were correlated with preprocedural decisions, the extraction procedure performed, and procedural outcomes., Results: Twenty-six women and 74 men with 125 right ventricular leads, 84 right atrial leads, and 26 coronary venous leads were evaluated. Major findings were present in 7% of patients, including six patients with lead perforation and one with a lead coursing outside a tricuspid annuloplasty ring. Moderately significant findings of endothelial fibrosis were found in 78% of patients. The central veins were narrowed or occluded in 42% of patients, and thrombus was present in 2% of patients. Thirty-six percent of patients had incidental findings, and 4% of patients had unexpected findings requiring immediate inpatient attention., Conclusion: MDCT performed before CIED lead extraction is able to identify major and moderately significant findings that can alter either percutaneous extraction or preprocedural planning. The use of dedicated preprocedural MDCT can help to stratify patient risk, guide decision making by the proceduralist, and identify non-catheter-related findings that affect patient management.

Background: Current guidelines for imaging surveillance after proximal aortic repair are not evidence based. This study sought to characterize the incidence and causes of reintervention after proximal aortic operations to provide data to guide the frequency and duration of postoperative surveillance., Methods: Data on all patients undergoing proximal aortic operations (ascending, with or without root, with or without aortic valve replacement, or with or without arch) during a 9-year period (n = 869) at a single institution were prospectively collected. Patients who required reintervention on the proximal or distal aorta were identified and causes for reintervention determined. Planned two-stage repairs and index procedures done at other hospitals were excluded. The primary end point was the time to the first reintervention, and competing-risk Cox regression was used to model reintervention risk., Results: Reinterventions occurred in 4.3% of patients (n = 37), with 48.6% (n = 18) involving the proximal aorta and 51.4% (n = 19) the distal. Median time to reintervention was 2.8 years (interquartile range, 1.5 to 3.6 years). For index aneurysm cases, reintervention for aneurysm of the descending/thoracoabdominal aorta and root were most common. Of the 6 root aneurysms/pseudoaneurysms, 5 (83%) were due to degeneration of a stentless porcine aortic root. For index type A dissections, reintervention for aneurysm of the descending/thoracoabdominal aorta and arch were most common. The mean duration of follow up was 4.2 ± 2.5 years. The 9-year actuarial freedom from reintervention was 92.9%. Cox regression showed index type A dissection was a significant predictor of time to aortic reintervention (hazard ratio, 2.01; 95% confidence interval, 1.04 to 3.9; p = 0.038)., Conclusions: Reinterventions after proximal aortic operations are uncommon; most occur within 3 years of the index operation and involve the proximal and distal aorta nearly equally. Patients with type A dissection or stentless porcine roots require aggressive surveillance, whereas a more liberal approach is suitable for patients without such risk factors. This strategy may reduce the lifetime radiation burden and health care costs., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A 76-year-old woman presented with progressive heart failure and transfusion-dependent hemolytic anemia due to severe paravalvular aortic regurgitation 4 years after bioprosthetic aortic valve replacement. She was deemed not to be a candidate for redo cardiac surgery due to a porcelain aorta and multiple comorbid medical conditions. We describe the role of pre-procedure contrast-enhanced, ECG-gated computed tomographic angiography to characterize the anatomy of the paravalvular leak connection for appropriate occluder device selection leading to successful percutaneous closure and resolution of the paravalvular regurgitation and hemolytic anemia.

Arterial gas embolism (AGE) can be clinically devastating, and is most often associated with exposure to changes in ambient pressure, medical procedure or congenital malformation. Here we report a case of AGE in a 78-year-old male without these traditional risk factors. Rather, the patient's history included chronic obstructive pulmonary disease, necrotizing pneumonia, bullous disease and coughing. He was safely treated with hyperbaric oxygen (HBO₂) therapy for AGE, with initial clinical improvement, but ultimately died from his underlying condition. Pathophysiology is discussed. This case illustrates the possibility that AGE can occur due to rupture of lung tissue in the absence of traditional risk factors. HBO₂ therapy should be considered in the management of such patients., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

Purpose: Active surveillance is an important alternative to definitive therapy for men with low risk prostate cancer. However, the impact of active surveillance on health related quality of life compared to that in men without cancer remains unknown. In this study we evaluated health related quality of life outcomes in men on active surveillance compared to men followed after negative prostate needle biopsy., Materials and Methods: A prospective study was conducted on men who were enrolled into the Center for Prostate Disease Research Multicenter National Database and underwent prostate needle biopsy for suspicion of prostate cancer between 2007 and 2014. Health related quality of life was assessed at biopsy (baseline) and annually for up to 3 years using SF-36 and EPIC questionnaires. Health related quality of life scores were modeled using generalized estimating equations, adjusting for baseline health related quality of life, and demographic and clinical characteristics., Results: Of the 1,204 men who met the initial eligibility criteria 420 had a negative prostate needle biopsy (noncancer comparison group). Among the 411 men diagnosed with low risk prostate cancer 89 were on active surveillance. Longitudinal analysis revealed that for most health related quality of life subscales there were no significant differences between the groups in adjusted health related quality of life score trends over time., Conclusions: In this study most health related quality of life outcomes in patients with low risk prostate cancer on active surveillance did not differ significantly from those of men without prostate cancer. A comparison group of men with a similar risk of prostate cancer detection is critical to clarify the psychological and physical impact of active surveillance., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose To investigate the feasibility of deformable, motion-coherent modeling based on electrocardiography-gated multidetector computed tomographic (CT) angiography of the thoracic aorta and to evaluate whether quantifiable information on aortic wall stress as a function of patient-specific cardiovascular parameters can be gained. Materials and Methods For this institutional review board-approved, HIPAA-compliant study, thoracic electrocardiography-gated dual-source multidetector CT angiographic images were used from 250 prospectively enrolled patients (150 men, 100 women; mean age, 79 years). On reconstructed 50-phase CT angiographic images, aortic strain and deformation were determined at seven cardiac and aortic locations. One-way analysis of variance was used by assessing the magnitude for longitudinal and axial strain and axial deformation, as well as time-resolved peak and maxima count for longitudinal strain and axial deformation. Interdependencies between aortic strain and deformation with extracted hemodynamic parameters were evaluated. Results With increasing heart rates, there was a significant decrease in longitudinal strain (P = .009, R(2) = 0.95) and a decrease in the number of longitudinal strain peaks (P < .001, R(2) = 0.79); however, a significant increase in axial deformation (P < .001, R(2) = 0.31) and axial strain (P = .009, R(2) = 0.61) was observed. Increasing aortic blood velocity led to increased longitudinal strain (P = .018, R(2) = 0.42) and longitudinal strain peak counts (P = .011, R(2) = 0.48). Pronounced motion in the longitudinal direction limited motion in the axial plane (P < .019, R(2) = 0.29-0.31). Conclusion The results of this study render a clinical basis and provide proof of principle for the use of deformable, motion-coherent modeling to provide quantitative information on physiological motion of the aorta under various hemodynamic circumstances. (©) RSNA, 2016 Online supplemental material is available for this article.

Background: Patients diagnosed with prostate cancer (PCa) are presented with several treatment options of similar efficacy but varying side effects. Understanding how and why patients make their treatment decisions, as well as the effect of treatment choice on long-term outcomes, is critical to ensuring effective, patient-centered care. This study examined treatment decision-making in a racially diverse, equal-access, contemporary cohort of patients with PCa counseled on treatment options at a multidisciplinary clinic., Methods: A prospective cohort study was initiated at the Walter Reed National Military Medical Center (formerly Walter Reed Army Medical Center) in 2006. Newly diagnosed patients with PCa were enrolled before attending a multidisciplinary clinic. Patients completed surveys preclinic and postclinic to assess treatment preferences, reasons for treatment choice, and decisional regret., Results: As of January 2014, 925 patients with PCa enrolled in this study. Surgery (54%), external radiation (20%), and active surveillance (12%) were the most common primary treatments for patients with low- and intermediate-risk PCa, whereas patients with high-risk PCa chose surgery (34%) or external radiation with neoadjuvant hormones (57%). Treatment choice differed by age at diagnosis, race, comorbidity status, and calendar year in both univariable and multivariable analyses. Patients preferred to play an active role in the decision-making process and cited doctors at the clinic as the most helpful source of treatment-related information. Almost all patients reported satisfaction with their decision., Conclusions: This is one of the first prospective cohort studies to examine treatment decision-making in an equal-access, multidisciplinary clinic setting. Studies of this cohort would aid in understanding and improving the PCa decision-making process., (Published by Elsevier Inc.)

Objective: The objective of our study was to assess whether the degree and distribution of iliac artery calcifications as determined by a CT-based calcium scoring system correlates with outcomes after renal transplant., Materials and Methods: A retrospective review of renal transplant recipients who underwent CT of the pelvis within 2 years before surgery yielded 131 patients: 75 men and 56 women with a mean age of 52 years. Three radiologists assigned a separate semiquantitative score for calcification length, circumferential involvement, and morphology for the common iliac arteries and for the external iliac arteries. The operative and clinical notes were reviewed to determine which iliac arterial segment was used for anastomosis, the complexity of the operation, and whether delayed graft function (DGF) occurred. Renal allograft survival and patient survival were calculated using the Kaplan-Meier technique., Results: Excellent interobserver agreement was noted for each calcification score category. The common iliac arteries showed significantly higher average calcification scores than the external iliac arteries for all categories. Advanced age and diabetes mellitus were independently predictive of higher scores in each category, whereas hypertension, cigarette smoking, hyperlipidemia, and sex were not. Based on multivariate analysis, only the calcification morphology score of the arterial segment used for anastomosis was independently predictive of a higher rate of surgical complexity and of DGF. None of the scores was predictive of graft or patient survival. However, patients with CT evidence of iliac arterial calcification had a lower 1-year survival after transplant than those who did not (92% vs 98%, respectively; p = 0.05)., Conclusion: Only the calcification morphology score of the arterial segment used for anastomosis was significantly predictive of surgical complexity and of DGF. Routine pretransplant CT for calcification scoring in patients of advanced age or those with diabetes mellitus may enable selection of the optimal artery for anastomosis to optimize outcomes.

Multiple studies have evaluated the use of PDE5 inhibitors in penile rehabilitation following nerve-sparing prostatectomy. These studies have evaluated the use of various pharmacologic agents as well as various approaches to treatment (on-demand vs. rehabilitative). Most of these studies relied on self-reported outcomes to determine efficacy of the therapy which could allow response bias to affect their results. The aim of this study was to evaluate the effects of nightly sildenafil citrate therapy during penile rehabilitation, using nocturnal penile rigidity (RigiScan(™), Gotop Medical, Inc., St. Paul, MN, USA) in addition to the IIEF-EF. Patients with localized prostate cancer and normal erectile function prior to nsRP were randomized to take either nightly 50 mg sildenafil citrate or placebo starting the night following surgery. Both groups were allowed on-demand sildenafil citrate. Erectile function was evaluated at 2 weeks, 3, 6, 9 and 12 months post-operatively, with a final assessment made at 13 months, following a 1 month drug washout. At all time points, self-reported (IIEF-EF) and objective (RigiScan(™)) measures were obtained and evaluated. About 74 of 97 randomized patients completed the study. On completion, 40% of patients in each group had normal erectile function based on RigiScan(™) (p = 1.0). Additionally, no statistical differences were seen using the IIEF-EF domain (32.4% of placebo, 29% of treatment; p = 0.79). Multivariable analysis showed no significant differences in erectile function based on treatment intervention. Results did show that African-American men in this cohort were at higher risk for lower RigiScan(™) scores over time (OR: 0.48, p = 0.0399). This study demonstrates that nightly sildenafil citrate does not provide a therapeutic benefit for recovery of erectile function post-prostatectomy when compared to on-demand dosing using both self-reported as well as objective measures. Differences in objective recovery parameters based on patients' race/ethnicity warrant further investigation., (© 2015 American Society of Andrology and European Academy of Andrology.)

Objective: The purpose of this study was to investigate, both in a phantom experiment and a within-patient clinical study the relationships among radiation dose, image noise, pitch, and body size in MDCT angiography of the thoracoabdominal aorta, with the use of high-pitch dual-source and standard-pitch single-source acquisitions., Materials and Methods: A proprietary tapered phantom consisting of four ultrahigh-molecular-weight polyethylene cylinders was used to mimic the body size ranges (small, medium, large, and extra large) of patients in the United States. The phantom was imaged using both standard-pitch (0.8) and various high-pitch (range, 2.0-3.2 [in increments of 0.4]) settings. Standard-pitch and high-pitch acquisitions were also performed in 45 patients (27 men, 18 women; mean age, 67.6 years)., Results: At standard pitch, the volume CT dose index (CTDIvol) increased with phantom size, in a logistic sigmoid relationship. At high-pitch settings, the CTDIvol increased gradually in relation to phantom size, up to a threshold (denoted by tCTDI[pitch] ≈ 48.3-7.5 pitch), which linearly decreased (R(2) = 0.99) with pitch (maximum CTDIvol output at pitch [maxCTDI(pitch)] ≈ 18.9-3.9 pitch). A linear decrease in the size-specific dose estimate (SSDE) was observed beyond phantom size thresholds (tSSDE[pitch] ≈ 47.6-8.6 pitch) linearly decreasing (R(2) = 0.98) with pitch (maximum SSDE output at pitch [maxSSDE(pitch)] ≈ 15.5-1.3 pitch). Image noise was statistically significantly lower at standard pitch than at high-pitch settings (p = 0.01). In patients, statistically significant differences were noted between standard and high-pitch settings in the mean CTDIvol(10.8 ± 2.6 and 8.3 ± 0.7 mGy, respectively), SSDE (11.3 ± 2.1 and 8.8 ± 1.5 mGy, respectively), and noise (9.7 ± 2.2 and 14 ± 4.2, respectively) (p < .0001, for all comparisons)., Conclusion: Lower radiation dose levels achieved with the use of a high-pitch technique reflect limitations in tube output occurring for medium to large body sizes, with an associated exponential increase in noise. The standard- and high-pitch techniques yield similar radiation dose levels for small body sizes.