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Failure of conventional therapies is the root cause for the progression of cancer. Intrinsic revelation states that Cancer metastasis is due to subclonal diversification of normal cells into subsets of stem-like cells. These cells can be termed as stem cells of cancer or cells that initiate cancer. These diversified cells can differentially activate and escape from the resistant mechanisms causes tumor heterogeneity. Because of these metastatic fuelling which is malignant, it expresses its persistence towards treatment and provokes drugresistant recurrence. Annihilation of these subsets of stem-like cells in cancer tissues has now become a prime objective to develop and design novel classes of anti-cancer therapeutics to improve clinical efficacy. In this review, the properties and hallmarks of different cancer stem cells that are responsible for disease recurrence and metastases which are elusive targets for present oncotherapies were presented. [ABSTRACT FROM AUTHOR]

Purpose: To examine whether serum levels of potassium and sodium were associated with long-term cancer risk in initially healthy men. Patients and Methods: A cohort of 1994 initially healthy men with no use of medication, aged 40–59 years, was followed for cancer during 40 years of follow-up. Associations between fasting electrolyte levels and cancer risk were assessed with incidence rates and Cox proportional hazards models. Results: Potassium, but not sodium, was linearly associated with cancer risk. This association remained significant after adjustment of several potential confounding factors, and also after excluding the first 10 years of follow-up. The age-adjusted risk of all-site cancer increased with 16% for each SD increase in potassium level. Men with hyperkalemia showed an incidence rate that was 40% higher than for men with normal potassium levels. Conclusion: Fasting serum potassium level in healthy men was positively associated with long-term cancer risk. Potassium or potassium ion channels may have a role in cell proliferation or differentiation. These findings might imply future cancer strategies for targeting individuals with high serum potassium levels. [ABSTRACT FROM AUTHOR]

Objective: Existing research indicates that moderate-to-vigorous physical activity (PA) alleviates treatment side effects and is associated with survival in men with prostate cancer. We aimed to ascertain the state of research investigating barriers and facilitators to PA in men with prostate cancer and synthesise existing qualitative research on this topic.Methods: A systematic review of qualitative and quantitative studies was conducted. MEDLINE, Embase, PsycINFO, Web of Knowledge, CINAHL, PEDro, OATD, and WorldCat were searched to June 2019 for quantitative studies investigating causes or predictors of PA or qualitative studies describing patient-reported barriers/facilitators to PA, amongst men with prostate cancer of any stage. Thirty-two studies (n = 17 quantitative; n = 15 qualitative) were included from 3698 screened articles.Results: Heterogeneity and unsystematic reporting of quantitative study methods prohibited a quantitative data synthesis. Thematic synthesis of qualitative studies produced five analytical themes: individual needs by treatment pathway, self-determination and its relationship with prostate cancer-related events, co-ordination and support of the clinical care team, individual preferences in discrete aspects of PA engagement style, and the potential for a bidirectional facilitative relationship between structured group PA and spontaneous peer support. Both qualitative and quantitative studies indicated incontinence as a barrier.Conclusions: Unsystematic reporting of interventions hinders a robust quantitative understanding of behavioural intervention research in this subject area. Good co-ordination of multidisciplinary care personnel could facilitate PA, by enabling a more comprehensive approach to targeting social cognitive processes. Well-timed intervention and access to highly individualised PA support, including optional group PA classes, seem to also be important facilitators. [ABSTRACT FROM AUTHOR]

Background: The American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and North American Association of Central Cancer Registries provide annual updates on cancer occurrence and trends by cancer type, sex, race, ethnicity, and age in the United States. This year's report highlights the cancer burden among men and women age 20-49 years.Methods: Incidence data for the years 1999 to 2015 from the Centers for Disease Control and Prevention- and National Cancer Institute-funded population-based cancer registry programs compiled by the North American Association of Central Cancer Registries and death data for the years 1999 to 2016 from the National Vital Statistics System were used. Trends in age-standardized incidence and death rates, estimated by joinpoint, were expressed as average annual percent change.Results: Overall cancer incidence rates (per 100 000) for all ages during 2011-2015 were 494.3 among male patients and 420.5 among female patients; during the same time period, incidence rates decreased 2.1% (95% confidence interval [CI] = -2.6% to -1.6%) per year in men and were stable in females. Overall cancer death rates (per 100 000) for all ages during 2012-2016 were 193.1 among male patients and 137.7 among female patients. During 2012-2016, overall cancer death rates for all ages decreased 1.8% (95% CI = -1.8% to -1.8%) per year in male patients and 1.4% (95% CI = -1.4% to -1.4%) per year in females. Important changes in trends were stabilization of thyroid cancer incidence rates in women and rapid declines in death rates for melanoma of the skin (both sexes). Among adults age 20-49 years, overall cancer incidence rates were substantially lower among men (115.3 per 100 000) than among women (203.3 per 100 000); cancers with the highest incidence rates (per 100 000) among men were colon and rectum (13.1), testis (10.7), and melanoma of the skin (9.8), and among women were breast (73.2), thyroid (28.4), and melanoma of the skin (14.1). During 2011 to 2015, the incidence of all invasive cancers combined among adults age 20-49 years decreased -0.7% (95% CI = -1.0% to -0.4%) among men and increased among women (1.3%, 95% CI = 0.7% to 1.9%). The death rate for (per 100 000) adults age 20-49 years for all cancer sites combined during 2012 to 2016 was 22.8 among men and 27.1 among women; during the same time period, death rates decreased 2.3% (95% CI = -2.4% to -2.2%) per year among men and 1.7% (95% CI = -1.8% to -1.6%) per year among women.Conclusions: Among people of all ages and ages 20-49 years, favorable as well as unfavorable trends in site-specific cancer incidence were observed, whereas trends in death rates were generally favorable. Characterizing the cancer burden may inform research and cancer-control efforts. [ABSTRACT FROM AUTHOR]

Purpose: The previous epidemiological studies about the associations between obesity and bladder cancer risk have reported inconsistent results. Therefore, we analyzed whether the abdominal obesity effected on the risk of developing bladder cancer according to body mass index (BMI) using nationally representative data from the National Health Insurance System (NHIS). Patients and methods: Among people who underwent at least one health examination from 2009 to 2012 in Korea, 11,823,876 men without a previous diagnosis of bladder cancer were followed up until December 2015. Multiple Cox regression analysis was conducted to determine the hazard ratio (HR) and 95% confidence interval (CI) for the association between bladder cancer and BMI or waist circumference (WC). Results: Significant upward trends in the risk of bladder cancer were observed with increasing BMI or WC according to the multivariate-adjusted model. However, the association between BMI and bladder cancer is influenced by the presence of abdominal obesity. In the group with WC < 90 cm, there was no significant change in the HRs for bladder cancer development beyond the reference BMI. In contrast, the HRs for bladder cancer showed statistically significant increase as the BMI increased beyond the reference BMI in the group with WC ≥ 90 cm. Conclusion: This population-based study showed that increasing BMI and increasing WC were risk factors for developing bladder cancer in men, independent of confounding variables. However, there was a discrepancy in the trend of bladder cancer development according to BMI between the groups with abdominal obesity and without abdominal obesity. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most frequently diagnosed cancer among men. However, the major modifiable risk factors for PCa are poorly known and its specific mechanism of progression remains unclear. Here we reported that, in prostate cancer cells, the autophagy level was elevated under hypoxic condition, as well as the mRNA and protein level of ATG5, which is an important gene related to autophagy. Furthermore, we found HIF1α could directly bind to the promoter of ATG5 and promote the expression of ATG5 on transcriptional level by luciferase assay and ChIP assay. Intriguingly, overexpression of HIF1α by HIF1α-M could increase tumor size and the effect could be abolished by knockdown ATG5 by si-ATG5 in BALB/cA-nu/nu nude mice. Importantly, HIF1α could also promote the metastasis of PC-3 cells by upregulating the ATG5 and autophagy level and knockdown ATG5 and inhibition autophagy both could abolish the effect of overexpression of HIF1α on the migration of PC-3 cells. Taken together, our results, for the first time, proved that HIF1α could promote the proliferation and migration of PC-3 cells by direct upregulating ATG5 and autophagy level in PC-3 prostate cancer cells. Our findings not only provide new perspective for the relationship between hypoxia and autophagy, but also add new potential therapeutic regimens for the treatment of prostate cancers. [ABSTRACT FROM AUTHOR]

It remains unclear what the optimum management strategy is for young men with low‐risk prostate cancer. The authors address the increasing role, safety, and acceptance of active surveillance as a management option for these younger patients. [ABSTRACT FROM AUTHOR]

Background: National and international bodies acknowledge the benefit of exercise for people with cancer, yet limited accessibility to related programing remains. Given their involvement in managing the disease, cancer centers can play a central role in delivering exercise-oncology services. The authors developed and implemented a clinically integrated exercise-oncology program at a major cancer center and evaluated its effectiveness and participant experience.Methods: A hospital-based program with prescribed at-home exercise was developed and accepted referrals over a 42-month period (3.5 years). Implementation was conducted in 2 phases: a pilot phase for women with breast cancer and men with genitourinary cancer and a roll-out phase for all patients with cancer. Enrolled patients were assessed and received an exercise prescription as well as a program manual, resistance bands, and a stability ball from a kinesiologist. Program participation and effectiveness were evaluated up to 48 weeks after the baseline assessment using intention-to-treat analyses. Participants in the roll-out phase were asked to complete a program experience questionnaire at the completion of the 48-week follow-up.Results: In total, 112 participants enrolled in the pilot, and 150 enrolled in the roll-out phase. Program attrition to 48 weeks was 48% and 65% in the pilot and roll-out phases, respectively. In participants who consented to research evaluation of their performance, objective and patient-reported measures of functional capacity improved significantly from baseline in both phases. Participants were highly satisfied with the program.Conclusions: Despite significant drop-out to program endpoints, our cancer-exercise program demonstrated clinically relevant improvement in functional outcomes and was highly appreciated by participants. [ABSTRACT FROM AUTHOR]

Purpose: To examine the association of smoking history and multiple measures of smoking intensity and duration with risk of biochemical recurrence in men treated for prostate cancer.Methods: We conducted a prospective cohort study of 1641 men (773 ever-smokers) treated with radical prostatectomy or radiation between 2003 and 2010. The association between ever-smoking and risk of biochemical recurrence was examined using Cox Proportional Hazards models with adjustment for confounders. Among ever-smokers, we further assessed the association between multiple measures of smoking duration and intensity and risk of biochemical recurrence.Results: In the full cohort, we observed no association between ever-smoking and risk of biochemical recurrence. However, among ever-smokers, a smoking duration of greater than or equal to 10 years was significantly associated with biochemical recurrence (hazard ratio: 2.32, 95% confidence interval: 1.01, 5.33). Our results also suggested that greater than or equal to 10 pack-years of smoking may be associated with an increased risk of biochemical recurrence (hazard ratio: 1.75, 95% confidence interval: 0.97, 3.15). No association was observed between packs smoked per day or years since smoking cessation (among former smokers) and risk of biochemical recurrence.Conclusion: Smoking duration is a significant predicator of biochemical recurrence among men with prostate cancer who are current or former smokers. [ABSTRACT FROM AUTHOR]

Objective: To evaluate barriers to implementation of patient decision aids (PDAs) issued in an electronic medical record (EMR). We undertook an implementation outcomes analysis focused on what proportion of men eligible for the PDA received it (penetration), and of the men who received it, how many used it as intended (fidelity). We also evaluated various patient-centered outcomes related to decision-making.Materials and Methods: Men with incident localized prostate cancer were recruited from at UCLA from 2013 to 2017. PDA eligibility was determined via weekly EMR review. We also performed a retrospective chart review of all patients seen in clinic for one sample week to identify patients that were missed by the initial eligibility algorithm, and investigated the cause for miscategorization. We analyzed differences in patient-centered outcomes between those who did and did not receive the PDA.Results: About 314/374 men with incident prostate cancer completed the PDA conferring 84% fidelity. PDA penetration under initial identification prospective algorithm was assessed at 100% (n = 2/n = 2). However, penetration assessed by manual retrospective chart review was 20% (n = 2/n = 10). Improvements to the identification algorithm, including new EMR visit types, were identified. PDA completion was associated with less decisional conflict and higher perceived Shared decision-making (all P<.03).Conclusion: No previous studies have investigated the challenges of implementing a PDA facilitated by the EMR. We identified modifiable system and EMR-related factors that limited program penetration. Our PDA showed decisional quality benefits. [ABSTRACT FROM AUTHOR]

Androgen deprivation therapy (ADT) improves survival in men with advanced prostate cancer (PCa), but has been associated with compromised skeletal health and increased fracture risk. However, limited previous research has investigated determinants of bone strength beyond DXA-derived areal bone mineral density (aBMD) in this population group. The aim of this cross-sectional study was to investigate the effects of ADT in men with PCa on BMD, bone structure, estimates of whole bone strength and cortical bone distribution. A total of 70 ADT-treated men, 52 PCa controls and 70 healthy controls had DXA lumbar spine and proximal femur aBMD and pQCT distal (4%) and proximal (66%) tibia and radius cortical and trabecular volumetric BMD (vBMD), bone structure, strength and cortical bone distribution assessed. Analyses included BMI and/or tibia/radius length as covariates. On average, ADT-treated men had a higher BMI than PCa (P < 0.05) but not healthy controls. ADT-treated men had 7.2–7.8% lower lumbar spine aBMD than PCa (P = 0.037) and healthy controls (P = 0.010), with a trend for a lower total hip aBMD in the ADT-treated men (P = 0.07). At the distal tibia, total bone area was 6.2–7.3% greater in ADT-treated men than both controls (P < 0.01), but total vBMD was 8.4–8.7% lower in ADT-treated men than both controls (P < 0.01). Moreover, bone strength index (BSI) was 10.8% lower relative to healthy controls only (P < 0.05). At the distal radius, ADT-treated men had lower total and trabecular vBMD (10.7–14.8%, P < 0.05) and BSI (23.6–27.5%, P < 0.001) compared to both controls. There were no other differences in bone outcomes at the proximal tibia or radius. In conclusion, ADT treatment for PCa was associated with lower BMD and estimated compressive bone strength, particularly at trabecular skeletal sites (lumbar spine, and distal tibia and radius), compared to controls, but there were no consistent differences in cortical bone structure, distribution or bending strength. • Bone density, structure, strength and distribution were compared between prostate cancer men treated with androgen deprivation therapy (ADT) and controls. • ADT treated men had lower bone density and estimated compressive strength at trabecular skeletal sites compared to controls. • Cortical bone structure, strength and distribution did not differ between ADT treated men and controls. [ABSTRACT FROM AUTHOR]

Introduction: Fatigue is a commonly reported symptom in men receiving radiation therapy and androgen deprivation therapy (ADT) for prostate cancer. Despite this, the complex mechanisms remain unclear. This study aims to investigate factors which correlate with development of fatigue.Methods: Twenty-seven men with high-risk prostate cancer undergoing radiation therapy and 18 months of ADT were assessed for fatigue, haemoglobin (Hb), testosterone, magnetic resonance imaging (MRI) fat fraction (FF) and apparent diffusion coefficient (ADC), at baseline and at intervals after radiotherapy. Changes from baseline were analysed using paired t-tests. Linear time trends were assessed using linear mixed effect models.Results: Overall, mean fatigue score increased from baseline to the 18-month time interval (difference 4.5, P = 0.0114). The mean value for Hb significantly decreased (P < 0.001) from baseline to 18 months. The mean value for testosterone significantly decreased (P < 0.001) from baseline to 12 months, and remained low. Mean for MRI FF showed a significant increase (P < 0.001) from baseline to 6 months. MRI ADC showed a non-significant decrease from baseline to 6 months (P = 0.4416).Conclusion: Radiotherapy and ADT resulted in a significant increase in fatigue scores. Statistically significant changes were noted in Hb, testosterone and MRI FF and ADC, however, none were shown to have a strong association with worsening fatigue. Further investigation in a larger cohort is required to assess the interaction between fatigue and possible biological factors. [ABSTRACT FROM AUTHOR]

Bladder cancer is the fourth most common cancer in men and fifth most common overall. The use of next-generation sequencing (NGS) approaches is crucial to precisely characterize the molecular defects of tumors, and this information could be combined with other clinical data, such as tumor histology and TNM staging, with the goal of precise tumor classification. In many settings, targeted NGS is evaluated in patients with first- and second-line metastatic cancer. Yet, in the decade to come we anticipate increased application of precision oncology at all stages of bladder cancer with the aim of customizing cancer treatment. Here, we review the genomic and transcriptomic features associated with risk stratification in bladder cancer and summarize the current efforts for precision oncology in localized urothelial carcinomas. [ABSTRACT FROM AUTHOR]

Introduction: lung cancer is the most common cancer in men living Eastern Morocco. We here present the first report on the clinical, pathological and therapeutic features of lung cancer in Eastern Morocco. Methods: we conducted a retrospective study of 738 patients diagnosed with lung cancer at the Hassan II, Oncology Center between October 2005 and December 2014. Results: among the cases studied, 671 patients were men and 67 women; 95.01% of men and 1.54% of women were smokers. The average age of patients was 59.1 ± 11.9 years. Most patients (97%) were diagnosed at advanced stage disease. Only 4 out of 227 patients with advanced adenocarcinoma underwent molecular test. In addition, no patient in our series received targeted therapy. In this series, 20.46% of patients had less than 50 years. Compared to patients aged 50 years and older, cannabis consumption was higher (p<0.001) in patients less than 50 years and as well as a higher rate of adenocarcinoma (p<0.01). By contrast, in these patients, tobacco consumption was lower (p<0.001) as well as the rate of squamous cell carcinoma (p<0.01) and small cell cancer (p<0.05). Conclusion: unlike Western countries, in Eastern Morocco lung cancer is diagnosed late, affects younger people and access to molecular tests is still very limited. These results justify the need to implement effective programs against lung cancer as well as to facilitate access to molecular tests and new therapeutic tools in Eastern Morocco. [ABSTRACT FROM AUTHOR]

Objective: To compare the negative predictive value (NPV) of multiparametric MRI for Gleason score (GS) ≥ 3+4 cancer and evaluate predictors of these tumors in men with suspected disease and under active surveillance (AS). Materials and Methods: This retrospective study included 38 men with suspected prostate cancer and 38 under AS with scans assigned PI-RADS v2 scores 1 or 2 between May 2016 and September 2017. Biopsy results were no cancer, GS = 3+3, or GS ≥ 3+4. Pre-MRI PSA, gland volume, and PSA density were recorded. Chi-square, equality of proportions, and logistic regressions were used to analyze the data. Results: Intermediate to high-grade cancer was found in 12.8% (95% CI = 2.3–23.3) and 35.9% (95% CI = 20.8–50.9) of men with suspected cancer, and under AS (p = 0.02), respectively. The NPV for GS ≥ 3+4 were 87.2% (suspected cancer; 76.7–97.7) and 64.1% (AS; 49.0–79.2). In neither group PSA significantly predicted cancer grade (p = 0.75 and 0.63). Although it did not reach conventional statistical significance, PSA density was a good predictor of cancer grade in men with suspected disease (p = 0.06), but not under AS (p = 0.62). Conclusion: The NPV of multiparametric MRI for GS ≥ 3+4 is higher in men with suspected prostate cancer than in men under AS. PSA density ≤ 0.15 improved the prediction of intermediate to high-grade disease in patients without known cancer. [ABSTRACT FROM AUTHOR]

Background: Risk models (RM) need external validation to assess their value beyond the setting in which they were developed. We validated a RM combining mpMRI and clinical parameters for the probability of harboring significant prostate cancer (sPC, Gleason Score ≥ 3+4) for biopsy-naïve men. Material and methods: The original RM was based on data of 670 biopsy-naïve men from Heidelberg University Hospital who underwent mpMRI with PI-RADS scoring prior to MRI/TRUS-fusion biopsy 2012–2015. Validity was tested by a consecutive cohort of biopsy-naïve men from Heidelberg (n = 160) and externally by a cohort of 133 men from University College London Hospital (UCLH). Assessment of validity was performed at fusion-biopsy by calibration plots, receiver operating characteristics curve and decision curve analyses. The RM`s performance was compared to ERSPC-RC3, ERSPC-RC3+PI-RADSv1.0 and PI-RADSv1.0 alone. Results: SPC was detected in 76 men (48%) at Heidelberg and 38 men (29%) at UCLH. The areas under the curve (AUC) were 0.86 for the RM in both cohorts. For ERSPC-RC3+PI-RADSv1.0 the AUC was 0.84 in Heidelberg and 0.82 at UCLH, for ERSPC-RC3 0.76 at Heidelberg and 0.77 at UCLH and for PI-RADSv1.0 0.79 in Heidelberg and 0.82 at UCLH. Calibration curves suggest that prevalence of sPC needs to be adjusted to local circumstances, as the RM overestimated the risk of harboring sPC in the UCLH cohort. After prevalence-adjustment with respect to the prevalence underlying ERSPC-RC3 to ensure a generalizable comparison, not only between the Heidelberg and die UCLH subgroup, the RM`s Net benefit was superior over the ERSPC`s and the mpMRI`s for threshold probabilities above 0.1 in both cohorts. Conclusions: The RM discriminated well between men with and without sPC at initial MRI-targeted biopsy but overestimated the sPC-risk at UCLH. Taking prevalence into account, the model demonstrated benefit compared with clinical risk calculators and PI-RADSv1.0 in making the decision to biopsy men at suspicion of PC. However, prevalence differences must be taken into account when using or validating the presented risk model. [ABSTRACT FROM AUTHOR]

Background: Although diabetes is inversely related to prostate cancer (PC) risk, to the authors' knowledge the impact of glycemic control on PC progression is unknown. In the current study, the authors tested the association between hemoglobin A1c (HbA1c) and long-term PC outcomes among diabetic men undergoing radical prostatectomy (RP).Methods: The authors retrospectively reviewed data regarding men undergoing RP from 2000 to 2017 at 8 Veterans Affairs hospitals. Diabetic patients were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes (250.x) or by an HbA1c value >6.5% at any time before RP. Cox models tested the association between HbA1c and biochemical disease recurrence (BCR), castration-resistant PC (CRPC), metastases, PC-specific mortality, and all-cause mortality. The model for BCR was adjusted for multiple variables. Due to limited events, models for long-term outcomes were adjusted for biopsy grade and prostate-specific antigen only.Results: A total of 1409 men comprised the study population. Of these, 699 patients (50%) had an HbA1c value <6.5%, 631 (45%) had an HbA1c value of 6.5% to 7.9%, and 79 (6%) had an HbA1c value ≥8.0%. Men with an HbA1c value ≥8.0% were younger (P < .001) and more likely to be black (P = .013). The median follow-up after RP was 6.8 years (interquartile range, 3.7-10.6 years). On multivariable analysis, HbA1c was not found to be associated with BCR. However, a higher HbA1c value was associated with metastasis (hazard ratio [HR], 1.21; 95% CI, 1.02-1.44 [P = .031]) and CRPC (HR, 1.27; 95% CI, 1.03-1.56 [P = .023]). Although not statistically significant, there were trends between higher HbA1c and risk of PC-specific mortality (HR, 1.24; 95% CI, 0.99-1.56 [P = .067]) and all-cause mortality (HR, 1.09; 95% CI, 0.99-1.19 [P = .058]).Conclusions: Among diabetic men undergoing RP, a higher HbA1c value was associated with metastases and CRPC. If validated in larger studies with longer follow-up, future research should test whether better glycemic control improves long-term PC outcomes. [ABSTRACT FROM AUTHOR]

Background: To the authors' knowledge, the relationship between cardiorespiratory fitness (CRF) and lung and colorectal cancer outcomes is not well established.Methods: A retrospective cohort study was performed of 49,143 consecutive patients who underwent clinician-referred exercise stress testing from 1991 through 2009. The patients ranged in age from 40 to 70 years, were without cancer, and were treated within the Henry Ford Health System in Detroit, Michigan. CRF, measured in metabolic equivalents of task (METs), was categorized as <6 (reference), 6 to 9, 10 to 11, and ≥12. Incident cancer was obtained through linkage to the cancer registry and all-cause mortality from the National Death Index.Results: Participants had a mean age of 54 ± 8 years. Approximately 46% were female, 64% were white, 29% were black, and 1% were Hispanic. The median follow-up was 7.7 years. Cox proportional hazard models, adjusted for age, race, sex, body mass index, smoking history, and diabetes, found that those in the highest fitness category (METs ≥12) had a 77% decreased risk of lung cancer (hazard ratio [HR], 0.23; 95% CI, 0.14-0.36) and a 61% decreased risk of incident colorectal cancer (HR, 0.39; 95% CI, 0.23-0.66; with additional adjustment for aspirin and statin use). Among those diagnosed with lung and colorectal cancer, those with high fitness had a decreased risk of subsequent death of 44% and 89%, respectively (HR, 0.56 [95% CI, 0.32-1.00] and HR, 0.11 [95% CI, 0.03-0.37], respectively).Conclusions: In what to the authors' knowledge is the largest study performed to date, higher CRF was associated with a lower risk of incident lung and colorectal cancer in men and women and a lower risk of all-cause mortality among those diagnosed with lung or colorectal cancer. [ABSTRACT FROM AUTHOR]

Introduction: Two recent observational studies have investigated the association between androgen deprivation therapy (ADT) and rheumatoid arthritis (RA), but generated discrepant findings and had important methodological limitations. Thus, the objective of this study was to determine whether the use of ADT is associated with an increased risk of RA in men with prostate cancer.Patients and Methods: We conducted a population-based cohort study using the United Kingdom Clinical Practice Research Datalink. The cohort included all men, at least 40 years of age, newly diagnosed with prostate cancer between 1 January 1988 and 31 March 2014, with follow-up until 30 September 2014. Exposure to ADT was treated as a time-varying variable and lagged by 1 year to account for diagnostic delays and latency. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of RA, comparing use of ADT with non-use. Secondary analyses were conducted to assess whether the association varied according to ADT type and cumulative duration of use. Finally, we conducted several sensitivity analyses to assess the robustness of our findings.Results: The cohort included 32,302 men followed for a median of 3.3 years. During follow-up, 63 patients were newly diagnosed with RA, generating an incidence rate of 46.5/100,000 person-years. Compared with non-use, the use of ADT was not associated with an increased risk of RA (HR 0.84, 95% CI 0.49-1.45). In secondary analyses, the association did not vary according to ADT type or with cumulative duration of use (p trend = 0.53). The results remained consistent in sensitivity analyses.Conclusion: In this population-based study, the use of ADT was not associated with an increased risk of RA in men with prostate cancer. [ABSTRACT FROM AUTHOR]

Introduction: Prostate Cancer (PCA) is the second most common cancer diagnosed in men worldwide. Prostate Specific Antigen (PSA) is the readily used biomarker for PCA screening, but lack of specificity limits its usefulness. Hence, role of Androgen receptor (AR) CAG repeat polymorphism and Cytochrome P450 3A5*3 gene polymorphism involved in the metabolism of testosterone, growth and differentiation of prostate gland were evaluated to assess their association with pathogenesis of prostate lesions. Aim: To determine CAG repeats in AR gene and CYP3A5*3 gene polymorphism in South Indian men with PCA and Benign Prostate Hyperplasia (BPH). Materials and Methods: Genomic DNA was isolated from 312 (100 men with PCA, 109 BPH patients and 103 controls). Formalin fixed paraffin embedded tissue/peripheral blood samples using salting out method were used. Polymerase Chain Reaction (PCR) procedure was carried out using specific primers for AR and CYP3A5*3 genes. Bands were visualised by electrophoresis on 2% ethidium bromide (EtBr) stained agarose gel. Odds ratios were calculated using MedCalcR version 18.2.1 and Chi-square analysis was carried out to determine the association among groups. Results: AR gene with <22 CAG repeats and 'GG' genotype of CYP3A5*3 gene polymorphism were identified in 61 (61%), PCA patients, 11 (10%) BPH and 13 (13%) control individuals. A statistically significant association was observed between AR short repeats and CYP3A5*3 'GG' genotype with PCA (p-value <0.05). Conclusion: The results suggest that the best age for PCA screening is 48 years or above for early detection and prevention of this malignancy. A <22 CAG repeats in AR gene and 'GG' genotype of CYP3A5*3 (rs#776746) gene can be together considered as specific molecular marker for identifying men at a risk of developing PCA. [ABSTRACT FROM AUTHOR]

Prostate cancer incidence, treatment, and survival rates vary throughout the UK, but little is known about regional differences in quality of survival. To investigate variations in patient-reported outcomes between UK countries and English Cancer Alliances. A cross-sectional postal survey of prostate cancer survivors diagnosed 18–42 mo previously. Urinary, bowel, and sexual problems and vitality were patient reported using the Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire. General health was also self-assessed. Regional variations were identified using multivariable log-linear regression. A total of 35 823 men responded, 60.8% of those invited. Self-assessed health was significantly lower than the UK average in Wales and Scotland. Respondents reported more urinary incontinence in Scotland, more urinary irritation/obstruction in Scotland and Northern Ireland (NI), poorer bowel function in Scotland and NI, worse sexual function in Scotland, and reduced vitality/hormonal function in Scotland, Wales, and NI. Self-assessed health was poorer than the English average in South Yorkshire and North-East and Cumbria, with more urinary incontinence in North-East and Cumbria and Peninsula, greater sexual problems in West Midlands, and poorer vitality in North-East and Cumbria and West Midlands. Limitations include difficulty identifying clinically significant differences and limited information on pretreatment conditions. Despite adjustment for treatment, and clinical and sociodemographic factors, quality of survival among prostate cancer survivors varied by area of residence. Adoption of best practice from areas performing well could support enhanced survival quality in poorer performing areas, particularly with regard to bowel problems and vitality, where clinically relevant differences were reported. We conducted a UK-wide survey of patient's quality of life after treatment for prostate cancer. Outcomes were found to vary depending upon where patients live. Different service providers need to ensure that all prostate cancer patients receive the same follow-up care. Prostate cancer survivors from England report better quality of survival than those from Scotland, Wales, and Northern Ireland, with differences unrelated to treatment type, and patient and disease characteristics. Within England, regional variations in general health and functional outcome also exist. [ABSTRACT FROM AUTHOR]

Aim: The role of germline testing in prostate cancer is evolving and knowledge of an individual's genetic profile may be used to guide not only an assessment of their familial risk but also have prognostic and therapeutic implications. Although international guidelines have incorporated recommendations for germline testing in prostate cancer, there is little Australian data to guide referrals. The aim of this study is to review the frequency of relevant pathogenic mutations in an Australian center, their associated clinical factors and clinical impact. Methods: We conducted a single‐center retrospective review of men with prostate cancer that undertook prospective germline testing using a targeted next generation sequencing panel. Results: Results for 100 men were analyzed. Median age at diagnosis was 62 years (range 43–84); 92% had metastatic disease at referral. A pathogenic mutation was confirmed in 9%, a likely pathogenic variant in 2% and a variant of uncertain significance in 15%. Age ≤60 years was associated with an increased risk for a pathogenic germline variant (P = 0.0096). Two of the nine (22%) with pathogenic variants went on to receive targeted treatment. Conclusions: In this single center study, the incidence of germline mutations in genes associated with DNA‐repair was consistent with rates seen previously published international series of men with metastatic disease. A pathogenic variant was only seen in one patient >60 years of age and no man referred solely on the basis of age or high‐risk localized disease had a relevant finding. [ABSTRACT FROM AUTHOR]

Objectives: To develop a consensus statement on current best practice of active surveillance (AS) in the UK, informed by patients and clinical experts. Subjects and Methods: A consensus statement was drafted on the basis of three sources of data: systematic literature search of national and international guidelines; data arising from a Freedom of Information Act request to UK urology departments regarding their current practice of AS; and survey and interview responses from men with localized prostate cancer regarding their experiences and views of AS. The Prostate Cancer UK Expert Reference Group (ERG) on AS was then convened to discuss and refine the statement. Results: Guidelines and protocols for AS varied significantly in terms of risk stratification, criteria for offering AS, and protocols for AS between and within countries. Patients and healthcare professionals identified clinical, emotional and process needs for AS to be effective. Men with prostate cancer wanted more information and psychological support at the time of discussing AS with the treating team and in the first 2 years of AS, and a named healthcare professional to discuss any questions or concerns they had. The ERG agreed 30 consensus statements regarding best practice for AS. Statements were grouped under headings: 'Inclusion/Exclusion Criteria'; 'AS follow‐up protocol' and 'When to stop AS'. Conclusion: Significant variation currently exists in the practice of AS in the UK and internationally. Men have clear views on the level of involvement in treatment decisions and support from their treating professionals when receiving AS. The Prostate Cancer UK AS ERG has developed a set of consensus statements for best practice in AS. Evidence for best practice in AS, and the use of multiparametric magnetic resonance imaging in AS, is still evolving, and further studies are needed to determine how to optimize AS outcomes. [ABSTRACT FROM AUTHOR]

A cross-sectional survey was performed among partners and men who received treatment for prostate cancer to investigate whether demographic and clinical characteristics are associated with the extent of how difficult partners found it dealing with sexual side effects and the degree of having experienced sexual problems after treatment. Moreover, an aim was to determine whether sexual side effects have an impact on the relationship. A total of 171 partners were included. In all, 104 men (70.7%) experienced an increase in erectile complaints after treatment. Almost half of partners of men with an increase in erectile complaints (63.6%, n = 63) found it difficult to deal with sexual side effects and 63.5% (n = 66) experienced sexual problems. Partners with lower education levels experienced fewer sexual problems than partners with higher education levels (p < .001). Furthermore, no significant associations were found on demographic characteristics, number of comorbidities, clinical characteristics (prostate-specific antigen level; tumor, node, and metastasis staging; Gleason grading), and type of treatment. The majority of men (58.4%, n = 59) and partners (62.5%, n = 65) indicated to not have experienced the impact of sexual side effects on their relationship. [ABSTRACT FROM AUTHOR]

Background: Trefoil Factor 3 (TFF3) has been implicated in Prostate Cancer (PCa) progression. However, its prognostic value and association with other biomarkers have not been fully explored. We assessed the combined value of TFF3 and PTEN in two cohorts: one is managed surgically for localized PCa and the second is managed non-surgically by androgen deprivation therapy for advanced disease. Design: 228 radical prostatectomies (RP) and 318 transurethral resection of prostate (TURP) samples were assessed by immunohistochemistry (IHC) for TFF3 and by IHC and fluorescent in situ hybridization (FISH) for PTEN. Results of biomarkers expression were correlated with various pathological and clinical outcome parameters including biochemical recurrence (BCR) in the RP cohort and cancer-specific mortality (PCSM) and overall survival (OS) in the TURP cohort. Results: TFF3 expression was detected in 131/226 (57.9%) RP samples and 148/318 (46.5%) of TURP cases. In general, TFF3 positivity was less frequently observed with advanced Gleason Groups. TFF3 expression was also assessed in relation to PTEN expression. Only 15–16% of TFF3-expressed cases were present in association with complete loss of PTEN expression in the TURP and localized cohorts, respectively. Loss of TFF3 expression was not related to BCR after RP, but was prognostic in the non-surgical cohort and associated with decrease OS and PCSM (HR 2.31, CI: 1.67–3.18, p < 0.0001) and (HR 3.99, CI: 2.43–6.56; p < 0.0001), respectively. Adjusting for Gleason score, combined loss of TFF3/PTEN was most associated with OS (HR 2.33, CI: 1.49–3.62; p < 0.0001) and PCSM (HR = 3.44, CI: 1.75–6.78, p < 0.0001). Conclusion: The study documents for the first time significant association for combined status of TFF3 expression and PTEN loss in OS and PCSM in patients not managed by surgical intervention. Prospective assessment of PTEN and TFF3 may provide further insight into molecularly subtyping PCa and aid in stratifying patients at risk for lethal disease. [ABSTRACT FROM AUTHOR]

Men are at a higher risk of developing bladder cancer than women. Although the urinary bladder is not regarded as an sex organ, it has the potential to respond to androgen signals. The mechanisms responsible for the gender differences remain unexplained. Androgen receptor (AR) after binding with 5α-dihydrotestosteron (DHT) undergoes a conformational change and translocates to nucleus to induce transcriptional regulation of target genes. However androgen/AR signaling can also be activated by interacting with several signaling molecules and exert its non-genomic function. The aim of present study was to explain whether the progression of bladder cancer in men is dependent on androgen/AR signaling. Studies were carried out on human bladder cancer cell lines: HCV29, T24, HT1376 and HTB9. Bladder cancer cells were treated for 48 h with 10 nM DHT or not, with replacement after 24 h. Expression of cell signaling proteins, was analyzed using Western Blot and RT-PCR. Subcellular localization of protein was studied using the ProteoExtract Subcellular Proteome Extraction Kit and Western blot analysis. We showed that DHT treatment significantly increased AR expression in bladder cell line HCV29. We also observed DHT-mediated activation of Akt/GSK-3β signaling pathway which plays a central role in cancer progression. Presented results also show that androgen/AR signaling is implicated in phosphorylation of eIF4E which can promote epithelial–mesenchymal transition (EMT). We indicate that AR plays an essential role in bladder cancer progression in male patients. Therefore, androgen-activated AR signaling is an attractive regulatory target for the inhibition or prevention of bladder cancer incidence in men. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the relationship between periprostatic adipose tissue (PPAT) adipokine expression and prostate cancer (PCa) aggressiveness using both pathological features of radical prostatectomy (RP) and multiparametric magnetic resonance imaging (MRI) variables. Patients and Methods: Sixty‐nine men were recruited to assess immunohistochemical expression of tumour necrosis factor (TNF)α and vascular endothelial growth factor (VEGF) of periprostatic fat of RP specimens. Per cent immunopositivity was quantified on scanned slides using the Aperio Positive Pixel Count algorithm for PPAT TNFα, VEGF and androgen receptors. Periprostatic fat volume (PFV) was segmented on contiguous T1‐weighted axial MRI slices from the level of the prostate base to apex. PFV was normalized to prostate volume (PV) to account for variations in PV (normalized PFV = PFV/PV). MRI quantitative values (Kep, Ktrans and apparent diffusion coefficient) were measured from the PCa primary lesion using Olea Sphere software. Patients were stratified into three groups according to RP Gleason score (GS): ≤6, 7(3 + 4) and ≥7(4 + 3). Results: The mean rank of VEGF and TNFα was significantly different between the groups [H(2) = 11.038, P = 0.004] and [H(2) = 13.086, P = 0.001], respectively. Patients with stage pT3 had higher TNFα (18.2 ± 8.95) positivity than patients with stage pT2 (13.27 ± 10.66; t [67] = −2.03, P = 0.047). TNFα expression significantly correlated with Ktrans (ρ = 0.327, P = 0.023). TNFα (P = 0.043), and VEGF (P = 0.02) correlated with high grade PCa (GS ≥ 7) in RP specimens and also correlated significantly with upgrading of GS from biopsy to RP histology. Conclusions: The expression levels of TNFα and VEGF on immunostaining significantly correlated with aggressivity of PCa. As biomarkers, these indicate the risk of having high grade PCa in men undergoing RP. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that lifestyle factors may decrease the risk of prostate cancer progression. Lifestyle guidelines and tools may support lifestyle modification after diagnosis. To determine the feasibility and acceptability of a digital lifestyle intervention among men with prostate cancer. A 12-wk pilot randomized controlled trial among 76 men with clinical stage T1–T3a prostate cancer. Eligibility included Internet access, no contraindications to aerobic exercise, and engaging in four or fewer of eight targeted behaviors at baseline. Website, Fitbit One, and text messaging to facilitate adoption of eight behaviors: vigorous activity, smoking cessation, and six diet improvements. Our primary outcomes were feasibility and acceptability based on recruitment and user data, and surveys, respectively. Secondarily, we evaluated the change in eight lifestyle behaviors, and also objective physical activity. Each factor was assigned one point, for an overall "P8 score" (range 0–8). Analysis of covariance (ANCOVA) was conducted. Exploratory outcomes included quality of life, anthropometrics, and circulating biomarkers after 12 wk, and behaviors after 1 yr. At baseline, men in both arms met a median of three targeted behaviors. Sixty-four men (n = 32 per arm) completed the study; 88% completed 12-wk assessments (intervention, 94%; control, 82%). Intervention participants wore their Fitbits a median of 82 d (interquartile range [IQR]: 72–83), replied to a median of 71% of text messages (IQR: 57–89%), and visited the website a median of 3 d (IQR: 2–5) over 12 wk. Median (IQR) absolute changes in the P8 score from baseline to 12 wk were 2 (1, 3) for the intervention and 0 (−1, 1) for the control arm. The estimated mean score of the intervention arm was 1.5 (95% confidence interval: 0.7, 2.3) higher than that of the control arm at 12 wk (ANCOVA p < 0.001). Changes were driven by diet rather than exercise. Limitations include self-reported diet and exercise data. Overall, in this novel pilot trial, the intervention was feasible and acceptable to men with prostate cancer. Next steps include improving the intervention to better meet individuals' needs and focusing on increasing physical activity in men not meeting nationally recommended physical activity levels. Tailored print materials combined with technology integration, including the use of a website, text messaging, and physical activity trackers, helped men with prostate cancer adopt healthy lifestyle habits, in particular recommended dietary changes, in the Prostate 8 pilot trial. Tailored print materials combined with technology integration, including the use of a website, text messaging, and physical activity trackers, helped men with prostate cancer adopt healthy lifestyle habits, in particular recommended dietary changes, in the Prostate 8 pilot trial. [ABSTRACT FROM AUTHOR]

PURPOSE: The ratio of cancer mortality and cancer incidence rates in a population has conventionally been used as an indicator of the completeness of cancer registration. More recently, the complement of the mortality-to-incidence ratio (1-M/I) has increasingly been presented as a surrogate for cancer survival. We discuss why this is mistaken in principle and misleading in practice. METHODS: We provide an empirical assessment of the extent to which trends in the 1-M/I ratio reflect trends in cancer survival. We used national cancer incidence, mortality and survival data in England to compare trends in both the 1-M/I ratio and net survival at 1, 5, and 10 years for 19 cancers in men and 20 cancers in women over the 29-year period from 1981 to 2009. RESULTS: The absolute difference between the 1-M/I ratio and 5-year net survival for 2009 was less than 5% for only 12 of the 39 cancer/sex combinations examined. For an additional 12, the 1-M/I ratio differed from 5-year net survival by at least 15%. The comparison is also unstable over time; thus, even when differences were small for 2009, the difference between 5-year net survival and the 1-M/I ratio had changed dramatically for most cancers between 1981 and 2009. CONCLUSION: The 1-M/I ratio lacks any theoretical basis as a proxy for cancer survival. It is not a valid proxy for cancer survival in practice, either, whether at 5 years or at any other time interval since diagnosis. It has none of the useful properties of a population-based survival estimate. It should not be used as a surrogate for cancer survival. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and the fourth most common cancer in men in Korea, where the prevalence of chronic hepatitis B infec-tion is high in middle-aged and elderly patients. These prac-tice guidelines will provide useful and constructive advice for the clinical management of patients with HCC. A total of 44 experts in hepatology, oncology, surgery, radiology and radia tion oncology in the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2014 Korean guidelines and developed new rec-ommendations that integrate the most up-to-date research findings and expert opinions. [ABSTRACT FROM AUTHOR]

Purpose: Sperm cryopreservation before cancer treatment is the most effective method to preserve the fertility of male patients. We present our 21 years experience with sperm cryopreservation for cancer patients, including an examination of semen quality, the current status of cryopreserved sperm, and the rate of sperm use for assisted reproductive technology (ART). Materials and Methods: A total of 721 cancer patients at Fertility Center of CHA Gangnam Medical Center successfully performed sperm cryopreservation for fertility preservation from January 1996 to December 2016. Medical chart review was used to analyze patient age, marital status, cancer type, semen volume, sperm counts and motility, length of storage, and current banking status. Results: The major cancers of the 721 patients were leukemia (28.4%), lymphoma (18.3%), testis cancer (10.0%). The mean age at cryopreservation was 27.0 years, and 111 patients (15.4%) performed sperm cryopreservation during or after cancer treatment. The mean sperm concentration was 66.7±66.3 ×106/mL and the mean sperm motility was 33.8%±16.3%. During median follow-up duration of 75 months (range, 1-226 months), 44 patients (6.1%) used their banked sperm at our fertility center for ART and 9 patients (1.2%) transferred their banked sperm to another center. The median duration from cryopreservation to use was 51 months (range, 1-158 months). Conclusions: Sperm cryopreservation before gonadotoxic treatment is the most reliable method to preserve the fertility of male cancer patients. Sperm cryopreservation should be offered as a standard of care for all men planning cancer therapy. [ABSTRACT FROM AUTHOR]

The survival rates of boys and men with cancer have increased due to advances in cancer treatments; however, maintenance of quality of life, including fertility preservation, remains a major issue. Fertile male patients who receive radiation and/or chemotherapy face temporary, long-term, or permanent gonadal damage, particularly with exposure to alkylating agents and whole-body irradiation, which sometimes induce critical germ cell damage. These cytotoxic treatments have a significant impact on a patient's ability to have their own biological offspring, which is of particular concern to cancer patients of reproductive age. Therefore, various strategies are needed in order to preserve male fertility. Sperm cryopreservation is an effective method for preserving spermatozoa. Advances have also been achieved in pre-pubertal germ cell storage and research to generate differentiated male germ cells from various types of stem cells, including embryonic stem cells, induced pluripotent stem cells, and spermatogonial stem cells. These approaches offer hope to many patients in whom germ cell loss is associated with sterility, but are still experimental and preliminary. This review examines the current understanding of the effects of chemotherapy and radiation on male fertility. [ABSTRACT FROM AUTHOR]

Abstract Background The homeobox B13 (HOXB13) G84E mutation has been recommended for use in genetic counselling for prostate cancer (PCa), but the magnitude of PCa risk conferred by this mutation is uncertain. Objective To obtain precise risk estimates for mutation carriers and information on how these vary by family history and other factors. Design, setting, and participants Two-fold: a systematic review and meta-analysis of published risk estimates, and a kin-cohort study comprising pedigree data on 11 983 PCa patients enrolled during 1993–2014 from 189 UK hospitals and who had been genotyped for HOXB13 G84E. Outcome measurements and statistical analysis Relative and absolute PCa risks. Complex segregation analysis with ascertainment adjustment to derive age-specific risks applicable to the population, and to investigate how these vary by family history and birth cohort. Results and limitations A meta-analysis of case-control studies revealed significant heterogeneity between reported relative risks (RRs; range: 0.95–33.0, p < 0.001) and differences by case selection (p = 0.007). Based on case-control studies unselected for PCa family history, the pooled RR estimate was 3.43 (95% confidence interval [CI] 2.78–4.23). In the kin-cohort study, PCa risk for mutation carriers varied by family history (p < 0.001). There was a suggestion that RRs decrease with age, but this was not significant (p = 0.068). We found higher RR estimates for men from more recent birth cohorts (p = 0.004): 3.09 (95% CI 2.03–4.71) for men born in 1929 or earlier and 5.96 (95% CI 4.01–8.88) for men born in 1930 or later. The absolute PCa risk by age 85 for a male HOXB13 G84E carrier varied from 60% for those with no PCa family history to 98% for those with two relatives diagnosed at young ages, compared with an average risk of 15% for noncarriers. Limitations include the reliance on self-reported cancer family history. Conclusions PCa risks for HOXB13 G84E mutation carriers are heterogeneous. Counselling should not be based on average risk estimates but on age-specific absolute risk estimates tailored to individual mutation carriers' family history and birth cohort. Patient summary Men who carry a hereditary mutation in the homeobox B13 (HOXB13) gene have a higher than average risk for developing prostate cancer. In our study, we examined a large number of families of men with prostate cancer recruited across UK hospitals, to assess what other factors may contribute to this risk and to assess whether we could create a precise model to help in predicting a man's prostate cancer risk. We found that the risk of developing prostate cancer in men who carry this genetic mutation is also affected by a family history of prostate cancer and their year of birth. This information can be used to assess more personalised prostate cancer risks to men who carry HOXB13 mutations and hence better counsel them on more personalised risk management options, such as tailoring prostate cancer screening frequency. Take Home Message Men with a G84E mutation in the HOXB13 gene are at a high risk of developing prostate cancer. The risk is however heterogeneous, and is modified by both family history and birth cohort. Genetic counselling should account for this heterogeneity. [ABSTRACT FROM AUTHOR]

Background: Smoking is one of the well-established risk factors for gastric cancer incidence, yet whether men are more or equally susceptible to gastric cancer due to smoking compared with women is a matter of controversy. The aim of this study was to investigate and compare the effect of sex on gastric cancer risk associated with smoking.Methods: We conducted a systemic literature search in MEDLINE, EMBASE, and the Cochrane CENTRAL databases to identify studies published from inception to December 2018. We included prospective observational studies which reported effect estimates with 95% confidence intervals (CIs) for associations of current or former smokers with the incidence of gastric cancer by sex. We calculated the ratio of relative risk (RRR) with corresponding 95% CI based on sex-specific effect estimates for current or former smokers versus non-smokers on the risk of gastric cancer.Results: We included 10 prospective studies with 3,381,345 participants in our analysis. Overall, the summary RRR (male to female) for gastric cancer risk in current smokers was significantly increased compared with non-smokers (RRR: 1.30; 95% CI: 1.05-1.63; P = 0.019). Furthermore, there was no significant sex difference for the association between former smokers and gastric cancer risk (RRR: 1.20; 95% CI: 0.92-1.55; P = 0.178). However, the result of sensitivity analysis indicated the pooled result was not stable, which was altered by excluding a nested case-control study (RRR: 1.31; 95% CI: 1.10-1.57; P = 0.002).Conclusion: This systematic review showed a potential sex difference association between current smokers and the risk of gastric cancer. The sex differential in smokers can give important clues for the etiology of gastric cancers and should be examined in further studies. [ABSTRACT FROM AUTHOR]

Objective: Rare disease. Background: Male breast cancer is rare, accounting for approximately 1% of all malignancies in men. The lack of awareness of this rare cancer results in delayed diagnosis and its aggressive behavior can result in poor prognosis. This report is of a case of locally advanced, high-grade breast cancer in a 59-year-old man who was reluctant to undergo diagnostic procedures, and describes the approach to clinical management. Case Report: A 59-year-old man presented with a large left breast mass with enlarged axillary lymph nodes. The patient had ignored the mass and declined all diagnostic procedures. After modifying the diagnostic workup and involving a psychiatrist, the patient agreed to undergo a modified radical mastectomy. Histopathology showed a highgrade invasive ductal carcinoma with lymph node metastasis. The breast cancer was triple-positive for human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR). Adjuvant treatment included herceptin, tamoxifen, and radiation therapy. Conclusions: This case demonstrates the importance of raising public awareness of breast cancer in men, and to assess and overcome the factors leading to delay in accessing medical attention. In challenging cases, modifying the diagnostic workup and the treatment approach with the least deviation from the standard of care, including counseling may be required. [ABSTRACT FROM AUTHOR]

Objective: High levels of red cell distribution width (RDW) may be associated with adverse outcomes in patients with cancer. The purpose of the present study was to investigate the prognostic impact of pretreatment RDW levels on overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) in a large cohort of male laryngeal squamous cell cancer (LSCC) patients. Methods: A total of 809 LSCC patients who were treated between 2007 and 2011 at the Eye & ENT Hospital of Fudan University were enrolled and evaluated retrospectively. OS, CSS, and DFS were analyzed using the Kaplan–Meier method. To evaluate the prognostic significance of RDW levels, univariate, and multivariate Cox analyses were applied. Results: Higher pretreatment RDW levels were significantly associated with high death events, red blood cell count, hemoglobin, radiotherapy, operation therapy, and advanced tumor stage (p < 0.05). From the univariate analysis, we observed that the higher (13.2–13.5%) and the highest (>13.5%) quartiles of RDW level were consistent factors for poor OS, CSS, and DFS in LSCC patients. In the multivariate analysis, after adjusting for confounding factors, the higher and highest quartiles of RDW levels were identified as independent prognostic factors in male LSCC patients. Conclusion: Higher pretreatment RDW levels were demonstrated to be associated with poor clinical outcome in male LSCC patients and might be novel markers for patient stratification in LSCC management. [ABSTRACT FROM AUTHOR]

Aims: The goal of this study was to analyze cancer risk in stroke survivors followed for up to 10 years in general practices in Germany. Methods: The current study sample included patients who received an initial stroke diagnosis in one of 1262 general practices in Germany between 2006 and 2015 (index date). Patients without stroke were matched (1:1) to patients with stroke by age, gender, index year, and 16 comorbidities diagnosed in the 12 months prior to the index date using a propensity score method. The main outcome of the study was the risk of cancer as a function of stroke within 10 years of the index date. Results: The stroke and non-stroke groups included 9579 men and 9089 women. After 10 years of follow-up, 29.3% of men with stroke and 23.8% of those without stroke developed any of the included types of cancer (log-rank p value < 0.001). During the same time, the prevalence of cancer was 25.0% in women with stroke and 20.5% in women without stroke (log-rank p value < 0.001). There was a positive association between stroke and any cancer in men (hazard ratio [HR] = 1.18, 95% confidence interval [CI] 1.09–1.28) and in women (HR = 1.22, 95% CI 1.12–1.34). This association was significant for cancers of respiratory and intrathoracic organs in men and women and for cancers of digestive organs in men. Conclusions: This study, including more than 37,000 patients from Germany, found that stroke was associated with an increased cancer risk. [ABSTRACT FROM AUTHOR]

Objective: Prostate cancer (PCa) is one of the most prevalent types of cancer among men worldwide. The incidence of PCa is increasing in China. Therefore, there is an urgent need to identify novel diagnostic and prognostic markers for PCa to improve the treatment of the disease.Methods: The Cancer Genome Atlas (TCGA) and GEO database were used to analyze the expression of miR-192, and the relationship between miR-192 and the clinical features of patients with PCa. Cell cycle and cell proliferation assay were used to detect the functional roles of miR-192 in PCa. Bioinformatic analysis for miR-192-5p was performed using gene ontology and KEGG analysis.Results: By analyzing the dataset of TCGA, we found that miR-192 was overexpressed in PCa samples compared to normal tissues and was upregulated in high-grade PCa compared to low-grade PCa. We also observed that higher miR-192 expression was associated with a shorter biochemical recurrence-free survival time. Our results also demonstrated that miR-192 promoted PCa cell proliferation and cell cycle progression.Conclusion: These results suggest that miR-192 may be considered for use as a potential diagnostic and therapeutic target of PCa. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is the second leading cause of cancer death in men. Several articles have reported that microRNA-21 (miR-21) and microRNA-30c (miR-30c) have diagnostic values for PCa, but the results are inconclusive. In order to precisely assess the diagnostic values of miR-21 and miR-30c for PCa, this meta-analysis is performed. Methods: Articles were searched in the databases of PubMed, Embase, and Web of Knowledge (search date: September 6, 2018). Studies were included if they were designed to evaluate the diagnostic performance of miR-21 or miR-30c for PCa. Using Stata 12.0 and Meta-Disc 1.4, the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under curve (AUC) of the summary receiver-operating characteristic (SROC) curve with the corresponding 95% CI were calculated. Results: Overall, ten studies (six studies for miR-21 and four for miR-30c) involving1,371 participants were included in this meta-analysis. For miR-21, the pooled SEN and SPE were, respectively, 0.91 (95% CI: 0.87–0.94) and 0.88 (95% CI: 0.82–0.93), the pooled PLR and NLR were, respectively, 7.74 (95% CI: 4.81–12.47), 0.1 (95% CI: 0.06–0.15), the DOR was 77.64 (95% CI: 34.64–174.02), AUC of SROC was 0.95 (95% CI: 0.93–0.97). For miR-30c, the pooled SEN and SPE were, respectively, 0.74 (95% CI: 0.65–0.81) and 0.78 (95% CI: 0.72–0.83), the pooled PLR and NLR were, respectively, 3.39 (95% CI: 2.69–4.26), and 0.34 (95% CI: 0.26–0.44), the DOR was 10.06 (95% CI: 6.96–14.55), and AUC of SROC was 0.83 (95% CI: 0.79–0.86). Conclusion: For PCa, miR-21 is a good diagnostic biomarker and miR-30c is a moderate diagnostic biomarker. [ABSTRACT FROM AUTHOR]

Introduction: Prostate cancer is the most common cancer among men, but overall mortality rates remain low, due to the preponderance of low-risk disease. Over the last decade, there has been a shift toward more conservative management in low-risk prostate cancer, in order to minimize unnecessary intervention. This study aimed to evaluate the number of low-risk radical prostatectomies (RPs) being performed at the Southern Alberta Institute of Urology over a 10-year period. Methods: We retrospectively reviewed all patients who underwent RP from 2005 to 2014 at our institution. Patients were stratified by D'Amico risk classification and grade group based on 12-core transrectal ultrasound–guided biopsy (TRUS-bx) results. RP findings are reported from February 2005 to October 2014 to describe concordance between TRUS-bx and RPs. Basic descriptive analyses were used for this study. Results: Over the study period, 2,310 RPs were performed in our institution. Overall, 35.2% of these were performed on men with low-risk prostate cancer. From 2005 to 2014, the proportion of RPs performed for low-risk prostate cancer dropped from 54.0% to 8.9%, and 49.8% of patients who underwent RP for low-risk disease experienced pathologic upgrading, though only 3.8% were upgraded to grade group 3 or greater. Other adverse pathological findings were uniformly low among the low-risk group. Conclusion: The proportion of patients undergoing RP at our center for low-risk prostate cancer decreased significantly over the 10 years evaluated in this study, reflecting current global trends toward active surveillance in the management of low-risk prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate long-term gastric cancer risk in male smokers with and without atrophic gastritis. Materials and methods: A total of 22,346 elderly male smokers participated in the Helsinki Gastritis Study between the years 1989 and 1993. Serum pepsinogen I (PGI) was measured for the men, and 2,132 men with low PGI (<25 µg/L; a marker of atrophic corpus gastritis) were invited to undergo gastroscopy because of increased gastric cancer risk. Endoscopy was performed to 1,327 men, who were followed up for a median of 13.6 years and a maximum of 25.3 years thereafter. In addition, the gastric cancer risk of men with low PGI was compared to that of the men with normal PGI and to the general Finnish male population of the same age. Results: Thirty-five cases of gastric cancer were diagnosed in men with gastroscopy during the follow-up. The incidence rate was 1.94 per 1000 patient years. The men with a history of gastric surgery (n = 180) due to a benign cause had even higher gastric cancer incidence (3.2 per 1000 patient-years). Gastric cancer risk was highest in men with marked intestinal metaplasia in primary biopsies. Compared to the general Finnish male population of the same age, the cancer risk was 1.13 times higher in male smokers with normal serum PGI, and 2.43 times higher in men with low serum PGI. Conclusion: In male smokers, atrophic gastritis and intestinal metaplasia increase the risk of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Tomato and soy intake is associated with reduced prostate cancer risk or severity in epidemiologic and experimental studies.Objective: On the basis of the principle that multiple bioactives in tomato and soy may act on diverse anticancer pathways, we developed and characterized a tomato-soy juice for clinical trials. In this phase 2 dose-escalating study, we examined plasma, prostate, and urine biomarkers of carotenoid and isoflavone exposure.Methods: Men scheduled for prostatectomy were recruited to consume 0, 1, or 2 cans of tomato-soy juice/d before surgery (mean ± SD duration: 24 ± 4.6 d). The juice provided 20.6 mg lycopene and 66 mg isoflavone aglycone equivalents/177-mL can. Plasma carotenoids and urinary isoflavone metabolites were quantified by HPLC-photometric diode array and prostate carotenoids and isoflavones by HPLC-tandem mass spectrometry.Results: We documented significant dose-response increases (P < 0.05) in plasma concentrations of tomato carotenoids. Plasma concentrations were 1.86-, 1.69-, 1.73-, and 1.69-fold higher for lycopene, β-carotene, phytoene, and phytofluene, respectively, for the 1-can/d group and 2.34-, 3.43-, 2.54-, and 2.29-fold higher, respectively, for the 2-cans/d group compared with 0 cans/d. Urinary isoflavones daidzein, genistein, and glycitein increased in a dose-dependent manner. Prostate carotenoid and isoflavone concentrations were not dose-dependent in this short intervention; yet, correlations between plasma carotenoid and urinary isoflavones with respective prostate concentrations were documented (R2 = 0.78 for lycopene, P < 0.001; R2 = 0.59 for dihydrodaidzein, P < 0.001). Secondary clustering analyses showed urinary isoflavone metabolite phenotypes. To our knowledge, this is the first demonstration of the phytoene and phytofluene in prostate tissue after a dietary intervention. Secondary analysis showed that the 2-cans/d group experienced a nonsignificant decrease in prostate-specific antigen slope compared with 0 cans/d (P = 0.078).Conclusion: These findings provide the foundation for evaluating a well-characterized tomato-soy juice in human clinical trials to define the impact on human prostate carcinogenesis. This trial is registered at clinicaltrials.gov as NCT01009736. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer in men (BCM) accounts for approximately 1% of all breast cancer cases. The present study aimed at describing the clinical and demographic characteristics of BCM in Mexican population. Methods: We performed a retrospective analysis of the men with newly diagnosed breast cancer treated in an oncology referral center in Northeast Mexico from 2007 to 2017. Results: Fifteen patients were included in the analysis. Mean age at diagnosis was 60.7 years and median time from diagnosis to the start of treatment was 2 months. About 73% of patients presented with locoregional disease (clinical stage [CS] I-III) and 26.7% were classified as Stage IV disease on their first assessment. All patients had invasive ductal carcinoma and 60.0% were Grade II tumors. Twelve cases were positive for hormone receptors and none showed overexpression of human epidermal growth factor receptor 2. Regarding primary treatment, 12 patients underwent a modified radical mastectomy and two underwent breast-conserving surgery. The majority of patients received chemotherapy and radiotherapy in the adjuvant setting and tamoxifen was the drug of choice in all patients considered as candidates for hormonal therapy. Conclusion: While most of the data presented matches that reported by other authors, some interesting differences unique to our population were observed. [ABSTRACT FROM AUTHOR]

Prostate cancer is the second most common cancer and the fifth leading cause of cancer deaths in men worldwide. This review article contains a summary of analyzes performed by chromatographic methods used for the determination of abiraterone acetate, bicalutamide, cabazitaxel, docetaxel, enzalutamide, flutamide, goserelin acetate, leuprolide acetate, and mitoxantrone hydrochloride drugs used in prostate cancer applications in biological and pharmacological samples. In this review, sample preparation procedures, chromatographic procedures, and detectors used for analytical determinations of these drugs are discussed. [ABSTRACT FROM AUTHOR]

Abstract Psychological distress is prevalent among men with prostate cancer (PCa). However, the variation in antidepressant use among individuals throughout the survivorship period is unknown. We sought to examine the variation and trends in receipt of antidepressants after PCa treatment, among patients with nonmetastatic PCa. Using population-based linked administrative data, we identified men ≥66 yr old who underwent surgery (n = 4952), radiotherapy (n = 4994), or surveillance (n = 2136), and these men were matched to general population controls (n = 57 127). One year prior to PCa treatment, 7.7% of men received an antidepressant prescription, which increased to 10.5% in the year after treatment. In difference-in-differences analysis, adjusted for demographic and health characteristics, men had increased odds of antidepressant receipt up to 5 yr after surgery (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.35–1.64; p ≤ 0.0001) or radiotherapy (OR 1.33; 95% CI 1.21–1.47; p ≤ 0.0001). Men did not have an increased risk of antidepressant receipt up to 5 yr after surveillance (OR 1.15; 95% CI 0.94–1.41; p = 0.16). Limitations include the potential for selection bias and misclassification due to the retrospective design of the study and the use of administrative databases. Thus, men with nonmetastatic PCa who initially receive surgery or radiotherapy, but not those who initially undergo surveillance, have an increased risk of antidepressant receipt after treatment. Patient summary In this report, we examined antidepressant prescription for men after treatment of nonmetastatic prostate cancer across the entire population of men ≥66 yr in Ontario, Canada, from 2002 to 2009. For men diagnosed with nonmetastatic prostate cancer, the risk of antidepressant receipt at 5 yr after treatment was significantly increased after surgery or radiotherapy, but not after surveillance. Providers and patients should consider the psychological effects of prostate cancer treatment during the survivorship period. Take Home Message Patients treated for nonmetastatic prostate cancer with surgery or radiation have an increased risk of receiving antidepressant prescriptions for at least 5 yr, whereas patients undergoing surveillance do not. Thus, psychological support after treatment is an important part of prostate cancer care. [ABSTRACT FROM AUTHOR]

Abstract Causes of high mortality of prostate cancer in men of African ancestry living in the French West Indies are still debated, between suspicions of environmental factors and genetic susceptibility. We report an integrated genomic study of 25 tumour tissues from radical prostatectomy of aggressive (defined by International Society of Urological Pathology ≥3) prostate cancer patients (10 African Caribbean and 15 French Caucasian) using single nucleotide polymorphism arrays, whole-genome sequencing, and RNA sequencing. The results show that African Caribbean tumours are characterised by a more frequent deletion at 1q41-43 encompassing the DNA repair gene PARP 1, and a higher proportion of intrachromosomal rearrangements including duplications associated with CDK12 truncating mutations. Transcriptome analyses show an overexpression of genes related to androgen receptor activity in African Caribbean tumours, and of PVT1 , a long non-coding RNA located at 8q24 that confirms the strong involvement of this region in prostate tumours from men of African ancestry. Patient summary: Mortality of prostate cancer is higher in African Caribbean men than in French Caucasian men. Specificities of the former could be explained by genomic events linked with key genes such as DNA damage pathway genes PARP1 , CDK12 , and the oncogenic long non-coding RNA gene PVT1 at the 8q24 prostate cancer susceptibility locus. Take Home Message The higher prostate cancer mortality observed in African Caribbean men could be explained by genomic events linked with DNA damage pathway genes: PARP1 , CDK12 , and the oncogenic long non-coding RNA PVT1 located at the 8q24 prostate cancer susceptibility locus. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC), also known as colon cancer, is the third most common form of cancer worldwide in men and the second in women and is characterized by several genetic alterations, among them the expression of several genes. 1,2-dimethylhydrazine (DMH) and its metabolite azoxymethane (AOM) are procarcinogens commonly used to induce colon cancer in rats (DMH/AOM rat model). This rat model has been used to study changes in mRNA expression in genes involved in this pathological condition. However, a lack of proper detailed PCR primer design in the literature limits the reproducibility of the published data. The present study aims to design, optimize and validate the qPCR, in accordance with the MIQE (Minimum Information for Publication of Quantitative Real-Time PCR Experiments) guidelines, for seventeen genes commonly used in the DMH/AOM rat model of CRC (Apc, Aurka, Bax, Bcl2, β-catenin, Ccnd1, Cdkn1a, Cox2, Gsk3beta, IL-33, iNOs, Nrf2, p53, RelA, Smad4, Tnf α and Vegfa) and two reference genes (Actb or β-actin and B2m). The specificity of all primer pairs was empirically validated on agarose gel, and furthermore, the melting curve inspection was checked as was their efficiency (%) ranging from 90 to 110 with a correlation coefficient of r² >0:980. Finally, a pilot study was performed to compare the robustness of two candidate reference genes. [ABSTRACT FROM AUTHOR]