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[en] We have previously shown that a functional polymorphism of the UGT2B15 gene (rs1902023) was associated with increased risk of prostate cancer (PC). Novel functional polymorphisms of the UGT2B17 and UGT2B15 genes have been recently characterized by in vitro assays but have not been evaluated in epidemiologic studies. Fifteen functional SNPs of the UGT2B17 and UGT2B15 genes, including cis-acting UGT2B gene SNPs, were genotyped in African American and Caucasian men (233 PC cases and 342 controls). Regression models were used to analyze the association between SNPs and PC risk. After adjusting for race, age and BMI, we found that six UGT2B15 SNPs (rs4148269, rs3100, rs9994887, rs13112099, rs7686914 and rs7696472) were associated with an increased risk of PC in log-additive models (p < 0.05). A SNP cis-acting on UGT2B17 and UGT2B15 expression (rs17147338) was also associated with increased risk of prostate cancer (OR = 1.65, 95% CI = 1.00-2.70); while a stronger association among men with high Gleason sum was observed for SNPs rs4148269 and rs3100. Although small sample size limits inference, we report novel associations between UGT2B15 and UGT2B17 variants and PC risk. These associations with PC risk in men with high Gleason sum, more frequently found in African American men, support the relevance of genetic differences in the androgen metabolism pathway, which could explain, in part, the high incidence of PC among African American men. Larger studies are required
[en] A descriptive and cross-sectional study was carried out in 28 917 men over 50 years of age, belonging to 8 health areas of Santiago de Cuba, from November 2007 to July 2010, to determine the prostate-specific antigen (PSA) and thus detect prostate cancer hidden morbidity. The test was performed in 18 007 screened individuals, of whom 1 745 had pathological findings, and of them 1 630 were evaluated at the urology department of the selected polyclinic according to the established flow chart. Finally, 125 males were diagnosed with the disease, so that it was confirmed the importance of having a greater dissemination of PSA test, benefits of which allow the family physician to know the health of their patients, and the risk population obtain such assistance annually through the doctor's offices
[en] Prostate cancer (PCA) is the most commonly diagnosed cancer in men in the United States with growing worldwide incidence. Despite intensive investment in improving early detection, PCA often escapes timely detection and mortality remains high; this malignancy being the second highest cancer-associated mortality in American men. Collectively, health care costs of PCA results in an immense financial burden that is only expected to grow. Additionally, even in cases of successful treatment, PCA is associated with long-term and pervasive effects on patients. A proactive alternative to treat PCA is to prevent its occurrence and progression prior to symptomatic malignancy. This may serve to address the issue of burgeoning healthcare costs and increasing number of sufferers. One potential regimen in service of this alternative is PCA chemoprevention. Here, chemical compounds with cancer preventive efficacy are identified on the basis of their potential in a host of categories: their historical medicinal use, correlation with reduced risk in population studies, non-toxicity, their unique chemical properties, or their role in biological systems. PCA chemopreventive agents are drawn from multiple broad classes of chemicals, themselves further subdivided based on source or potential effect, with most derived from natural products. Many such compounds have shown efficacy, varying from inhibiting deregulated PCA cell signaling, proliferation, epithelial to mesenchymal transition (EMT), invasion, metastasis, tumor growth and angiogenesis and inducing apoptosis. Overall, these chemopreventive agents show great promise in PCA pre-clinical models, though additional work remains to be done in effectively translating these findings into clinical use
[en] Prostate cancer is the most common cancer occurring in American men of all races. It is also the second leading cause of cancer death among men in the USA. Bone metastasis is a frequent occurrence in men with advanced prostate cancer, with skeletal-related events being a common complication and having negative consequences, leading to severe pain, increased health care costs, increased risk of death, and decreased quality of life for patients. Bone loss can also result from antiandrogen therapy, which can further contribute to skeletal-related events. Treatment with antiresorptive agents bisphosphonates, and the newly approved denosumab, a receptor activator of nuclear factor kappa-B ligand (RANK-L) inhibitor, has been shown to reduce the risk of skeletal-related complications and prevent treatment-induced bone loss in patients with advanced prostate cancer. This review discusses the role of antiresorptive agents bisphosphonates and RANK-L inhibitor in the current treatment of advanced prostate cancer by examining the primary literature and also focuses on the likely role of the bisphosphonates in the treatment of advanced prostate cancer in the future
[en] To evaluate the impact of PTV reduction when delivering image-guided IMRT (IG-IMRT) for patients with prostate cancer. Between 2001 and 2007, 165 men were treated with daily IG-IMRT using a 3D ultrasound-based system. Median dose prescribed to the prostate was 78 Gy [74 Gy–78 Gy]. Patients were stratified regarding the CTV to the PTV margin: group A (n = 87) = 5 mm or group B (n = 78) = 10 mm. Late toxicity was scored using the CTC v3.0 scale. Biochemical progression-free survival (bPFS) was calculated using the Phoenix definition. Grade 2 genitourinary toxicity was 7.0% for group A and 6.6% for group B (p = 1.00). Grade 2 gastrointestinal toxicity was 1.2% and 2.6% (p = 0.38). With a median follow-up of 38.3 months [5.25–87.3], bPFS at 3 years was 92.5% [82.4%–96.9%] in group A and 94.3% [85.5%–97.8%] in group B (p = 0.84). IG-IMRT yielded very low rates of late toxicity. Margin had impact neither on short-term bPFS nor late toxicity.
[en] The current pathway for men suspected of having prostate cancer [transrectal biopsy, followed in some cases by magnetic resonance imaging (MRI) for staging] results in over-diagnosis of insignificant tumours, and systematically misses disease in the anterior prostate. Multiparametric MRI has the potential to change this pathway, and if performed before biopsy, might enable the exclusion of significant disease in some men without biopsy, targeted biopsy in others, and improvements in the performance of active surveillance. For the potential benefits to be realized, the setting of standards is vital. This article summarizes the outcome of a meeting of UK radiologists, at which a consensus was achieved on (1) the indications for MRI, (2) the conduct of the scan, (3) a method and template for reporting, and (4) minimum standards for radiologists
[en] Full text: The main role of imaging in prostatic diseases is for prostate cancer. Transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) are the most commonly used imaging tools used for the diagnosis of the diseases of the prostate gland. The main indications for TRUS is the evaluation for prostate cancer and guidance for prostate biopsy. On TRUS, the transition zone with a hypoechoic appearance can be differentiated from the peripheral zone, which appears relatively echogenic and homogenous in echotexture. Prostate cancer mainly involves the peripheral zone, though one fifth of the disease can be detected in the transition zone, which is the major site for hyperplastic changes in older men. Color Doppler ultrasound may be helpful for the differentiation of low-risk, hypovascular tumors from high-risk, hypervascular tumors, as the latter group is associated with higher Gleason tumor grades consistent with higher risk for extraprostatic spread. Nevertheless, targeted prostate biopsy solely based on high-frequency color or power Doppler imaging is not recommended, as the technique has inherent risk of missing a significant number of cancers. Although power Doppler ultrasound can enable the operator to perform more accurate sampling of the prostate by determining sites of focal hypervascularity, it has not been found to be superior to color Doppler ultrasound. It has been reported to be useful only for targeted biopsies with limited number of biopsy cores. Microbubble contrast agents may enable better visualization of prostatic microvasculature and cancerous prostate tissue. By means of contrast-enhanced ultrasound (CEUS), the number of cores may be decreased by performing targeted biopsies. Importantly, the detection of the signals reflected by the microbubbles can be enhanced by the phase inversion (pulse-inversion) technology. Prostate cancer appears as a dark zone on elastography representing limited elasticity or compressibility. By means of the technique, cancerous tissue can be differentiated from benign tissues depending on the hardness gradient and degree of elasticity loss. Nevertheless, the technique is not sufficient yet to preclude the requirement for systematic prostate biopsies. TRUS-guided prostate biopsy has been accepted as the 'gold standard' tool for the detection of prostate cancer. Currently, extended sampling protocols involving 10-12 cores with additional laterally directed cores at the aforementioned levels have been used to increase the diagnostic yield. Magnetic resonance imaging (MRI) is useful for prostate cancer detection primarily in patients with persisting suspicion for undisclosed cancer, despite having negative transrectal US and biopsy findings. MRI can also be used for the localization of cancer within the prostate and in local and distant staging of the disease. Technically, fast spin echo imaging preferably with the combination of endorectal and pelvic phased array coils is recommended for an ideal prostate MRI examination. MRI also aids in the local staging of prostate cancer, as it enables the assessment of the capsular penetration, extracapsular spread and local and distant metastasis. Accordingly, the data derived from endorectal MRI can be used with Partin nomograms to predict extracapsular spread of prostate cancer, in intermediate and high risk patients. MRI is a complementary technique to improve tumor detection by the assessment of tumor metabolism. Dynamic contrast-enhanced MRI, on the other hand, enables direct assessment of the angiogenesis associated with prostate cancer and relative peak enhancement has been accepted as the most accurate perfusion parameter for cancer detection. Diffusion- Weighted Imaging is based on the restriction of diffusion and elevation of apparent diffusion coefficient (ADC) in cancerous tissue compared to the normal prostate tissue. However, the diagnostic accuracy of the technique is diminished by the variability of the ADC values
[en] Prostate and urinary bladder cancer are the most frequently encountered malignancies of the urinary tract. Appropriate use of the different imaging techniques is crucial for accurate assessment of prognosis and for the development of appropriate treatment planning. Especially determination of local tumor extension and detection of nodal or bone metastases is extremely important. In this regard MR imaging is the most promising imaging technique. Therefore, in this review its role in staging these malignancies is evaluated and compared with clinical staging, and other imaging techniques. Finally, future developments, such as new sequences, new contrast agents, the role of surface coils and MR-guided biopsy, are considered. Also, the preferred radiological approach is discussed. (orig.)
[en] Purpose: Prostate-specific antigen (PSA) velocity, like PSA level, can be confounded. In this study, we estimated the impact that confounding factors could have on correctly identifying a patient with a PSA velocity >2 ng/ml/y. Methods and Materials: Between 2006 and 2010, a total of 50 men with newly diagnosed PC comprised the study cohort. We calculated and compared the false-positive and false-negative PSA velocity >2 ng/ml/y rates for all men and those with low-risk disease using two approaches to calculate PSA velocity. First, we used PSA values obtained within 18 months of diagnosis; second, we used values within 18 months of diagnosis, substituting the prebiopsy PSA for a repeat, nonconfounded PSA that was obtained using the same assay and without confounders. Results: Using PSA levels pre-biopsy, 46% of all men had a PSA velocity >2 ng/ml/y; whereas this value declined to 32% when substituting the last prebiopsy PSA for a repeat, nonconfounded PSA using the same assay and without confounders. The false-positive rate for PSA velocity >2 ng/ml/y was 43% as compared with a false-negative rate of PSA velocity >2 ng/ml/y of 11% (p = 0.0008) in the overall cohort. These respective values in the low-risk subgroup were 60% and 16.7% (p = 0.09). Conclusion: This study provides evidence to explain the discordance in cancer-specific outcomes among groups investigating the prognostic significance of PSA velocity >2 ng/ml/y, and highlights the importance of patient education on potential confounders of the PSA test before obtaining PSA levels.