Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Lidocaine suppository for transrectal ultrasound-guided biopsy of the prostate: a prospective, double-blind, randomized study

AIMS: To investigate analgesia using lidocaine suppositories for prostate biopsy. ----- METHODS: From 2007 to 2009, 160 patients underwent transrectal ultrasound-guided prostate biopsy at the Department of Urology, KBC Zagreb. 80 patients received a 60-mg lidocaine suppository intrarectally at different time points from 15 to 120 min before biopsy and 80 patients received a glycerin suppository as placebo. The pain level was evaluated using a visual analogue scale (VAS). ----- RESULTS: There were no statistically significant differences between the groups, i.e. they were similar regarding patients' age, prostate-specific antigen levels, prostate volume and the incidence of diagnosis of malignancy on biopsy. The mean pain score in the lidocaine group (3 ± 1) was significantly lower than the mean pain score in the glycerin group (4.1 ± 1.3) (p < 0.001). A noticeable trend towards lower pain scores in the lidocaine group was observed with more time elapsing from placing the suppository till the biopsy and the optimal time for performing biopsy starting approximately 1 h after placing the suppository. ----- CONCLUSIONS: Lidocaine suppositories are an easy-to-use, self-applicable (by the patient) and cheap method of local analgesia, with acceptable results. Possible complications related to this procedure are insignificant

Laparoscopic adrenalectomy: lessons learned from 306 cases

INTRODUCTION: Laparoscopic adrenalectomy has become the standard of care for the surgical treatment of benign adrenal pathology. We present the following case series documenting our experience in refinement of this approach. PAIENTS AND METHODS: Analysis of patient records identified those in whom laparoscopic adrenalectomy was performed from January 1997 through February 2010. Study variables included indications, operative time, blood loss, length of hospital stay, histopathological evaluation, and complications. ----- RESULTS: Laparoscopic adrenalectomy was performed in 306 patients using the transperitoneal lateral approach. No major operative complications were noted, and postoperative complications included a pulmonary embolism and 2 cases of pneumonia. Conversion to the open approach was necessitated in two cases. The median operative time was 95±29 minutes (range, 45-145 minutes). Estimated blood loss was 60 mL (range, 30-150 mL). The mean size of the removed gland was 5.9±1.6 cm (range, 3-13 cm). The mean size of the tumor was 5±2 cm (range, 0.5-12 cm). The median hospitalization was 4±3.7 days (range, 2-22 days). Adrenal pathology included adenoma (n=164), pheochromocytoma (n=79), hyperplasia (n=35), metastatic carcinoma (n=22), cyst (n=9), myelolipoma (n=9), hemangioma (n=3), ganglioneuroma (n=3), and melanoma (n=2). ----- CONCLUSION: Laparoscopic adrenalectomy is a safe and feasible approach to adrenal pathology, providing the patients with all the benefits of minimally invasive surgery

Histopathological features of time-zero kidney biopsy are predictive factors for posttransplant anemia

Posttransplant anemia is a common complication of kidney transplantation, associated with reduced graft survival and higher mortality. We aimed to determine the association of posttransplant anemia with histopathological characteristics of time-zero allograft biopsy and donor clinical characteristics. Methods We conducted a retrospective, observational cohort study that included 587 patients who underwent kidney transplantation in our Centre. Hemoglobin levels were assessed at 6 and 12 months after transplantation, and anemia was defined according to World Health Organization criteria. The kidney allograft time-zero biopsy has been done in all investigated cases. The evaluated histopathological parameters of the kidney allografts included glomerulosclerosis, arteriolar hyalinosis, vascular fibrous intimal thickening, interstitial fibrosis, tubular atrophy, and interstitial fibrosis and tubular atrophy. The Banff Classification of Allograft Pathology criteria were followed to assess the allograft histopathological changes. Results The prevalence of anemia was 31.3% at 6 months after transplantation and 23.5% at 12 months. There was an association between 20-50% glomerulosclerosis and posttransplant anemia in both time points, independently from eGFR. Arteriolar hyalinosis and interstitial fibrosis were identified as independent risk factors for anemia at 6 months after transplantation. Conclusion Histopathological features of time-zero kidney biopsy may be predictors of PTA. Among them, our study recognized 20-50% degree of glomerulosclerosis, AH, and CV as the most significant risk factors for PTA

Health-related quality of life and fatigue in patients with adrenal incidentaloma

The objective of the present study was to examine several dimensions of quality of life (QoL) and fatigue in patients with adrenal incidentaloma. This was a case-control study designed to analyze patient outcomes using three validated generic QoL questionnaires, EQ-5D, SF-36, and MFI-20, the results of which were compared to those obtained for age- and sex-matched controls. The study population comprised 139 consecutive patients with nonfunctioning adrenal masses (104 females, 35 males; age 59.1 ± 10.8) and 139 age- and sex-matched controls. Reduced QoL was found in patients with adrenal incidentaloma as compared to controls. Dimensions of QoL that were notably affected included mobility (P = 0.03), performance of usual activities (P = 0.002), and anxiety/depression (P = 0.04) as evaluated using the EQ-5D; physical functioning (P < 0.001), physical role (P < 0.001), general health (P < 0.001), vitality (P = 0.001), social functioning (P = 0.001), and emotional role (P < 0.001) as evaluated using the SF-36; and physical fatigue (P = 0.04) as assessed using the MFI-20 questionnaire. In addition, perceived health on a visual analogue scale was also significantly lower in patients than in controls (64.8 ± 19.2 vs. 77.1 ± 15.1; P < 0.001). Patients with adrenal incidentaloma reported reduced QoL and a higher level of physical fatigue compared to age- and sex-matched controls. This subject will benefit from further studies comparing QoL outcomes of laparoscopic adrenalectomy versus no treatment in patients with adrenal incidentaloma