BackgroundMutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations.ObjectiveTo report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status.Design, setting, and participantsMen aged 40–69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy.Outcome measurements and statistical analysisPSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians.Results and limitationsA total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65).ConclusionsAfter 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers.Patient summaryWe demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening.
Introduction Ureterorenoscopy (URS) is a popular and growing option for management of ureteric and renal stones. The CROES URS Global Study was set up to assess the outcomes of URS in a large worldwide cohort of patients involving multiple centres. In this paper, we analysed the database for intra-operative and post-operative complications associated with ureterorenoscopy. MethodsThe CROES database was established via collaboration between 114 centres in 32 countries worldwide, and information on both intra-operative and post-operative complications was collected electronically between January 2010 and October 2012.ResultOn analysis of a total of 11,885 patients, the overall complication and stone-free rates were found to be 7.4 and 85.6 %, respectively. The intra-operative and post-operative complication rates were 4.2 and 2.6 %, respectively, and in total 5 deaths were reported in the study period. Taking into account different world economies, there were no differences in the complication rates between the developing and developed nations or between different centres from different continents.ConclusionUreterorenoscopy is a safe and effective procedure for treatment of stones, the outcomes of which are broadly comparable in different parts of the world for similar patient and stone demographics.
BackgroundIrrigation and instrumentation during ureterorenoscopic procedures may cause increased pressure in the renal pelvis (PP) with potential harmful adverse effects. In order to assess the pressure increases during ureterorenoscopy, we measured the intraluminal renal pelvic pressure during retrograde intrarenal stone surgery (RIRS).MethodsTwelve patients admitted for RIRS were included. Irrigation rate was standardized to 8 ml/min. A ureteral catheter was retrogradely placed in the renal pelvis for PP measurements. PP was measured one time per second during insertion of the Storz Flex-X2 ureteroscope and during stone treatment.ResultsBaseline PP was mean 10(±4.0) mmHg. During simple ureterorenoscopy, PP was mean 35(±10) mmHg. During stone management the average PP was 54(±18) mmHg and pelvic pressure peaks up to 328 mmHg occurred. In a 5-min standardized period of simple ureterorenoscopy, 83 pressure peaks >50 mmHg were measured in average per patient (range 2–238). Forced irrigation with a 20 ml syringe resulted in pressure peaks up to 288 mmHg.ConclusionVery high pelvic pressures are obtained during flexible ureterorenoscopy. Taking into consideration that the threshold for pyelovenous backflow is around 30 mmHg, it is concerning that PPs >300 mmHg are not uncommon during these procedures. Methods to monitor and lower the PP during ureterorenoscopy, therefore, are considered of importance.
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