A urine-based DNA methylation assay, ProCUrE, to identify clinically significant prostate cancer.

BACKGROUND: Prevention of unnecessary biopsies and overtreatment of indolent disease remains a challenge in the management of prostate cancer. Novel non-invasive tests that can identify clinically significant (intermediate-risk and high-risk) diseases are needed to improve risk stratification and monitoring of prostate cancer patients. Here, we investigated a panel of six DNA methylation biomarkers in urine samples collected post-digital rectal exam from patients undergoing prostate biopsy, for their utility to guide decision making for diagnostic biopsy and early detection of aggressive prostate cancer. RESULTS: We recruited 408 patients in risk categories ranging from benign to low-, intermediate-, and high-risk prostate cancer from three international cohorts. Patients were separated into 2/3 training and 1/3 validation cohorts. Methylation biomarkers were analyzed in post-digital rectal exam urinary sediment DNA by quantitative MethyLight assay and investigated for their association with any or aggressive prostate cancers. We developed a Prostate Cancer Urinary Epigenetic (ProCUrE) assay based on an optimal two-gene (HOXD3 and GSTP1) LASSO model, derived from methylation values in the training cohort, and assessed ProCUrE's diagnostic and prognostic ability for prostate cancer in both the training and validation cohorts. ProCUrE demonstrated improved prostate cancer diagnosis and identification of patients with clinically significant disease in both the training and validation cohorts. Using three different risk stratification criteria (Gleason score, D'Amico criteria, and CAPRA score), we found that the positive predictive value for ProCUrE was higher (59.4-78%) than prostate specific antigen (PSA) (38.2-72.1%) for all risk category comparisons. ProCUrE also demonstrated additive value to PSA in identifying GS ≥ 7 PCa compared to PSA alone (DeLong's test p = 0.039), as well as additive value to the PCPT risk calculator for identifying any PCa and GS ≥ 7 PCa (DeLong's test p = 0.011 and 0.022, respectively). CONCLUSIONS: ProCUrE is a promising non-invasive urinary methylation assay for the early detection and prognostication of prostate cancer. ProCUrE has the potential to supplement PSA testing to identify patients with clinically significant prostate cancer.

Prevalence of ciprofloxacin-resistant Enterobacteriaceae in the intestinal flora of patients undergoing transrectal prostate biopsy in Norwich, UK.

OBJECTIVE: To determine the efficacy of fluoroquinolone prophylaxis in patients undergoing transrectal ultrasonography (TRUS)-guided biopsy of the prostate in the Norwich population, and its correlation with ciprofloxacin resistance in the faecal flora. We also aimed to determine the usefulness of a pre-biopsy rectal screen for resistant bacteria in these patients. PATIENTS AND METHODS: The incidence and microbiology of sepsis after TRUS-guided prostate biopsies between 2007 and 2011 was audited retrospectively. Subsequently, in 2012, a prospective study was performed, collecting the same data but also culturing rectal swabs from all patients undergoing TRUS-guided biopsy, with a post-biopsy follow-up period of 6 months. All patients were given prophylactic oral ciprofloxacin, as per Trust policy (750 mg 1 h before biopsy, followed by 250 mg twice daily for 3 subsequent days). RESULTS: Between 2007 and 2011, 3600 patients underwent TRUS-guided biopsy. Among these, 11 (0.3%) were admitted to hospital for post-biopsy related sepsis but only 4 (0.1%) had ciprofloxacin-resistant Escherichia coli confirmed from blood cultures: three had ciprofloxacin-susceptible Enterobacteriaceae, and four had no ciprofloxacin susceptibility data. In 2012, 10 (3.7%) of 267 patients sampled before biopsy had ciprofloxacin-resistant E. coli recovered on rectal swab culture but none of these men presented with post-biopsy sepsis; during the 6-month follow-up period, seven patients were diagnosed with urinary tract infections. CONCLUSION: Ciprofloxacin-resistant Enterobacteriaceae remains rare in the intestinal flora of the Norwich TRUS population, meaning that the drug remains adequate as prophylaxis. Pre-biopsy rectal swabs may be useful for individual departments to periodically assess their own populations and to ensure their antibiotic policy remains valid. In populations where resistance is known to be highly prevalent, pre-biopsy rectal swabs can help guide addition of further antibiotics to prevent post-biopsy septicaemia.

Isolated unilateral tongue oedema: the adverse effect of Angiotensin converting enzyme inhibitors.

Angiotensin converting enzyme inhibitors (ACEI) are widely used to treat benign hypertension. These drugs are generally well tolerated. Serious side effects such as angio-oedema are very rare. The authors report a 64-year-old Caucasian woman with a history of liver transplant on Mammalian Target Of Rapamycin (mTOR) inhibitor, who attended Emergency department with angio-oedema only on the left side of her tongue. Her airway was patent and she was haemodynamically stable. Trauma was denied. Her physician had 2 days earlier commenced her on Lisinopril for newly diagnosed benign hypertension. Intravenous steroids and anti-histamine were immediately administered. A good response of oedema subsidence was noted. In general, angio-oedema can present in a spectrum of severity. Precipitating factors are often difficult to pre-determine and avoid. Early recognition of risk factors for and diagnosis of angio-oedema can often be life-saving.