Prostate cancer remains among the most commonly diagnosed malignancies worldwide. Early diagnosis and curative treatment appear to improve survival in men with unfavorable-risk cancers, but significant concerns exist regarding the overdiagnosis and overtreatment of men with lower-risk cancers. To this end, active surveillance (AS) has emerged as a primary management strategy in men with favorable-risk disease, and contemporary data suggest that use of AS has increased worldwide. Although published surveillance cohorts differ by protocol, reported rates of metastatic disease and prostate cancer-specific mortality are exceedingly low in the intermediate term (5–10 years). Such outcomes appear to be closely associated with program-specific criteria for selection, monitoring, and intervention, suggesting that AS – like other management strategies – could be individualized based on the level of risk acceptable to patients in light of personal preferences. Additional data are needed to better establish the risks associated with AS and to identify patient-specific characteristics that could modify prognosis.
Summary
The prostate health index (phi) is a FDA-approved blood test combining total, free and −2proPSA with greater specificity than free and total PSA for clinically-significant prostate cancer. This article reviews the evidence on the performance of phi to predict prostate biopsy outcome, its incorporation into multivariable risk-assessment tools, and its ability to predict prognosis after conservative management or prostate cancer treatment.
INTRODUCTION AND OBJECTIVE: Host microbiome is critical for maintaining immune homeostasis and priming systemic and local immune responses. Little is known about whether microbiome perturbation affects innate responses of the bladder against infections caused by uropathogenic E. coli (UPEC). A recent population-based study showed a link between antibiotic use, gut microbiome perturbation and recurrent urinary tract infection (UTI). This study was to explore the effects of antibiotic-induced host microbiome perturbation on experimental UTI.METHODS: Antibiotic (Abx) treatment (1 g/L each of ampicillin, neomycin, metronidazole, 0.5 g/L of vancomycin in drinking water) started for conventionally raised female mouse breeders (129/SvEv strain), continued during pregnancy until after weaning of the offspring which were treated for 2 more weeks. Treatment ceased 10 days before UPEC infection. Control mice received no Abx. Due to technical difficulties to quantify urine microbiome in mice, fecal microbiome was used as a surrogate by Q-PCR and 16S-rDNA MiSeq. Female mice (n[15) were transurethrally infected with UPEC strain UTI89 (10 7 cfu in 50 ul). Bladders were homogenized/plated to enumerate UPEC or immunostained with anti-E.coli, uroplakin Ia, p65 of NF-kB and Ly6G. Neutrophil infiltration was assessed by myeloperoxidase (MPO) assay.RESULTS: Abx treatment resulted in a 90% reduction of fecal microbiome and its diversity by 34% but it did not affect urinary tract anatomy, urothelial morphology or apical distribution of uroplakin Ia e the urothelial receptor for type 1-piliated UPEC. UPEC induced rapid activation of NF-kB in the umbrella cells in both the Abx-treated and control mice at 2 hours post-infection (hpi). However, bacterial colonization at 24 hpi was 5-fold higher in the Abx-treated mouse bladders than the controls. The number of intracellular bacterial communities at 12 and 24 hpi was 2.5-fold and 5-folder higher, respectively, in the Abx mice than in controls. In contrast, neutrophil infiltration and neutrophil MPO activity were significantly lower in the Abx mice.CONCLUSIONS: Our study provides the first experimental evidence demonstrating that the host microbiome plays a critical role in innate immune defenses against UTI and that its deficiency caused by early-age antibiotic exposure leads to compromised neutrophil infiltration and increased bacterial burden in the bladder. Further studies are needed to ascertain whether these effects are caused by gut and/or urinary microbiome.
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