Can epigenetic and inflammatory biomarkers identify clinically aggressive prostate cancer?

Prostate cancer (PCa) is a highly prevalent malignancy and constitutes a major cause of cancer-related morbidity and mortality. It emerges through the acquisition of genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone modifications and microRNA deregulation. These generate heritable transformations in the expression of genes but do not change the DNA sequence. Alterations in DNA methylation (hypo and hypermethylation) are the most characterized in PCa. They lead to genomic instability and inadequate gene expression. Major and minor-specific modifications in chromatin recasting are involved in PCa, with signs suggesting a dysfunction of enzymes modified by histones. MicroRNA deregulation also contributes to the initiation of PCa, including involvement in androgen receptor signalization and apoptosis. The influence of inflammation on prostate tumor carcinogenesis is currently much better known. Recent discoveries about microbial species resident in the urinary tract suggest that these are the initiators of chronic inflammation, promoting prostate inflammatory atrophy and eventually leading to PCa. Complete characterization of the relationship between the urinary microbiome and prostatic chronic inflammation will be crucial to develop plans for the prevention of PCa. The prevalent nature of epigenetic and inflammatory alterations may provide potential biomarkers for PCa diagnosis, treatment decisions, evaluation of prognosis and posttreatment surveillance.

Is robotic-assisted radical cystectomy (RARC) with intracorporeal diversion becoming the new gold standard of care?

BACKGROUND: Totally intracorporeal robotic-assisted radical cystectomy (RARC) has perceived difficulties compared to open radical cystectomy (ORC). As the technique is increasingly adopted around the world, the benefits of RARC with intra- or extracorporeal urinary diversion or ORC for the patients are still unclear. In this article, we consider the current evidence for this issue. METHODS: We assessed two questions through using expert opinion and the medical literature: (A) Is RARC better than ORC for removing the cancer surgery and outcome? (B) Is RARC better than ORC for the urinary diversion? OUTCOMES: (A) RARC is better than ORC for shorter length of stay, blood loss and complication rates. (B) Intracorporeal orthotopic neobladder may have a significant physiological and surgical benefit to the patient recovery. CONCLUSIONS: RARC with total intracorporeal reconstruction has potential benefits to the patient. We recommend that all surgeons document patient-related outcome measures, urodynamics and enhanced recovery protocols for cystectomy patients to help us understand the real improvements within bladder cancer surgery and reconstruction.

Impact of positive surgical margins on biochemical relapse after radical retropubic prostatectomy (RRP).

INTRODUCTION: RP (radical prostatectomy) technique continues the major treatment option for men with potential cure and life expectancy exceeding 10 years. The aim of the study is to assess the impact of PSM on BR (biochemical relapse), to identify PSM risk factors, to clarify the factors involved in BR in the absence of PSM. MATERIAL AND METHODS: Consultation of 171 medical-records from patients submitted to RRP (radical retropubic prostatectomy) between January/2000-December/2005. Mean-age: 64 yr. Mean - PSA (positive surgical margin): 11.88 ng/ml. Clinical staging: 67.8% cT1, 32.2% cT2. GS: ≤6 (66.1%), =7 (21.1%), 8-10 (12.3%). PS: pT0 1.2%, pT2 50.3%, pT3a 36.3%, pT3b 12.9%, pT4 0.6%. pathological Gleason score: ≤6 39.2%, =7 40.9%, 8-10 19.3%. RB definition was PSA ≥0.2 ng/ml. Adjusted Odds-Ratios with 95% confidence intervals (CI) were estimated through univariate logistic regression. RESULTS: There were PSM in 46 specimens, 28 had single PSM and 18 multiple PSM (≥2). BR occurred in 57 patients (33.3%), with an average time after surgery of 23.5 months - 26 patients had PSM and 31 had not. Statistical significant results for BR in variables PSA, PS and PSM. Quadruples if PSM (p <0.0001), triples in single PSM (p = 0.01) and is 6x higher in multiple PSM (p = 0.001). Regarding factors that influence the presence of PSM, only PS ≥pT3a reach statistical significance (p <0.0001). Patients with BR but without PSM (54.38%), variables statistically significant were: initial PSA >10, (p = 0.029) and pathological Gleason score ≥8 with a risk nearly 4x higher than pathological Gleason score ≤6 (p = 0.027). CONCLUSIONS: Statistical risk analysis concluded that the presence of PSM in RRP is strongly influenced by PS ≥pT3a. The presence of PSM and their number increase significantly the risk of BR compared to other factors. In the absence of PSM, the factors that seem to be crucial and with greater impact on BR are initial PSA>10 and pathological Gleason score ≥8.