Aspirin and NSAID use in association with molecular subtypes of prostate cancer defined by TMPRSS2:ERG fusion status.

BACKGROUND: The TMPRSS2:ERG (T2E) gene fusion is the most common rearrangement in prostate cancer (PCa). It is unknown if these molecular subtypes have a different etiology. We evaluated aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) in association with T2E fusion status. METHODS: Subjects were from a population-based case-control study of PCa. T2E fusion status for prostatectomy cases (n=346) was determined by fluorescence in situ hybridization. Medication use was determined from questionnaires. Logistic regression, controlling for age, race, PCa family history and PSA screening, was used to evaluate the association of T2E fusion status according to medication use. RESULTS: T2E fusion was present in 171 (49%) cases, with younger cases more likely to be fusion positive (P<0.01). Current aspirin use was associated with a 37% risk reduction of T2E-positive tumors (adjusted odds ratio (OR) 0.63, 95% confidence interval 0.43-0.93). Aspirin use was not associated with T2E negative PCa (adjusted OR 0.99, 0.69-1.42). There were no associations between PCa fusion status and use of nonaspirin NSAIDs or acetaminophen. CONCLUSIONS: Aspirin was associated with a significant reduction in the relative risk of T2E fusion positive, but not T2E negative, PCa. As inflammation and androgen pathways are implicated in prostate carcinogenesis, additional studies of anti-inflammatory medications in relation to these PCa subtypes are warranted.

Metabolic syndrome, dyslipidemia and prostate cancer recurrence after primary surgery or radiation in a veterans cohort.

BACKGROUND: Metabolic syndrome (MetS) has been hypothesized to be associated with cancer, including prostate cancer (PCa), but the relationship is not well characterized. We analyze the relationship between MetS features and localized PCa recurrence after treatment. METHODS: Men having primary treatment for localized PCa were included from a multi-site regional veteran network. Recurrence was defined as nadir PSA +2 ng ml(-1) (radiation) or PSA⩾0.2 ng ml(-1) (prostatectomy). MetS was based on consensus professional society guidelines from the American Heart Association and International Diabetes Federation (three of: hypertension >130/85 mm Hg, fasting blood glucose ⩾100 mg dl(-1), waist circumference >102 cm, high-density lipoprotein <40 mg dl(-1), triglycerides ⩾150 mg dl(-1)). Closely related abnormality in low-density lipoprotein (LDL; >130 mg dl(-1)) was also examined. Analysis of PCa recurrence risk included multivariable Cox proportional hazards regression with propensity adjustment. RESULTS: Of the 1706 eligible men, 279 experienced recurrence over a median follow-up period of 41 months (range 1-120 months). Adjustment variables associated with PCa recurrence included: index PSA, Gleason, and tumor stage. Independent variables of interest associated with PCa recurrence were hyperglycemia and elevated LDL. Elevated LDL was associated with PCa recurrence (multivariable hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.03, 1.74; propensity adjusted HR 1.33, 95% CI 1.03, 1.72). There was also an association between impaired fasting glucose and PCa recurrence in (multivariable HR 1.54, 95% CI 1.10, 2.15; propensity adjusted HR 1.41, 95% CI 1.01, 1.95). MetS was not associated with PCa recurrence (multivariable: HR 0.96, 95% CI 0.61, 1.50; propensity adjusted HR 1.04, 95% CI 0.67, 1.62). CONCLUSIONS: PCa recurrence is not associated with MetS but is associated with elevated LDL and impaired fasting glucose. If confirmed, these data may help provide modifiable targets in preventing recurrence of PCa.

Renal insufficiency is an independent risk factor for complications after partial nephrectomy.

PURPOSE: We identify and describe the postoperative outcomes of a single surgeon partial nephrectomy cohort. We performed univariate and multivariate analysis on preoperative patient characteristics, and their association with increased length of stay and postoperative complication rates. MATERIALS AND METHODS: Perioperative characteristics of 146 consecutive patients undergoing partial nephrectomy were recorded. Postoperative complications were defined as those occurring within 30 days using the Clavien postoperative complication scale. We conducted logistic regression analysis to evaluate the development of complications and linear regression analysis to determine the effect on length of stay. RESULTS: In a linear regression model patients with renal insufficiency had a mean of 1.7 +/- 0.6 days longer length of stay compared to those with normal renal function (p = 0.006). Complications occurred in 48.5% in the renal insufficiency group compared with 16.8% in the other cohort (p = 0.0004). There were no mortalities. On univariable analysis 4 factors were significantly associated with the development of complications including race (p = 0.03), preoperative Modification of Diet in Renal Disease less than 60 (p <0.0001), tumor size greater than 4 cm (p = 0.03) and estimated blood loss (p = 0.04). On multivariable analysis the 2 factors of Modification of Diet in Renal Disease less than 60 (p = 0.003) and race (p = 0.03) remained significant. The odds ratio for complications comparing patients with renal insufficiency to the normal cohort, adjusting for confounding factors, was 4.58 (95% CI 1.65-12.65). CONCLUSIONS: Preoperative renal insufficiency defined as Modification of Diet in Renal Disease less than 60 and non African-American race, which may be related to Modification of Diet in Renal Disease, are predictive of complications after partial nephrectomy. Decreased Modification of Diet in Renal Disease is an independent risk factor for increased length of hospital stay and increased complication rate in partial nephrectomy.

Exploitation of high-yields in hard-rock aquifers: downscaling methodology combining GIS and multicriteria analysis to delineate field prospecting zones.

Based on research work in the Truyère River catchment of the Massif Central (Lozère Department, France), a methodology has been developed for delineating favorable prospecting zones of a few square kilometers within basement areas of several hundred, if not thousand, square kilometers for the purpose of sitting high-yield water wells. The methodology adopts a functional approach to hard-rock aquifers using a conceptual model of the aquifer structure and of the functioning of the main aquifer compartments: the alterites (weathered and decayed rock), the underlying weathered-fissured zone, and the fractured bedrock. It involves an economically feasible method of mapping the thickness and spatial distribution of the alterites and the weathered-fissured zone, on which the long-term exploitation of the water resource chiefly depends. This method is used for the first time in hydrogeology. The potential ground water resources were mapped by GIS multicriteria analysis using parameters characterizing the structure and functioning of the aquifer, i.e., lithology and hydrogeological properties of the substratum, nature and thickness of the alterites and weathered-fissured zone, depth of the water table, slope, fracture networks and present-day tectonic stresses, and forecasted ground water quality. The methodology involves a coherent process of downscaling that, through applying methods that are increasingly precise but also increasingly costly, enables the selection of sites with diminishing surface areas as the work advances. The resulting documents are used for ground water exploration, although they can also be applied to the broader domain of land-use management.