A multi-institutional randomized controlled trial comparing first-generation transrectal high-resolution micro-ultrasound with conventional frequency transrectal ultrasound for prostate biopsy.

Objectives: To study high-frequency 29 MHz transrectal side-fire micro-ultrasound (micro-US) for the detection of clinically significant prostate cancer (csPCa) on prostate biopsy, and validate an image interpretation protocol for micro-US imaging of the prostate. Materials and methods: A prospective randomized clinical trial was performed where 1676 men with indications for prostate biopsy and without known prostate cancer were randomized 1:1 to micro-US vs conventional end-fire ultrasound (conv-US) transrectal-guided prostate biopsy across five sites in North America. The trial was split into two phases, before and after training on a micro-US image interpretation protocol that was developed during the trial using data from the pre-training micro-US arm. Investigators received a standardized training program mid-trial, and the post-training micro-US data were used to examine the training effect. Results: Detection of csPCa (the primary outcome) was no better with the first-generation micro-US system than with conv-US in the overall population (34.6% vs 36.6%, respectively, P = .21). Data from the first portion of the trial were, however, used to develop an image interpretation protocol termed PRI-MUS in order to address the lack of understanding of the appearance of cancer under micro-US. Micro-US sensitivity in the post-training group improved to 60.8% from 24.6% (P < .01), while specificity decreased (from 84.2% to 63.2%). Detection of csPCa in the micro-US arm increased by 7% after training (32% to 39%, P < .03), but training instituted mid-trial did not affect the overall results of the comparison between arms. Conclusion: Micro-US provided no clear benefit over conv-US for the detection of csPCa at biopsy. However, it became evident during the trial that training and increasing experience with this novel technology improved the performance of this first-generation system.

Active treatment in low-risk prostate cancer: a population-based study.

Background: Active surveillance instead of active treatment (at) is preferred for patients with low-risk prostate cancer (lr-pca), but practice varies widely. We conducted a population-based study to assess the proportion of patients who underwent at between January 2011 and December 2014, and to evaluate factors associated with at. Methods: The provincial cancer registry was linked to administrative health datasets to identify patients with lr-pca and to acquire demographic, tumour, and treatment data. The primary outcome was receipt of at during the first 12 months after diagnosis, defined as any receipt of external-beam radiotherapy, brachytherapy, radical prostatectomy, cryotherapy, or androgen deprivation. Univariate and multivariate logistic regression were used to analyze the correlation between patient and tumour factors and at. Results: Of 1565 patients with lr-pca, 554 (35.4%) underwent at within 12 months of diagnosis. Radical prostatectomy was the most common treatment (58%), followed by brachytherapy (29.6%). Younger age [odds ratio (or) 0.92; 95% confidence interval (ci): 0.91 to 0.94], lower score (≥3) on the Charlson comorbidity index (OR: 0.36; 95% ci: 0.19 to 0.68), T2 stage (or: 3.05; 95% ci: 2.03 to 4.58), higher prostate-specific antigen (psa) at diagnosis (or: 1.13; 95% ci: 1.06 to 1.21), radiation oncologist consultation (or: 3.35; 95% ci: 2.55 to 4.39), and earlier diagnosis year (2012 or: 0.46; 95% ci: 0.34 to 0.63; 2013 or: 0.45; 95% ci: 0.32 to 0.63; 2014 or: 0.33; 95% ci: 0.23 to 0.47) were associated with a higher probability of at. Conclusions: This contemporary population-based study demonstrates that approximately one third of patients with lr-pca undergo at. Patients of younger age, with less comorbidity, a higher tumour stage, higher psa, earlier year of diagnosis, and radiation oncologist consultation were more likely to undergo at. Further investigation is needed to identify strategies that could minimize overtreatment.

Pelvic lymph node dissection is associated with symptomatic venous thromboembolism risk during laparoscopic radical prostatectomy.

PURPOSE: Venous thromboembolism is a potentially catastrophic complication of radical prostatectomy. It is unknown whether pelvic lymph node dissection is related to the development of venous thromboembolism. We hypothesized that omitting pelvic lymph node dissection may be associated with a decreased incidence of venous thromboembolism. MATERIALS AND METHODS: The records of 773 consecutive patients who underwent laparoscopic radical prostatectomy by a single surgeon from 2001 to 2009 were reviewed for postoperative venous thromboembolism. All patients underwent laparoscopic radical prostatectomy with or without pelvic lymph node dissection and had at least 3 months of followup. Generally only patients at increased risk for lymph node metastasis received pelvic lymph node dissection. Diagnostic studies were not routinely performed but were initiated for clinical symptoms of venous thromboembolism. Separately a meta-analysis of radical prostatectomy studies with or without pelvic lymph node dissection was performed to evaluate associations with venous thromboembolism. RESULTS: Of the 773 patients 468 (60.8%) underwent laparoscopic radical prostatectomy plus pelvic lymph node dissection, 302 (39.2%) underwent laparoscopic radical prostatectomy without pelvic lymph node dissection, and 3 were missing preoperative data and were excluded from study. Patients in the laparoscopic radical prostatectomy plus pelvic lymph node dissection and laparoscopic radical prostatectomy only groups were similar in age, body mass index and prostate volume, although they differed in pathological characteristics and operative time. Venous thromboembolism occurred in 7 of 468 (1.5%) patients who underwent laparoscopic radical prostatectomy plus pelvic lymph node dissection and in 0 of 302 (0%) who underwent laparoscopic radical prostatectomy only (p = 0.047). Patients in whom venous thromboembolism developed had greater body mass index (30.8 vs 27.1 kg/m(2), p = 0.015) than those in whom venous thromboembolism did not develop. No patient had a symptomatic lymphocele. Meta-analysis of the literature demonstrated a significant association between venous thromboembolism and radical prostatectomy plus pelvic lymph node dissection compared to radical prostatectomy only (RR 2.15, CI 1.14-4.04, p = 0.018). CONCLUSIONS: Pelvic lymph node dissection during radical prostatectomy increases the risk of venous thromboembolism. In carefully selected low risk patients omitting pelvic lymph node dissection may decrease the incidence of venous thromboembolism.

Improvement of endothelial function in insulin-resistant carotid arteries treated with pravastatin.

OBJECT: Insulin resistance and hypertension are independent risk factors for stroke. Endothelial dysfunction in response to risk factors and carotid artery (CA) disease are important in the pathogenesis of stroke. Pravastatin may have cholesterol-independent pleiotropic effects. In the present study the authors examined the effects of short-course pravastatin treatment on endothelial function in CAs obtained in control and insulin-resistant rats with fructose-induced hypertension. METHODS: Thirty rats were divided into two experimental groups, in which 14 were fed a regular diet and 16 were fed a fructose-enriched diet for 3 weeks. The rats were then divided into four groups: control, pravastatin-treated control, fructose-fed, and pravastatin-treated fructose-fed. Pravastatin was administered (20 mg/kg/day) for 2 weeks. Excretion of the urinary nitric oxide (NO) metabolite nitrite (NO2-) was also assayed. The CAs from all rats were subsequently removed and assessed for endothelium-dependent and -independent vascular reactivity in vitro. The rats in the fructose-fed group were insulin resistant, hyperinsulinemic, and hypertensive relative to the rats in the control and pravastatin-treated control groups and exhibited diminished endothelium-dependent vasomotion and urinary NO2- excretion (p < 0.05), with preserved endothelium-independent vasomotion. Strikingly, pravastatin treatment restored endothelium-dependent vasomotion and urinary NO2- excretion in rats in the fructose-fed pravastatin-treated relative to the fructose-fed group (p < 0.05). CONCLUSIONS: The authors report, for the first time, that pravastatin restores endothelial function in CAs from insulin-resistant rats with fructose-induced hypertension. These beneficial effects were ascribed to direct, cholesterol-independent vascular effects of pravastatin and are likely the result of augmentation of NO production. These data provide impetus for further investigation of nonlipid-lowering indications for pravastatin therapy in the prevention and treatment of CA disease.

Effect of heterozygosity for the methionine synthase 2756 A-->G mutation on the risk for recurrent cardiovascular events.

Increased dietary intake of folate has been shown to significantly reduce the risk for fatal myocardial infarction, possibly by lowering homocysteine levels. We therefore investigated the association between recurrent cardiovascular events and a mutation in methionine synthase (2756 A-->G)--an enzyme directly involved in folate and homocysteine metabolism. This mutation significantly reduced the risk for recurrent cardiovascular events and elevated red blood cell folate levels.

Hyperhomocyst(e)inemia and the prevalence of atherosclerotic vascular disease in patients with end-stage renal disease.

Hyperhomocyst(e)inemia is now recognized as an independent risk factor for atherosclerotic cardiovascular disease in patients with normal renal function. Hyperhomocyst(e)inemia is common in patients with chronic renal failure. This study is designed to look for an association between hyperhomocyst(e)inemia and atherosclerotic vascular disease in patients with end-stage renal disease (ESRD). Two hundred eighteen patients undergoing hemodialysis were enrolled onto the study and had predialysis bloodwork performed for total homocyst(e)ine, red blood cell folate, and vitamin B(12) levels. A history of clinically significant atherosclerotic vascular disease (ischemic heart disease, cerebrovascular disease, or peripheral vascular disease) was elicited by patient questionnaire and verified by careful inpatient and outpatient chart review. Atherosclerotic vascular disease was present in 45.9% of patients. Mean homocyst(e)ine concentration was 26.7 micromol/L (95% confidence interval [CI], 25.0 to 28.4) overall. Mean homocyst(e)ine concentration was 28.6 micromol/L (95% CI, 25.6 to 31.7) and 25.0 micromol/L (95% CI, 23.2 to 26.8) in patients with and without atherosclerotic disease, respectively (P = 0.036). The adjusted odds ratio for atherosclerotic disease was 2.12 (95% CI, 1.03 to 4.39) for those subjects with a homocyst(e)ine level in the highest quartile compared with the lowest 3 quartiles. In the 126 men, the adjusted odds ratio for atherosclerotic disease was 3.4 (95% CI, 1. 24 to 9.42) for those with homocyst(e)ine levels in the highest quartile compared with the lowest 3 quartiles. No association was found between homocyst(e)ine level and atherosclerotic disease in women. In conclusion, there is an association between hyperhomocyst(e)inemia and atherosclerotic vascular disease in patients undergoing dialysis. Prospective studies need to further examine the relationship between homocyst(e)ine level and atherosclerosis in women with ESRD.

Hyperhomocysteinemia, anticardiolipin antibody status, and risk for vascular access thrombosis in hemodialysis patients.

BACKGROUND: Vascular access failure is an important cause of morbidity in end-stage renal failure patients on hemodialysis. Currently, little is known about risk factors that predispose certain hemodialysis patients to recurrent access thrombosis. Hyperhomocysteinemia (common in patients with renal failure) predisposes people with normal renal function to recurrent and early-onset venous thrombosis, although the effect on vascular access thrombosis is currently unknown. Previous studies have suggested that high titers of IgG anticardiolipin antibody (IgG-ACA) predispose hemodialysis patients to access thrombosis. This cross sectional study was designed to assess for an association between two predictive variables, hyperhomocysteinemia and elevated titers of IgG-ACA, and vascular access thrombosis in patients undergoing chronic hemodialysis. METHODS: Risk factors for vascular access thrombosis were documented, and the number of episodes of access thrombosis was recorded for the previous three years in patients undergoing hemodialysis. Midweek predialysis total homocysteine and IgG-ACA levels were measured in all subjects. RESULTS: Of the 118 patients who were enrolled, 75.4% had a native arteriovenous fistula. Episodes of vascular access thrombosis were recorded for the previous three years; 34 (28.8%, 95% CI 20.9 to 37.9%) patients had 72 episodes of access thrombosis over the period of risk. Mean homocysteine levels were not significantly different between these 34 patients (28.6 micromol/liter, 95% CI 24.5 to 32.7) and the patients who had no episodes of graft thrombosis (29.8 micromol/liter, 95% CI 26.7 to 32.9). Sixty-seven unselected patients had IgG-ACA levels drawn for analysis, and all assays were negative. The only variable that was associated with a higher risk for graft thrombosis was the type of vascular access placed (odds ratio 4.0, 95% CI 1.6 to 9.6 for patients with a synthetic graft compared with those with an arteriovenous fistula). CONCLUSIONS: No association was found between homocysteine levels or anticardiolipin antibody and vascular access thrombosis in our patient population.