Periprostatic adipose tissue from obese prostate cancer patients promotes tumor and endothelial cell proliferation: a functional and MR imaging pilot study.

BACKGROUND: Obesity, particularly visceral adiposity, confers a worse prognosis for prostate cancer (PCa) patients, and increasing periprostatic adipose (PPA) tissue thickness or density is positively associated with more aggressive disease. However, the cellular mechanism of this activity remains unclear. Therefore, in this pilot study, we assessed the functional activity of PPA tissue secretions and established a biochemical profile of PPA as compared to subcutaneous adipose (SQA) tissues from lean, overweight and obese PCa patients. METHODS: Adipose tissues were collected from PCa patients undergoing surgical prostate removal. Tissues were analyzed by histologic and magnetic resonance (MR) techniques. Explant tissue culture secretions were used in proliferation assays on PCa and endothelial cells. RESULTS: PPA secretions obtained from obese patients were significantly more pro-proliferative in both PCa and endothelial cells as compared to PPA obtained from lean or overweight men and SQA tissues. Consistent with this, PPA microvessel density was increased, and the T2 relaxation time was decreased, compared to SQA tissues, and we observed a modest, inverse correlation between the T2 and tumor stage. Moreover, the ratio of unsaturated to saturated fatty acids, obtained using MR spectroscopy, showed a modest, inverse correlation with Gleason score. CONCLUSIONS: These pilot data show that PPA stimulates PCa cell proliferation and angiogenesis and that obesity intensifies this activity, thus generating a mechanistic hypothesis to explain the worse prognosis observed in obese PCa patients. Our pilot study also shows that MR technology may be useful in further elucidating the relationship between obesity and PCa progression.

The prognostic significance of perineural invasion and race in men considering active surveillance.

OBJECTIVE: To determine the importance of perineural invasion (PNI) on diagnostic biopsy in men enrolled in active surveillance (AS). PATIENTS AND METHODS: Eligibility criteria for AS included clinical stage ≤ T2a and Gleason score ≤6, ≤3 cores positive, maximum single core involvement <50%, and total tumour volume ≤5% on diagnostic biopsy. All men received 12-core confirmation biopsy at ≤6 months. AS 'failure' on confirmatory biopsy was defined as failure to meet one or more eligibility criteria. Risk of AS failure was compared in men with and without PNI. RESULTS: For the 165 men comprising the study population, the mean (sd) age was 66.9 (6.5) years and the median (interquartile, IQR) PSA level of men at study entry was 4.4 (3.2-6.0) ng/mL. The median (IQR) follow-up was 5.5 (1.1-9.9) months. In all, 8.5% (14/165 men) had PNI on diagnostic biopsy. Compared with those without PNI, men with PNI tended to have more cores involved with cancer, at a mean (sd) of 2.0 (0.7) vs 1.6 (0.8) cores (P = 0.08) but did not have significantly a greater mean (sd) total tumour length on diagnostic biopsy, at 3.0 (2.1) vs 2.3 (3.6) mm (P = 0.27). Men with PNI on diagnostic biopsy were significantly more likely to meet criteria for disease progression on confirmatory biopsy (57% [8/14] vs 21% [32/151]; P = 0.006). PNI remained a significant predictor for AS failure after adjustment for number of positive cores, maximum percentage core involvement, and total tumour length (odds ratio 4.4, 95% confidence interval 1.4-14.2). CONCLUSIONS: PNI on diagnostic biopsy is associated with disease progression on confirmatory biopsy. The presence of PNI should factor into appropriate patient selection and counselling in AS.

Primary care physician PSA screening practices before and after the final U.S. Preventive Services Task Force recommendation.

OBJECTIVES: In May 2012, United States Preventive Services Task Force (USPSTF) finalized its recommendation against prostate-specific antigen (PSA) screening in all men. We aimed to assess trends in PSA screening frequency amongst primary care physicians (PCPs) surrounding the May 2012 USPSTF recommendation. METHODS AND MATERIALS: The electronic data warehouse was used to identify men aged between 40 and 79 years with no history of prostate cancer or urology visit who were evaluated by an internal medicine or family practice physician between 2007 and 2012. Analyses were directed toward PSA testing within 6-month time period from June to November, with particular focus on the 2011 (pre-USPSTF recommendation) and 2012 (post-USPSTF recommendation) cohorts. The primary outcome measure was proportion of men with at least 1 PSA test during the 6-month pre- and post-USPSTF recommendation periods. RESULTS: A total of 112,221 men met inclusion criteria. There was a significant decrease in screening frequency between the 2011 and 2012 cohorts (8.6% vs. 7.6%, P = 0.0001; adjusted odds ratio 0.89, 95% confidence interval 0.83-0.95). This decrease was most evident amongst patients aged 40 to 49 years (5.6% vs. 4.6%, P = 0.004) and 70 to 79 years (7.9% vs. 6.2%, P = 0.01). A significant decrease was also observed in patients with highest previous PSA value<1.0 (P<0.0001) and 1.0 to 2.49 ng/ml (P = 0.0074). CONCLUSIONS: Since the USPSTF recommendation was finalized, there is evidence of continuing decreases in PSA testing by PCPs. PCPs may be shifting toward more selective screening practices, as decreases in screening are most pronounced in the youngest and oldest patients and in those with history of PSA values<2.5 ng/ml.

Ancillary alpha-methylacyl-CoA racemase immunocytochemistry in the diagnosis of adenocarcinoma of the prostate in urinary cytology: a case report.

BACKGROUND: Alpha-methylacyl-coA racemase (AMACR) was recently shown to be a sensitive immunohistochemical marker for substantiating a diagnosis of adenocarcinoma of the prostate. Its applicability to exfoliative urinary cytology has not been investigated before. CASE: The patient was a 77-year-old male with a history of persistent intermittent hematuria who was evaluated with urine cytology. Cytopathologic studies were interpreted to demonstrate "atypical urothelial cells." The patient was evaluated with computed tomography, which demonstrated new left hydroureter and hydronephrosis. He underwent cystoscopy, which showed an abnormal left hemitrigone with the left ureteral orifice obscured by an infiltrative mass. This area was biopsied, and histologic studies of the tissue chips demonstrated underlying prostatic adenocarcinoma directly invading the urothelium. We used AMACR immunoreactivity on a retrospectively studied, catheterized urine slide to confirm the diagnosis. CONCLUSION: This case suggests that combined cytomorphology and immunocytochemisty for AMACR may allow an accurate identification of cells of prostatic adenocarcinoma when cytomorphologic studies or the clinical history raises the differential diagnosis of prostate cancer presenting with exfoliation of malignant cells into the urine.

Continuing experience with liver resection and vena cava reconstruction using cardiopulmonary bypass and hypothermic circulatory arrest.

When the suprahepatic vena cava or the hepatic vein confluence with the inferior vena cava (IVC) is obscured by tumor or a clot in the IVC extends above the liver, cross-clamping the IVC during liver or retroperitoneal resection is hazardous. This report describes a 10-year experience with ten patients who had liver (seven) or retroperitoneal (three) resections with vena cava reconstruction using cardiopulmonary bypass and hypothermic circulatory arrest. There were no perioperative deaths. Morbidity consisted of prolonged bile leak (one), pulmonary embolism (one), and stroke (one). Control of the liver was secured in six of seven patients who had a liver resection. There were three significant advantages to this technique. First, the median sternotomy provided superior exposure to the suprahepatic IVC. Second, the bypass technique avoided the risks of hemodynamic instability and prevented air embolism and sudden uncontrolled hemorrhage incurred by resection or IVC cross-clamping. Third, hypothermia provided a method of protection for residual liver function especially in the face of chronic liver disease induced by infection or chemotherapy.