Affinity Captured Urinary Extracellular Vesicles Provide mRNA and miRNA Biomarkers for Improved Accuracy of Prostate Cancer Detection: A Pilot Study.

Serum prostate-specific antigen (sPSA) testing has helped to increase early detection of and decrease mortality from prostate cancer. However, since sPSA lacks specificity, an invasive prostate tissue biopsy is required to confirm cancer diagnosis. Using urinary extracellular vesicles (EVs) as a minimally invasive biomarker source, our goal was to develop a biomarker panel able to distinguish prostate cancer from benign conditions with high accuracy. We enrolled 56 patients in our study, 28 negative and 28 positive for cancer based on tissue biopsy results. Using our Vn96 peptide affinity method, we isolated EVs from post-digital rectal exam urines and used quantitative polymerase chain reaction to measure several mRNA and miRNA targets. We identified a panel of seven mRNA biomarkers whose expression ratio discriminated non-cancer from cancer with an area under the curve (AUC) of 0.825, sensitivity of 75% and specificity of 84%. We also identified two miRNAs whose combined score yielded an AUC of 0.744. A model pairing the seven mRNA and two miRNA panels yielded an AUC of 0.843, sensitivity of 79% and specificity of 89%. Addition of EV-derived PCA3 levels and clinical characteristics to the biomarker model further improved test accuracy. An AUC of 0.955, sensitivity of 86% and specificity of 93% were obtained. Hence, Vn96-isolated urinary EVs are a clinically applicable and minimally invasive source of mRNA and miRNA biomarkers with potential to improve on the accuracy of prostate cancer screening and diagnosis.

Governing therapy choices: power/knowledge in the treatment of progressive renal failure.

This article outlines the struggle between the power of the health care professional and the rights of the individual to choose freely a modality of treatment. Nurses are instrumental in assisting patients in making the best decision for a therapy they will have to assume for the rest of their lives. In guiding patients' decision, nurses must take into account these unavoidable contingencies: changes in lifestyle, nutritional restrictions, level of acceptance, compliance issues, ease of training and availability of support/facilities. Ensuring that the patient makes an informed decision is therefore an ongoing challenge for nurses as they are taking part in a delicate balancing act between not directly influencing the patient's decision while making sure the patient is accurately informed.

A prospective study measuring penile length in men treated with radical prostatectomy for prostate cancer.

PURPOSE: Some patients report that the penis is smaller after radical retropubic prostatectomy for prostate cancer. We performed a prospective study which measured penile length before and after radical retropubic prostatectomy. MATERIALS AND METHODS: A total of 124 men consented to penile measurements before radical prostatectomy performed by the same surgeon. Repeat measurements were performed at 3-month intervals following surgery. Penile measurements (cm.) consisted of flaccid length, stretched length, depth of prepubic fat pad and circumference. Statistical analysis of penile measurements was performed using the paired samples and independent Student's t test, Pearson's correlation and analysis of variance. RESULTS: Mean patient age was 59.1 (range 42 to 76). No patient had a penile abnormality, for example Peyronie's disease, or history of penile or urethral surgery. The size of the penis was significantly smaller after prostatectomy, and there was a significant difference for flaccid (p <0.001), stretched (p <0.001), prepubic fat pad (p = 0.02) and circumference measurements (p <0.01). Twelve patients (19%) had a 15% or greater decrease in stretched penile length. When dichotomizing groups at the cut point of 15% decrease, the independent t test of prostate size was not significant (t[df 36.7] = -1.83, p = 0.076). Nerve sparing was not significant in relation to change in penile stretched length, (F[df 2, 62] = 0.501, p = 0.609). CONCLUSIONS: Our findings support observations of decreased penile length after radical prostatectomy. Men should be counseled before radical prostatectomy that penile shortening may occur.

A pelvic drain may be avoided after radical retropubic prostatectomy.

PURPOSE: We reassessed the role of routine pelvic cavity drainage to prevent complications after radical retropubic prostatectomy (RRP). MATERIALS AND METHODS: RRP was performed in 116 consecutive patients with clinically localized adenocarcinoma of the prostate. Clinical and pathological information was recorded for each patient. After the prostate was removed and the anastomotic sutures were tied the bladder was filled with saline through the urethral catheter. If there was no significant leakage, a drain was not placed. RESULTS: We did not place a drain in 85 of the 116 patients (73%). There were 3 immediate postoperative complications. In a patient without a drain, a urinoma developed that required percutaneous placement of a drain on postoperative day 2. None of the 116 patients had clinical evidence of infection, lymphocele or hematoma. Two patients had hematuria 2 weeks after catheter removal and needed bladder irrigation. Neither patient had a drain. Three patients (drain and no drain in 1 each) were in urinary retention after catheter removal, which required catheter reinsertion for an additional week. None had an anastomotic stricture. CONCLUSIONS: The morbidity of RRP is low when performed by those who regularly perform this procedure. If the bladder neck is preserved or meticulously reconstructed, there may be little or no extravasation and, thus, routine drainage may be unnecessary. In properly selected cases morbidity is not increased by omitting a drain from the pelvic cavity after RRP.

Biochemical and pathological predictors of the recurrence of prostatic adenocarcinoma with seminal vesicle invasion.

PURPOSE: We assessed biochemical and pathological factors as predictors of recurrence in men with seminal vesicle invasion. MATERIALS AND METHODS: A consecutive series of 812 men who underwent radical retropubic prostatectomy between 1992 and 2000 included 106 (13%) with seminal vesicle invasion. Disease recurrence was defined as prostate specific antigen (PSA) 0.4 ng./ml. or greater. Patients with less than 12 months of followup, salvage radical retropubic prostatectomy, lymph node metastases and adjuvant therapy were excluded from study. Data on the remaining 66 cases were analyzed using the chi-square test, bivariate logistic regression, Kaplan-Meier analyses and Cox proportional regression. Variables included demographics, recurrence, time from surgery to recurrence, positive margins, capsular invasion, extracapsular extension, Gleason score (2 to 6, 7 and 8 to 10), and dichotomized values of preoperative PSA (10 or less versus 10 ng./ml.) and tumor volume (20% or less versus greater than 20%). RESULTS: Mean patient age was 62 years (range 48 to 74). At an average followup of 47.7 months (range 13 to 109) 53% of the patients were free of biochemical recurrence. Mean time to recurrence was 18.6 months (range 1.7 to 51.6). Univariate analyses revealed a statistical significant increased risk of recurrence in patients with PSA greater than 10 ng./ml. (p <0.0001), capsular invasion (p = 0.01) and age (p = 0.036). When adjusting for potential covariates, Cox proportional regression analysis indicated that higher PSA (hazard ratio 7.33, 95% CI 2.57 to 20.95), larger tumor volume (hazard ratio 5.64, 95% CI 1.97 to 16.19) and higher age (hazard ratio 1.13, 95% CI 1.04 to 1.22) were significantly associated with shorter time to recurrence. CONCLUSIONS: PSA greater than 10 ng./ml., tumor volume greater than 20% and age are significant predictors of recurrence after radical retropubic prostatectomy in patients with prostate cancer and seminal vesicle invasion. Hopefully future randomized trials may show a survival benefit of adjuvant therapy in patients at high risk.