Cryopreserved placental tissue allograft accelerates time to continence following robot-assisted radical prostatectomy.

Intra-operatively placed cryopreserved placental tissue allograft (CPTA) has shown promise in expediting the recovery urinary continence (UC) following robot-assisted radical prostatectomy (RARP). In this retrospective review of a prospectively maintained single-surgeon, single-institution RARP database, we compare three groups of patients: historical controls (C; N = 183 men) that received no allograft versus two different CPTA products (total CPTA N = 162 [A1 N = 81; A2 N = 81]). The CPTA product was intra-operatively placed as an onlay over the area of the neurovascular bundles during RARP. CPTA cases had significantly faster median time to UC (A1 = 1.4 months; A2 = 1.45 months) versus controls (1.64 months), p = 0.01. On multivariable analysis, use of A1 (HR 1.55, 95% CI [1.14-2.09], p = 0.005) and use of A2 (HR 1.53, CI [1.11-2.11], p = 0.01) were significantly associated with quicker return of UC. Older age (HR 0.97, CI [0.96-0.99], p = 0.001) and non-organ-confined clinical stage (HR 0.51, CI [0.26-1.0] p = 0.05), were significantly associated with slower return of UC. In a propensity score-matched analysis of 77 CPTA patients with sufficient follow-up versus controls, there was significantly less biochemical recurrence (BCR; p = 0.01). Our study indicates that CPTA use appears to accelerate time to UC in age- and performance status-matched men undergoing RARP without increased risk of BCR.

Sentinel node evaluation in prostate cancer.

Sentinel lymph node (SLN) based pelvic lymph node dissection (PLND) in prostate cancer (PCa) is appealing over the time, cost and morbidity classically attributed to conventional PLND during radical prostatectomy. The initial report of feasibility of the SLN concept in prostate cancer was nearly 20 years ago. However, PLND based on the SLN concept, either SLN biopsy of a single node or targeted SLN dissection of multiple nodes, is still considered investigational in PCa. To better appreciate the challenges, and potential solutions, associated with SLN-based PLND in PCa, this review will discuss the rationale behind PLND in PCa and evaluate current SLN efforts in the most commonly diagnosed malignancy in men in the US.

Validation of a novel, tissue-based simulator for robot-assisted radical prostatectomy.

PURPOSE: To create a tissue-based simulator that allows practice of key steps of robot-assisted radical prostatectomy (RARP) in a sequential fashion. MATERIALS AND METHODS: A model was created from female porcine genitourinary tract tissue to represent the male pelvic genitourinary anatomy. The following steps of RARP were simulated: dorsal venous complex ligation, division of bladder neck, seminal vesicle dissection, prostatic pedicle ligation with nerve sparing, urethral division, bladder neck reconstruction, and vesicourethral anastomosis. Ten novices and 10 experts performed RARP on the model. Face validity was calculated by ratings of realism. Content validity was calculated by experts' rating of usefulness of the model as a training tool. Construct validity was calculated by comparison of time to complete the simulator and rating of performance on the objective structured assessment of technical skill (OSATS) questionnaire, between novices and experts. RESULTS: The model was determined to have good face and content validity with an average score of 3.7/5 and 4.8/5, respectively. The mean time for completion of the simulator was 121.5 minutes for the novice and 62 minutes for the expert group (P<0.001), and the mean overall OSATS performance ratings were 4.6/5 for experts and 2.6/5 for novices (P<0.001), yielding good construct validity. CONCLUSIONS: We created and validated a realistic, tissue-based simulator to allow for training of key surgical steps of RARP in a sequential fashion. Ultimately, this simulator could be incorporated into urology training, credentialing, and facilitate surgeon transitioning from open prostatectomy to RARP.

Effect of pretreatment prostate volume on urinary quality of life following intensity-modulated radiation therapy for localized prostate cancer.

BACKGROUND: The aim of this study was to describe the effect of pretreatment prostate volume on urinary quality of life after intensity-modulated radiation therapy (IMRT) for clinically localized prostate cancer. METHODS: A total of 368 men treated with prostate IMRT (77.4-81 Gy) were stratified into three gland volume groups, ie, <30 g (group 1), 30-60 g (group 2), and >60 g (group 3). Post-IMRT urinary function was evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 genitourinary guidelines at one year post-IMRT, and surveyed by the International Prostate Symptom Score (IPSS) before treatment, and then at one month and one year post-IMRT. RESULTS: Late (one year post-IMRT) CTCAE version 4.0 genitourinary toxicity occurred in 11/368 (3.0%) men, but was not severe (grade ≥ 3); total toxicity was similar between the prostate volume groups (P = 0.86). Continuous prostate volume neither correlated with (P = 0.50) nor predicted late genitourinary toxicity (univariate odds ratio 0.99, 95% confidence interval 0.96-1.02). The total IPSS cohort, group 1 (<30 g) and 2 (30-60 g), showed a similar IPSS trend of elevation from pretreatment baseline to one month post-IMRT (each P < 0.01), then a reduction to baseline at one year (each P < 0.01). Group 3 (>60 g) had the highest pretreatment IPSS, but uniquely showed a better urinary symptom trend than the smaller volume groups, with similar IPSS from baseline to one month post-IMRT (P = 0.88) and improved post-treatment IPSS from baseline at one year (P = 0.003). CONCLUSION: Pretreatment prostate volume and initial IPSS scores were not associated with increased late genitourinary toxicity after IMRT in our series. Patients with smaller prostates had an initial increase in urinary symptoms, but returned to baseline at one year. Larger prostate glands (>60 g) had comparatively worse pretreatment symptoms, but at one year showed an overall improvement in IPSS versus baseline.

Comparative analysis of mutagenic potency of 1-nitro-acridine derivatives.

The anticancer effect of 1-nitro-9-hydroxyethylamino acridine (C-857), a compound belonging to the 1-nitroacridine class, has been well documented. Despite its therapeutic efficacy, the clinical development of C-857 has been impeded partly due to its high systemic toxicity. In an effort to enhance antitumor efficacy and lower toxicity, derivatives of C-857 have been synthesized with substitutions made at position C-4 and/or an esterified hydroxyl group in side chain at the C-9 position. The introduction of a methyl group at C-4 resulted in C-1748, which has a significantly higher therapeutic efficacy and is being clinically developed as an anticancer agent for solid tumors. The present study was undertaken to correlate the mutagenicity of C-857, C-1748, C-1790, C-1872 and C-1873 with their cytotoxicity and their anti-tumor efficacy. The mutagenicity of these drugs was determined using three Ames Salmonella typhimurium strains TA1537, TA98 and TA102. The bacteria were treated with different molar concentrations, ranging from 10(-3) to 10(-12) M, of the drugs and drug-induced histidine revertants were then counted after a 48 h incubation. C-1748 did not induce any revertants in both TA1537 and TA98 at a dose of 10(-6) M, whereas, C-857 at the same dose induced approximately 842 and approximately 1034 revertants respectively. In TA102, mutagenicity was lower than observed with TA98 and TA1537 with highest revertants observed at 10(-5) M with C-857 (approximately 606) and C-1748 (approximately 108). Higher mutagenicity was observed in the derivatives C-1790, C-1872 and C-1873 compared to C-1748, but lower than C-857. These studies demonstrate that C-1748 has the least mutagenic potential, with a much higher antitumor effect in prostate cancer and is a promising chemotherapeutic agent for clinical development.