Magnetic resonance imaging in the prediction of biochemical recurrence of prostate cancer after radical prostatectomy.

OBJECTIVE: To investigate whether magnetic resonance imaging (MRI) findings, when converted into a scoring system, can predict the biochemical recurrence of prostate cancer after radical prostatectomy (RP). PATIENTS AND METHODS: Between January 2000 and October 2004, 610 patients with biopsy-confirmed prostate cancer had MRI before RP, with whole-mount step-sectioning of the pathology sample. MRI findings were retrospectively scored on a seven-point scale based on Tumour-Node-Mestastasis staging (1, no tumour seen, to 7, lymph node metastasis). MRI scores were added to published 5- and 10-year clinical preoperative nomograms for predicting recurrence. The predictive accuracy of MRI was quantified as the differences in bootstrap-corrected concordance indices of the models with and without MRI. RESULTS: As of August 2007, 64 (10.5%) patients had a biochemical recurrence. MRI scores were associated with recurrence (P < 0.001) with hazard ratios of 1.76 and 1.81 in the 5- and 10-year models, respectively. Actual recurrence rates by MRI score were: 1, 0%; 2, 4.5%; 3, 9%; 4, 24.1%; 5, 33.3%; 6, 69.2%; 7, 100%. When MRI was added, the concordance indices of the 5- and 10-year models increased, from 0.762 to 0.776 (P = 0.081) and 0.773 to 0.788 (P = 0.107), respectively; the improvement was not significant. CONCLUSION: The MRI scoring system devised was a strong predictor of biochemical recurrence after RP. Although MRI did not provide added prognostic value to standard clinical nomograms, in centres where MRI is used routinely, it might increase the confidence of the clinician in assessing the risk of recurrence by contributing supporting data.

The functional and structural consequences of cavernous nerve injury are ameliorated by sildenafil citrate.

INTRODUCTION: Radical prostatectomy (RP) is associated with erectile dysfunction (ED). A single, placebo-controlled, human study has assessed the effects of regular sildenafil use after RP and demonstrated an increased chance of preservation of preoperative erectile function. Aim. This study was undertaken to define the effects of such a regimen in an animal model. METHODS: Using the cavernous nerve (CN) crush injury model, animals were divided into a number of groups: no CN injury (sham), bilateral CN injury exposed to either no sildenafil (control) or sildenafil at two doses (10 and 20 mg/kg) subcutaneously daily for three different durations (3, 10, 28 days). MAIN OUTCOME MEASURES: At these time points, CN electrical stimulation was used to assess erectile function by mean intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio. For the structural analyses, whole rat penes were harvested. Staining for Masson's trichrome was utilized to calculate the smooth muscle-collagen ratio. Immunohistochemical antibody staining was performed for endothelial (CD31 and eNOS) and neural (GAP43, NGF, and nNOS) factors and immunoblotting was performed to analyze the AKT/eNOS pathway. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay was used for the assessment of apoptotic indices and the CN architecture was evaluated by transmission electron microscopy (TEM). RESULTS: Erectile function was improved with sildenafil in a time- and dose-dependent fashion with maximization of erectile function recovery occurring with daily 20 mg/kg at the 28-day time point. Sildenafil use resulted in smooth muscle-collagen ratio protection and CD31 and eNOS expression preservation. Sildenafil reduced apoptotic indices significantly compared with control. Animals exposed to sildenafil had increased phosphorylation of akt and eNOS. Tem demonstrated distinct differences in architecture between control and sildenafil groups toward an increased amount of myelinized nerve fibers. CONCLUSIONS: Sildenafil use in the CN crush injury model preserves erectile function that appears to be mediated predominantly through preservation of smooth muscle content and endothelial function as well as through reduction in apoptosis.

The impact of shock wave therapy at varied energy and dose levels on functional and structural changes in erectile tissue.

OBJECTIVES: Only minimal literature exists on consequences of shock wave therapy (SWT) on erectile function in treatment of Peyronie's disease (PD). This study was undertaken to define SWT impact at varied energy/dose levels at different time points on functional and structural changes in erectile tissue. METHODS: In 45 rats 2000 shock waves (sw) at 2 BAR were applied to the penis weekly sorted by one, two, and three sessions (high-dose/energy level, HD-1, HD-2, HD-3). Each group was followed for 1, 7, or 28 d before measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). Fifteen control animals (C1, C7, C28) underwent anesthesia alone. Another 15 animals were exposed to three SWT sessions applying 1000 sw at 1 BAR and analyzed identically (low-dose/energy level, LD-3-1, -7, -28). Terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling assay was used to define the apoptotic index (AI) and Masson's trichrome (MT) staining was prepared to evaluate smooth muscle-to-collagen ratios. RESULTS: ICP/MAP ratios for all C groups displayed a mean of 64%. All SWT groups demonstrated significantly reduced ICP/MAP ratios compared to their corresponding C groups (p<0.05). The LD-3 groups showed a trend toward improved ICP/MAP ratios. LD-3-28 demonstrated significant recovery compared to HD-3-28 (55+/-8% vs. 41+/-10%, p=0.004), but remained reduced compared to C28 (63+/-5%, p=0.03). No statistical differences were seen for MT staining in SWT groups compared to C (p>0.05). AIs for the LD-3 groups were significantly lower compared to the HD-3 groups (p<0.001), but all AIs were significantly increased compared to C groups (p<0.01). CONCLUSIONS: Overall, at both energy/dose levels, SWT resulted in a time- and treatment-dependent reduction of ICP/MAP ratios, which might be mediated partly through apoptosis and collagenization of corporal smooth muscle.

Poorly differentiated prostate cancer treated with radical prostatectomy: long-term outcome and incidence of pathological downgrading.

PURPOSE: Patients with high grade (Gleason score 8 to 10) prostate cancer on biopsy are at high risk for cancer recurrence after local treatment, such as radiation therapy and radical prostatectomy. We examined long-term outcomes in patients with high grade prostate cancer on biopsy who were treated with radical prostatectomy alone. We also investigated the impact on outcomes of changes in the radical prostatectomy Gleason score. MATERIALS AND METHODS: Of 5,662 patients who underwent radical prostatectomy during 20 years 238 had a biopsy Gleason score of 8 to 10. We analyzed the rate of biochemical recurrence in this subgroup according to the Gleason grade of cancer in the radical prostatectomy specimen. RESULTS: Ten-year biochemical recurrence-free probability in the cohort was 39%. However, 45% of patients (95% CI 38 to 51%) with Gleason score 8 to 10 cancer on biopsy had a Gleason score of 7 or less in the radical prostatectomy specimen. These patients had a 10-year biochemical recurrence-free probability of 56% compared to 27% in those with a final Gleason score that remained 8 to 10 (p = 0.0004). On multivariate analysis neither prostate specific antigen nor biopsy features, including total number of cores, number of cores with cancer and percent of cancer in the cores, was a significant predictor of downgrading. However, clinical stage and biopsy Gleason score were significant with 58% of cT1c and 51% of biopsy Gleason score 8 cancers downgraded. Almost 65% of cT1c Gleason score 8 cancers were downgraded compared to 11% of cT3 Gleason score 9 cancers. CONCLUSIONS: Patients diagnosed with poorly differentiated prostate cancer (Gleason score 8 to 10) on biopsy do not uniformly have a poor prognosis. Of the patients 39% remain free of cancer recurrence 10 years after radical prostatectomy. Of these cancers 45% have a lower Gleason score in the radical prostatectomy specimen and a correspondingly more favorable long-term outcome. Predictors of downgrading are lower clinical stage (cT1c) and Gleason score 8 in the biopsy specimen.

Basic laparoscopic surgical training: examination of a low-cost alternative.

OBJECTIVE: "Dry lab" facilities are integral to laparoscopy training, but access is often limited due to the high costs of video-laparoscopy equipment. We assessed the effectiveness of a cheap and simple training model compared to conventional video-laparoscopy for basic training using a randomised, blinded study. METHODS: Thirty-six third-year medical students without previous surgical skills were randomised into two groups: group A students were taught basic laparoscopy skills using a conventional video-laparoscopy pelvic trainer and group B students were taught similar techniques using a cardboard box with a cut-out top to allow light and visualisation. Participants in group B had one eye obscured to reduce their stereoscopic vision. After eight sessions of training amounting to 24h, the two groups were assessed by a blinded adjudicator on set tasks using both the video-laparoscopy pelvic trainer and the cardboard box. Accuracy, timing and depth perception were assessed and the results compared. RESULTS: There was no significant difference in performance scores or times between the two groups in any of the parameters when tested on the cardboard box. However, when assessed on the video trainer, the cardboard box-trained group had significantly faster times with equivalent scores in the majority of tasks. CONCLUSION: For basic laparoscopic training the cardboard box, costing nothing, is a simple and effective alternative, which can be used in conjunction with sophisticated video-laparoscopy equipment costing thousands of dollars.

Randomized, placebo-controlled trial showing that finasteride reduces prostatic vascularity rapidly within 2 weeks.

OBJECTIVE: To measure expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in the prostates of men after transurethral resection of the prostate (TURP) following 2 weeks of treatment with finasteride. PATIENTS AND METHODS: Sixty-four men scheduled to undergo TURP were randomized to receive 5 mg of finasteride or placebo daily for 2 weeks before surgery. Sections of prostatic urothelium were stained for VEGF expression and for CD31 to assess MVD. Ten consecutive, non-overlapping high-power fields were analysed in a blinded fashion. RESULTS: In all, 31 men received finasteride and 33 placebo; the groups were similar in patient age, resected prostate weight, preoperative catheterization, prostate-specific antigen level, aspirin use, spinal anaesthesia and postoperative diagnosis of prostate cancer. The mean (95% confidence interval) MVD was significantly lower in the finasteride group (60, 55-65) than in the placebo group (71, 64-78; P < 0.01). Similarly, the mean expression of VEGF was significantly lower in the finasteride group (47, 43-52 vs 61, 54-67; P < 0.001) CONCLUSION: Finasteride inhibits angiogenic growth factors leading to reduced vascularity, and this is the basis of its action in reducing haematuria of prostatic origin. The present study shows that finasteride influences the prostatic microvasculature after only 2 weeks exposure.

Transurethral prostate resection and bleeding: a randomized, placebo controlled trial of role of finasteride for decreasing operative blood loss.

PURPOSE: Bleeding associated with transurethral prostate resection can often be significant and lead to increased morbidity and occasionally mortality. It has been shown that finasteride decreases bleeding in patients with hematuria of prostatic origin. We hypothesized that bleeding in patients undergoing transurethral prostate resection could be decreased by giving finasteride for 2 weeks before surgery. MATERIALS AND METHODS: A total 70 patients scheduled to undergo elective transurethral prostate resection were randomized to receive 5 mg. finasteride daily or placebo for 2 weeks before surgery. Serum hemoglobin was measured before and after surgery, and the following day. The volume of irrigation fluid used and its hemoglobin concentration as well as resected prostate weight were recorded. RESULTS: Of the 68 patients who underwent transurethral prostate resection 2 were withdrawn before surgery, and so 32 received finasteride and 36 received placebo. There was significantly less mean blood loss in irrigation fluid in the finasteride group than in the control group (43.6 versus 69.3 gm. hemoglobin, p = 0.011). The mean difference was more significant when blood loss per gm. resected prostate was calculated (2.65 versus 4.65 gm. hemoglobin per gm. prostate, p < 0.01). CONCLUSIONS: This study shows that finasteride given for 2 weeks preoperatively decreases bleeding in patients undergoing transurethral prostate resection. Further study is required to determine the optimal timing and dose duration to minimize blood loss and identify how relevant such a decrease in bleeding is in clinical practice.