Faculty Bibliography

OBJECTIVE: The purpose of this study was to assess the possible clinical significance of bladder urine T1 hyperintensity based upon comparison with urinalysis findings, using a cohort of patients who underwent prostate MRI and urinalysis at a similar point in time during preoperative work-up. METHODS: We identified 56 patients who underwent prostatectomy at our institution who obtained prostate MRI and urinalysis within 1 day of each other preoperatively. A control group of 160 consecutive adult men who underwent pelvic MRI during the same time period for other indications was also identified. Two radiologists independently and in consensus reviewed the T1-weighted images to assess the frequency of bladder urine T1 hyperintensity in both groups. The urinalyses in the 56 men undergoing prostatectomy were reviewed, with the results compared between patients with and without bladder urine T1 hyperintensity. RESULTS: Four (7.1%) of 56 men with prostate cancer exhibited T1 hyperintense bladder urine, compared with six (3.8%) of 160 patients exhibiting this finding in the control group (P=.288). Of the four prostate cancer patients with this finding, all exhibited a normal urinalysis. An abnormal urinalysis was identified for four of the prostate cancer patients, all of whom exhibited normal urine T1 signal intensity. CONCLUSION: Bladder urine T1 hyperintensity may be seen occasionally in patients with prostate cancer but is not associated with abnormal urinalysis and therefore should not be regarded as a sign of acute urinary pathology

BACKGROUND: Prostate-specific antigen (PSA) is the only independent predictor of biochemical recurrence (BCR) following radical prostatectomy (RP) subject to change over time. OBJECTIVE: To determine whether an ultrasensitive PSA measured at 3 yr following RP is a predictor of subsequent BCR. DESIGN, SETTING, AND PARTICIPANTS: There were 1197 consecutive men with clinically localized prostate cancer who underwent an open radical retropubic prostatectomy (ORRP) at a tertiary referral academic medical center. Exclusions included 107 men (8.9%) who developed a PSA level >/=0.2 ng/ml or underwent hormone therapy or radiation therapy (RT) within the first 3 r after surgery, 191 men (16%) who did not undergo a 3-yr ultrasensitive PSA assay, and 98 men (8.2%) who had PSA levels >/=0.1 and <0.2 at 3 yr. The remaining 801 men were stratified into two groups based on their ultrasensitive PSA level at 3 yr postoperatively: group 1, which consisted of patients whose PSA was </=0.04 (n=765), and group 2, which consisted of patients whose PSA was >0.04 and <0.10 (n=36). MEASUREMENTS: Delayed BCR was the primary end point and represented those men in this cohort who developed a PSA level >/=0.2 or underwent salvage RT for a persistently rising PSA level after 3 yr of follow-up. RESULTS AND LIMITATIONS: The 7-yr cumulative BCR-free survival rate for groups 1 and 2 was 0.957 (95% confidence interval [CI], 0.920-0.978) and 0.654 (95% CI, 0.318-0.855), respectively. In multivariable Cox proportional hazards models, ultrasensitive PSA level at 3 yr remained the only significant predictor of delayed BCR (likelihood ratio chi(2) for full model: 27.03; df=1; p < 0.001). A limitation of the study is that no uniform PSA assay was obtained. CONCLUSIONS: Our findings provide compelling evidence that an ultrasensitive PSA at 3 yr following RP provides useful insights into delayed BCR and is a source of reassurance for the overwhelming majority of men being followed for delayed recurrences

We have shown previously that during branching morphogenesis of the mouse prostate gland, Bone morphogenetic protein 7 functions to restrict Notch1-positive progenitor cells to the tips of the prostate buds. Here, we employed prostate-specific murine bi-genic systems to investigate the effects of gain and loss of Notch function during prostate development. We show that Nkx3.1(Cre) and Probasin(Cre) alleles drive expression of Cre recombinase to the prostate epithelium and periepithelial stroma. We investigated the effects of gain of Notch function using the Rosa(NI1C) conditional allele, which carries a constitutively active intracellular domain of Notch1 receptor. We carried out the analysis of loss of Notch function in Nkx3.1(Cre/+);RBP-J(flox/flox) prostates, where RBP-J is a ubiquitous transcriptional mediator of Notch signaling. We found that gain of Notch function resulted in inhibition of the tumor suppressor PTEN, and increase in cell proliferation and progenitor cells in the basal epithelium and smooth muscle compartments. In turn, loss of Notch/RBP-J function resulted in decreased cell proliferation and loss of epithelial and smooth muscle progenitors. Gain of Notch function resulted in an early onset of benign prostate hyperplasia by three months of age. Loss of Notch function also resulted in abnormal differentiation of the prostate epithelium and stroma. In particular, loss of Notch signaling and increase in PTEN promoted a switch from myoblast to fibroblast lineage, and a loss of smooth muscle. In summary, we show that Notch signaling is necessary for terminal differentiation of the prostate epithelium and smooth muscle, and that during normal prostate development Notch/PTEN pathway functions to maintain patterned progenitors in the epithelial and smooth muscle compartments. In addition, we found that both positive and negative modulation of Notch signaling results in abnormal organization of the prostate tissue, and can contribute to prostate disease in the adult organ

PURPOSE: To our knowledge we report the first large, randomized, prospective penile rehabilitation clinical trial to compare the effectiveness of nightly intraurethral alprostadil vs sildenafil citrate after nerve sparing prostatectomy. MATERIALS AND METHODS: We performed a prospective, randomized, open label, multicenter American study in men with normal erectile function who underwent bilateral nerve sparing radical prostatectomy. The International Index of Erectile Function erectile function domain was the primary end point. Subjects initiated nightly treatment within 1 month of surgery with intraurethral alprostadil or oral sildenafil citrate (50 mg) for 9 months. After 1-month washout and before sexual activity subjects self-administered sildenafil citrate (100 mg) for a total of 6 attempts in 1 month. Secondary end points were the global assessment question, sexual encounter profile, Erectile Dysfunction Inventory of Treatment Satisfaction and measured stretched penile length. RESULTS: Of 139 men who started intraurethral alprostadil and 73 who started sildenafil citrate, 97 and 59, respectively, completed the trial. There were no statistically significant differences in International Index of Erectile Function erectile function domain and intercourse success rates to intraurethral alprostadil. The global assessment question was significantly better only at 6 months for intraurethral alprostadil (p <0.028). At completion there were no differences between treatments for any of the end points. CONCLUSIONS: This is the first study to directly compare the ability of alprostadil and a phosphodiesterase-5 inhibitor to enhance penile recovery subsequent to bilateral nerve sparing radical prostatectomy. The use of nightly subtherapeutic intraurethral alprostadil is well tolerated after radical prostatectomy. The benefit to return of erectile function of nightly sildenafil citrate and subtherapeutic intraurethral alprostadil appears to be comparable within the first year of surgery

OBJECTIVES: To critically examine the cardiovascular and thromboembolic risks associated with erythropoietin stimulating proteins (ESPs) in men with normal hemoglobin levels undergoing open radical retropubic prostatectomy. METHODS: Between October 1, 2000, through December 31, 2006, a total of 1308 men underwent open radial retropubic prostatectomy by a single surgeon. Of these men, 1095 received preoperative ESPs. Hematocrit levels measured at baseline, immediately before anesthesia induction and at hospital discharge, were prospectively entered into a database. Thromboembolic and cardiovascular complications were prospectively captured during the hospitalization and after surgery. RESULTS: The mean Delta preoperative hematocrit level was 5.9 g/dL. The pre-anesthesia induction hematocrit level was 49.2%. Hospital discharge hematocrit level was 33.6 g/dL. The overall risk of cardiovascular and thromboembolic complications in men receiving ESP were 0.55% and 0.45%, respectively. The risk of cardiovascular and thromboembolic complications were independent of the Delta in preoperative hematocrit or the absolute level of the pre-anesthesia induction hematocrit. CONCLUSIONS: ESPs represent a safe and effective preoperative blood management strategy for men undergoing open radical retropubic prostatectomy

OBJECTIVES: To examine the pathologic findings and biochemical recurrence rates for a consecutive cohort of candidates for active surveillance who underwent radical prostatectomy. The role of active surveillance for the treatment of low-risk prostate cancer is highly controversial. METHODS: Between October 2000 and February 2008, a single surgeon performed 1565 open radical retropubic prostatectomies for clinically localized prostate cancer. Cases were selected for extraction if they fulfilled 1 of 2 published criteria for active surveillance in our prospective longitudinal outcomes database. A retrospective review of the prospectively collected database was executed to elucidate the outcomes of candidates for active surveillance who underwent radical retropubic prostatectomy. Gleason score, pathologic stage, and surgical margins were prospectively captured in our database. The 5-year, biochemical-free survival rates were estimated using Kaplan-Meier analysis plots. RESULTS: Overall, 45.9%-47.2% of cases were pathologically upgraded to a Gleason score >/= 7. Moreover, 12.3%-13.1% of cases were found to have a primary Gleason pattern of 4 or 5. Extracapsular extension (pT3a disease) was observed in 7.8%-10.9% of cases. A total of 28.8%-32.2% of cases had an estimated percentage of cancer volume in the surgical specimen exceeding 20%. The 5-year biochemical-free survival was estimated to be 83.2%-92.9%. CONCLUSIONS: Our pathologic findings and risk of biochemical recurrence after open radical prostatectomy questions the wisdom of active surveillance in men with low-risk disease who have 'long' life expectancies

Abstract Relief of benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms by alpha-blockers (alpha1-adrenoceptor antagonists) is mediated primarily through the blockade of alpha(1A)-receptors, leading to relaxation of smooth muscle in the prostate and bladder neck. Early alpha-blockers that were nonselective for adrenoceptor subtypes have been associated with blood pressure-related adverse effects, such as orthostatic hypotension, that may be attributed at least in part to the blockade of alpha(1B)-adrenoceptors in arterial vessels. Silodosin, a novel alpha-blocker with exceptionally high selectivity for alpha(1A-) versus alpha(1B)-adrenoceptors, was recently approved in the United States for the treatment of urinary symptoms related to BPH. The unique receptor selectivity profile likely accounts for some of the desirable clinical features of the drug. Silodosin possesses an excellent cardiac- and blood pressure-related safety profile, and data have demonstrated that it does not promote QT-interval prolongation. Therapeutic doses of silodosin are safe for men with mild-to-moderate liver dysfunction; dosage adjustment is recommended in those with moderate renal impairment. The drug should not be taken with potent cytochrome P450 3A4 inhibitors. Silodosin may be especially beneficial in patients who need to maximize cardiovascular tolerability

Study Type - Diagnostic (exploratory cohort)Level of Evidence 2b OBJECTIVE: To evaluate the role of magnetic resonance imaging (MRI) and up-standing ultrasonography (USUS) for the detection of inguinal hernias (IHs) before open radical retropubic prostatectomy (ORRP) and to assess factors associated with the presence of IHs in these men. PATIENTS AND METHODS: From 1 July 2007 to 1 February 2009, 164 men underwent preoperative evaluation for ORRP by one surgeon. Of these men 113 (69%) were evaluated for IHs by physical examination (PE), USUS and MRI. In all 226 groins were examined. Any IH diagnosed by any method was considered a true positive. The sensitivity, negative predictive value (NPV), and concordance were calculated for the three diagnostic methods. Possible predictive factors of IHs were evaluated. RESULTS: Of the 226 groins evaluated, 72 (32%) IHs were diagnosed. USUS had the greatest sensitivity (69.4%) and the highest NPV (87.5%). MRI had fair agreement with PE and USUS, while USUS and PE had moderate agreement with each other. No factor was associated with an increased likelihood of preoperative diagnosis of IH. CONCLUSIONS: This study was limited by the lack of a reference standard to diagnose IH. USUS was the most sensitive method for the detection of IH. We recommend that all men undergoing ORRP should be evaluated for IHs by PE and at least one imaging method and that IHs be repaired at the time of ORRP, obviating the need for a second surgical procedure