Faculty Bibliography

PURPOSE: We determined the long-term effect of radical prostatectomy on lower urinary tract symptoms. MATERIALS AND METHODS: Between October 1, 2000 and January 30, 2003, 587 men underwent open radical retropubic prostatectomy. Of these men 453 completed the American Urological Association symptom index at baseline, and 12 and 48 months. Mean changes in American Urological Association total, voiding and storage symptom scores were ascertained between baseline and 12 months (short term), baseline and 48 months (long term), and between 12 and 48 months (natural history of lower urinary tract symptoms without a prostate). Symptom scores were ascertained independently for men with baseline mild vs moderate/severe lower urinary tract symptoms. RESULTS: Clinically and statistically significant short-term and long-term improvements were observed in mean American Urological Association total, storage and voiding symptom scores for men presenting with moderate/severe lower urinary tract symptoms. The previously reported progression of lower urinary tract symptoms in the general population of men older than 40 years was not observed in our patients with an absent prostate. CONCLUSIONS: The current study provides compelling evidence that radical prostatectomy prevents the progression of lower urinary tract symptoms in men with and without baseline clinically significant lower urinary tract symptoms. This beneficial effect of radical prostatectomy on the natural history of lower urinary tract symptoms should be considered when weighing the risks and benefit of the treatment option for localized prostate cancer

As the terminal differentiation products of human urothelium, uroplakins (UPs) would be expected to diminish during urothelial tumorigenesis. Surprisingly, recent studies found UPs to be retained even by well-advanced urothelial carcinomas, suggesting that the loss of UPs does not strictly parallel urothelial transformation. Little is known, however, about whether the status of UPs is associated with a particular pathologic parameter, the tumor's biological behavior, or patient outcome. Here we assessed UP expression by immunohistochemistry on tissue arrays from 285 patients with bladder urothelial carcinomas or nontumor conditions. UPs were expressed in all 9 normal urothelial specimens, 63 of 74 (85%) patients with non-muscle-invasive urothelial carcinomas on transurethral resection, 104 of 202 (51.5%) patients who underwent radical cystectomy for advanced urothelial carcinomas, and 33 of 50 (66%) lymph node metastases. Normally associated with urothelial apical surface, UPs were localized aberrantly in tumors, including microluminal, basal-laminal, cytoplasmic, or uniform patterns. In non-muscle-invasive diseases, there was no association between UP expression and disease recurrence, progression, or mortality. In contrast, in invasive diseases, absent UP expression was significantly associated with advanced pathologic stage, lymph node metastases, disease recurrence, and bladder cancer-specific mortality (P = .042, P = .035, P = .023, and P = .022, respectively) in univariate analyses. Furthermore, UP status was independent of key cell-cycle regulators, including p53, pRb, p27, and cyclin D1, thus excluding a functional link between these 2 groups of proteins. Our data demonstrate for the first time that persistent UP expression is associated with a favorable clinical outcome and that UPs may be used as adjunct markers for predicting the prognoses of patients with invasive and metastatic bladder carcinomas. Our results also suggest that UP-positive and -negative carcinomas have different clonal origins or may be derived from different cancer stem cells

OBJECTIVES: To determine the incidence of inguinal hernias in men undergoing open radical retropubic prostatectomy (RRP). METHODS: The incidence of preoperative and postprostatectomy inguinal hernias were determined by a retrospective chart review and questionnaire survey of 1130 consecutive men who underwent open RRP by a single surgeon from October 2000 to October 2005. A preoperative inguinal hernia was diagnosed by the physical examination or abdominal computed tomography findings. The incidence of new postoperative hernias was ascertained by the patients' responses to a survey indicating the development of a new groin bulge or hernia. RESULTS: Of the 1130 patients, 146 (13%) had a preoperative inguinal hernia. Increasing age and lower body mass index were significantly associated with the detection of a preoperative inguinal hernia. The sensitivity of detecting an inguinal hernia by physical examination and routine abdominal computed tomography preoperatively was 96.3% and 42.5%, respectively. Also, 8% of men developed a new hernia. CONCLUSIONS: Although abdominal computed tomography can identify inguinal hernias in men undergoing open RRP, the test's sensitivity is inferior to that of a simple physical examination. All candidates for open RRP should undergo a careful physical examination to identify asymptomatic inguinal hernias. Our findings suggest that the previously reported high incidence of symptomatic inguinal hernias that developed after open RRP can be explained by a failure to diagnose preexisting inguinal hernias and the development of new hernias

PURPOSE: We evaluated the effectiveness of single or combination drug therapy on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 3,047 men with lower urinary tract symptoms/benign prostatic hyperplasia enrolled in the Medical Therapy of Prostatic Symptoms trial were randomly assigned to receive doxazosin alone, finasteride alone, combination therapy or placebo. Treatment effectiveness was assessed according to intent to treat by mean reduction in self-reported nightly nocturia at 1 and 4 years. A subgroup analysis by age (younger than 70 vs 70 years old or older) was also performed. RESULTS: Of the men 2,583 reported 1 or more episodes of nocturia and finished 12 or more months of the trial. Mean nocturia was similar in all groups at baseline. Mean nocturia was reduced at 1 year by 0.35, 0.40, 0.54 and 0.58 in the placebo, finasteride, doxazosin and combination groups, respectively. Reductions with doxazosin and combination therapy were statistically greater than with placebo (p <0.05). At 4 years nocturia was also significantly reduced in patients treated with doxazosin and combination therapy (p <0.05 vs placebo). In men older than 70 years (495) all drugs significantly reduced nocturia at 1 year (finasteride 0.29, doxazosin 0.46 and combination 0.42) compared to placebo (0.11, p <0.05). CONCLUSIONS: Doxazosin and combination therapy reduced nocturia more than placebo, but the net benefit of active drug compared to placebo was often modest with a net difference of less than 0.20 fewer nightly nocturia episodes at 1 and 4 years. Findings in men 70 years old or older were similar, with an even smaller effect observed for finasteride

Although ras is a potent mitogenic oncogene, its tumorigenicity depends on cellular context and cooperative events. Here we show that low-level expression of a constitutively active Ha-ras in mouse urothelium induces simple urothelial hyperplasia that is resistant to progression to full-fledged bladder tumors even in the absence of Ink4a/Arf. In stark contrast, doubling of the gene dosage of the activated Ha-ras triggered early-onset, rapidly growing, and 100% penetrant tumors throughout the urinary tract. Tumor initiation required superseding a rate-limiting step between simple and nodular hyperplasia, the latter of which is marked by the emergence of mesenchymal components and the coactivation of AKT and STAT pathways as well as PTEN inactivation. These results indicate that overactivation of Ha-ras is both necessary and sufficient to induce bladder tumors along a low-grade, noninvasive papillary pathway, and they shed light on the recent findings that ras activation, via point mutation, overexpression, or intensified signaling from FGF receptor 3, occurs in 70%-90% of these tumors in humans. Our results highlight the critical importance of the dosage/strength of Ha-ras activation in dictating its tumorigenicity - a mechanism of oncogene activation not fully appreciated to date. Finally, our results have clinical implications, as inhibiting ras and/or its downstream effectors, such as AKT and STAT3/5, could provide alternative means to treat low-grade, superficial papillary bladder tumors, the most common tumor in the urinary system

The evolution of alpha blocker therapy for benign prostatic hyperplasia (BPH) has focused on improving convenience and tolerability. Indications for treating BPH include reversing signs and symptoms or preventing progression of the disease. The indication that most commonly drives the need for intervention is relief of lower urinary tract symptoms (LUTS) with the intent of improving quality of life. Alpha blockers are the most effective, least costly, and best tolerated of the drugs for relieving LUTS. Four long-acting alpha 1 blockers are approved by the Food and Drug Administration for treatment of symptomatic LUTS/BPH: terazosin, doxazosin, tamsulosin, and alfuzosin. All are well tolerated and have comparable dose-dependent effectiveness. Tamsulosin and alfuzosin SR do not require dose titration. Alfuzosin, terazosin, and doxazosin have all been shown to be effective in relieving LUTS/BPH independent of prostate size

Spontaneous renal artery dissection (SRAD) is a rare event, and thus may be a challenge for physicians to diagnose and treat. We report a case of SRAD in a healthy 56-year-old male who presented with flank pain, fever, and elevated white blood cell count. The patient was initially diagnosed with nephrolithiasis versus pyelonephritis and was admitted for observation. Multiple imaging modalities, including non-contrast computed tomography (CT), magnetic resonance imaging (MRI) with gadolinium, CT angiogram, and intraoperative angiogram, were used to make the final diagnosis of SRAD. The patient was treated with endovascular stent placement and is currently free of pain with normal laboratory values and blood pressure

This article reviews the issues and controversies relevant to the treatment of advanced prostate cancer with androgen deprivation therapy. Initially, diethylstilbestrol was used for achieving androgen deprivation, but was replaced by luteinizing hormone-releasing hormone (LHRH). Adverse events associated with LHRH agonists include the flare phenomenon, hot flashes, loss of libido, erectile dysfunction, depression, muscle wasting, anemia, and osteoporosis. Intermittent therapy has been advocated to reduce morbidity of treatment. The addition of an antiandrogen provides maximum androgen blockade. There remains controversy regarding the timing of the addition of an antiandrogen. Secondary hormonal therapies include antiandrogens, adrenal androgen inhibitors, and estrogens