Faculty Bibliography

Preliminary clinical observations suggest that the efficacy of combination therapy (alpha 1 blockade + androgen suppression) is superior to the individual monotherapies. Several randomized double-blind multicenter placebo controlled studies are being done to define the efficacy and safety of combination therapy relative to the monotherapies. The ultimate role of combination therapy in clinical practice depends on a critical assessment of relative efficacy, safety, and cost

OBJECTIVES. To characterize nitric oxide synthase (NOS), which catalyzes nitric oxide (NO) production, in the human prostate using biochemical and immunohistochemical techniques. METHODS. NOS catalytic assay and NOS immunohistochemistry were performed on histologically verified nonmalignant prostate tissue obtained from the peripheral and transition zones of seven radical prostatectomy specimens. RESULTS. Biochemical analysis revealed NOS activity in the human prostate, with a greater amount in the peripheral zone than in the transition zone (P < 0.01). In both prostate zones, NOS was immunohistochemically localized to nerve fibers and ganglia coursing throughout the smooth musculature of the stroma and to subepithelial nerve plexuses. NOS immunoreactivity was also localized to glandular epithelium. CONCLUSIONS. The presence, activity, and distribution of NOS were described in two regions of the human prostate. The present evidence implicates NO in the automatic innervation and physiology of the human prostate. It is proposed that NO may modulate smooth muscle tone and secretory functions in the human prostate, although functional studies are needed to support these hypotheses

OBJECTIVES. To determine whether nitric oxide (NO) is a mediator of prostatic smooth muscle activity. METHODS. Pharmacologic experiments using electrical field stimulation (EFS) were performed on strips of human and canine prostate. RESULTS. EFS alone elicited frequency-dependent contractions in preparations of human and canine prostates. The greatest contractile activity was achieved at 30 Hz. In the presence of 10(-5) M guanethidine (GUA) and 2 x 10(-6) M atropine (ATR), EFS elicited relaxation of canine prostate strips relative to baseline tension. A weak biphasic response consisting of initial relaxation and subsequent contraction relative to baseline tension was observed in the human prostate strips exposed to similar conditions. The smooth muscle activity observed in the presence of GUA plus ATR was attributed to nonadrenergic, noncholinergic (NANC) nerve transmission. 10(-4) M L-NG-nitroarginine methylester (NAME) significantly increased EFS-elicited NANC smooth muscle activity both in human and canine prostates. L-arginine, 10(-2) M, reversed the effect of L-NAME in human and canine prostates. Sodium nitroprusside, 10(-4) M, a donor of NO, caused relaxation of both human and canine prostates. The mean magnitude of the relaxant response/cross-sectional area in human prostate (2.64 +/- 0.4 g/cm2) was significantly greater than in the canine prostate (1.09 +/- 0.17 g/cm2) (P < 0.005). CONCLUSIONS. These results provide compelling evidence that NO plays a role in mediating contractile function of human and canine prostates

OBJECTIVES. To evaluate long-term efficacy and safety of terazosin, a selective alpha 1 blocker, in the treatment of benign prostatic hyperplasia (BPH). METHODS. This was a long-term (42 months), open-label, multicenter study with patients evaluated at 1- to 6-month intervals. Twenty-three outpatient clinics throughout the United States and Canada participated in the study. A total of 494 men with symptomatic BPH, lacking absolute indications for surgery, were enrolled in this study; 298 were transferred into the study from randomized, placebo-controlled studies of terazosin and 196 had no prior terazosin therapy. Terazosin was given starting at 1 mg/d and titrated upward until symptoms were relieved or a maximum dose of 20 mg/d was achieved, whichever came first. RESULTS. Peak urinary flow rates at all visits were significantly higher than baseline values, with mean improvements ranging from 1.0 to 4.0 mL/s. At 3 months, 40% of patients exhibited a 30% or greater improvement in peak flow rate; this improvement was maintained through 42 months. Boyarsky symptom scores improved significantly at all visits; mean total score improved by at least 4.0 points (40%) at all visits beyond 3 months. The most common adverse events resulting in premature termination from the study were dizziness (6.7%), asthenia (3.8%), and somnolence (2.0%). CONCLUSIONS. This study suggests that terazosin is well tolerated and effective in longterm treatment of patients with BPH

OBJECTIVES. The present study represents the first attempt to improve urinary continence following radical prostatectomy (RP) by perianastomotic injection of autologous fat at the time of the surgical procedure. METHODS. A total of 15 consecutive men with clinically localized carcinoma of the prostate underwent nerve-sparing radical retropubic prostatectomy (RRP) with perianastomotic injection of autologous fat. The autologous fat was obtained using a liposuction cannula connected to a power aspirator. The fat was harvested from the adipose tissue immediately adjacent to the lower midline incision. After the pelvic floor musculature was perforated, a total of 30 mL of autologous fat was injected through a 12 gauge angiocatheter under cystoscopic guidance. RESULTS. There were no complications resulting from the harvesting or injection of the autologous fat. All of the patients were evaluated for 6 months. Of the 15 patients, 12 (80%) achieved total urinary control within 6 months. The average time required to achieve total urinary continence was 89 days. None of the patients experienced total or nocturnal incontinence. Of the 3 patients with stress urinary incontinence (S

The present study was designed to compare the prostate cancer detection rate, sensitivity, specificity, and positive predictive value of digital rectal examination (DRE) and serum prostatic specific antigen (PSA) in a consecutive cohort of males presenting to a single institution with clinically significant prostatism. The study population was comprised of 224 consecutive males with clinically significant prostatism referred to the Prostate Center at the Medical College of Wisconsin between June 1990 and December 1991. Subjects were considered to have clinically significant prostatism if they elected to pursue medical or surgical therapy following exclusion of carcinoma of the prostate. The initial examination consisted of a Boyarsky symptom score assessment, DRE, uroflowmetry, postvoid residual determination, serum PSA level, and transrectal prostatic ultrasonography. Subjects with an abnormality on DRE or serum PSA > 4 ng/dl were advised to undergo transrectal prostatic biopsy. Of the 224 subjects, 40 (17.9%) had an abnormal DRE and 57 (25.4%) had an elevated serum PSA > 4 ng/dl. The overall detection rate of prostate cancer in the study population was 6.7%. The prostate cancer detection rates for PSA alone and DRE alone were 5.8% and 5.3%, respectively. The sensitivity, specificity, and positive predictive values of PSA alone were 86.7%, 80.9%, and 25.0% and of DRE alone 80.0%, 86.3%, and 30.0%, respectively. Receiver operator characteristic (ROC) curves were constructed for the entire study population in order to compare the screening measures serum PSA and PSA density. The area under the curves was 0.88 for both tests, indicating that these screening tests for prostate cancer were not significantly different. The present study demonstrated that males with clinically significant prostatism represent a high risk cohort for detecting prostate cancer. DRE and PSA are equally effective measures for detecting prostate cancer. PSA density does not offer any advantage over serum PSA in screening for prostate cancer, except in the subset of patients with a normal DRE and serum PSA levels between 4.0 and 9.9 ng/dl