Association of SRD5A2 genotype and pathological characteristics of prostate tumors.

The enzyme product of SRD5A2, 5alpha-reductase type II, is responsible for converting testosterone to the more metabolically active dihydrotestosterone. Therefore, SRDSA2 may be involved in the development or growth of prostate tumors. To examine the effects of allelic variants in the gene SRDSA2 on the presentation of prostate tumors, we studied a sample, primarily Caucasian, of 265 men with incident prostate cancer who were treated by radical prostatectomy. We assessed the relationship of the A49T and V89L polymorphisms at SRD5A2 with clinical and pathological tumor characteristics of these patients. We found no association of V89L genotypes with any of the characteristics studied. The presence of the A49T variant was associated with a greater frequency of extracapsular disease [odds ratio (OR), 3.16; 95% confidence interval (CI), 1.03-9.68] and a higher pathological tumor-lymph node-metastasis (pTNM) stage (OR, 3.11; 95% CI, 1.01-9.65). In addition, the A49T variant was overrepresented in two poor prognostic groups, which have been correlated with reduced rates of biochemical disease-free survival. One group included men with at least two of the following poor prognostic variables: (a) stage T3 tumor; (b) PSA level >10; and/or (c) Gleason score, 7-10 (OR, 3.46; 95% CI, 1.04-11.49). The second group included men with positive margins and high Gleason score (OR, 6.28; 95% CI, 1.05-37.73). Our results suggest that the A49T mutation may influence the pathological characteristics of prostate cancers and, thus, may affect the prognosis of these patients.

The use of combined radiation therapy and hormonal therapy in the management of lymph node-positive prostate cancer.

PURPOSE: To determine the rate of tumor response and patterns of relapse following combined hormonal-radiation therapy of adenocarcinoma of the prostate and to measure the survival in a group of men with tumor metastatic to pelvic lymph nodes. METHODS AND MATERIALS: 66 patients with adenocarcinoma of the prostate with pathologically confirmed pelvic lymph node involvement were treated with combined radiation therapy and hormonal therapy. An additional five patients declined hormonal therapy. The patients treated with combined therapy represented a group with locally advanced disease including 44 patients (67%) with T3 or T4 tumors and 51 patients (80%) had N2 or N3 lymph node metastases. The pelvic lymph nodes were treated to a dose of 45 Gy and the prostate was boosted to a dose of 65 to 71 Gy. Hormonal therapy began up to 2 months before radiation and continued indefinitely. Patients were allowed to select their hormonal therapy and could choose DES (2 patients), orchiectomy (21 patients), LHRH agonist (7 patients) or combined androgen blockade (34 patients). RESULTS: Median follow-up is 49 months (range 12 to 131 months) and 21 patients have been followed for longer than 5 years. There have been 15 recurrences the entire group including three local recurrences in the prostate, seven patients with distant metastases, four patients with biochemical recurrences without clinical evidence of disease, and one patient where the location was unknown. Two of the PSA recurrences occurred in patients who elected to discontinue hormones after less than 3 years of therapy. The overall survival at 5 and 8 years is 94 and 84%, the clinical disease free survival is 85 and 67%, and the biochemical disease-free survival is 78 and 47%. There was no increased toxicity of the combined modality regimen compared to the expected effects of radiation and hormonal therapy. CONCLUSION: Combined hormonal and radiation therapy represents an effective treatment option for patients with adenocarcinoma of the prostate metastatic to pelvic lymph nodes. Combined modality therapy appears to extend the disease-free survival and allow patients to maintain their independent function.

Solitary late recurrence of renal cell carcinoma presenting as duodenal ulcer.

The natural history of renal cell carcinoma is often unpredictable and even bizarre. We report a case of solitary late recurrence of renal cell carcinoma presenting as a duodenal ulcer and review the relevant literature.

Deep vein thrombosis and prostatectomy.

A research protocol to evaluate the prevention of deep vein thrombosis in sequential patients undergoing prostatectomy is presented. There is an overall incidence of deep vein thrombosis in 8 per cent of patients. There was no advantage with intermittent leg compression when compared with elastic stockings.

Combined hormonal and radiation therapy for lymph node-positive prostate cancer.

OBJECTIVES: To evaluate the efficacy of combined radiation and hormonal therapy in patients with prostate cancer metastatic to the pelvic lymph nodes. METHODS: Fifty consecutive patients with node-positive prostate cancer were evaluated by the Departments of Urology and Radiation Oncology at the University of Pennsylvania and offered combined hormonal and radiation therapy. All patients received pelvic radiation to 45 Gy, with a boost dose to the prostate to 65 to 71 gy. Forty-five of the patients were treated with concurrent hormonal therapy consisting of diethylstilbestrol (2 patients), orchiectomy (18 patients), leuprolide (5 patients), or combined androgen blockade (20 patients); the other 5 patients declined hormonal therapy. Patients represented a group with locally advanced disease with a high incidence of T3 tumors (66%), high grade (74%; Gleason score more than 7), high prostate-specific antigen (PSA) (40%; more than 30.0 ng/mL), and a high incidence of gross (36%) or bilateral (30%) adenopathy and a high incidence of multiply involved lymph nodes (62%). RESULTS: Median follow-up of patients is 42 months (range, 10 to 102). All 5 patients declining hormonal therapy relapsed within 18 months and only 1 patient survived longer than 3 years. Among patients treated with combined hormonal and radiation therapy, the 6-year survival rate is 82%, the clinical disease-free survival at 6 years is 71%, and the probability of survival free of recurrence, with a PSA less than 0.2 ng/mL, is 62%. Only two PSA recurrences occurred, both in patients who elected to discontinue hormone therapy. There was no synergistic toxicity observed as a result of combined therapy. CONCLUSIONS: Combined hormonal and radiation therapy offers the potential for extended disease-free survival and may represent an effective treatment option for patients with locally advanced prostate cancer.

Drug-induced male sexual dysfunction.

Many commonly used drugs can interfere with male sexual function, either by decreasing libido, interfering with erectile function, or causing absent seminal emission or retrograde ejaculation. Although drug-related effects on sexual function may be difficult to distinguish from the effects of organic disease, anxiety, or depression, it is important for the physician to be aware of the drugs most commonly associated with sexual dysfunction. This article considers these drugs and the potential mechanism by which they exert their adverse effects.

Radiographic imaging and urologic decision making in the management of renal and ureteral calculi.

Without question, significant changes, and for the most part significant advances, have been made in the management of patients with urolithiasis during the past decade. The newer therapeutic measures have generally made it easier for patients to be treated, but the decision-making process for the urologist has become more complex. In the past, the issue whether to follow a patient with a stone or to intervene with surgery or transurethral cystoscopic basketing was decided based on well-established guidelines that had developed over many years. Today, the indications for intervention appear to be less stringent, and in the minimally symptomatic or asymptomatic patient who would not have been operated on previously, there appears to be an expanding desire for prophylactic management. For whatever reasons, once it has been established that a stone is present and the decision has been made to intervene, subsequent decisions regarding the technical approach may also not be as simple as in the past. Ten years ago, for example, a stone in the abdominal ureter was removed by a ureterolithotomy, and the principal decision involved placement of the incision. Today, the same calculus may be approached by ESWL with or without a stent, by antegrade percutaneous techniques, or by retrograde ureteroscopic techniques using rigid or flexible endoscopes with baskets, ultrasonic lithotrites, or lasers. Although the specific indication for specific techniques continue to evolve, it has become evident that information obtained by the radiographic evaluation of the urinary tract is critical in the decision-making process. The intravenous urogram, including the initial plain film, remains the primary diagnostic modality and, in the absence of extenuating clinical features, is often the sole test required to make a decision regarding the best therapeutic modality. A variety of clinical features from the history or physical examination, or concerns raised by the intravenous urogram, may necessitate alternative or additional techniques to better define the anatomy, the renal function, or other pathology. The urologist therefore needs to be familiar with the information that can be obtained from the uroradiologist's vast armamentarium in order to make the most appropriate recommendations to the patient for diagnosis and management.

Imipramine-induced erection, masturbation, and ejaculation in male horses.

Imipramine hydrochloride was administered to five male horses (400-500 kg b.wt.): one experienced young stallion, two mature normal breeding stallions, one 5-year-old stallion with erection and ejaculatory dysfunction, and one long-term castrated male horse. Oral imipramine treatment (100 to 600 mg, twice daily) led to frequent erection and masturbation while at rest in the stall in a nonsexual context. Intravenous imipramine treatment over a range of doses (50 to 1000 mg) similarly induced erection and masturbation in all animals. Erection typically occurred within 10 minutes after injection, and the erection and masturbation continued intermittently for 1 to 2 hours. These erections proceeded as during sexual excitement to a normal firmness and eventual engorgement of the glans penis. Two stallions ejaculated while masturbating. Mild ataxia and drowsiness appeared at the higher doses, but the animals remained responsive to auditory, visual, and tactile stimuli. Erection and masturbation were often interrupted by activities about the barn or the approach of the handler, suggesting cortical inhibitory control of the erection. When tested in a sexual context immediately following IV treatment (500 mg), the two mature breeding stallions bred normally. The 5-year-old stallion, which had not ejaculated over several months of breeding attempts, spontaneously ejaculated following IV imipramine treatment. Subsequently, this stallion has ejaculated during copulation while on low dose oral (100 mg. twice daily) imipramine treatment. Plasma total androgens increased during treatment in these stallions. The long-term castrate showed erection and masturbation following IV imipramine treatment, suggesting that the effect of imipramine is not testosterone dependent.

Prostate surgery.

Benign prostatic hyperplasia is probably the most common neoplasm in man, and carcinoma of the prostate now leads the list of newly diagnosed malignancies in males. Even though there is no known direct etiologic relationship between these disorders, they are by no means mutually exclusive; if a man lives long enough, he is likely to be afflicted by one or both. Although most men will not require surgery, the increasing size of the geriatric population and the frequency of these disorders result in a problem of impressive magnitude from both a medical and a socioeconomic standpoint. Newer diagnostic and therapeutic modalities continue to evolve in this rapidly changing field. In many areas, further investigation is required to determine the true value of certain techniques, such as transrectal ultrasonography for screening or magnetic resonance imaging for staging of prostate cancer. Controversy now exists regarding the relative safety of transurethral and open surgical techniques for benign disease, and further comparisons will need to be made with the newer, less invasive interventional and pharmacologic techniques that are being developed. Will the advances in radical surgery result in improved survival of patients with localized prostate cancer? These and other questions will need to be addressed by the primary care physicians, geriatricians, and urologists who care for these patients.

Comparative analysis of blood plasma epidermal growth factor concentrations, hormonal profiles and semen parameters of fertile and infertile males.

The relationship between male reproductive function and the blood plasma level of epidermal growth factor (EGF) is of interest in the light of the role that circulating EGF appears to play in regulating mouse spermatogenesis. We measured the concentrations of EGF in the blood plasma of 39 fertile men (sperm count > 20 x 10(6)/ml) and compared them with those of 31 infertile men (sperm < 20 x 10(6)/ml). Blood plasma levels of follicle stimulating hormone (FSH), luiteinising hormone (LH), prolactin and testosterone were also determined. The infertile patients had mean blood plasma EGF concentrations of 0.75 +/- 0.10 ug/L. The value was significantly lower than that of the fertile group (1.28 +/- 0.14 ug/L; P < 0.005). There were statistically significant differences between the fertile and infertile groups in sperm count, sperm viability, mean forward progression, testosterone, LH and FSH (P values between 0.0001 and 0.023). There was no significant difference in the prolactin concentrations between the two groups. Although overall average blood plasma EGF concentrations are significantly lower in the infertile males, regression analysis failed to reveal any direct relationships among the various parameters studied.

Pathogenesis of renal calculi.

Urolithiasis involving the upper urinary tract is a multifactorial disease that remains a significant health problem. A variety of intrinsic and extrinsic factors influence the incidence of disease in individuals and in all populations. At the level of the kidney, natural physicochemical processes result in crystalluria and the formation and growth of stones. Urinary supersaturation of some degree must be present but its significance may be altered by changes in urinary volume, pH, epitaxial relationships, and the presence or absence of naturally occurring inhibitors. A variety of environmental parameters acting through effects on the local urinary conditions determine which patients among a group of people inherently at risk will form stones. The above factors are considered herein with regard to the four major types of stone disease encountered today.

Distribution of a seminal plasma-associated protein kinase inhibitor in normal, oligozoospermic, and vasectomized men.

Human sperm-free seminal plasma contains an inhibitor, which is protein in nature, of the histone kinase present in seminal plasma. Since protein kinase inhibitors have been observed to be present in spermatozoa, the objective of the present study was to determine whether this seminal plasma-associated enzyme inhibitor originates from the sperm, or whether it is a component of accessory secretion(s) comprising the seminal plasma. Sperm-free seminal plasma from normospermic (greater than 20 X 10(6) sperm/ml), oligozoospermic (less than or equal to 20 X 10(6) sperm/ml), and vasectomized donors was obtained, and inhibitor-enriched fractions were prepared by (NH4)2SO4 fractionation and gel filtration. Contamination of the sperm-free seminal plasma by spermatozoa or spermatozoan components was negligible as assessed by light microscopy, polyacrylamide gel electrophoresis, and measurement of the activity of cyclic adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase. Specific (inhibitory units/mg protein) and total inhibitory activities were determined in each of the donors by constructing linear inhibition curves using various concentrations of inhibitor. The results were correlated with the initial sperm concentration. There was no apparent relationship between the amount of inhibitory activity present and the initial sperm concentration. The histone kinase inhibitor also did not appear to be associated with testicular or epididymal secretions since it was observed in the seminal plasma of vasectomized donors. It is concluded that this inhibitor of histone kinase originates from the accessory secretions comprising the human ejaculate.

Organ-sparing surgery for bilateral leydig cell tumor of the testis.

Leydig cell tumors of the testis are uncommon, and bilateral lesions are extremely rare. We report a case of bilateral Leydig cell tumor of the testis treated with radical orchiectomy and contralateral subtotal orchiectomy with the intent of preservation of hormonal function and fertility.