Biochemical methods for predicting metastatic ability of prostatic cancer utilizing the dunning R-3327 rat prostatic adenocarcinoma system as a model.

At present, there is no established diagnostic method by which the metastatic ability of an individual prostatic cancer can be accurately predicted. Metastasis is a multistep process, the first critical step of which is invasion. Tumor invasion has been suggested to involve a variety of hydrolytic enzyme activities; therefore, the tumor levels of these activities might be indicative of the overall metastatic ability of the cancer. In order to evaluate if the quantitative levels of hydrolytic enzymes can be used to predict the metastatic ability of individual prostatic cancers, five different Dunning R-3327 rat prostatic adenocarcinoma sublines, with widely varying metastatic abilities, were assayed for the respective levels of a variety of hydrolytic enzyme activities (collagenase, trypsin-like, cathepsin B, neutral protease, N-acetyl-beta-glucosaminidase, chymotrypsin-like, leucine aminopeptidase, elastase, and plasminogen activator). These studies demonstrated that most hydrolytic activities are not elevated when going from normal prostate to prostatic cancer. In addition, only the levels of elastase and chymotrypsin-like activity were found to be consistently higher in highly metastatic prostatic cancers than in either the normal prostate or low-metastatic prostatic cancers. It was found that, by combining the relative activities of elastase and chymotrypsin-like activity and then dividing by the relative activities of N-acetyl-beta-glucosaminidase, a biochemical metastatic index could be constructed which accurately reflected the respective metastatic ability of the Dunning sublines.

Risk factors for disease progression in patients with lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH): a systematic analysis of expert opinion.

Disease progression has become an important issue for the management of lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). Although several risk factors have been identified, no specific patient risk profiles have been established that can be useful in the day-to-day management of LUTS/BPH. In this study, an international panel of urologists developed a risk classification based on the attribution of a risk score to 243 unique patient profiles. From the perspective of clinical decision making, it was concluded that postvoid residual, symptom severity and maximum flow rate are the most relevant determinants of the risk of disease progression.

Safety assessment of terazosin in the treatment of patients with symptomatic benign prostatic hyperplasia: a combined analysis.

OBJECTIVES: This study reviews and assesses the safety of terazosin for the treatment of symptomatic benign prostatic hyperplasia (BPH). METHODS: Six placebo-controlled trials (including two unpublished series) involving 996 patients provide the database for this evaluation. Six hundred thirty-six patients received terazosin from 1 to 20 mg daily for a total of 229 patient-years of exposure to terazosin. The most common final dose of terazosin was 10 mg once daily. RESULTS: Side effects were generally mild or moderate in severity and resolved following cessation of therapy. Side effects resulted in premature withdrawal in 9% of terazosin-treated patients and 7% of placebo-treated patients (difference not significant). Dizziness (2.0%) and headache (1.1%) were the most common symptoms leading to premature withdrawal from the studies. Although postural symptoms and dizziness were slightly more common in those terazosin-treated patients 65 or more years old compared with patients less than 65 years old, this difference was not statistically significant. Only 4 of the 636 patients (0.6%) had syncopal episodes; 2 of these occurred at initiation of terazosin therapy or at dose escalation. Minimal reductions in blood pressure were observed in normotensive patients and patients with hypertension controlled by concomitant medication, whereas patients with untreated hypertension had substantial decreases in both systolic and diastolic blood pressures. Statistically significant increases in high density lipoprotein to cholesterol ratio and reductions in total cholesterol, low density lipoprotein, and triglycerides were also seen. CONCLUSIONS: This combined analysis suggests that terazosin can be safely administered to both normotensive and hypertensive patients with symptomatic BPH.

Squamous cell carcinoma of scrotum.

Squamous cell carcinoma of the scrotum is a rare malignancy in the United States. This series includes the eighth reported case of this lesion in a black American. Surgery still remains the only effective therapeutic modality. The use of sentinel and superficial inguinal node biopsies was important in determining whether or not radical ilioinguinal lymphadenectomy was needed in 2 patients.

Genitourinary manifestations of the acquired immunodeficiency syndrome.

As the number of HIV-1 infected individuals and AIDS patients continues to increase, more cases involving the genitourinary tract will be encountered. Often, genitourinary manifestations will be the initial presentation of AIDS. Proper diagnosis will require awareness and a high index of suspicion. In addition to routine cultures, opportunistic infections with unusual organisms will require staining for fungi and acid-fast bacilli. Repeat cultures of blood, urine, seminal fluid, and abscess cavities may be required to establish a diagnosis. Prolonged courses of antibiotic treatment for prophylaxis and for relapses are usually required. Clinical understaging and rapid progression of tumors distinguish HIV-1-associated malignancies involving the genitourinary tract. Treatment for these malignancies will depend on the stage of HIV-1 infection. Any concomitant drug therapy and evidence of malnutrition will be important factors in selecting the proper timing and mode of therapeutic intervention. Although AIDS predominantly affects individuals between 30 and 50 years of age, an increasing percentage of patients over 50 years of age are being diagnosed. Common risk factors for acquisition of HIV include homosexuality or bisexuality and transfusion of blood or blood products. For the urologist, it is important to recognize that older patients more frequently present with AIDS at the time of diagnosis of HIV infection. A more rapid course of deterioration and high mortality is noted in this population. Clearly, protocols including surveillance, dosing regimens, and surgical intervention will need to be established and clarified to treat an anticipated increasing number of affected patients. In addition, it appears that adequate adherence to universal precautions is far from being achieved. Close monitoring and active surveillance of infection control may be needed to improve compliance.

Ketoconazole in initial management and treatment of metastatic prostate cancer to spine.

Ketoconazole in high doses causes castrate levels of testosterone within twenty-four to forty-eight hours; therefore it is extremely useful in the initial medical treatment of patients with metastatic prostate cancer who need a prompt therapeutic response. Review of 17 patients who presented with severe radicular pain or acute paraparesis/paraplegia showed that there was frequent delay in urologic consultation, pathologic confirmation, and initiation of efficacious therapy. In fact, 5 of 12 patients (42%) who received radiation therapy prior to effective hormonal therapy suffered significant morbidity and mortality. The case is made for the use of ketoconazole for initial empirical therapy for these patients.

Placebo-controlled study of oral terbutaline and pseudoephedrine in management of prostaglandin E1-induced prolonged erections.

Prolonged erections, priapism, secondary to pharmacologic stimulation are usually treated by drainage of the corporeal bodies and irrigation with a sympathomimetic. To study the efficacy of oral medical therapy in the treatment of priapism, 75 patients with pharmacologically induced (prostaglandin E1) prolonged erections were randomized to receive terbutaline, pseudoephedrine, or placebo. Detumescence occurred in 36 percent, 28 percent, and 12 percent, respectively. Terbutaline was significantly better than placebo (p < 0.05) in achieving detumescence. The results of this study suggest that oral terbutaline should be considered in the initial management of pharmacologically induced prolonged erections.

Penile gangrene associated with extensive Kaposi's sarcoma in patients with the acquired immunodeficiency syndrome.

Kaposi's sarcoma (KS) of the penis is a well-recognized manifestation of the acquired immunodeficency syndrome. Extensive KS of the genitalia progressed and caused penile gangrene in 2 cases. Management is palliative with urinary diversion via percutaneous suprapubic cystostomy.

Ureteropelvic junction obstruction in adults.

Ureteropelvic junction obstruction (UPJ) in adults is more common than generally appreciated. It may mimic other diseases and may be associated with abdominal pain, hypertension, and recurrent pyelonephritis. Diagnosis and surgical correction were frequently delayed with an average duration of symptoms of 3.2 years for 31 adult patients. Only 4 adults (13%) were diagnosed at the time of their initial onset of symptoms. Nephrectomies were performed on 24 per cent of renal units. Accessory lower pole renal vessels were found in 52 per cent of the adults with UPJ obstruction, twice the rate found in children. Intravenous digital subtraction angiography and diuretic radionucleotide renography should be considered in the evaluation of an adult patient with a UPJ obstruction because of the high rate of accessory vessels. If accessory vessels are present on the contralateral side, especially postnephrectomy, there is heightened concern for the remaining kidney and close follow-up with ultrasonography is recommended.

Epididymocutaneous fistula in a patient with the acquired immunodeficiency syndrome and Marfan's syndrome.

Epididymocutaneous fistula is a rare entity. A recent case in a patient with the acquired immunodeficiency syndrome and Marfan's syndrome led to this review. The patient's immunocompromised status as well as his past medical history necessitated special considerations in the diagnosis and management of his epididymocutaneous fistula.

Phytotherapy in treatment of benign prostatic hyperplasia: a critical review.

Phytotherapeutic agents have enjoyed widespread use, especially in Europe, for the treatment of BPH. With the recent proliferation of nutrition and vitamin stores in the United States, use of these agents has greatly increased. Although SPB extract is the most extensively studied of the phytotherapeutic agents used for BPH, no well-defined mechanism of action has been proposed. Evidence for an antiandrogenic or antiestrogenic effect is conflicting, and there are no clinical data suggesting an effect on 5-alpha-reductase activity. Furthermore, clinical trials with SPB have largely been uncontrolled and are thus of limited value in ascertaining the true clinical impact of this agent. Double-blind, controlled studies with SPB also have limitations in that most were of very short duration (none longer than 3 months) and did not provide entry or exclusion criteria. In addition, standardized symptom scores were not utilized. Only two of seven studies showed an appropriate placebo response, and the results and conclusions of both these studies were contradictory. The best and most convincing study of the efficacy of phytotherapeutic agents (using Harzol) was recently published in the Lancet. This study was rigorous and matched in design and format with pharmaceutical industry trials. A mild but appropriate placebo response was detected, which further validates the study. However, a prior placebo-controlled study showed no efficacy of beta-sitosterol-beta-D-glucoside. This dichotomy of results possibly reflects the different composition of the agents tested. This is a major confounding factor in this field of study, especially because the active ingredients are unknown. Standardization of the compounds is needed to compare and assess accurately the effect of the different extracts.

Indications for use of ketoconazole in management of metastatic prostate cancer.

Newer methods of androgen ablation for the treatment of metastatic prostatic carcinoma have been developed as alternatives to the standard forms of therapy, oral estrogens and surgical castration. The purpose of this review is to elucidate the indications and to determine the role of ketoconazole in the management of metastatic prostatic cancer. Eighteen patients have been treated with ketoconazole. The indications for usage have included: prompt therapeutic response, when orchiectomy is contraindicated, when estrogens are contraindicated, initial empirical therapy, and hormonally refractory disease. It can also be used in conjunction with luteinizing hormone-releasing hormone analogues. Ketoconazole is excellent for short-term usage prior to bilateral orchiectomy and when prompt therapeutic response is needed but orchiectomy cannot be performed. However, it is not particularly useful for long-term hormonal therapy.

Tamoxifen for flutamide/finasteride-induced gynecomastia.

OBJECTIVES: Current therapies for advanced prostate carcinoma lead to a marked decrease in serum testosterone levels, which renders patients impotent. In preliminary studies, combination therapy with flutamide and finasteride has been used as an alternative therapy for the treatment of prostate carcinoma because potency can be preserved. Both of these agents can cause gynecomastia and breast/nipple tenderness. METHODS: Six men being treated for advanced prostate carcinoma with flutamide/finasteride combination therapy developed painful gynecomastia, which was treated with tamoxifen 10 to 30 mg/day for 1 month. Clinical follow-up included breast measurements and determination of prostate-specific antigen (PSA), testosterone, and estradiol levels. RESULTS: While on this combination therapy for prostate carcinoma, 4 of 6 patients experienced a decrease in PSA level to less than 0.5 ng/mL. All patients remained potent. Serum testosterone increased in each patient who had a baseline level drawn. Estradiol levels were noted to be elevated in 4 of 6 patients at the time of evaluation for gynecomastia. After treatment with tamoxifen, circulating estradiol levels increased in 3 patients from 1.3 to 2.2 times the baseline level. Five patients experienced complete resolution of breast and nipple pain on tamoxifen 10 mg/day within the first month. The other patient had to be treated with 30 mg/day for 1 additional month, which subsequently resulted in pain resolution. CONCLUSIONS: These preliminary results suggest that low-dose tamoxifen is useful in treating painful gynecomastia for those patients on flutamide/finasteride combination therapy for advanced prostate carcinoma.

Urologic manpower issues for the 21st century: assessing the impact of changing population demographics.

OBJECTIVES: To evaluate the impact of changing population demographics on urologic staffing over the coming decades. METHODS: A model was constructed using data obtained from the U.S. Bureau of the Census for population projections; clinical studies to assess the percentages of men with symptomatic benign prostatic hyperplasia (BPH) and those undergoing prostatectomy; the American Medical Association regarding numbers and annual percent change of practicing urologists; and the American Urological Association regarding numbers of physicians completing residency training programs. Sensitivity analyses were performed varying both the rate of surgical intervention for symptomatic BPH and the annual increase in the number of practicing urologists. RESULTS: Regardless of variations in the surgical rate to as low as 4%, the average number of transurethral resections of the prostate gland/surgical interventions for BPH per urologist will increase by the year 2020 when compared with the known basepoint value obtained for 1990. Additionally, even with an annual net increase of 200 urologists per year, by 2020, the rapidly expanding population over 65 years of age will nearly offset even such a large increase in the number of practicing urologists. CONCLUSIONS: The greatest factor concerning future urologic staffing issues will be the changing population demographics. The need for urologic services will continue to rise. An oversupply of urologists can be avoided as long as the net increase does not exceed an average of 200 urologists annually.

Renal failure in patients with AIDS-related complex.

The acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) can be associated with nephropathy and renal failure. As the number of AIDS and ARC patients continues to increase dramatically, urologists will be called upon more frequently to help evaluate these patients for reversible causes of renal failure and to obtain tissue for pathologic diagnosis. Eight patients with ARC and renal failure were recently evaluated. Renal biopsies in 4 patients revealed focal and segmental glomerulosclerosis while 2 others showed proliferative and necrotizing glomerulonephritis with crescents. The implications of this study are that ARC patients with renal failure should be fully evaluated and be considered for long-term dialysis. However, the results of renal biopsies in these patients are unlikely to affect patient treatment.

Computerized tomography in evaluation of transitional cell carcinoma in bladder diverticula.

Between 1981 and 1985, 6 patients with transitional cell carcinoma in bladder diverticula had preoperative computerized tomography (CT). CT suggested no invasion through the wall of the diverticulum in all 5 patients who had pathologic confirmation. CT is a useful staging procedure and is helpful in determining the management of patients with transitional cell carcinoma.

Use of magnetic resonance urography.

OBJECTIVES: Magnetic resonance urography (MRU) is a new technique that uses heavily weighted T2 coronal images with fat suppression pulse. Urine appears white on MRU, resembling an intravenous urogram (IVU). Contrast agents are not necessary. This study describes the use of MRU in the diagnosis and treatment of patients with hematuria. METHODS: One hundred six patients with microscopic or gross hematuria and 6 normal volunteers underwent MRU between 1992 and 1995. A modified, heavily weighted T2 technique with intravenous administration of furosemide and ureteral compression was used. Thirty-two patients had other imaging techniques as well for comparison. RESULTS: MRU provided high-resolution images in almost all cases; 73 (69%) had a normal MRU. Significant findings in the 33 patients with abnormalities included renal cysts in 17 (51%), renal cell carcinoma in 6 (18%), transitional cell carcinoma in 5 (15%), ureteropelvic junction obstruction in 3 (9%), and stones causing obstruction in 6 (18%). Five patients with renal failure also had good visualization of the entire urinary tract. MRU was comparable to other imaging modalities except in identifying nonobstructing calculi. CONCLUSIONS: MRU provides an alternative to conventional imaging of the urinary tract, especially in those patients who have contraindications to ionizing radiation and contrast agents. Improvements in resolution, technique, and cost have to be addressed before it can be used regularly in urologic practice.

Computerized tomography in diagnosis of bladder rupture.

Patients with significant pelvic fractures and hematuria must be carefully evaluated for concomitant urinary tract injuries. Computerized tomography may be a useful adjunct to retrograde cystography for diagnosing bladder rupture in those patients with either equivocal or unexpectedly negative findings on cystograms.

Management of prostatic abscess in patients with human immunodeficiency syndrome.

OBJECTIVE: To review and assess the management and evaluation of prostatic abscess in patients with the acquired immunodeficiency syndrome (human immunodeficiency virus [HIV]). METHODS: Retrospectively reviewed 7 cases of prostatic abscess in HIV-positive patients treated at our institution. RESULTS: All 7 patients presented with fever and irritative voiding symptoms. Only 1 patient had a positive initial urine culture; 3 of 5 operative cases only had positive intraoperative culture. Organisms cultured were Staphylococcus aureus, enterococcus. Mycobacterium tuberculosis, and Mycobacterium avium. CONCLUSIONS: Transrectal ultrasonography is the imaging modality of choice for diagnosing this condition; it also directs the appropriate surgical approach. Transurethral unroofing should be attempted whenever significant extension outside the prostate is not found. Intraoperative cultures for aerobes, anaerobes, fungi, and mycobacteria must be obtained.

Monitoring radiation exposure to medical personnel during percutaneous nephrolithotomy.

To ascertain radiation exposure to medical personnel during percutaneous nephrolithotomy, lithium fluoride thermoluminescent dosimeters (TLDs) were utilized for the radiographic monitoring of 7 consecutive patients. Average fluoroscopy time per procedure was 27.8 minutes of which 15.1 minutes were for nephrostomy tube insertion and 12.7 minutes were for calculi extraction. The 2 radiologists received 4.5 and 5.1 mrad per procedure, while the 2 urologists received 2.5 and 3.7 mrad. All other ancillary personnel received less than 2.1 mrad per procedure except the anesthesiologists whose mean exposure was 4.7 mrad. By taking appropriate precautions and using the proper equipment, percutaneous nephrolithotomy can be performed with a low level of radiation exposure for all involved physicians and personnel.