A multicenter comparison of oral lomefloxacin versus parenteral cefotaxime as prophylactic agents in transurethral surgery.

This report presents the pooled results from two randomized trials of lomefloxacin and cefotaxime used as prophylaxis in patients undergoing transurethral surgical procedures. A total of 499 patients were enrolled at seven centers in the United States. Patients received either 400 mg of lomefloxacin orally 2-6 hours prior to surgery, or 1 g of cefotaxime intravenously or intramuscularly 30-90 minutes preoperatively. Patients undergoing simple cystoscopy or retrograde pyelograms were not eligible for inclusion. Urine cultures were obtained prior to surgery, 24 hours post-surgery, prior to catheter removal, and 3-5 days post operatively. Treatment failure was defined as isolation of greater than or equal to 10(5) colony-forming units (CFU)/mL of pathogenic bacteria from any post-surgical urine culture. Lomefloxacin was successful in preventing post operative infections in 204 of 207 evaluable patients (98.6%); there were three prophylactic failures. Cefotaxime was successful in 196 of 206 (95.1%) evaluable patients; 10 were prophylactic failures. Lomefloxacin concentrations were measured simultaneously in serum and in samples of prostate tissue from 29 patients undergoing transurethral resection of the prostate. Lomefloxacin prostate concentrations were 1.0-22.3 micrograms/g, with a mean of 5.0 micrograms/g. The average tissue:plasma ratio was 2.0. The safety profile of the two study drugs was excellent, and both were well tolerated. Adverse events were reported by 12.7% of the patients treated with lomefloxacin and 13.8% of those treated with cefotaxime. The majority of events were mild and required no treatment.

Intraoperative autotransfusion in urologic oncology.

The value of autotransfusion is widely recognized in the surgical community and may be of increasing importance in prevention of acquired immunodeficiency syndrome and hepatitis. The concern of potential contamination of the blood with viable tumor cells has resulted in limited use of autotransfusion in cancer surgery. The objective of this study was to examine the benefits and safety of autotransfusion in patients undergoing major surgery of genitourinary tumors. Autotransfusion was used in 49 consecutive patients. Twenty-four patients had radical cystectomy, ten had radical prostatectomy, 13 had radical nephrectomy, and two had other types of operations. An autotransfusion machine (Haemonetics Cell Saver) was used. The follow-up included physical examination, chest roentgenogram every three months, and bone scan and computed tomographic scan if clinically indicated. Liver and renal profiles were routinely performed every three months. Five of 49 patients developed metastases during follow-up examination from 12 to 23 months. The low incidence of metastatic spread and the pattern of spread fall to implicate autotransfusion as a cause of tumor dissemination. Autotransfusion and predeposited blood banking may result in elimination of or significant reduction in homologous transfusions.

Renal cell carcinoma and idiopathic thrombocytopenic purpura.

A syndrome resembling idiopathic thrombocytopenic purpura has been described previously to occur in association with diverse forms of cancer. Herein we present the first reported case of renal cell carcinoma associated with idiopathic thrombocytopenic purpura, a review of the literature, and the pathophysiology of platelet destruction.

Hemorrhage from congenital renal arteriovenous malformation in pregnancy.

A case report of life-threatening hemorrhage from a congenital renal arteriovenous malformation during pregnancy is presented. The hyperdynamic circulatory state that exists during pregnancy may predispose to bleeding from vascular malformations. We review the classification and clinical presentation of renal arteriovenous malformations.

Evaluation of an implant that delivers leuprolide for 1 year for the palliative treatment of prostate cancer.

OBJECTIVES: To evaluate the Viadur implant, which delivers leuprolide acetate for the palliative treatment of advanced prostate cancer. METHODS: Inserted subcutaneously, the 4 x 45-mm implant uses osmotic pressure to deliver leuprolide continuously at a controlled rate for 1 year. This 19-center open-label study enrolled patients with prostate cancer who had had no prior therapy or showed biochemical evidence of treatment failure after prostatectomy or radiotherapy. Each patient received one implant. After 1 year, that implant was removed, another was inserted, and patients were followed up for 2 additional months. The primary efficacy measure was suppression of testosterone to less than the castrate threshold (50 ng/dL). RESULTS: Eighty patients were enrolled. The implant effectively suppressed testosterone in 79 patients (99%) within 2 to 4 weeks and maintained that suppression through the study period. In 1 patient, the testosterone was suppressed to less than 100 ng/dL within 4 weeks but was not less than 50 ng/dL until week 24. Prostate-specific antigen levels normalized (4 ng/mL or less) or a clinically significant decrease occurred in all patients. Leuprolide was rapidly absorbed, resulting in mean serum concentrations of 16.8 ng/mL 4 hours after implant insertion and 2.4 ng/mL at 24 hours; steady mean serum leuprolide concentrations were then maintained throughout the year, at approximately 0.9 ng/mL. Investigators were satisfied with the insertion and removal procedures. All patients reported satisfaction after 1 year of treatment. The safety profile of the implant was consistent with androgen ablation therapy. Most adverse events were mild, and the most common event was hot flashes. CONCLUSIONS: The leuprolide implant effectively suppressed testosterone concentrations to less than the castrate threshold and maintained that suppression throughout the study period.

Absolute ethanol renal angioinfarction for control of hypertension.

Six patients (11 renal units) underwent ethanol renal angioinfarction for medically uncontrollable hypertension. The mean preablation blood pressure was 175/112 mm Hg despite antihypertensive medications. Five of the patients demonstrated elevated renal vein renin levels prior to angioinfarction. Hypertension was improved in all 6 patients, during a mean follow-up period of fifty-one months. Systemic hypertension was completely eliminated in 4 patients. Two patients continue to require antihypertensive medication to control their hypertension. There were no major complications directly related to intra-arterial injection of ethanol. Transcatheter renal ablation employing intra-arterial injection of absolute ethanol for control of severe hypertension appears to be a safe and efficacious procedure. It should be considered an alternative to nephrectomy in selected high-risk patients.

Intravesical bacillus Calmette-Guerin for patients with high-risk superficial bladder cancer.

Intravesical bacillus Calmette-Guérin (BCG) was employed in the treatment of 55 patients with aggressive superficial transitional cell carcinoma of the bladder (cTa, cT1, cTis). All of the patients had a previous history of recurrent superficial disease, and 41 (75%) were treatment failures following other intravesical therapy. Thirty-six (66%) patients responded to treatment, and 19 (34%) were treatment failures. Twenty-seven (66%) of 41 patients with cTa-cT1 tumors and 9 (64%) of 14 patients with cTis responded, with a mean follow-up period of 30.5 months. Disease progression was noted in 8 (15%) of the patients and muscle invasive disease in 6. Patients with a history of three or more previous events of tumor recurrence, positive urinary cytology, and multicentric disease, all fared worse than patients without these characteristics (p less than 0.05). BCG is an effective agent in controlling superficial transitional cell carcinoma of the bladder, even in a high-risk group of patients who failed previous intravesical therapy. BCG should be employed in this group of patients prior to radical surgery.

Levofloxacin versus ciprofloxacin versus lomefloxacin in acute pyelonephritis.

OBJECTIVES: To evaluate, in two randomized, multicenter trials, levofloxacin compared with ciprofloxacin and lomefloxacin for efficacy and safety in treating acute pyelonephritis. METHODS: We enrolled a total of 186 patients with bacteriologically proved infection. Of these, 89 patients in both trials combined received levofloxacin 250 mg once daily; 58 received ciprofloxacin 500 mg twice daily in the first trial (double blind); and 39 received lomefloxacin 400 mg once daily in the second trial (open label). Microbiologic response of patients evaluable for microbiologic efficacy was the primary efficacy variable, and clinical response of microbiologically evaluable patients was the secondary efficacy variable in both studies. RESULTS: Escherichia coli was the most prevalent pathogen. At 5 to 9 days after the end of treatment, 95% of uropathogens were eradicated in patients who received levofloxacin compared with 94% in the ciprofloxacin-treated group and 95% in the lomefloxacin-treated group. The clinical cure rate was 92% for levofloxacin in both studies combined, 88% for ciprofloxacin, and 80% for lomefloxacin. Drug-related adverse events were reported by 2% of levofloxacin-treated patients, 8% of ciprofloxacin-treated patients, and 5% of lomefloxacin-treated patients. CONCLUSIONS: The once-daily oral administration, proven efficacy, and good tolerability make levofloxacin an excellent choice for empiric treatment of acute pyelonephritis.

A controlled trial of levofloxacin and lomefloxacin in the treatment of complicated urinary tract infection.

OBJECTIVES: The efficacy and safety of levofloxacin and lomefloxacin in complicated urinary tract infections (UTIs) were compared in a randomized, open-label, multicenter study. METHODS: Outpatients were randomized to receive levofloxacin (250 mg once daily) for 7 to 10 days or lomefloxacin (400 mg once daily) for 14 days. Three hundred thirty-six patients (171 with levofloxacin, 165 with lomefloxacin) were evaluable for microbiologic efficacy, and 461 patients (232 with levofloxacin, 229 with lomefloxacin) for safety. RESULTS: The overall microbiologic eradication rate of pathogens was 95.5% (168 of 176) for levofloxacin and 91.7% (154 of 168) for lomefloxacin. Eradication rates with respect to patients were 95.3% (163 of 171) and 92.1% (152 of 165) for levofloxacin and lomefloxacin, respectively. At the 5 to 9-day post-therapy visit, symptoms were completely resolved in 84.8% of levofloxacin-treated patients and were decreased in 8.2% (93.0% clinical success). Among the lomefloxacin-treated patients, complete resolution was seen in 82.4%, with decreased symptoms in 6.1% (88.5% clinical success). Drug-related adverse events (AEs) were reported by 10 (2.6%) and 18 (5.2%) levofloxacin- and lomefloxacin-treated patients, respectively. Compared with levofloxacin-treated patients, more lomefloxacin-treated patients experienced photosensitivity reactions (3 [1.3%] versus 0) and dizziness (2 [0.9%] versus 0). Nausea (3 [1.3%] versus 1 [0.4%]) was more frequent in the levofloxacin-treated group. Six patients in each treatment group had a gastrointestinal AE (1.7%); rash was reported more frequently with lomefloxacin (4 patients [0.4%]) than with levofloxacin (1 patient [0.4%]). Discontinuation because of AEs was observed in 8 (3.4%) levofloxacin- and 14 (6.1%) lomefloxacin-treated patients. CONCLUSIONS: Once-daily levofloxacin is as effective as and has a superior tolerability profile than lomefloxacin in the treatment of complicated UTIs.

Single-dose oral ciprofloxacin versus placebo for prophylaxis during transrectal prostate biopsy.

OBJECTIVES: To determine whether antimicrobial prophylaxis could prevent infections after transrectal needle biopsy of the prostate using automated biopsy devices. METHODS: We conducted a prospective, randomized, double-blind, multicenter trial in which a total of 537 patients received either oral ciprofloxacin 500 mg or placebo before transrectal needle biopsy of the prostate. Repeated urine cultures and urinalysis were obtained at 2 to 6 days after biopsy and 9 to 15 days after biopsy. The primary determinant of efficacy was bacteriologic response (bacteriuria [more than 10(4) colony-forming units (CFU)/mL] versus no bacteriuria) at the 9- to 15-day follow-up evaluation. RESULTS: Two hundred twenty-seven (84%) of 269 ciprofloxacin patients and 230 (86%) of 268 placebo patients were valid for efficacy analysis in which a mean of four biopsies was performed. Six ciprofloxacin-treated (3%) and 19 placebo-treated (8%) patients had bacteriuria (more than 10(4) CFU/mL) after the procedure (P = 0.009). Six ciprofloxacin recipients (3%) and 12 placebo recipients (5%) had clinical signs and symptoms of a urinary tract infection (UTI) (P = 0.15). In addition, no ciprofloxacin-treated patients compared with 4 placebo-treated patients (2%) were admitted to the hospital for febrile UTI after the procedure. Ciprofloxacin reduced the expected net costs of treating infectious complications after biopsy by $23 per patient for an overall annual savings of $68,195 in the five study groups when compared with placebo. CONCLUSIONS: Single-dose oral ciprofloxacin reduced bacteriuria after biopsy compared with placebo in patients undergoing transrectal prostatic biopsy and provided an economic advantage. In addition, this study establishes the actual rate of bacteriuria after transrectal needle biopsy of the prostate without antibiotic prophylaxis to be 8% with a clinical rate of UTI of 5% and a hospitalization rate of 2%.

A dose-response study of the effect of flutamide on benign prostatic hyperplasia: results of a multicenter study.

OBJECTIVES: The objective of this study was to evaluate efficacy, safety, and dose-response profiles of four dosing schemes of flutamide over 24 weeks. METHODS: Patients were randomized to receive one of the following five treatment regimens for a period of 24 weeks: placebo capsule, flutamide capsules 125 mg twice daily, 250 mg once daily, 250 mg twice daily, and 250 mg three times daily. Patients were then evaluated at baseline (0 weeks) and at 4, 6, 12, 18, and 24 weeks after the start of treatment, and 8 weeks after the end of treatment (32 weeks). Evaluation of efficacy was performed by noting changes in urine flow rate, residual urine volume, symptom score, prostate volume, and prostate-specific antigen level. A total of 372 patients were enrolled into the study at 32 centers (14 centers in the United States and 18 international centers). RESULTS: Baseline peak urinary flow rate and percent change from baseline in maximum flow rate showed a dose-related increase at 4 and 6 weeks; this increase was significant in the 250 mg three times daily group. At later time points, no significant differences between the flutamide and placebo groups were observed, largely because of the decreasing number of evaluable patients. At 4 and 6 weeks, 25% of patients in the 250 mg three times daily group had more than 3 cc/s increase in uroflow compared to about 10% of placebo patients (P < 0.05). All flutamide-treated groups had a significant decrease in prostate volume from baseline to the last treatment visit compared to placebo and this reduction was dose related (in comparison to placebo: P < 0.05 for 125 mg twice daily and P < 0.001 for all other treatment arms). Median decrease for the flutamide-treated groups ranged from 6% to 23% at 12 weeks and from 14% to 29% at 24 weeks. All treatment groups showed a subsequent increase in prostate volume after treatment was stopped. Furthermore, there was a significant reduction in residual urine volume at 24 weeks only in the 250 mg three times daily group. It increased following cessation of therapy. Urinary symptoms at 6, 12, 18, and 24 weeks did not show any significant difference between placebo and any flutamide dose group. The most common adverse events were nipple and breast tenderness (42% to 52%), diarrhea (29% to 34%), and gynecomastia (14% to 19%). Each of these adverse events had a significantly higher incidence in all flutamide dose groups compared with placebo, but none appeared to occur in a dose-related fashion. Sixteen percent of patients in the placebo group and 25% to 39% of patients in flutamide groups were discontinued due to diarrhea (12% to 17%) or nipple and breast tenderness (4% to 8%). A total of 1% to 3% of patients in various treatment arms discontinued due to deranged liver enzymes (1% for placebo); and 1% to 4% due to impotence (1% for placebo). CONCLUSIONS: Flutamide reduced the prostate volume in a dose-related fashion and resulted in an increase in peak flow rate at 4 weeks (3% for 250 mg three times daily, P value < 0.05), but the early positive effects did not maintain statistical significance due to an increasing number of dropouts due to adverse events. Effect on postvoid residual volume was observed only at the highest dose and at 24 weeks (median reduction, 23 mL, P < 0.05). Despite volume reduction and early improvement in peak flow rate, there were no significant differences in urinary symptoms among the placebo and flutamide groups. Higher incidences of diarrhea, breast tenderness, and gynecomastia, however, were the main limiting factors in this study and until these problems are overcome, the role of flutamide in the management of benign prostatic hyperplasia remains investigational.

Long-term safety and efficacy of oral phentolamine mesylate (Vasomax) in men with mild to moderate erectile dysfunction.

The objectives of this study were to evaluate long-term safety and efficacy of phentolamine mesylate, an orally active, rapid-acting alpha-adrenergic receptor antagonist, for the treatment of men suffering from erectile dysfunction (ED). It was an open-label study involving more than 2000 patients. Men received phentolamine mesylate 40 mg or 80 mg (10 tablets/month) as needed for up to 13 months and self-assessed erectile performance using two validated questionnaires. Treatment with phentolamine mesylate was associated with increases in Erectile Function Domain score of the IIEF, successful vaginal penetrations, and in overall satisfaction. Most adverse events were mild or moderate in severity and consistent with the known pharmacodynamic properties of phentolamine. In conclusion, phentolamine mesylate is safe and effective in the long-term treatment of men with mild to moderate ED.

Early prostate cancer: is there a need for new treatment options?

Improvements in diagnostic techniques have led to prostate cancer being diagnosed in younger patients and at an earlier stage of disease. The question therefore arises as to what is the best treatment for early prostate cancer. The main issues to be considered are whether the cancer is likely to progress quicker if these patients do not receive early treatment and what the quality of life implications are for patients receiving early treatment. As yet, due to the lack of valid comparisons of treatments, there is no clear "best treatment" for early prostate cancer. A number of clinical trials, comparing current treatments or investigating potential new treatment options for early prostate cancer, are in progress. The results of these should clarify the relative benefits of currently available treatments. This article reviews the latest information on the incidence, prognosis and current treatments for early prostate cancer and discusses the need for new treatments. Potential clinical benefits and cost implications of new treatments for early prostate cancer, such as improved surgical and radiotherapy techniques and adjuvant medical therapy, are also evaluated.

Needle aspiration and needle biopsy procedures.

Needle biopsy of the prostate, employing large "core" needles and performed via the transperineal or transrectal routes, is a well-established method for diagnosing prostatic malignancy. This procedure can be performed safely under local anesthesia in an outpatient setting. Rectal cleansing and prophylactic antibiotics have minimized infectious complications following transrectal biopsy, and it remains the favored technique in patients with small lesions. Repeat biopsy under anesthesia is indicated when the clinical suspicion of malignancy remains high despite negative biopsies. In contrast to "core" needle biopsy, which obtains a cylinder of tissue for histologic examination, the fine-needle biopsy obtains a specimen for cytologic examination. If cytologic expertise is unavailable locally, the specimen may be fixed in the office and shipped to a major medical center for interpretation. Fine-needle aspiration may be safely employed to biopsy the prostate, pelvic masses, and inguinal and pelvic lymph nodes. Biopsy of palpable masses can be done simply and safely with morbidity akin to venipuncture. Nonpalpable tissues may be biopsied under radiographic guidance. Fine-needle aspiration biopsy is safe and cost-effective, has resulted in a significant improvement in the accuracy of our clinical staging, and has spared many patients unnecessary surgical procedures.

Randomized trial of a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) on symptoms of benign prostatic hyperplasia (BPH).

Because benign prostatic hyperplasia (BPH) is relatively common, it is important to discover safe and effective means to treat this often debilitating perturbation. Accordingly, we examined the effectiveness of a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) in treating symptoms of BPH. We undertook a randomized, placebo-controlled, double-blind study. Patients were enrolled from 3 urological practices in the USA. 144 subjects were randomized for study. 17 subjects eventually withdrew, leaving 70 patients in the test group and 57 in the placebo group to complete the study. Inclusion criteria consisted of a diagnosis of BPH, no evidence of cancer, and a maximal urinary flow rate between 5 and 15 ml/second. Patients received either placebo or the combined natural products for 3 months. Evaluations were performed via the American Urological Association (AUA) Symptom Index score, urinary flow rate, PSA measurement, and residual bladder volume. Nocturia showed a markedly significant decrease in severity in patients receiving the combined natural products compared to those taking placebo (p < 0.001). Daytime frequency was also lessened significantly (p < 0.04). When the average individual total AUA Symptom Index score in the test group was compared to that in the placebo group at the end of the study, the difference proved highly significant (p < 0.014). PSA measurements, maximal and average urinary flow rates, and residual volumes showed no statistically significant differences. When taken for 3 months, a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) compared to placebo can significantly lessen nocturia and frequency and diminish overall symptomatology of BPH as indicated by an improvement in the total AUA Symptom Index score. The combination of natural products caused no significant adverse side effects.

Multicenter prospective randomized 52-week trial of calcium hydroxylapatite versus bovine dermal collagen for treatment of stress urinary incontinence.

OBJECTIVES: To evaluate the safety and effectiveness of soft-tissue augmentation of the urethral sphincter with calcium hydroxylapatite (CaHA; Coaptite) compared with glutaraldehyde cross-linked bovine collagen (Contigen) in female patients with stress urinary incontinence due to intrinsic sphincter deficiency and without associated urethral hypermobility. METHODS: This 12-month prospective, randomized, comparative, multicenter, single-blind, parallel, clinical trial of CaHA and collagen for soft-tissue augmentation of the urethral sphincter in the treatment of stress urinary incontinence enrolled 296 women. Up to five injections were performed in the first 6 months of the trial. Twelve-month postinjection efficacy data were available for 231 patients. RESULTS: The results indicated that CaHA and collagen were both well tolerated in this study. No systemic adverse events were observed with either product. We used the Stamey Urinary Incontinence Scale to grade the improvement, which was the primary endpoint of the study. At 12 months, 83 (63.4%) of 131 CaHA patients compared with 57 (57.0%) of 100 collagen patients showed improvement of one Stamey grade or more (P = 0.34). More CaHA patients required only one injection (n = 60; 38.0%) during the study compared with the Contigen patients (n = 36; 26.1%; P = 0.034). Also, the average total volume of material injected during the course of the study was less for CaHA than for collagen (4.0 mL versus 6.6 mL, respectively; P <0.0001). CONCLUSIONS: The results of the study have demonstrated that Coaptite is an appropriate and well-tolerated treatment for patients with incontinence due to intrinsic sphincter deficiency. This new soft-tissue augmentation material has a good safety profile and appears to provide durable improvement.

Autotransfusion and blood conservation in urologic oncology.

Autotransfusion is the reinfusion of the patient's own blood. Currently utilized forms include preoperative donation, perioperative hemodilution, and intraoperative salvage. The principal benefit of autotransfusion is a reduction in the complications associated with receipt of homologous blood products. Principal among these are febrile reactions, allergic and hemolytic reactions, alloimmunization, and the transmission of hepatitis and acquired immune deficiency syndrome. An additional benefit in the management of cancer patients is the avoidance of transfusion induced immunosuppression. Predeposit autologous transfusion is a simple and safe method to reduce patient's requirements for exogenous blood. Although well suited for cancer patients, predeposit programs remain underutilized with only 5% participation. Perioperative hemodilution can be a valuable adjunct in selected patients. Although the presence of malignancy has been regarded as a contraindication to the use of intraoperative autotransfusion, preliminary reports suggest that intraoperative autotransfusion can be safely used in patients undergoing surgery for urologic malignancies.

Duplicated inferior vena cava simulating retroperitoneal lymphadenopathy in a patient with embryonal cell carcinoma of the testicle.

Computerized tomography has become the most widely applied staging technique in the assessment of retroperitoneal lymph nodes in patients with nonseminomatous testicular carcinoma. Errors in clinical staging of testicular carcinoma can have serious implications for the treatment afforded these patients. We describe a duplicated inferior vena cava that simulated retroperitoneal lymphadenopathy on abdominal computerized tomography in a patient with embryonal cell carcinoma of the testicle. The embryology and implications of anomalous lymphatic drainage of the testicle are discussed.

Treatment alternatives for invasive bladder cancer.

Radical cystectomy remains the gold standard in the treatment of patients with muscle invasive bladder cancer. However, the specter of high failure rates coupled with morbid treatment methods has caused urologists, oncologists, and radiotherapists to explore modifications in, and alternatives to, the traditional treatments for invasive bladder cancer. The identification of the active methotrexate-platinum-based combination chemotherapy regimens heralds a new era in our ability to treat advanced disease effectively. Patients with less extensive muscle invasive tumors may be efficiaciously treated using conservative surgical excision, either alone or in combination with adjunctive treatments. In addition, definitive radiation therapy, given via the interstitial route or in combination with radiosensitizers, may result in long-term survival and preservation of bladder function. Progress has been made on multiple fronts in our ability to improve overall survival rates while allowing for the preservation of bladder function. The ability of these new mixed multimodality treatment initiatives to produce viable statistics equal to that of radical exenteration is an important landmark on the route towards an ideal treatment for invasive bladder cancer.