Craig V. Comiter

Ciprofloxacin or Tamsulosin in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Randomized, Double-Blind Trial

Context Although the cause of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is unknown, physicians sometimes try to treat it with antibiotics or -receptor blockers. Contribution In this multicenter, double-blind factorial trial, 196 men with moderately severe CP/CPPS were randomly assigned to 6 weeks of treatment with ciprofloxacin, tamsulosin, both drugs, or placebo. Neither ciprofloxacin nor tamsulosin substantively reduced symptoms. Implications Ciprofloxacin and tamsulosin were not effective treatments for CP/CPPS. Cautions Patients had long-standing, refractory CP/CPPS and received trial treatments for only 6 weeks. Patients with new diagnoses who are given longer courses of the trial treatments might respond differently. The Editors Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder and accounts for approximately 2 million visits to physicians annually in the United States (1). The substantial impact of CP/CPPS includes bothersome lower urinary tract symptoms, sexual dysfunction, reduced quality of life (2-5), and increased health care expenditures (6). The syndrome is diagnosed only on the basis of symptoms, principally pain or discomfort in the pelvic region. No objective measures can help define the disease. Although bacteria can infect the prostate, most men with prostatitis have a negative midstream urine culture, indicating that bacteria may not be the cause of their symptoms (2). Such men are classified as having National Institutes of Health (NIH) category III prostatitis, the most common of the clinically defined prostatitis syndromes (7). It is by no means clear that the disease is characterized by inflammation of the prostate or that the prostate is responsible for symptoms in a substantial proportion of patients. Because of this uncertainty, the term CP/CPPS is used. Chronic prostatitis/chronic pelvic pain syndrome is commonly seen by primary care practitioners, internists, and urologists. In the Olmsted County Study of Urinary Symptoms and Health Status Among Men (8), a population-based study in Olmstead County, Minnesota, the overall prevalence rate of a physician-assigned diagnosis of prostatitis was 9%. Population-based surveys of symptoms have estimated that the prevalence of the syndrome ranges from 9% to 12% among men (9, 10). It is difficult to estimate the proportion of patients with symptoms lasting longer than 3 months whose disorder remains refractory to empirical therapy. These patients are commonly seen by urologists, but whether they represent a minor subpopulation of the overall symptomatic group or make up the majority of patients is unknown. We chose to study these patients because they present with a troubling, long-standing problem and are usually treated with agents of unclear benefit. Even if a relatively large number of men whose symptoms last 3 months or more are cured by standard empirical therapy and the clinical scenario we describe is uncommon, men with refractory symptoms still present a substantial problem to internists and urologists who have little information to guide therapy. Because the cause of CP/CPPS is unknown, affected men receive many empirical therapies. The 2 most common treatments prescribed by physicians are antimicrobial agents and -adrenergic receptor antagonists (2), although there is little objective evidence to support their use (11). Quinolones, such as ciprofloxacin, are commonly used to treat CP/CPPS because of their excellent penetration into the prostate and broad spectrum of coverage for uropathogens and other organisms traditionally believed to be associated with the syndrome (12). Tamsulosin, an -blocker, is an effective treatment for lower urinary tract symptoms in men with benign prostatic hyperplasia, and it has been hypothesized that tamsulosin may improve these symptoms in men with CP/CPPS. This randomized clinical trial was designed to evaluate whether ciprofloxacin or tamsulosin reduces symptoms of long-standing CP/CPPS of at least moderate severity, typical of the 488 men in our Chronic Prostatitis Cohort Study (2). The primary purpose of the trial was to test the most common prescription treatments given to men with CP/CPPS, who are commonly seen in our referral-based urologic practices. Methods Organization The Chronic Prostatitis Collaborative Research Network, a consortium sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), conducted the trial. Urologists and their clinical associates recruited patients at 10 sites in the United States and 1 site in Canada. The NIDDK established an independent data and safety monitoring board to review the progress, safety, and final analysis of the trial. The individual institutional review boards at each of the 10 participating clinical centers approved the study, and all men gave written informed consent. Participants The design of this trial has been described in detail previously (13). Participating urologists recruited both newly referred patients and patients with established CP/CPPS from their referral-based clinical practices at 10 tertiary medical centers in North America. Trial referrals came from primary care providers, internists, and other urologists. The primary diagnostic criterion was pain or discomfort in the pelvic region for at least 3 months in the previous 6 months. Severity of symptoms was assessed by using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) (14, 15). This instrument is a validated questionnaire, completed by the patient, consisting of 4 questions about pain, 3 about voiding symptoms, and 2 about quality of life. The scores in these 3 individual domains (pain, voiding, and quality of life) are combined without weighting to yield the NIH-CPSI total score. Eligible men were required to have at least moderate symptoms, defined as an NIH-CPSI score of at least 15 of 43 possible points, at the time of randomization. We excluded men who had a documented urinary tract infection (midstream urine culture > 100000 colonies/mL) within the past 3 months, a history of active genital herpes within the previous year, a history of genitourinary cancer, inflammatory bowel disease, active urethral stricture, prostate or bladder surgery, or neurologic disease affecting the bladder. We used ligase chain reaction to screen for Chlamydia in urethral urine samples and excluded men whose tests yielded positive results. Previous treatment with antimicrobial agents or -adrenergic receptor blockers, including the study drugs, had to be completed at least 4 weeks before eligibility screening. Additional details of the eligibility criteria are available elsewhere (13). Study Design and Interventions Men were randomly assigned in equal proportions within a 2 2 factorial design to receive placebo; ciprofloxacin alone, 500 mg twice daily; tamsulosin alone, 0.4 mg once daily; or a combination of both drugs (Table 1). Patients were treated for 6 weeks, at which time the primary end point was assessed. Symptoms at 9 and 12 weeks after randomization (6 weeks after completion of treatment) were also assessed to evaluate longer-term treatment response. The 2 baseline screening contacts and the primary end point contact at 6 weeks were clinic visits; interim contacts at 3, 9, and 12 weeks were conducted by telephone. Table 1. Study Design Each patient was randomly assigned by computer. A permuted block randomization schedule with varying block sizes was used, stratified by clinical site. The research pharmacist at each site provided the blinded study drugs in 2 tamper-evident bottles. All clinical investigators, research nurses, and patients were blinded to treatment assignments until all patients had completed follow-up. Outcomes The primary outcome was the change in the NIH-CPSI total score from baseline to 6 weeks. The NIH-CPSI was administered at each of the 2 baseline screening visits, 1 to 3 weeks apart, and every 3 weeks thereafter until 12 weeks. The average of the 2 scores before randomization was used as the baseline score. Evaluation of the responsiveness of the NIH-CPSI indicates that a 4-point change on a scale of 0 to 43 points represents a difference detectable by the patient. Secondary outcomes included changes in the pain, voiding, and quality-of-life subscales of the NIH-CPSI; physical and mental summary scores on the Medical Outcomes Study 12-Item Short-Form Health Survey (16); and a 7-point patient-reported global response assessment. Responders for the global response assessment were defined as men reporting that they were markedly improved or moderately improved at 6 weeks compared with baseline. Men for whom the global response assessment was missing were considered nonresponders and were included in the denominator for the assessment of response rates. Adverse events were monitored throughout the study and graded according to the National Cancer Institute Common Toxicity Criteria (ctep.cancer.gov/reporting/ctc.html). Patients were asked at each contact to report any adverse events that had occurred since the previous contact. The questions were open-ended, and researchers did not ask about any specific categories of adverse events. All events, regardless of whether they were expected reactions to the study drugs, were recorded. Attribution to treatment was also assessed. However, because it was difficult to determine whether certain adverse events, such as pain, were related to treatment or to CP/CPPS, all events were analyzed. Statistical Analysis For each of the 2 primary treatment comparisons, the recruitment goal of 184 patients provided 80% power, at a 2-sided significance level of 5%, to detect a 4-point treatment difference in the NIH-CPSI total score between baseline and 6 weeks. We recognized that although patients could detect this difference, most might not perceive it as a major improvement. However, we did not want to miss even a minor change in

THE MALE SLING FOR STRESS URINARY INCONTINENCE: A PROSPECTIVE STUDY

PURPOSE This is a report of a prospective study of the male sling for treating stress urinary incontinence. MATERIALS AND METHODS A total of 21 men underwent sling surgery. There were 2 titanium screws loaded with polypropylene suture placed in each descending pubic ramus through a 3.5 cm. perineal incision at the level of the bulbar urethra. A polypropylene mesh was placed over the urethra and tied to the bone anchors, adjusting sling tension to a compression pressure of 60 cm. water. Followup was done with the incontinence section of the University of California, Los Angeles/RAND Prostate Cancer Index. RESULTS Mean followup was 12 months (range 5 to 21). Overall, incontinence was cured in 16 (76%) patients, substantially improved (stress urinary incontinence very small or small problem, 1 pad daily) in 3 (14%), somewhat improved (moderate problem-2 pads) in 1 and procedure failed (no improvement) in 1 (5%). The patients with stress urinary incontinence after undergoing transurethral prostatectomy were cured, as was the individual with myelomeningocele. Of the 18 patients with stress urinary incontinence after radical prostatectomy 13 were cured, including 1 of 2 who underwent previous artificial urinary sphincter placement and 2 of 3 adjuvant radiation. There was significant improvement in each survey question, and the total score improved from a mean plus or minus standard deviation of 65 +/- 11 preoperatively to 397 +/- 29 postoperatively (p <0.001). There was no retention, infection, erosion or de novo voiding dysfunction. CONCLUSIONS This minimally invasive sling surgery has not been associated with any significant complication, and early results compare favorably with artificial urinary sphincter. By compressing only the ventral urethra the risk of urethral erosion and atrophy is reduced. Prior radiation or artificial urinary sphincter does not appear to be a contraindication to sling surgery.

Endometriosis of the urinary tract

Genitourinary endometriosis is a rare manifestation of a common disease. Ectopic endometrial tissue may extrinsically involve or intrinsically invade the bladder or ureter, and, less commonly, the urethra or kidney. Bladder involvement usually presents with irritative symptoms, whereas ureteral disease may present with asymptomatic renal failure. Therefore, a high index of suspicion is necessary, and genitourinary endometriosis should be considered in all symptomatic women with a history of cesarean delivery of other gynecologic surgery. In women beyond reproductive age, definitive surgical treatment is preferred, with removal of the ectopic tissue, relief of obstruction, and castration with or without hysterectomy. In those who desire future fertility, conservative surgery and/or hormonal therapy is often recommended.

Surgical treatment of stress incontinence in men.

The committee was charged with the responsibility of reviewing and evaluating all published data relating to surgical treatment of male urinary incontinence since the previous consultation in 2004.

Prognostic features of teratomas with malignant transformation : a clinicopathological study of 21 cases

PURPOSE Teratomas with malignant transformation comprise up to 6% of metastatic teratomas. The prognosis of patients with these tumors can vary considerably. We delineate factors that may be related to prognosis in a cohort of men with teratoma with malignant transformation. MATERIALS AND METHODS We analyzed pathological features, treatment, response, recurrence, time to recurrence, subsequent followup and survival for 21 patients (median age 28 years) diagnosed with teratoma with malignant transformation during a 7-year period at our institution. RESULTS Malignant nongerm cell elements were present in the primary tumor in 11 cases (52%). Of 18 patients with testicular primaries 17 (94%) presented with metastatic disease. Despite aggressive treatment with surgery and chemotherapy 17 of 21 cases (81%) recurred (median time 6 months). Overall, 5 patients (24%) died of disease (median survival 23 months), 5 (24%) are alive with metastases (median followup 41 months) and 11 (52%) have no evidence of disease (median followup 50 months). Progression/recurrence was substantially greater for 2 of 2 cases with a mediastinal origin, 3 of 4 with rhabdomyosarcomatous differentiation and 5 of 6 with neural differentiation compared with the remainder of the cohort (p < 0.05). CONCLUSIONS Teratomas with malignant transformation are usually metastatic at presentation, have a high recurrence rate and are more aggressive than teratomas without malignant transformation. Prognosis is especially poor for mediastinal teratomas with malignant transformation and for those with neural or rhabdomyosarcomatous differentiation. Complete surgical resection of residual or recurrent disease appears to offer the best chance for prolonged survival.

Results of a Prospective, Randomized, Multicenter Study Evaluating Sacral Neuromodulation With InterStim Therapy Compared to Standard Medical Therapy at 6-Months in Subjects With Mild Symptoms of Overactive Bladder

This prospective, randomized, multicenter trial evaluated the 6‐month success rate of sacral neuromodulation (SNM) with InterStim® Therapy versus standard medical therapy (SMT) for overactive bladder (OAB).

Burned-Out Primary Testicular Cancer: Sonographic and Pathological Characteristics

PURPOSE Rarely, a testicular scar is discovered in a patient with a presumed extragonadal germ cell tumor. Of 6 patients originally diagnosed with retroperitoneal extragonadal germ cell tumors who had echogenic foci on scrotal sonography 5 had definite histological evidence of a regressed primary testicular cancer. MATERIALS AND METHODS Six men 21 to 36 years old presented with palpably normal testes and a presumed retroperitoneal extragonadal germ cell tumor. After chemotherapy each patient underwent retroperitoneal lymph node dissection and ipsilateral orchiectomy. The entire testis was submitted for histological evaluation and all calcifications were identified. RESULTS Scrotal sonography revealed an echogenic focus or foci in all cases, which corresponded to intratubular hematoxyphilic bodies in 2. In 3 cases the echogenic foci were intratubular psammoma bodies close to a fibrous scar with hemosiderin deposition, 1 of which contained a focus of intratubular germ cell neoplasia. The hematoxyphilic bodies appeared larger and more intensely echogenic on sonography than the psammoma bodies. The remaining case had stromal calcifications near the rete testis. CONCLUSIONS The hematoxyphilic bodies and fibrosis with hemosiderin deposits are believed to represent remnants of testicular carcinoma. Our finding of intratubular germ cell neoplasia provides further proof that testicular carcinomas regress. In 5 of 6 patients (83%) with presumed extragonadal germ cell tumors we showed definite pathological evidence of a burned-out testicular carcinoma. With a presumed retroperitoneal germ cell tumor and palpably normal testes, sonographic demonstration of an echogenic lesion in the absence of a hypoechoic mass probably represents a burned-out primary neoplasm.

Psychosocial variables affect the quality of life of men diagnosed with chronic prostatitis/chronic pelvic pain syndrome

To examine interactions between demographic, pain, urinary, psychological and environmental predictors of quality of life (QOL) in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Cross-Linked Polydimethylsiloxane Injection for Female Stress Urinary Incontinence: Results of a Multicenter, Randomized, Controlled, Single-Blind Study

PURPOSE In a pivotal trial we evaluated the effectiveness and safety of Macroplastique(R) as minimally invasive endoscopic treatment for female stress urinary incontinence primarily due to intrinsic sphincter deficiency. MATERIALS AND METHODS A total of 247 females with intrinsic sphincter deficiency were randomized 1:1 and treated with a transurethral injection of Macroplastique or Contigen. The latter group served as the control. Repeat treatment was allowed after the 3-month followup. Effectiveness was determined 12 months after the last treatment using Stamey grade, pad weight and Urinary Incontinence Quality of Life Scale scores. Safety assessment was recorded throughout the study. RESULTS After 12 patients were excluded from study 122 patients received Macroplastique injection and 125 received Contigen injection. Mean patient age was 61 years and the average history of incontinence was 11.2 years. Of the patients 24% had undergone prior incontinence surgery. At 12 months after treatment 61.5% of patients who received Macroplastique and 48% of controls had improved 1 Stamey grade. In the Macroplastique group the dry/cure rate was 36.9% compared to 24.8% in the control group (p <0.05). In the Macroplastique and control groups the 1-hour pad weight decrease was 25.4 and 22.8 ml from baseline (p = 0.64), and the mean improvement in Urinary Incontinence Quality of Life Scale score was 28.7 and 26.4 (p = 0.49), respectively. CONCLUSIONS Macroplastique injection was statistically more effective than Contigen for stress urinary incontinence primarily due to intrinsic sphincter deficiency with a 12.1% cure rate difference. Macroplastique can be administered on an outpatient basis. It should be considered a primary or secondary treatment option for stress urinary incontinence.

Robot-Assisted Versus Open Sacrocolpopexy: A Cost-Minimization Analysis

PURPOSE Abdominal sacrocolpopexy is considered a standard of care operation for apical vaginal vault prolapse repair. Using outcomes at our center we evaluated whether the robotic approach to sacrocolpopexy is as cost-effective as the open approach. MATERIALS AND METHODS After obtaining institutional review board approval we performed cost-minimization analysis in a retrospective cohort of patients who underwent sacrocolpopexy at our institution between 2006 and 2010. Threshold values, that is model variable values at which the most cost effective approach crosses over to an alternative approach, were determined by testing model variables over realistic ranges using sensitivity analysis. Hospital billing data were also evaluated to confirm our findings. RESULTS Operative time was similar for robotic and open surgery (226 vs 221 minutes) but postoperative length of stay differed significantly (1.0 vs 3.3 days, p <0.001). Base case analysis revealed an overall 10% cost savings for robot-assisted vs open sacrocolpopexy (