Randomized multicenter clinical trial of myofascial physical therapy in women with interstitial cystitis/painful bladder syndrome and pelvic floor tenderness.

PURPOSE: We determined the efficacy and safety of pelvic floor myofascial physical therapy compared to global therapeutic massage in women with newly symptomatic interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: A randomized controlled trial of 10 scheduled treatments of myofascial physical therapy vs global therapeutic massage was performed at 11 clinical centers in North America. We recruited women with interstitial cystitis/painful bladder syndrome with demonstrable pelvic floor tenderness on physical examination and a limitation of no more than 3 years' symptom duration. The primary outcome was the proportion of responders defined as moderately improved or markedly improved in overall symptoms compared to baseline on a 7-point global response assessment scale. Secondary outcomes included ratings for pain, urgency and frequency, the O'Leary-Sant IC Symptom and Problem Index, and reports of adverse events. We compared response rates between treatment arms using the exact conditional version of the Mantel-Haenszel test to control for clustering by clinical center. For secondary efficacy outcomes cross-sectional descriptive statistics and changes from baseline were calculated. RESULTS: A total of 81 women randomized to the 2 treatment groups had similar symptoms at baseline. The global response assessment response rate was 26% in the global therapeutic massage group and 59% in the myofascial physical therapy group (p=0.0012). Pain, urgency and frequency ratings, and O'Leary-Sant IC Symptom and Problem Index decreased in both groups during followup, and were not significantly different between the groups. Pain was the most common adverse event, occurring at similar rates in both groups. No serious adverse events were reported. CONCLUSIONS: A significantly higher proportion of women with interstitial cystitis/painful bladder syndrome responded to treatment with myofascial physical therapy than to global therapeutic massage. Myofascial physical therapy may be a beneficial therapy in women with this syndrome.

Impact of medical therapy on transurethral resection of the prostate: a decade of change.

OBJECTIVES: To assess whether medical therapy has delayed the need for eventual transurethral prostatectomy (TURP), causing a shift in the population characteristics of men undergoing TURP (ie, older, more comorbidities, more advanced disease), resulting in more complications and poorer outcomes. The introduction of medical therapy for symptomatic benign prostatic hyperplasia (BPH) during the past decade may have changed the indications for TURP. METHODS: All patients who underwent TURP for symptomatic BPH at our institution in 1988 (before general introduction of medical therapy for BPH) and 1998 (medical therapy the primary initial therapy for BPH) were reviewed. We compared the two groups with respect to the total number of TURPs, indications for surgery, patient age, health status, weight of resected tissue, and preoperative and postoperative complications. RESULTS: Despite a 16% increase in men at risk of BPH-related events, a 60% decrease in the total number of TURPs performed for symptomatic BPH occurred in 1998 (n = 64) compared with 10 years earlier (n = 157). No significant difference was found in age between the two groups, and no increase in comorbid status was observed. Previous medical management had failed in 36% of men who required TURP in 1998. A significantly higher percentage of patients presented in acute urinary retention (55%) and upper tract obstructive uropathy (12.5%) in 1998 compared with 1988 (23% acute urinary retention and 1.3% obstructive uropathy). Patients in 1998 were healthier, underwent smaller resections, had their catheters removed earlier, and were discharged home earlier. Although they were more likely to be discharged home with a catheter in situ, no significant difference was observed in the incidence of postoperative complications. CONCLUSIONS: There has been a dramatic decrease in the number of TURPs performed for symptomatic BPH at our institution since the advent of medical therapy. The proportion of TURP patients presenting with urinary retention and hydronephrosis increased, but the average age, medical comorbidities, operative parameters, and postoperative complications have not significantly changed.

Pentosan polysulfate therapy for chronic nonbacterial prostatitis (chronic pelvic pain syndrome category IIIA): a prospective multicenter clinical trial.

OBJECTIVES: Chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CPPS) has clinical and perhaps etiologic characteristics similar to interstitial cystitis. Pentosan polysulfate sodium (PPS), an oral medication indicated for the treatment of interstitial cystitis, has shown moderate benefit in reducing chronic pelvic pain and voiding symptoms in patients with interstitial cystitis. We undertook a prospective open-label, multicenter Phase II pilot study to examine the potential efficacy of PPS in the treatment of CPPS in men, using outcome tools validated for CPPS in men. METHODS: Patients with a diagnosis consistent with National Institutes of Health (NIH) CPPS category IIIA (inflammatory) were treated with PPS, 100 mg three times daily, for 6 months. The evaluation at baseline, 3 months, and 6 months consisted of the Symptom Severity Index, a Symptom Frequency Questionnaire, the NIH-Chronic Prostatitis Symptom Pain Index (NIH-CPSI), a quality-of-life assessment, and a subjective global assessment. RESULTS: Thirty-two patients (mean age 45.5 +/- 11 years; duration of symptoms 9.2 +/- 12 years) were enrolled in five centers; 28 patients were available for evaluation. Seven patients experienced drug-related side effects, including hair loss (n = 2), headache (n = 2), mild nausea (n = 1), mild weight gain (n = 1), and skin flushing (n = 1). The decrease in frequency (Symptom Frequency Questionnaire 28.1 to 17.9), severity (Symptom Severity Index 53.6 to 36.3), and combined location/frequency/severity of pain (NIH-CPSI pain 14.5 to 9.2) symptom scores at 6 months compared with baseline was significant. The decrease was associated with a significant improvement in patients' quality of life (quality-of-life assessment 5.3 to 3.8). Forty-three percent of the patients had a greater than 50% improvement in the Symptom Frequency Questionnaire, Symptom Severity Index, and NIH-CPSI (rated as clinically significant improvement). At 6 months, mild, moderate, and marked improvement was noted (subjective global assessment) by 33%, 19%, and 15% of the patients, respectively. CONCLUSIONS: PPS is well tolerated and appears to have efficacy in reducing the severity and frequency of general symptoms, reducing specific pain symptoms, and improving the quality of life in many male patients with CPPS. The results of this study justify the initiation of a randomized controlled trial comparing the safety and efficacy of PPS to placebo.

Asymptomatic inflammation and/or infection in benign prostatic hyperplasia.

OBJECTIVE: To determine the extent, pattern and clinical significance of asymptomatic histological inflammation and latent infection (National Institute of Health Category IV prostatitis) in benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study included 80 patients (from a cohort of 100 consecutive potentially eligible subjects) with a diagnosis of BPH, but no history or symptoms of prostatitis. Histological sections were obtained from specimens collected prospectively at transurethral resection of the prostate (TURP), immunostained for leukocyte common antigen and scanned using a computerized image-analysis system. Foci of inflammation were categorized as glandular, periglandular, stromal or peri-urethral, and the inflammatory cell density graded from 1 to 3. Relationships and correlations were calculated between the volume, degree and type of inflammation, presence and type of bacteria (culture of deep prostatic biopsies), the use of catheters and prostate specific antigen (PSA) levels. RESULTS: Inflammation was identified in all patients but the mean tissue surface area involved was only 1.1% of the total specimen, with periglandular inflammation being the predominant pattern (0.5%). Of the prostate specimens, 44% showed bacterial growth (in 67% of the catheterized patients and 28% of those uncatheterized; 42% of patients were catheterized before TURP). There was no significant difference between any combination of inflammation pattern, volume or grade of inflammation in those catheterized or not (P=0.15) or culture-positive (pathogenic or not) and culture-negative cases (P=0.06). Neither total PSA or PSA density was significantly correlated (P>0.05) with the amount, degree or distribution of inflammation. CONCLUSION: Prostatic inflammation is an extremely common histological finding in patients with symptoms of BPH who have no symptoms of prostatitis. There was no correlation between the degree and pattern of inflammation, catheterization, presence of bacteria, serum PSA or PSA density. The clinical significance of asymptomatic Category IV chronic prostatitis associated with BPH has yet to be determined.

Repetitive prostatic massage therapy for chronic refractory prostatitis: the Philippine experience.

Patients frustrated with failure of traditional therapy for prostatitis have traveled to the Philippines and elsewhere for repetitive prostatic massage combined with antibiotic therapy. The aim of our study was to evaluate prospectively the response of patients who traveled to Manila to undergo this treatment. Twenty-six patients consented and were registered by the Prostatitis Foundation (B.H.) and subsequently evaluated (J.C.N., J.D.) prior to and following treatment (A.E.F.). Evaluation at baseline and after treatment consisted of standardized history and previously validated prostatitis-specific Symptom Frequency Questionnaire (SFQ) and Symptom Severity Index (SSI), International Prostate Symptom Score (I-PSS) and Quality of Life (QoL) questionnaire, the O'Leary Sexual Function Inventory (SFI), and a Subjective Global Assessment (SGA). Treatment in Manila consisted of triweekly prostatic massage combined with specific culture directed and/or empirical antimicrobial therapy for 6 to 12 weeks. Twenty-two patients completed at least one follow-up assessment and 12 patients completed 2-year assessment (average follow-up of 17 months in 22 patients). There was a significant decrease in average symptom severity (SSI) by 4 months that continued for 2 years, but less improvement in symptom frequency (SFQ) and quality of life (QoL), and no significant improvement in voiding symptoms (I-PSS) or sexual function (SFI) at time of last assessment. Forty-six percent of the 22 evaluable patients had >60% decrease (significant improvement) in symptom severity (SSI), whereas 27% had similar significant improvement in frequency of symptoms (SFQ) when last assessed. Thirty-three percent reported marked subjective improvement (SGA) at last evaluation. Of the 12 patients who completed the 2-year follow-up, 5 of the original 26 had a significant and sustainable improvement in objective and subjective measurements of frequency and severity of symptoms. The combination of prostatic massage and antibiotics for treating difficult refractory cases of prostatitis may be promising, but its ultimate value needs to be confirmed. Studies in patients with less refractory and shorter duration disease may allow us to predict who will respond to this therapeutic approach.

Prostatitis unplugged? Prostatic massage revisited.

Repetitive prostatic massage is not a new tool in the urologists' armatarium. Once the most popular therapeutic maneuver used to treat prostatitis, it was abandoned as primary therapy almost 3 decades ago. Based on experience reported outside North America and anecdotal experiences of some patients and their physicians, it may be making a comeback. Unfortunately, there are almost no prospective data that would substantiate a claim as to its effectiveness. This article discusses the historic aspects of prostatic massage, suggests possible mechanisms of action, and describes the opinions of North American urologists who are associated with academic clinical research centers and are universally acknowledged as experts in the diagnosis and treatment of prostatitis. At this time, the science of prostatic massage must rely on anecdotal experiences, small, uncontrolled studies, and perhaps somewhat biased opinions of the major thought leaders in the field of chronic prostatitis/chronic pelvic pain syndrome.

Transurethral radiofrequency hot balloon thermal therapy in chronic nonbacterial prostatitis.

There is no universally successful therapy for chronic nonbacterial prostatitis. Successful outcomes of treatment have been independently reported with transurethral heat therapy and balloon dilation. The THERP transurethral "hot balloon" uses balloon dilation of the prostatic urethra and radiofrequency heating of the prostate. Patients with refractory chronic nonbacterial prostatitis were assessed with validated prostatitis-specific symptom indices prior to, 3, and 6 months after 900 seconds of THERP treatment. Although early results appeared promising the long-term results in four patients led to early termination of the study. Although one patient did have improvement at 6 months, no patient reported improvement at 9 months, and the adverse events (urinary retention, retrograde ejaculation, hematuria, urethral stricture, worsening of symptoms) of this treatment in prostatitis patients was significant. This study demonstrated no sustainable efficacy and substantial adverse effects for the use of combination balloon dilation and heat therapy for patients with chronic nonbacterial prostatitis.

The Pre and Post Massage Test (PPMT): a simple screen for prostatitis.

The segmented quantitative culture technique originally described more than 25 years ago is acknowledged as the best test to diagnose prostatitis. However, it, is not widely used in clinical practice. This is especially true in primary care settings, but even most urologists appear to have abandoned the procedure. Herein is proposed a simple and cost-effective screen for prostatitis, which involves the culture and microscopic examination of urine before and after prostatic massage. This Pre and Post Massage Test (PPMT) was applied to a personal series of 53 patients and 59 patients from the literature in whom the results of the segmented cultures are available and the results were reevaluated. In this selected patient population the PPMT alone led to the same diagnosis in 102 (91.1%). Within the expected limitations of this retrospective review, the calculated sensitivity and specificity of the PPMT were both 91%. This report should provoke researchers to review their prostatitis data, stimulate discussion, and hopefully convince physicians that adoption of a simpler diagnostic plan for prostatitis is far superior to doing no workup at all.

Mycobacterium cell wall: an alternative to intravesical bacillus Calmette Guerin (BCG) therapy in orthotopic murine bladder cancer.

PURPOSE: The antitumor effect of intravesical mycobacterium cell wall (MCW) therapy on orthotopic and heterotopic bladder tumors in the mouse was assessed with magnetic resonance imaging (MRI). MATERIALS AND METHODS: The live bacillus Calmette Guerin (BCG) organism was replaced with a cell wall extract derived from the outer capsule of Mycobacterium phlei. This alternative form of intravesical therapy was used with the aim of reducing the toxicity associated with the live mycobacterium organism without compromising efficacy. Response to multiple doses of intravesical MCW and BCG was assessed in mice with established MBT-2 tumors after transurethral tumor implantation. RESULTS: Serial MRI of BCG-treated mice revealed significant tumor regression. The MR images correlated well with the corresponding histology of the whole mount bladder sections. Treatment with MCW also resulted in significant inhibition of tumor growth compared with control untreated animals (p < 0.05) although the antitumor effect was less pronounced than that of live BCG. Treatment was well tolerated in the MCW group with no apparent ill effects. Flow cytometric (FCM) analysis of bladder washings with phenotype-specific monoclonal antibodies revealed predominantly a CD3+ T cell infiltrate in the control and BCG-treated as well as the MCW-treated mice. The CD4+ (helper/inducer) subset of T cells predominated over the CD8+ (suppressor/cytotoxic) subset in both the BCG- and MCW-treated animals, and the CD4+/CD8+ ratio in both of the treated groups differed significantly from that of the control untreated groups. CONCLUSION: Intravesical MCW appears to invoke a similar inflammatory response in the mouse bladder mucosa as the live BCG organism and retains an antitumor action. It deserves further evaluation as a potential antitumor agent against bladder cancer. A Phase II clinical trial is now underway.

Transurethral microwave thermotherapy for nonbacterial prostatitis: a randomized double-blind sham controlled study using new prostatitis specific assessment questionnaires.

PURPOSE: We investigated the effectiveness and durability of transurethral microwave thermotherapy in the treatment of chronic nonbacterial prostatitis using 2 new prostatitis specific assessments in a randomized, double-blind, sham controlled trial. MATERIALS AND METHODS: Patients with nonbacterial prostatitis were randomly assigned to receive either transurethral microwave thermotherapy or sham therapy. Patients were assessed using a symptom severity index and symptom frequency questionnaire. These 2 new prostatitis symptom assessment tools were validated by applying them to 30 similar patients without prostatitis. All nonresponders received transurethral microwave thermotherapy at 3 months and were reassessed at 6 months. Long-term followup of the responder group averaged 21 months. RESULTS: The symptom severity index and symptom frequency questionnaire were confirmed to be valid for symptom assessment in prostatitis patients. The transurethral microwave thermotherapy group benefited from therapy compared to the sham group. Of the sham group 50% had a favorable response after subsequent transurethral microwave thermotherapy. The 7 responders in the treatment group continued to improve during the subsequent 21 months. CONCLUSIONS: Transurethral microwave thermotherapy appears to be an effective, safe and durable treatment for some patients with nonbacterial prostatitis unresponsive to traditional therapy.

Treatment of refractory interstitial cystitis.

Interstitial cystitis is the most therapeutically frustrating condition of the urinary tract. The vast array of treatments available clearly indicates that none is particularly effective. As the majority of patients fail to experience a significant and prolonged response to standard treatments, new options are frequently being developed. These include the oral administration of cimetidine, the intravesical use of hyaluronic acid and BCG, and total cystectomy with the formation of a continent urinary diversion. Unfortunately, the acceptance of many new treatments is based on incomplete evaluation, and this has resulted in a confusing array of disparate alternatives. Effective and durable treatment will not be available until the nature of the disease is better understood and the mechanisms of action of current therapies are elucidated.

Transurethral microwave thermotherapy of nonbacterial prostatitis and prostatodynia: initial experience.

OBJECTIVES: To report our early experience using transurethral microwave thermotherapy (TUMT) to treat patients with nonbacterial prostatitis (NBP) and prostatodynia. METHODS: Nineteen patients with NBP (symptoms, negative cultures, no response to antibiotics, leukocytosis in expressed prostatitic fluid) and 5 patients with prostatodynia (symptoms, negative cultures, no response to antibiotics, no leukocytosis in expressed prostatitic fluid) were treated with TUMT at interstitial temperatures of 45 degrees to 60 degrees C for 1 hour. Response was assessed by a consistent symptom severity index and global assessment of symptoms. RESULTS: A marked and significant early (3 months) favorable response was noted in nearly one half of the NBP group but little benefit was found in the prostatodynia group. The treatment was associated with few adverse experiences. CONCLUSIONS: TUMT appears to be a potentially effective therapy for NBP, but its real efficacy as well as the durability of the response needs to be confirmed with a randomized double-blind sham-controlled trial.

Pyrophosphate inhibition of Proteus mirabilis-induced struvite crystallization in vitro.

Struvite (MgNH4PO4.6H2O) crystals, the major mineral component of infectious urinary calculi, were produced in vitro by growth of a clinical isolate of Proteus mirabilis in artificial urine. P. mirabilis growth and urease-induced struvite production were monitored by phase contrast light microscopy and measurements of urease activity, pH, ammonia concentrations, turbidity, and culture viability. In the absence of pyrophosphate, struvite crystals appeared within 3-5 h due to the urease-induced elevation of pH and initially assumed a planar or 'X-shaped' crystal habit (morphology) characteristic of rapid growth. When pyrophosphate was present, initial precipitation and crystal appearance were significantly impaired and precipitates were largely amorphous. When crystals did appear (usually after 7 or 8 h) they were misshapen or octahedral in shape indicative of very slow growth. X-ray diffraction and Fourier transform infrared spectroscopy (FTIR) identified all crystals as struvite. Trace contaminates of carbonate-apatite (Ca10(PO4)6CO3) or newberyite (MgHPO4.H2O) were produced only in the absence of pyrophosphate. P. mirabilis viability and culture pH elevation were unaffected by the addition of pyrophosphate, whereas urease activity and ammonia concentrations were marginally reduced. Struvite could also be produced chemically by titration of the artificial urine with NH4OH. If pyrophosphate was present during titration, the same inhibitory effect on crystal growth occurred, so it is unlikely that urease inhibition is important. Lowering of pyrophosphate concentration from 13-0.45 mumol/l did not reduce its inhibitory activity so it is unlikely to act by chelating free Mg2+. We propose that pyrophosphate inhibits struvite growth principally through direct interference with the chemical mechanisms involved in crystal nucleation and growth, because of its effectiveness at very low concentrations.

Observations of the ultrastructure of infected kidney stones.

Struvite stones are formed as the result of urinary tract infection by urease-producing bacteria. Ultrastructural examination of calculi removed from a patient revealed bacteria incorporated throughout the stone matrix. Exopolysaccharide stained by ruthenium red was associated with most of the bacteria, but it represented only a small portion of the organic matrix in the stone. Localised deposits of calcium and phosphorus, components of carbonate-apatite, and magnesium, a struvite component, were detected in close proximity to the cells. Histochemical examinations revealed that several of the gram-negative bacteria within the stone matrix possessed high levels of urease activity. We propose that bacterial slime production, intimately involved in the initiation of stone matrix deposition, is less prominent in mature stones because of the increased incorporation of host-derived mucoproteins and mucopolysaccharides.