A systematic review and meta-analysis on the efficacy of intravesical therapy for bladder pain syndrome/interstitial cystitis.

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic disease characterised by persistent irritating micturition symptoms and pain. The objective was to compare the clinical efficacy of currently available products for intravesical therapy of BPS/IC and to assess their pharmacoeconomic impact. A Pubmed/Medline database search was performed for articles on intravesical therapy for BPS/IC. A total of 345 publications were identified, from which 326 were excluded. Statistical evaluation was performed with effect size (ES) assessment of symptom reduction and response rates. The final set of 19 articles on intravesical BPS/IC therapy included 5 prospective controlled trials (CTs), the remaining were classified as uncontrolled clinical studies. The total number of patients included was 801, 228 of whom had been evaluated in a CT. For CTs, the largest ES for symptom reduction as well as response rate was observed for high molecular weight hyaluronic acid (HMW-HA), with similar findings in two uncontrolled studies with HMW-HA. The number needed to treat to achieve a response to intravesical therapy was 2.67 for intravesical pentosan polysulphate and 1.31 for HMW-HA which were superior to all other instillates. HMW-HA was significantly superior in cost effectiveness and cost efficacy to all other instillation regimes. The present meta-analysis combined medical and pharmacoeconomic aspects and demonstrated an advantage of HMW-HA over other instillation agents; however, direct comparisons between the different products have not been performed to date in properly designed controlled studies.

Long-term results of intravesical hyaluronan therapy in bladder pain syndrome/interstitial cystitis.

INTRODUCTION AND HYPOTHESIS: While the short-term efficacy of intravesical hyaluronan for bladder pain syndrome/interstitial cystitis (BPS/IC) has been demonstrated, no data exist on the long-term outcome of this therapy. METHODS: Seventy BPS/IC patients treated with intravesical hyaluronan therapy from 2001 to 2003 were asked to rate their present status of bladder symptoms on a visual analog scale. RESULTS: Forty-eight of 70 patients responded after a mean follow-up of 4.9 years. The average initial VAS score of 8.15 had been reduced to 2.71 after therapy and further to 2.14 5 years later. Fifty percent of patients (24/48) reported complete bladder symptom remission at 5 years follow-up without any additional therapy; 41.7% (20/48) with symptom recurrence was improved with hyaluronan maintenance therapy. No improvement was reported by four patients. CONCLUSIONS: Besides a high rate of acute symptom remission, intravesical hyaluronan also shows long-term efficacy in a considerable number of BPS/IC patients.

Association between asymptomatic inflammatory prostatitis NIH category IV and prostatic calcification in patients with obstructive benign prostatic hyperplasia.

BACKGROUND: The aim of this study was to evaluate the incidence of prostatic calcification and prostatitis NIH category IV in patients with obstructive BPH. METHODS: Ninety-six patients with obstructive BPH who had undergone transurethral electroresection of the prostate gland were evaluated. In accordance with a preoperative transrectal ultrasound examination, patients were divided into one group with prostatic calcification (N.=31) and one without (N.=65). Prostatitis NIH category IV was classified according to the grading system by Irani. Correlations between the incidence of prostatic calcification, histological prostatitis, PSA, uric acid, cholesterol, triglycerides, CRP, IPSS, IIEF-25, and NIC-CPSI were analyzed. A stone analysis of prostatic calcification was performed using X-ray powder diffraction. RESULTS: Sixty-nine (71.9%) patients had NIH category IV prostatitis, accounting for 83.9% of those with prostatic calcification versus 66.1% of those without (P<0.04). Significant correlations were found between prostatic calcification and the severity of inflammation (P<0.02) as well as the NIH-CPSI subdomain of urinary symptoms (P<0.02). The only predictor for prostatic calcifications were elevated levels of uric acid. Such patients were 1.4times more likely of having calcifications in the prostate gland (OR=1.4, P<0.047). Stone analysis revealed the following: apatite in 41.7%, whewellite in 29.2%, weddellite and brushite in 8.7% each, whitlockite, apatite/whewellite and organic substances in 4.2%. CONCLUSIONS: On ultrasound examination, one third of patients who were treated with TURP for obstructive BPH had prostatic calcification. These were significantly more common in patients with NIH category IV prostatitis.

Immunohistochemical expression of interleukin-2 receptor and interleukin-6 in patients with prostate cancer and benign prostatic hyperplasia: association with asymptomatic inflammatory prostatitis NIH category IV.

OBJECTIVE: This study prospectively investigated the immunohistochemical expression of interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6) in patients with prostate cancer and benign prostatic hyperplasia (BPH), and a possible association of these conditions with asymptomatic inflammatory prostatitis National Institutes of Health (NIH) category IV. MATERIALS AND METHODS: The study included 139 consecutive patients who underwent transurethral resection of the prostate and transvesical enucleation of the prostate (n = 82) or radical prostatectomy (n = 57). To characterize inflammatory changes the criteria proposed by Irani et al. [J Urol 1997;157:1301-3] were used. IL-2R and IL-6 expression was studied by a standard immunohistochemical method. Results were correlated with tumour, node, metastasis stage, Gleason scores, total prostate-specific antigen, International Prostate Symptom Score and body mass index. RESULTS: IL-2R and IL-6 expression was significantly higher in neoplastic prostate cancer tissue than in normal tissue of prostate cancer patients (p < 0.001 and p < 0.04, respectively). Prostate cancer patients with prostatitis showed significantly higher IL-2R expression than those without inflammation (p < 0.03). In patients with BPH, expression of IL-2R as well as IL-6 was higher in patients with prostatitis than in those without (p < 0.01 and p < 0.02, respectively). CONCLUSIONS: IL-2R and IL-6 expression was significantly higher in prostate cancer tissue than in normal tissue. Patients with asymptomatic inflammatory prostatitis NIH category IV showed significantly greater activity.

Heparin coating reduces encrustation of ureteral stents: a preliminary report.

The present study evaluated the inhibition of ureteral stent encrustation by heparin coating. In contrast to uncoated polyurethane stents, heparin coated ureteral stents did not show any organic (biofilms) or anorganic (crystals) deposits after being in situ for up to 6 weeks and effectively inhibited the encrustation process.

Bacterial biofilm formation on urologic devices and heparin coating as preventive strategy.

In the process of endourological development a variety of foreign bodies have been invented besides urinary catheters, on which biofilm can be formed. Bacteria in the biofilm are less susceptible to antibiotics. An additional problem of medical biomaterials in the urinary tract environment is the development of encrustation and consecutive obstruction. The most promising prevention strategy for bacterial biofilms is the production of materials with anti-adhesive surfaces such as heparin. Although heparin-coated ureteral stents are expensive, they justify their cost. Our studies show that such devices are protected against incrustation and biofilm formation for a longer period of time: 6-12 months, both in vitro and in vivo.

Effects of one-year treatment with isoflavone extract from red clover on prostate, liver function, sexual function, and quality of life in men with elevated PSA levels and negative prostate biopsy findings.

OBJECTIVES: To asses the effect of an isoflavonoid extract from red clover on the prostate, liver function, quality of life, and sexual function in men with an initial elevated prostate-specific antigen (PSA) level and negative prostate biopsy findings during a 1-year treatment period. METHODS: A total of 20 men (mean age 65 years) were treated with a daily 60-mg dose of an isoflavone extract for 1 year. Liver function, sexual hormone levels (total testosterone, estrogen, luteotropic hormone, follicle-stimulating hormone, and dehydroepiandrosterone sulfate), transrectal ultrasonography volumetry of the prostate, PSA level, International Prostate Symptom Score, and International Index of Erectile Function score were recorded at the beginning of the study and every 3 months for 1 year. RESULTS: The average PSA level was 10.16 ng/mL at baseline versus 7.15 ng/mL after 12 months, for a statistically significant reduction of 33% (P <0.019). The mean prostate volume had decreased slightly from 49.3 cm3 to 44.3 cm3 after 12 months (P <0.097). The sexual hormone levels did not change throughout the study. We registered a significant increase in all three liver transaminases after 3 months (P <0.001). The International Prostate Symptom Score showed a mean value of 7.9 at baseline and 6.68 after 12 months (P <0.421). Sexual function was not influenced by the treatment. CONCLUSIONS: Daily oral administration of 60 mg of an isoflavone extract was well tolerated and caused no side effects. The significant increase in liver transaminases and the significant decrease in total PSA levels by >30% indicates that patients, general practitioners, and urologists should be informed about these potential effects of red clover extracts and possibly other phytoestrogens, on liver transaminases and elevated total PSA levels.

Hyaluronan treatment of interstitial cystitis/painful bladder syndrome.

The aim of this study is to evaluate the efficacy of intravesical hyaluronan therapy in interstitial cystitis/painful bladder syndrome (IC/PBS). One hundred twenty-six patients with IC/PBS and an average disease duration of 6.1 years were treated with weekly instillations of a 50-cm3 phosphate-buffered saline solution containing 40 mg sodium hyaluronate. To be eligible for hyaluronan treatment, a positive modified potassium test was requested as a sign of a urine-tissue barrier disorder. Data were obtained by a visual analogue scale (VAS) questionnaire rating from 0 to 10 that asked for global bladder symptoms before and after therapy. Additional questions evaluated the therapeutic impact on quality of life. A positive and durable impact of hyaluronan therapy on IC/PBS symptoms was observed--103 (85%) of the patients reported symptom improvement (> or =2 VAS units). The mean initial VAS score of 8.5 decreased to 3.5 after therapy (p < 0.0001). Out of 121 patients, 67 (55%) remained with no or minimal bladder symptoms after therapy (VAS 0-2). The majority (101, 84%) reported significant improvement of their quality of life. Intravesical therapy had to be initiated again with good success in 43 patients (34.5%) as symptoms recurred after discontinuation of treatment, while the rest stayed free of symptoms for up to 5 years. In general, hyaluronan therapy was well tolerated and, with the exception of mild irritative symptoms, no adverse reactions were reported for a total of 1,521 instillations. Timely hyaluronan instillation therapy may lead to complete symptom remission or even cure in part of the IC/PBS patients, while some responders need continuous intravesical therapy. The present results suggest that selection of patients for hyaluronan therapy by potassium testing improves the outcome of intravesical therapy with a response rate of >80%.

Effect of intravesical glycosaminoglycan substitution therapy on bladder pain syndrome/interstitial cystitis, bladder capacity and potassium sensitivity.

OBJECTIVE: To evaluate changes in bladder capacity and potassium sensitivity after glycosaminoglycan (GAG) substitution therapy. MATERIAL AND METHODS: The study population comprised two groups of female patients with bladder pain syndrome/interstitial cystitis (BPS/IC): responders (those with symptom improvement) and non-responders (those without symptom improvement) after a 10-week period of intravesical, episodic, weekly, GAG substitution therapy. A total of 27 volunteers with increased pre-therapeutic potassium sensitivity were enrolled in the study and re-evaluated using the modified comparative potassium test (maximal bladder capacity with a saline solution versus a 0.2 M KCl solution) following intravesical GAG substitution therapy. RESULTS: In the 13 responders, the average maximal bladder capacity increased by 17% with the saline solution and by 101.5% with the 0.2 M KCl solution. In the 14 non-responders, post-therapeutic average maximal bladder capacity was decreased by 35% with the saline solution and remained relatively unchanged after instillation with a 0.2 M KCl solution. CONCLUSION: These data demonstrate that in patients who respond symptomatically to intravesical GAG substitution therapy, cystometric bladder capacity is increased, whereas non-responders experience a decrease in bladder capacity.

Do cystometric findings predict the results of intravesical hyaluronic acid in women with interstitial cystitis?

INTRODUCTION AND OBJECTIVES: According to National Institute of Health (NIH) criteria, a bladder capacity of less than 350 cc is an automatic exclusion for a diagnosis of Interstitial Cystitis (IC). In the present study, patients, showing symptoms of IC and with bladder capacities of <350 and >/=350 cc were tested as to their response to a intravesical hyaluronic acid therapy. METHODS: The study included 48 patients with clinical symptoms of IC and a positive 0.4 M potassium sensitivity test. Maximum bladder capacity (C(max)) was assessed for the 0.9% NaCl solution first and then for the 0.2 M KCl solution. After the NaCl cystometry, patients were separated into two groups: Group I with a C(max) of <350 cc and Group II with a C(max) of >/=350 cc. Both groups were again separated in two further groups as to the respective percentage reduction of C(max) with the 0.2 M KCl solution: Group Ia/IIa (>/=30%) and Group Ib/IIb (<30%). Patients were treated with weekly instillations of 40 mg hyaluronic acid for 10 consecutive weeks. Pre- and post-treatment bladder symptoms were evaluated through their visual analog scale (VAS) scores. RESULTS: With the saline solution, 32 patients had a C(max) of <350 cc (Group I), while 16 patients had a C(max) of >/=350 cc (Group II). Evaluation of VAS scores confirmed a positive response, i.e. symptom relief, to hyaluronic acid therapy, irrespective of bladder capacity. The improvement was particularly evident in patients with a C(max) reduction of >/=30% versus those with a reduction of <30% with the 0.2 M KCl solution (p=0.003). CONCLUSION: The present study demonstrates that patients with typical IC symptoms and a cystometric bladder capacity of >/=350 cc, may have increased potassium sensitivity as a sign of IC and show symptom improvement after hyaluronic acid instillation therapy.

Liposomal recombinant human superoxide dismutase for the treatment of Peyronie's disease: a randomized placebo-controlled double-blind prospective clinical study.

OBJECTIVE: To demonstrate the efficacy and safety of a topical gel containing liposomally encapsulated recombinant human Superoxide Dismutase (lrhSOD) in the treatment of painful Peyronie's Disease. The theoretical background is that lrhSOD, by scavenging of free oxygen radicals, might interrupt inflammatory cascades and thereby limit further disease progression. METHODS: In a placebo-controlled randomized clinical trial, 39 patients with Peyronie's Disease and significant pain symptoms were treated with lrhSOD or placebo for a 4 week period. At this time, statistical evaluation of pain resolution was performed as primary study endpoint. Patients then were continued in a cross-over study design to ensure a total of 8 weeks of lrhSOD therapy for all study participants. Pain, plaque and curvature assessment was performed at study entry and every 4 weeks until week 12. RESULTS: LrhSOD treatment resulted in a statistically significant reduction of pain (p=0.017) compared to placebo already after 4 weeks. At week 12 pain was significantly reduced in 89% of patients who all had received 8 weeks of lrhSOD therapy at that time. Response to other disease parameters was assessed at week 12: plaque size was reduced in 47% of patients, as was plaque consistence in 38%. Penile curvature was improved at 5-30 degrees in 23% of patients. The expected spontaneous disease progression rate of up to 40%, as reported by several investigators, was significantly reduced to <10% under lrhSOD therapy, and patients satisfaction was high, also consequent to the lack of therapy-related side effects observed in the present study. CONCLUSION: LrhSOD is an easily administrable, safe and effective local therapeutic for the painful phase of Peyronie's Disease.

Long-term benefit of 5-aminolevulinic acid fluorescence assisted transurethral resection of superficial bladder cancer: 5-year results of a prospective randomized study.

PURPOSE: As shown in various studies 5-aminolevulinic acid (ALA) induces fluorescence of malignant and dysplastic bladder tissue and increases tumor detection rates by about 20%. However, data on the long-term benefits are sparse. Thus, the 5-year outcome data of a prospective randomized trial comparing patients who initially underwent bladder tumor resection (TUR) under standard white light or with ALA induced fluorescence were evaluated. MATERIALS AND METHODS: A total of 115 patients with suspected superficial bladder cancer were randomized to undergo standard or ALA assisted TUR. After the second look TUR at 6 weeks patients were followed for a median of 39 (standard) and 42 (ALA) months. RESULTS: Median time to first recurrence was 5 months in the standard and 12 months in the ALA group. Recurrence-free survival was 25% in the standard and 41% in the ALA group. The recurrence rate at 2, 12, 36 and 60 months after initial TUR was 41%, 61%, 73% and 75%, and 16%, 43%, 59% and 59% in the white light and ALA groups, respectively. The total number of recurrences was 82 in the standard and 61 in the ALA group. Tumor progression occurred in 9 patients in the standard and 4 in the ALA group. Cost analysis suggests a considerable economical advantage of ALA fluorescence assisted TUR compared to the standard procedure. CONCLUSIONS: The initial advantage of improved tumor detection and decreased recurrence rates by ALA fluorescence assisted TUR is maintained for years, and effectively reduces morbidity and costs in patients with superficial bladder tumors.

Comparative assessment of maximal bladder capacity, 0.9% NaCl versus 0.2 M Kcl, for the diagnosis of interstitial cystitis: a prospective controlled study.

PURPOSE: Increased urothelial permeability has been proposed as a cause of interstitial cystitis (IC). The potassium sensitivity test assesses bladder discomfort after instillation of 0.4 M KCl for identification of increased urothelial permeability. Since exposure to 0.4 M KCl may be extremely painful for patients with IC we investigated a less traumatic alternative. MATERIALS AND METHODS: The study comprised 38 controls and 40 patients with IC. In all subjects cystometry was performed with 0.9% NaCl followed by 0.2 M KCl, and filling volume at first urge and maximum bladder capacity (Cmax) were assessed for both solutions. RESULTS: Controls did not show a significant change in Cmax. KCl decreased Cmax in 37 of 40 (92%) patients with IC with a mean decrease of 30%. The examination was painless in all controls and in 33 of 40 (82%) patients with IC, and was moderately painful in 7. CONCLUSIONS: For demonstration of increased potassium sensitivity and diagnosis of IC, comparative assessment of Cmax is a well tolerated alternative to the 0.4 M potassium sensitivity test. Statistical evaluation of these results suggests that a decrease in Cmax greater than 30% is indicative of IC.