A prospective, randomized, placebo controlled, double-blind study of pelvic electromagnetic therapy for the treatment of chronic pelvic pain syndrome with 1 year of followup.

PURPOSE: Male chronic pelvic pain syndrome is a condition of uncertain etiology and treatment is often unsatisfactory. There is evidence that the symptom complex may result from pelvic floor muscular dysfunction and/or neural hypersensitivity/inflammation. We hypothesized that the application of electromagnetic therapy may have a neuromodulating effect on pelvic floor spasm and neural hypersensitivity. MATERIALS AND METHODS: Following full Stamey localization men with National Institute of Diabetes and Digestive and Kidney Diseases category III prostatitis were prospectively randomized to receive active electromagnetic or placebo therapy. Active therapy consisted of 15 minutes of pelvic floor stimulation at a frequency of 10 Hz, followed by a further 15 minutes at 50 Hz, twice weekly for 4 weeks. Patients were evaluated at baseline, 3 months and 1 year after treatment using validated visual analog scores. RESULTS: A total of 21 men with a mean age of 47.8 years (range 25 to 67) were analyzed. Mean symptom scores decreased significantly in the actively treated group at 3 months and 1 year (p <0.05), unlike the placebo group, which showed no significant change (p >0.05). Subanalysis of those receiving active treatment showed that the greatest improvement was in pain related symptoms. CONCLUSIONS: The novel use of pelvic floor electromagnetic therapy may be a promising new noninvasive option for chronic pelvic pain syndrome in men.

Biopsy of the red patch at cystoscopy: is it worthwhile?

OBJECTIVE: At cystoscopy red patches of urothelium are commonly seen within the bladder and frequently biopsied in order to exclude carcinoma in situ (CIS), which classically presents as a red, velvety patch. This appearance however is not specific and it is possible that many lesions are biopsied without significant benefit to the patient. The objective of this study was to determine whether routine biopsy of red patches seen in the bladder at cystoscopy is warranted. PATIENTS AND METHODS: 193 biopsies were taken from red patches seen at flexible and rigid cystoscopy during a 4-year period from December 1997 to January 2002 and examined by histopathology. Patients included in the study were those on cystoscopic follow-up for transitional cell carcinoma (TCC) of the bladder and those undergoing investigation for haematuria or lower urinary tract symptoms. RESULTS: In 193 (17.7% of total biopsies) red patch biopsies, malignancy was found in 23 (11.9%) and 18 of 23 (78.3%) were CIS. No malignancies were detected in red patches from patients under the age of 60 years. CONCLUSION: Red patch biopsy yields a positive finding of malignancy in 12% and was concluded to be a valuable exercise, particularly in those over the age of 60 years and on follow-up for TCC.

Oral cimetidine gives effective symptom relief in painful bladder disease: a prospective, randomized, double-blind placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of oral cimetidine as a treatment for painful bladder disease (PBD, variously described as a 'symptom complex' of suprapubic pain, frequency, dysuria and nocturia in the absence of overt urine infection) by assessing symptom relief and histological changes in the bladder wall tissue components, compared with placebo. PATIENTS AND METHODS: The study comprised 36 patients with PBD enrolled into a double-blind clinical study with two treatment arms, i.e. oral cimetidine or placebo, for a 3-month trial. Patients were asked to complete a symptom questionnaire (maximum score 35), and underwent cystoscopy and bladder biopsy before treatment allocation. On completing treatment the patients were re-evaluated by the questionnaire and biopsy. The symptom scores and bladder mucosal histology were compared before and after treatment, and the results analysed statistically to assess the efficacy of cimetidine. RESULTS: Of the 36 patients recruited, 34 (94%) completed the study. Those receiving cimetidine had a significant improvement in symptoms, with median symptom scores decreasing from 19 to 11 (P < 0.001). Suprapubic pain and nocturia decreased markedly (P = 0.009 and 0.006, respectively). However, histologically the bladder mucosa showed no qualitative change in the glycosaminoglycan layer or basement membrane, or in muscle collagen deposition, in either group. The T cell infiltrate was marginally decreased in the cimetidine group (median 203 before and 193 after) and increased in the placebo group (median 243 and 250, P > 0.3 and > 0.2, respectively). Angiogenesis remained relatively unchanged. The incidence of mast cells and B cells was sporadic in both groups. CONCLUSIONS: Oral cimetidine is very effective in relieving symptoms in patients with PBD but there is no apparent histological change in the bladder mucosa after treatment; the mechanism of symptom relief remains to be elucidated.

Bone loss associated with the use of LHRH agonists in prostate cancer.

Hypogonadism is a recognised cause of osteoporosis in men. When patients with advanced prostate cancer are treated with luteinising hormone releasing hormone (LHRH) agonist analogues their circulating testosterone levels decline and these patients may develop fractures.We have undertaken a cross-sectional study on a cohort of patients treated with goserelin (n=41) and compared their bone density and bone turnover with patients with prostate cancer not on goserelin and elderly patients living in the community.There was no difference in bone density between the patients on treatment and those living in the community and there was a similar incidence of osteoporosis (50 and 42%, respectively). The bone marker measurements were higher in the treated patients: urine N-telopeptide (NTX) 80.1 (9) (mean (s.e.)) BCE/mmol, compared to 30.1 (2.9), P<0.001 in elderly patients; and bone alkaline phosphatase 41.9 (6.1) u/l in treated patients and 20.7 (1.5) in untreated prostate cancer patients, P<0.002. Patients on treatment with radionuclide scan evidence of metastases did not have higher bone marker values than those with negative scans.As increased bone turnover and low bone density are associated with enhanced risk of osteoporotic fractures, we suggest that patients on LHRH agonist analogues should receive advice and possibly anti-bone resorptive treatment with bisphosphonates to prevent further bone loss and fractures.Prostate Cancer and Prostatic Diseases (2001) 4, 161-166.

Quantitative histopathology can aid diagnosis in painful bladder syndrome.

AIMS: To define the pathology of painful bladder syndrome using a morphometric method. METHODS: Bladder biopsy specimens from 31 patients with painful bladder syndrome and 11 controls were stained and examined at x260 magnification with the aid of a 100 square counting grid. Random counts of the different tissues and inflammatory components were made to ascertain whether constant differences occurred that could be used to define the pathology of this uncommon condition. RESULTS: In the lamina propria of painful bladder syndrome specimens, a significant increase was seen in the concentration of lymphocytes, T cells, and blood vessels; a decrease was seen in the number of fibroblasts, and no change was seen in the number of mast cells and macrophages. B cells were sporadic. The basement membrane in these specimens showed significant discontinuity and there was increased collagen deposition in the underlying muscle when compared with controls. CONCLUSION: Painful bladder syndrome exhibits constant histological features that may be used to aid diagnosis in this uncommon condition. Simple numerical cell/tissue measurement of this kind is also useful when treatment trials are considered, because objective statistical analysis (pretreatment and post-treatment) is possible without the need for expensive and complicated equipment.

Microwave thermotherapy: a long-term follow-up of 67 patients from a single centre.

OBJECTIVE: To determine the long-term therapeutic value of transurethral microwave thermotherapy (TUMT) in the treatment of bladder outflow obstruction secondary to benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: A total of 67 patients with BPH, assessed using symptom scores and measurements of urinary flow rate, underwent TUMT using the Leo Microthermer system (Laser Electro Optics Ltd, London, UK) between October 1990 and June 1992. Follow-up information was obtained on 60 patients (90%). If they had undergone no further treatment for their BPH, they were re-assessed with symptom scores and measurements of flow rate. RESULTS: The mean follow-up was 52.4 months; eight of the 6 7 patients had died and seven were lost to follow-up. Sixteen of the remaining 52 (31%) had undergone another treatment for BPH; one patient developed prostatitis and one developed localized carcinoma of the prostate. Thirty-four patients had had no further treatment, 29 of whom attended for assessment. In these patients, a statistically significant improvement in both the symptom score and flow rate was maintained at 4 years. No patients developed retrograde ejaculation. CONCLUSION: This is the first study to report a follow-up of at least 4 years after TUMT with any device. Treatment with the Leo Microthermer provided at least a 50% symptomatic improvement in 16 of 50 patients treated at 4 years. However, 30% of the patients needed further treatment for their BPH. TUMT is safe and effective in patients not wanting anaesthesia and in young patients concerned about retrograde ejaculation.

A clinicopathological approach to cystitis--recommendations for simplified pathology reporting.

OBJECTIVE: To assess the accuracy of histopathology reports of bladder biopsy specimens showing chronic cystitis and to develop a standard method of reporting in the form of a template which will aid both clinician and patient in the management of this condition. MATERIALS AND METHODS: Over a 4-year period, the reports of 134 bladder biopsy specimens diagnosed as chronic inflammation of the bladder were examined for clinical details, cystoscopy findings, pathology details and conclusions. Within each of these groups, the common terms were assessed for their relevance to the final outcome. RESULTS: The analysis of each part of these reports revealed no clinical details in 33%, no cystoscopy details in 26% and no histopathology conclusion in 20%. The commonest terms used were: macroscopic haematuria (25%) for clinical details; red patch/ inflamed (40%) for cystoscopic details, morphological site involved (65%) for pathology details; and mild chronic cystitis (37%) for the conclusions. Standardized criteria were devised and after reassessing the reports, 75% were considered to be accurate and complete. CONCLUSIONS: Overall, the histopathology reports examined were more than adequate for the clinicians' use but the spectrum of details provided did not add to the usefulness of the final report. By limiting the terms available, a more standardized report can be produced, benefiting both clinician and patient.

Radioligand-binding analysis of human prostatic alpha-1 adrenoreceptor density following transurethral microwave therapy.

OBJECTIVE: To determine the effects of single-session transurethral microwave treatment (TUMT) on human prostatic alpha-1 adrenoreceptor density in patients with symptomatic bladder outlet obstruction caused by benign prostatic hyperplasia. PATIENTS AND METHODS: Radioligand-binding assays using 3H-prazosin were performed on prostatic tissue obtained from 25 patients, 10 of whom had received a single TUMT whilst the remaining 15 patients had not, and acted as controls. Prostatic tissue was obtained by cold-punch biopsy immediately before transurethral resection of the prostate from 20 patients (10 following microwave treatment and 10 controls) and from a further five patients at the time of retropubic prostatectomy; these five patients again had undergone TUMT. There were no statistically significant differences in several variables between the groups except for the weight of resected tissue, which was greater for the patients undergoing retropubic prostatectomy. Differences in the maximum receptor density (Bmax) and dissociation constant (Kd) were analysed statistically using the Mann-Whitney U-test because the data were non-parametric. RESULTS: Binding was saturable and a single class of high-affinity binding sites was identified in all cases. In the control group, the mean and 95% confidence interval (CI) alpha-1 adrenoreceptor density (Bmax) was 96.4 (82.7-110.1) fmol/mg and the mean (95% CI) dissociation constant (Kd) was 0.56 (0.37-0.74) nmol/l. In those patients who had undergone TUMT, the mean Bmax was significantly lower at 71.3 (58.6-84.7) fmol/mg (P < 0.02) but the Kd of 0.56 (0.20-1.14) mmol/L was identical to that in the control group. CONCLUSIONS: Single-session TUMT, using a non-irrigated catheter, causes a significant reduction in prostatic alpha-1 adrenoreceptor density in the region of the prostate subjected to maximum beating. This may represent one possible mechanism of action by which microwave treatment exerts its beneficial effects.

A comparison of isotope penile blood flow and colour Doppler ultrasonography in the assessment of erectile dysfunction.

OBJECTIVES: To determine whether the measurement of penile blood flow by colour Doppler imaging (CDI) and the subjective impressions generated from CDI correlate with the results of measuring isotope penile blood flow (IPBF), and thus determine if CDI is a useful screening investigation for vasculogenic impotence. PATIENTS AND METHODS: The study comprised 37 men with impotence of > 6 months duration. All patients underwent CDI of the penis; the maximum systolic (vmax) and minimum diastolic velocity (vmin) were recorded. Video recordings of the CDI were reviewed subsequently with no knowledge of the erectile response. Twenty-seven patients then underwent measurement of IPBF. RESULTS: There was no relationship between the results obtained from IPBF and those from CDI, nor was there a significant difference between the vmax of patients identified as having arteriogenic impotence on IPBF and that of normal men or those with venous leakage on IPBF. There was no relationship between the subjective impressions from CDI and the results from IPBF, or with erectile response. CONCLUSIONS: There was no correlation between the results obtained on IPBF and those obtained from CDI; the latter is not useful in differentiating between venogenic and arteriogenic impotence in men who have failed to have a full response to papaverine.

Procoagulant properties of benign and malignant prostatic tissue.

OBJECTIVE: To determine the factor-X activating procoagulant activity (FXAA) of prostatic tissue removed at transurethral resection in a specific chromogenic assay. PATIENTS AND METHODS: FXAA was extracted from transurethrally resected prostatic tissue using a cryofragmentation technique. Tissue from 50 patients with prostate cancer was analysed and compared with that from 36 control patients with benign prostatic-hypertrophy. Enzyme activities were assayed in a two stage chromogenic assay and correlated with conventional markers of tumour aggressiveness. RESULTS: FXAA was found to be significantly lower (P < 0.001) in tissue from malignant prostates compared with benign prostatic hypertrophy tissue. Loss of FXAA was also related to Gleason grade (P < 0.03), percentage of chips involved by tumour (P < 0.04) and bone scan status (P < 0.02). Using antibody inhibition tests this procoagulant was characterized as being a factor VII/tissue factor complex. CONCLUSIONS: Malignant change in the prostate is associated with a reduction in FXAA and this may be an important factor in prostatic tumour growth and dissemination.

A sham controlled trial of transurethral microwave therapy with subsequent treatment of the control group.

To investigate whether there is a significant placebo component to the improvements seen after 1-session transurethral microwave treatment, 40 patients with significant symptoms of prostatism and unequivocally benign glands were recruited to take part in a sham controlled study. After an active treatment the mean American Urological Association symptom scores improved by 63% (19.2 to 7.1) while after a sham treatment symptom scores improved only marginally (18.8 to 16.2, p < 0.001). Residual volumes decreased by 50% (104 to 52 ml.) and flow rates increased by 2.3 ml. per second after an active treatment with no improvement after a sham treatment. There was a consistently greater improvement after an active treatment compared to a sham treatment. Patients who had received a sham treatment were then offered an active treatment and showed improvements similar to those in the original actively treated group and much greater than after the original sham treatment. Mean symptom scores decreased from 16.2 to 9.9 (p < 0.004). Residual volumes decreased from 94 to 40 ml. (p < 0.005) and flow rates increased by 1.6 ml. per second, while these same criteria had deteriorated after a sham treatment. Side effects were mild and short lived, with no patients reporting sexual dysfunction as a consequence of treatment. Transurethral microwave therapy is an effective well tolerated treatment for select patients with benign prostatic hypertrophy and the placebo effect of treatment is minimal.

Transurethral microwave therapy: patient selection and outcome.

Forty-one patients with benign prostatic disease awaiting transurethral resection of the prostate were offered transurethral microwave therapy as an alternative. Pre-operative assessment consisted of symptom scores, prostate-specific antigen levels, flow rates and urinary tract ultrasound with residual urine estimation. Patients were reassessed 6 weeks, 3 months and 6 months after microwave treatment. Twenty-three patients had a successful outcome and 18 an unsuccessful outcome to treatment. Fifteen of the 18 with an unsuccessful outcome could have been predicted by the presence of one or more of the following pretreatment features: glands over 50 g (10 patients), the presence of a median lobe (5 patients), high residual urine (6 patients), a history of recurrent urinary infection (2 patients) and coexisting neurological disorders such as parkinsonism (1 patient) and CVA (1 patient). Three failures had none of these criteria present and could not have been predicted from their pretreatment assessment. Transurethral microwave therapy produces subjective and objective improvements in appropriately selected patients. Patients with large glands or decompensated bladders fail to benefit and should continue to be treated by conventional surgery.

Phase contrast microscopic examination of urinary erythrocytes to localise source of bleeding: an overlooked technique?

AIMS: To localise the source of bleeding in the urinary tract in patients presenting with haematuria. METHODS: Urine samples were obtained from 109 patients with symptoms referable to the urinary tract. The sample was examined for the presence of red blood cells by phase contrast microscopy (PCM) and the proportion of dysmorphic and isomorphic red blood cells was determined. If more than 20% of the red blood cells were dysmorphic a glomerular origin for the site of bleeding was suspected; if less than 20% of the red blood cells were isomorphic a non-glomerular origin was suspected. Phase contrast microscopy and clinical findings were correlated. RESULTS: The correct bleeding site was shown in 27 of 30 (90%) patients with glomerulopathy and in all 17 patients with bleeding from the lower urinary tract, indicating that this method of analysis has a sensitivity of 90% and specificity of 100% for detecting the glomerular source of bleeding. CONCLUSIONS: The examination of urine for dysmorphic and isomorphic red blood cells by phase contrast microscopy is strongly recommended in routine clinical practice for the detection of glomerular and non-glomerular lesions. This technique may avoid unnecessary investigations for the diagnosis of the site of bleeding in patients with haematuria.