Long term follow up of men with Alfuzosin who voided successfully following acute urinary retention*.

INTRODUCTION: Acute urinary retention (AUR) is one of the commonest causes of admission in urology ward and successful voiding with alpha-blockers has been reported. However, long-term efficacy of Alfuzosin, following an episode of AUR is lacking. This is a continuation of our earlier reported study. We report the results of a 4 year follow-up on patients who were on Alfuzosin SR 5 mg BD, following resumption of voiding after an episode of AUR. PATIENTS AND METHODS: A total of 33 patients voided successfully following AUR in our original study. These patients continued on Alfuzosin SR 5 mg BD and were assessed at 2 and 4 years. Symptomatic assessment was performed with IPSS and QOL symptom score and objective assessment was with urinary flow rate and post void residual volume. Patients who continued to deteriorate symptomatically and objectively or developed further AUR were listed for surgery. RESULTS: Out of 33 patients, 28 patients were followed up at 2 years (three patients died due to various medical reasons and two did not attend for follow-up). Nineteen patients (68%) underwent transurethral resection of prostate (TURP) for severe lower urinary tract symptom (LUTS) . The mean peak flow rate at 2 years was 8.4 ml/s and the mean residual volume was 112 ml. Ten patients attended for follow up at 4 years. The mean flow rate was 5.17 ml/s and the mean post-void residual volume was 101 ml. Four patients underwent TURP for severe outflow symptoms. At 4 years follow up 24 out of 30 patients (80%) on Alfuzosin needed TURP. CONCLUSIONS: These data do not support the long term use of alpha-blockers in patients who voided successfully after acute urinary retention.

Randomised, placebo controlled, double blind study of alfuzosin SR in patients undergoing trial without catheter following acute urinary retention.

INTRODUCTION: Acute urinary retention caused by bladder outlet obstruction resulting from prostatic enlargement is one of the commonest causes for acute admission to urology wards. More recently, there has been a trend to commence treatment with alpha-blockers after catheterisation followed by a trial without catheter (TWOC), in the hope that surgery may be avoided in a significant proportion of patients. There is no conclusive evidence of the efficacy of this treatment. We conducted a study to evaluate the efficacy of using the alpha-blocker alfuzosin SR in patients with acute urinary retention. PATIENTS AND METHODS: All patients presenting with acute urinary retention to our unit were included in the trial. Exclusion criteria included patients with known bladder or prostate malignancy, bladder calculi, urinary tract infections, urethral stricture or patients on alpha-blockers. A total of 81 patients consented and were randomised. Sixty-two patients completed the study. The retention volume was recorded. Trial medicine was recorded on a twice-daily dose and the first TWOC was carried out after a minimum of three doses or 36 hours after admission. TWOC was considered successful on voiding with a residual volume of <200 ml. Unsuccessful patients were recatheterised and discharged home on trial medication, and called for a second TWOC after 2 weeks. Successful patients were continued on alpha-blockers and failures were put on the operating list for TURP. Patients on active treatments were reviewed at 2 year. RESULTS: Of the 34 patients treated with alfuzosin SR, 17 (50%) resumed voiding and of the 28 patients from placebo group, 16 (57%) voided successfully. All 33 patients were continued open labelled on alfuzosin SR 5mg BD. Out of 33 patients, 13 (43%) had TURP within first year after TWOC and three died due to various medical causes. Out of remaining 17 patients, 15 attended for follow-up. The mean peak flow rate was 8.4 ml/s and the mean residual volume was 112 ml. Six patients (40%) required TURP for severe lower urinary tract symptoms (LUTS). So out of 28 patients followed at 2 year, 19 (68%) had TURP. CONCLUSIONS: These data do not support the routine use of alpha-blockers in patients with acute urinary retention. Also continuing use of alpha-blockers does not seem to prevent further requirements of TURP, although larger studies are needed to support this.

A novel strategy for NQO1 (NAD(P)H:quinone oxidoreductase, EC 1.6.99.2) mediated therapy of bladder cancer based on the pharmacological properties of EO9.

The indolequinone EO9 demonstrated good preclinical activity but failed to show clinical efficacy against a range of tumours following intravenous drug administration. A significant factor in EO9's failure in the clinic has been attributed to its rapid pharmacokinetic elimination resulting in poor drug delivery to tumours. Intravesical administration of EO9 would circumvent the problem of drug delivery to tumours and the principal objective of this study is to determine whether or not bladder tumours have elevated levels of the enzyme NQO1 (NAD(P)H:quinone oxidoreductase) which plays a key role in activating EO9 under aerobic conditions. Elevated NQO1 levels in human bladder tumour tissue exist in a subset of patients as measured by both immunohistochemical and enzymatic assays. In a panel of human tumour cell lines, EO9 is selectively toxic towards NQO1 rich cell lines under aerobic conditions and potency can be enhanced by reducing extracellular pH. These studies suggest that a subset of bladder cancer patients exist whose tumours possess the appropriate biochemical machinery required to activate EO9. Administration of EO9 in an acidic vehicle could be employed to reduce possible systemic toxicity as any drug absorbed into the blood stream would become relatively inactive due to an increase in pH.

Telomerase activity in malignant and benign bladder conditions.

This study investigated whether the enzyme telomerase is active in bladder tumours, whether there is any correlation between activity and grade, and whether the enzyme is expressed in non-malignant conditions. Fifty-two patients undergoing cystoscopy or TURBT at a district general hospital were included, 25 with current bladder tumours, 13 with previous but no current tumours, and 14 with non-malignant pathology. Specimens were analysed by the telomerase repeat amplification protocol (TRAP assay), a highly-sensitive polymerase chain reaction (PCR)-based assay, and a commercially-available ELISA kit. Telomerase activity was detected in 80% of bladder tumours, more frequently in moderate- or poorly-differentiated (93%) than well-differentiated (56%) tumours. Activity was not uniform across individual tumours. Telomerase was also frequently (61%) detected in inflammatory lesions found in patients being followed up for previous bladder tumours, and in two (14%) patients with benign pathologies. In conclusion, telomerase was frequently but not uniformly detected in bladder tumours; its presence was not specific to malignancy. There is a possible correlation between tumour grade and telomerase activity.

Role of P-glycoprotein in chemoresistant superficial bladder tumours.

OBJECTIVE: The drug resistance at cellular level is mediated by P-glycoprotein (P-G), which is variably expressed in bladder tumours. The effect of intravesical chemotherapy on P-G status was studied in chemoresistant and recurrent superficial tumours which progressed to metastasis or needed further treatment. METHODS: Archival histological materials of 14 patients who received intravesical epirubicin for recurrent superficial transitional cell carcinoma of the bladder were studied for the presence of P-G using monoclonal antibody JSB-1. RESULTS: Four patients showed complete absence of P-G following chemotherapy although only 2 patients were recurrence-free. In 4 patients with extravesical metastasis, there was no evidence of increased P-G expression. CONCLUSIONS: The P-glycoprotein expression is not related to histological grading or clinical progression of bladder tumours.

Ultrasound in urological emergency: results of self audit and implications for training.

The efficacy of ultrasound examination by the trainee urologists in the management of urological emergencies admitted in a district general hospital was studied. Fifty patients (100 kidney units) had renal ultrasound performed by urological trainees on acute admission. The results were compared with subsequent definitive radiological investigations. On analysis of 100 renal units there were 7 discordant results, 2 false negatives and 5 false positives achieving 97% specificity (95% confidence interval 93% to 100%) and 84% sensitivity (95% confidence interval 71% to 97%). Adopting 50-patient analysis there was 89% specificity (95% confidence interval 74% to 100%) and 84% sensitivity (95% confidence interval 71% to 97%). These intervals indicate the levels of success to be expected in future studies. The study shows that urological trainees can use ultrasound with high levels of accuracy improving patient management.

Radiographer-performed abdominal and pelvic ultrasound: its value in a urology out-patient clinic.

OBJECTIVE: To assess the efficacy of radiographer-performed ultrasound examination as a routine investigative procedure in a urological out-patient clinic. PATIENTS AND METHODS: A total of 151 patients attending a District General Hospital Urological Out-patient Department underwent an ultrasound examination in the clinic. RESULTS: Diagnosis by ultrasound was achieved in 93% of patients. The remaining patients underwent further investigations. Two (1%) patients with normal scans had small bladder tumours. Subsequent intravenous urography in these individuals showed normal upper tracts. CONCLUSION: Abdominal and pelvic ultrasound examination performed in the urological out-patient clinic on unprepared patients was the only investigation necessary for evaluation of common problems such as non-specific urinary symptoms, recurrent urinary tract infections and bladder outlet obstruction.

Growth characteristics of early passage cell lines compared with established TCC bladder lines.

The growth patterns of established cell lines from bladder transitional cell carcinoma (TCC) were compared with early passage cell lines. The growth of established cell line 5637 was uninhibited in both serum free (basal) and serum containing media. The early passage line (DR) grew only in serum containing medium. This confirms the unreliability of results from biological studies on established (continuous) cell lines.

Rigid versus flexible cystoscopy. A controlled trial of patient tolerance.

The cost-efficiency and time-saving associated with out-patient flexible cystoscopy have propagated its use nationwide. However, only minimal attention has been paid to the feelings of patients exposed to this physically and emotionally invasive technique. We studied 53 consecutive patients attending for check cystoscopy at the time of their first flexible cystoscopy. Acting as their own historical controls, their feelings about rigid cystoscopy under general anaesthesia and subsequent flexible cystoscopy under local anaesthesia were assessed: 6/53 (11%) preferred rigid cystoscopy under general anaesthesia. The only significant association with their dislike of flexible cystoscopy, was their desire to stay in hospital overnight. It was concluded that with careful counselling and attention to individual needs, the preference for flexible cystoscopy over rigid cystoscopy under general anaesthesia can approach 100%.

Appendicitis presenting with painless hematuria.

Microscopic hematuria is a well recognized, incidental finding in many patients presenting with acute appendicitis. We report a case of gross, painless hematuria as the late and only presenting feature of appendicitis.