Showing papers in "BJUI in 1998"

Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial.

Abstract: Objective To test if supplemental dietary selenium is associated with changes in the incidence of prostate cancer. Patients and method A total of 974 men with a history of either a basal cell or squamous cell carcinoma were randomized to either a daily supplement of 200 μg of selenium or a placebo. Patients were treated for a mean of 4.5 years and followed for a mean of 6.5 years. Results Selenium treatment was associated with a significant (63%) reduction in the secondary endpoint of prostate cancer incidence during 1983–93. There were 13 prostate cancer cases in the selenium-treated group and 35 cases in the placebo group (relative risk, RR=0.37, P=0.002). Restricting the analysis to the 843 patients with initially normal levels of prostate-specific antigen (≤4 ng/mL), only four cases were diagnosed in the selenium-treated group and 16 cases were diagnosed in the placebo group after a 2 year treatment lag, (RR=0.26 P=0.009). There were significant health benefits also for the other secondary endpoints of total cancer mortality, and the incidence of total, lung and colorectal cancer. There was no significant change in incidence for the primary endpoints of basal and squamous cell carcinoma of the skin. In light of these results, the ‘blinded’ phase of this trial was stopped early. Conclusions Although selenium shows no protective effects against the primary endpoint of squamous and basal cell carcinomas of the skin, the selenium-treated group had substantial reductions in the incidence of prostate cancer, and total cancer incidence and mortality that demand further evaluation in well-controlled prevention trials.

Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder

Abstract: Objective To compare the efficacy and tolerability of tolterodine with that of oxybutynin in patients with an overactive bladder. Patients and methods A randomized, double-blind, placebo-controlled, parallel group, multinational phase-III study was conducted in urology and gynaecology clinics in the UK, Republic of Ireland and Sweden. The study enrolled 293 patients with urodynamically confirmed bladder overactivity, increased frequency of micturition (≥8 micturitions/24 h) and symptoms of urgency and/or urge incontinence (≥1 episode/24 h). Patients received either tolterodine (2 mg twice daily) or oxybutynin (5 mg three times daily) or placebo. Doses could be reduced, to prevent withdrawal, to 1 mg or 2.5 mg, respectively. The main outcome measures were the mean change from baseline in frequency of micturition/24 h, the number of incontinent episodes/24 h and volume voided per micturition. Results After 12 weeks’ treatment, the mean frequency of micturition decreased by 21% and 19.5% in those receiving tolterodine (n=118) and oxybutynin (n=118), respectively, and by 10.5% in those on placebo (n=57). Among those with urge incontinence at baseline (75% of patients), the mean number of incontinent episodes decreased by 47%, 71% and 19%, respectively, in those receiving tolterodine, oxybutynin and placebo. The effect of tolterodine and oxybutynin on these two micturition variables was statistically equivalent. There was also a comparable increase in mean volume voided per micturition in the tolterodine (27%) and oxybutynin groups (31%), compared with 7% in the placebo group. Dry mouth was the most common adverse event and was reported with greater frequency and intensity among patients receiving oxybutynin than among those receiving either tolterodine or placebo. In the oxybutynin group, more patients also withdrew because of adverse events and a greater proportion required dose reduction as a result of adverse events. Despite dose reduction, the frequency of adverse events and the intensity of dry mouth remained higher among those receiving oxybutynin (2.5 mg three times daily) than in patients who remained on tolterodine 2 mg twice daily. Conclusion Tolterodine 2 mg twice daily is effective and well tolerated in the treatment of bladder overactivity. Tolterodine was better tolerated than oxybutynin, particularly with respect to the frequency and intensity of dry mouth, but had comparable clinical efficacy. The superior tolerability of tolterodine therefore allows more patients to remain on effective therapy than the current most commonly prescribed agent for the treatment of the overactive bladder.

Conservative treatment of stress urinary incontinence in women: a systematic review of randomized clinical trials

Abstract: Objective To assess the efficacy of physical therapies for first-line use in the treatment and prevention of stress urinary incontinence (SUI) in women, using a systematic review of randomized clinical trials (RCTs). Materials and methods A computer-aided and manual search for published RCTs investigating treatment and prevention of SUI using physical therapies, e.g. pelvic floor muscle (PFM) exercises, with or without other treatment modalities, was carried out. The methodological quality of the included trials was assessed using criteria based on generally accepted principles of interventional research. Results Twenty-four RCTs (22 treatment and two prevention) were identified; the methodological quality of the studies included was moderate and 11 RCTs were of sufficient quality to be included in further analysis. Based on levels-of-evidence criteria, there is strong evidence to suggest that PFM exercises are effective in reducing the symptoms of SUI. There is limited evidence for the efficacy of high-intensity vs a low-intensity regimen of PFM exercises. Despite significant effects of biofeedback after testing as an adjunct to PFM exercises, there is no evidence that PFM exercises with biofeedback are more effective than PFM exercises alone. There is little consistency (of stimulation types and parameters) in the studies of electrical stimulation, but when the results are combined there is strong evidence to suggest that electrostimulation is superior to sham electrostimulation, and limited evidence that there is no difference between electrostimulation and other physical therapies. In the prevention of SUI the efficacy of PFM exercises, with or without other adjuncts, is uncertain. Conclusions More research of high methodological quality is required to further evaluate the effects of physical therapies used to treat and prevent SUI.

Composition and biomechanical properties of the bladder acellular matrix graft: comparative analysis in rat, pig and human

Abstract: Objective To compare the composition and mechanical properties of the newly developed bladder acellular matrix graft (BAMG) with the normal urinary bladder in rat, pig and human. Materials and methods Rat, pig and human urinary bladders were harvested and divided into control and experimental groups. For the latter, BAMGs were prepared, and light and transmission electron microscopic studies performed. Strips from the normal bladders and the BAMGs (10 in each group) were tested under tension, and the ultimate tensile strength, maximum strain, and elastic modulus were determined from stress/strain curves. Results Both types I and III collagen, as well as elastic fibres, were observed as major components of the matrix scaffold. There were more collagen type I fibres in the rat than in the pig and human BAMGs, whereas the pig, and particularly the human, both showed higher levels of type III collagen and elastic fibres. These different matrix scaffold patterns were confirmed by electron microscopy. Results from biomechanical testing showed no significant differences for strength, strain or elastic modulus between BAMG and control bladder strips, except in the rat where the maximum strain values were significantly lower. Conclusion There are variations in the acellular matrix structure with similar biomechanical properties between the BAMG and the normal urinary bladder in three different species. These results may underscore the potential of the BAMG. Furthermore, this in vitro model provides a suitable method to study the mechanical properties of the urinary bladder and may serve as a diagnostic tool for various investigations.

The effect of oral selenium supplementation on human sperm motility.

Abstract: Objectives To determine whether the decline in selenium intake and selenium status in men in the West of Scotland might be a contributory factor to male subfertility. Patients and methods Two semen samples were collected from patients attending a subfertility clinic and those patients with samples showing reduced motility were invited to participate in an ethically approved double-blind clinically controlled trial with informed consent. Sixty-nine patients were recruited and received either placebo, selenium alone or selenium plus vitamins A, C and E daily for 3 months. A further semen sample was collected at the end of the trial. Plasma selenium status was determined at the beginning and end of the trial period, as was total sperm density and motility. Results Plasma selenium concentrations were significantly (P<0.001) higher in both selenium-treated groups than in controls. No significant effect of treatment on sperm density was recorded. Sperm motility increased in both selenium-treated groups, in contrast to a slight decline in the placebo group, but the difference was not significant. However, as the provision of additional vitamins had no effect on any variable measured it was considered justified to combine the two selenium-treated groups and compare them with the placebo treatment. On this basis, selenium treatment significantly (P<0.002) increased plasma selenium concentrations and sperm motility (P=0.023) but sperm density was again unaffected. Five men (11%) achieved paternity in the treatment group, in contrast to none in the placebo group. Conclusion This trial confirms the result of an earlier study, that selenium supplementation in subfertile men with low selenium status can improve sperm motility and the chance of successful conception. However, not all patients responded; 56% showed a positive response to treatment. The low selenium status of patients not supplemented again highlights the inadequate provision of this essential element in the Scottish diet.

Fournier’s gangrene

Abstract: Twenty-five cases of gangrene of the scrotum and penis have been analysed. The anterior scrotum or the whole scrotum were the areas most frequently involved. The results of seminal analyses showed marked oligozoospermia during the infective period. Haemolytic streptococcus was the most common organism. The aetiology of the disease is reviewed and \"infective gangrene of the scrotum and penis\" is considered to be a more suitable diagnostic label than Fournier's gangrene.

The ICS-'BPH' Study: uroflowmetry, lower urinary tract symptoms and bladder outlet obstruction

Abstract: Objective To explore the relationship between uroflow variables and lower urinary tract symptoms (LUTS); to define performance statistics (sensitivity, specificity, positive and negative predictive values) for maximum urinary flow rate (Qmax ) with respect to bladder outlet obstruction (BOO) at various threshold values; and to investigate the diagnostic value of low-volume voids. Patients and methods The study comprised 1271 men aged between 45 and 88 years recruited from 12 centres in Europe, Australia, Canada, Taiwan and Japan over a 2-year period. Symptom questionnaires, voiding diaries, uroflowmetry and pressure-flow data were recorded. The relationship between uroflow variables and symptoms, Qmax and BOO, and the diagnostic performance of low volume voids were analysed. Results The relationship between symptoms and uroflow variables was poor. The mean difference between home-recorded and clinic-recorded voided volumes was −48 mL. Qmax was significantly lower in those with BOO (9.7 mL/s for void 1) than in those with no obstruction (12.6 mL/s; P 150 mL the likelihood of BOO was 56%. The addition of a specific threshold of 10 mL/s to these higher volume voiders improved the PPV for BOO to 69%. Conclusion While uroflowmetry cannot replace pressure-flow studies in the diagnosis of BOO, it can provide a valuable improvement over symptoms alone in the diagnosis of the cause of lower urinary tract dysfunction in men presenting with LUTS. This study provides performance statistics for Qmax with respect to BOO; such statistics may be used to define more accurately the presence or absence of BOO in men presenting with LUTS, so avoiding the need for formal pressure-flow studies in everyday clinical practice, while improving the likelihood of a successful outcome from prostatectomy. This study also shows that low-volume uroflowmetry can provide useful diagnostic information and that, as such, the data from such voids should not be discarded.

The management of men with acute urinary retention

Abstract: Objectives To determine the outcome of men with acute urinary retention undergoing prostatectomy and to assess whether discharge with a catheter before subsequent planned re-admission for prostatectomy had an adverse effect on outcome. Patients and methods A prospective cohort study was conducted of all men undergoing prostatectomy in five health care regions over a 6-month period in 56 hospitals where prostatectomies were performed under the care of 103 surgeons. The study included 3966 men undergoing prostatectomy, of whom 1242 presented with acute urinary retention; the complication rates and symptomatic outcome were assessed. Results Compared with those who underwent elective prostatectomy for symptoms alone, men presenting with acute retention had an excess risk of death at 30 days (relative risk [RR], 26.6, 95% confidence interval [CI], 3.5–204.5) and at 90 days after operation (RR 4.4, 95% CI 2.5–7.6), and an increased risk of peri-operative complications. Although men with retention were older, had larger glands and had more comorbidity, these factors did not totally explain the excess risk. The final symptomatic outcome of men with acute retention was no different from that of men presenting for elective treatment. Men with retention who were managed by initial catheterization, sent home and subsequently re-admitted for planned operation had similar pretreatment characteristics, post-operative complications and outcomes to those who were kept in hospital throughout, although the men kept in hospital had a total increased length of stay. Conclusions Men with acute retention have a high risk of developing complications after undergoing prostatectomy. We were unable to confirm that a short- term period of catheter drainage at home before re-admission for planned surgery carried increased risks of peri-operative complications.

Primary adenocarcinoma of the urinary bladder

Abstract: Objective To evaluate the outcome after the treatment of primary non-urachal vesical adenocarcinoma and to determine the significant prognostic factors. Patients and methods The records of 185 patients with vesical adenocarcinoma were reviewed. The pathological evaluation included the determination of pathological stage, tumour grade, presence or absence of mucin and its location, evidence of bilharzial infestation and flow-cytometric DNA analysis. The mean follow-up of the treated patients was 3.1 years. Disease-free survival was estimated and the results correlated with patient and tumour characteristics (univariate analysis). Cox’s proportional hazards analysis was used to determine prognostic factors. Results The overall 5-year disease-free survival was 55%; only three factors had a significant impact on survival, the tumour pathological stage and grade, and lymph node involvement. Conclusions Radical cystectomy remains the only satisfactory treatment option for primary vesical adenocarcinoma. Tumour stage, grade and lymph node involvement are the only significant prognostic factors.

Urethroplasty for balanitis xerotica obliterans

Abstract: Objective To review the results of different methods of urethroplasty for anterior urethral strictures caused by balanitis xerotica obliterans (BXO). Patients and methods Twenty-eight patients underwent urethroplasty for BXO; 12 had a one-stage pedicled penile skin-flap urethroplasty and 16 excision and a two-stage free-graft urethroplasty using nongenital skin. Results The treatment failed in all patients undergoing a one-stage pedicle penile skin urethroplasty because the disease recurred with BXO, whereas the treatment failed in only one patient using a two-stage free graft procedure. Conclusion A two-stage free-graft urethroplasty using nongenital skin is recommended for anterior urethral strictures caused by BXO.

Nephron‐sparing surgery for renal cell carcinoma

Abstract: In summary, NSS is the indicated treatment for patients with localized RCC and an intercurrent urological or medical condition that poses a threat to overall renal function. Recent studies have clarified the role of NSS in patients with localized unilateral RCC and a normal contralateral kidney. Recent results indicate that radical nephrectomy and NSS provide equally effective curative treatment for patients who present with a single, small (< 4 cm), and clearly localized RCC. The long-term renal functional advantage of NSS with a normal opposite kidney requires further study.

An Italian epidemiological multicentre study of nocturnal enuresis

Abstract: Objective To estimate the prevalence of enuresis in schoolchildren in Italy. Subjects and methods The Italian Club of Nocturnal Enuresis promoted a prevalence study of nocturnal enuresis using a self-administered questionnaire in seven cities in Northern, Central and Southern Italy. The association between enuresis and potential risk factors, e.g. a family history of enuresis, stress, socio-economic status and abnormal diurnal voiding habits, was investigated. The perceived impact on the child and on the family was also evaluated. A random-cluster sampling scheme was used to obtain a sample of primary and secondary schoolchildren from each city. One primary school and one secondary school for each socio-economic level was sampled in each city, giving a total of 42 schools surveyed; 9086 children were covered by the survey. In a cluster sampling method, the variance of prevalence is divided into two components, binomial and extra-binomial variability. Both the DSM III and DSM IV definitions of enuresis were used because at present, there is no consensus on the diagnostic criteria. Results Completed questionnaires were received from 7012 children, an overall response rate of 77.2%. Those aged 6–14 years were analysed, restricting the sample to 6892 children. There were 250 enuretic children using the DSM III definition of enuresis and 112 using the DSM IV definition. The overall prevalence was 3.8% and showed a decreasing trend with increasing age. Bedwetting was more frequent in boys than in girls. The prevalence of enuresis was higher when the child was from a family of low socio-economic status despite the child’s age group. The logistic analysis showed that familiality, stress, birthweight, age of attaining diurnal continence, soiling and, for girls, menstruation, were statistically significant variables and thus contributed to predicting the probability of bedwetting, confirming the findings of previous studies. There was a large difference in prevalence using the two DSM definitions; a high percentage of DSM III enuretic children had more than two wet nights per week. Conclusion It is important that a consensus about the ‘working definitions’ of enuresis is reached to avoid bias in the recruitment step, to carry out comparable epidemiological studies and to obtain adequate therapeutic responses.

Treatment of mid- and lower ureteric calculi: extracorporeal shock-wave lithotripsy vs laser ureteroscopy. A comparison of costs, morbidity and effectiveness

Abstract: Objectives To determine the efficacy and costs of extracorporeal shock-wave lithotripsy (ESWL) compared with ureteroscopy (URS) in the treatment of mid- and lower ureteric calculi. Patients and methods The records of patients treated primarily by ESWL and URS were analysed retrospectively. Treatment with ESWL included 63 patients (42 men and 21 women, mean age 52 years, range 23–78, 19 mid- and 44 lower ureteric calculi). All patients received 4000 shock waves at a mean energy setting of 18.1 kV. URS was used in 105 patients, with a 7.2 F miniscope or the 7.1 F flexible scope. Stones were fragmented with a pulsed-dye laser lithotripter at 504 nm and a power of up to 130 mJ (mean 53 mJ) using a 200 or 320 μm fibre. All ureteroscopies were performed with the patient under general (n=17) or spinal (n=87) anaesthesia in a mean treatment duration of 34 min. Stones were located in the mid-ureter in 24 patients and in the lower ureter in 80. The outcome was assessed by stone-free rates, re-treatment rates, time to become stone-free, complications and costs. Results ESWL for mid- and lower ureteric calculi resulted in a success rate of 90% and 81%, respectively, compared with 96% and 99% for URS. However, patients treated with URS were stone-free within 2 days, whereas patients in the ESWL group required up to 4 months. The best results for ESWL were achieved with stones of <50 mm2 . The costs of URS were higher than those for ESWL. Conclusions ESWL provides a noninvasive, simple and safe option for the management of mid- and lower ureteric calculi, provided that the stones are <50 mm2 ; larger stones are best treated by URS.

Percutaneous transperineal radiofrequency ablation of prostate tumour: safety, feasibility and pathological effects on human prostate cancer

Abstract: Objective To evaluate the safety of radiofrequency (RF) energy delivered interstitially in patients with prostate cancer scheduled for radical prostatectomy and to correlate the proposed theoretical lesion size with the pathological findings. Patients and methods Radiofrequency interstitial tumour ablation (RITA) was performed in 15 patients with localized prostate cancer before radical surgery. RF energy was delivered to the prostate by active needle electrodes (monopolar or bipolar) placed transperineally under transrectal ultrasonography guidance. Needle electrodes were used with different configurations and in some cases were covered by retractable shields to vary the length and circumference of the thermal lesions created. In eight patients, the procedure was performed immediately before radical prostatectomy, in six RITA was performed under spinal anaesthesia 1 week before surgery and in one patient, no surgery was performed but the patient was followed by serial determinations of prostate specific antigen (PSA). At least two lesions were created in each prostate, including both capsule and peripheral zones. NADPH and haematoxylin & eosin (H&E) staining were used to assess the extent of the necrotic lesion in the radical prostatectomy specimen. Results The mean energy delivered was 10.5 kJ, with central temperatures reaching up to 105 °C during 12 min of ablation; rectal temperature remained at <38 °C. There were no complications. Macroscopic examination showed well-demarcated lesions including the prostatic capsule, up to 2.2×1.5×4.5 cm. With monopolar energy, the observed lesion size was comparable to the predicted 2×2×2 cm lesion, while with bipolar energy, lesion size was related to interneedle distance and uncovered needle length. Microscopic examination showed clearly delineated lesions both with NADPH (in prostates immediately removed after surgery) and H&E (at 1 week after RITA) staining. The lesion size observed on pathological analysis correlated with the predicted lesion size. In one patient, no residual cancer was found in the specimen. In the patient whose entire prostate was targeted and followed by serial PSA measurements, the latter were undetectable at 3 months of follow-up. Conclusion Transperineally delivered RF energy is capable of safely creating extensive coagulative necrotic lesions in prostate cancer tissue, in a reproducible and controlled manner. The results presented here provide basic information for the potential future application of this form of energy for localized prostate cancer.

A novel therapy for nocturnal polyuria: a double‐blind randomized trial of frusemide against placebo

Abstract: Objective To report a randomized, double-blind, placebo-controlled trial of an afternoon dose of the diuretic frusemide, used to establish an early evening diuresis and so diminish nocturnal voiding frequency and voided volume in elderly men presenting with lower urinary tract symptoms (LUTS) Patients and methods After a 2-week placebo run-in period, 49 men aged >50 years were randomized to receive 40 mg of frusemide or placebo, taken 6 h before their usual bedtime Day and night-time frequency and voided volume during the run-in and treatment periods were compared between the placebo and frusemide groups Results In the 43 men completing the study, there was a significant reduction in night-time frequency (−05 and 0) and percentage night-time voided volume (−18% and 0%) in those taking frusemide compared with placebo Of patients on active treatment, seven of 19 had a reduction in night-time frequency of ≥1, compared with only one of 20 on placebo, and 14 of 21 felt that frusemide had helped their nocturia, compared with only five of 22 on placebo Conclusion Men with LUTS whose most prominent symptom is nocturia should complete a frequency-volume chart In those with nocturnal polyuria, 40 mg of frusemide resulted in a significant reduction in night-time frequency and percentage voided volume

Efficacy and safety of tolterodine in patients with detrusor instability: a dose-ranging study

Abstract: Objective To investigate the efficacy and safety of tolterodine, a new antimuscarinic agent, and define the optimum dosage in patients with symptoms of detrusor instability (urgency, increased frequency of micturition and/or urge incontinence). Patients and methods A double-blind, placebo-controlled, multicentre study was carried out; after a 1-week run-in period to establish baseline values, 81 patients were randomized to receive placebo or tolterodine 0.5, 1, 2 or 4 mg twice daily for 2 weeks. Micturition (diary) variables, urodynamics and subjective urinary symptoms were assessed after 2 weeks’ treatment. Results A per-protocol analysis of efficacy in 64 patients showed dose-related improvements in recorded micturition and urodynamic variables, e.g. at a dosage of 2 mg twice daily, the frequency of micturition, episodes of incontinence and pad use were reduced by 20%, 46% and 29%, respectively, while the volume at first contraction increased by 89 mL. The 4 mg dosage was associated with a large increase in residual urinary volume and an increased incidence of dry mouth. The incidence of adverse events (mainly mild or moderate antimuscarinic effects) was comparable with placebo at tolterodine dosages of≤2 mg. No serious adverse events were observed and tolterodine had no clinically significant impact on electrocardiographic or laboratory findings. Conclusion The results indicate that tolterodine offers an effective treatment for the symptoms of detrusor instability. The optimum dosage appears to be 1–2 mg twice daily.

The early clinical course of primary Ta and T1 bladder cancer: a proposed prognostic index

Abstract: Objective To develop a simple prognostic index for anticipating more precisely the early clinical course of primary superficial bladder cancer. Patients and methods The prognostic value of patient and tumour characteristics was examined in 333 patients with primary Ta or T1 bladder cancer who participated in a multicentre prospective study already completed. Primary tumour multiplicity, a diameter of >3 cm, stage T1, and grade 2 or 3 were independent predictors of earlier recurrence in a multivariate analysis. A simplified prognostic index consisted of the number of adverse tumour characteristics (ATCs) initially present. Results After a median follow-up of 35.3 months, the 60 patients free of ATCs (19%) had a recurrence-free probability at 12 and 24 months of 86% and 69%, respectively, and none experienced progression. Recurrence outcomes deteriorated consistently as the number of ATCs increased among the other three groups. In patients with 3–4 ATCs, the 12- and 24-month recurrence-free probability was as low as 30% and 19%, and recurrence and tumour rates were about 2.6 times higher than in patients free of ATCs; 7% of these patients experienced progression within 35 months of follow-up. Conclusion A prognostic index based on the number of ATCs (primary tumour multiplicity, diameter >3 cm, stage T1, and grade 2 or 3) is a strong indicator of the clinical course of superficial bladder cancer within 3 years of the first endoscopic resection. This proposal is suggested for discussion and for validation in future studies but if confirmed, this simple prognostic index may greatly help to identify indicators for adjuvant intravesical therapy and to determine the optimal periodicity of control cystoscopy regimens.

Urodynamic patterns in infants with normal lower urinary tracts or primary vesico‐ureteric reflux

Abstract: Objective To compare bladder function in infants with primary vesico-ureteric reflux (VUR) and those with normal lower urinary tracts Patients and methods The study comprised 42 patients (36 males) with VUR (grades III to V) and 21 (16 males) without VUR (mean age in both groups, 6 months) Intravesical catheters were placed suprapubically under general anaesthesia and, after at least 24 h, natural-filling urodynamics were monitored for three or more filling and voiding cycles Results Various urodynamics patterns were defined: for infants without VUR these were either normal or normal-immature (discoordinated micturition) and none showed features indicating abnormal bladder function By comparison, 24 of 42 infants with VUR showed abnormal urodynamic patterns (57%, 95% confidence interval 41% to 72%, P 30% capacity were seen only in the VUR group (in 24 patients) There were 18 infants with VUR that showed the normal or immature urodynamics patterns, but for the 14 males the voiding pressures were higher than for those without VUR (mean maximum detrusor pressure, 161 and 117 cmH2O, respectively; P<002) Conclusions There is an association between abnormal urodynamic variables and a diagnosis of primary VUR in young infants (notably males) that may have important implications for concepts about the genesis and persistence of VUR

The significance of lymphadenectomy in transitional cell carcinoma of the upper urinary tract

Abstract: Objective To determine the efficacy of lymphadenectomy after nephroureterectomy in patients with transitional cell carcinoma (TCC) of the upper urinary tract. Patients and methods Between January 1986 and December 1995, 72 patients (mean age 67 years, range 45–82) underwent nephroureterectomy for primary TCC of the upper urinary tract. In 35 patients, a lymphadenectomy was also performed. The clinicopathological data were analysed retrospectively, focusing on the significance of lymphadenectomy. Results Lymph vessel invasion was found in 28 patients and its incidence was closely correlated with both tumour grade and pathological stage. Of the 35 patients who underwent lymphadenectomy, lymph node metastases were found in 13 patients, all of whom had lymph vessel invasion. There was no significant difference in the survival rate between patients with and without lymphadenectomy; however, among the 44 patients with no lymph vessel invasion, the survival rate of those with lymphadenectomy was significantly higher than in those without (P<0.05). Conclusion Lymphadenectomy may provide a therapeutic advantage in patients with upper urinary tract TCC and no lymph vessel invasion. However, patients with lymph vessel invasion seem to have systemic disease; therefore, aggressive systemic adjuvant therapies rather than regional lymphadenectomy should be applied in these patients.

A review of our first 100 cases of laparoscopic nephrectomy: defining risk factors for complications

Abstract: Objective To present the complications from our first 100 cases of laparoscopic nephrectomy, a technically demanding procedure requiring lengthy experience, and to define the risk factors. Patients and methods Indications for laparoscopic nephrectomy included patients requiring nephrectomy for benign pathology and those requiring nephroureterectomy for upper tract transitional cell carcinoma confined to the upper ureter and/or renal pelvis. All patients were operated on by one surgeon (D.A.T.) via a transperitoneal route and data on diagnosis, outcome and complications collected prospectively. Results The overall complication rate was 18%, of which 3% were major and 15% minor complications. Five cases were converted to open surgery electively. Complications and conversions were associated with a history of pyonephrosis, previous renal surgery, staghorn calculi, polycystic kidney disease, and xanthogranulomatous pyelonephritis. While there was no discernible decline in the decrease in complications with experience, operative duration decreased from a mean of 204 min for the first 20 cases to 108 min for the last 20. Complications and conversions were more closely associated with diagnosis than with the surgeon’s experience. Conclusion Laparoscopic nephrectomy and nephroureterectomy can be undertaken for a variety of indications with reasonable complication and conversion rates. Although inflammatory conditions increase the difficulty of these procedures, we feel that patients requiring nephrectomy for benign disease should be offered a trial of laparoscopic surgery.

Cystic renal cell carcinoma: pathological features, survival and implications for treatment.

Abstract: Objectives To assess the incidence, clinicopathological features. prognosis and therapeutic options of cystic renal cell carcinoma (CRCC). Patients and methods The clinical records and nephrectomy specimens from 206 patients with renal cell carcinoma (RCC) were reviewed after a minimum follow-up of 5 years. The mode of presentation, tumour size, growth pattern. nuclear grade, cytoplasmic appearance and pathological stage at presentation were compared with the outcome, as measured by disease-free and overall survival of the patients. Results From the 206 patients with RCC. 25 (12%) were classified as having CRCC: most of these cases (96%) occurred in male patients, as opposed to 64% in the remaining patients RCC (P=0.0029). The clinical features at diagnosis were similar in both groups, although asthenia, anorexia and weight loss were uncommon in patients with CRCC (P=0.045). Nuclear grade and pathological stage were usually lower in those with CRCC than in those with RCC (P=0.0071 and P=0.0033, respectively). Survival was significantly longer in patients with CRCC (P=0.0342 ). Conclusions CRCC is a type of RCC that is usually identified at earlier stages, has a slower growth rate, and is therefore associated with a better prognosis and longer survival than conventional RCC. The differential diagnosis between CRCC, cystic multilocular nephroma and cysts with a superimposed infectious or haemorrhagic process can be extremely difficult in imaging studies, and even in intra-operative frozen-section analysis. Because of this, and with the better prognosis of CRCC, a conservative surgical approach would be the treatment of choice whenever technically feasible.

Immunotherapy of advanced prostate cancer: a phase I/II trial using Mycobacterium vaccae (SRL172).

Abstract: Objective To assess whether a new heat-killed Mycobacterium vaccae preparation (SRL172), which enhances cell-mediated immunity and has been proposed for use as an immunotherapeutic agent against cancer, is safe in patients with advanced hormone-refractory prostate cancer, can stimulate desirable cytokine changes in these patients and modulate the progression of the disease. Patients and methods Ten patients were given SRL172 intradermally at regular intervals. The serum prostate specific antigen (PSA) level was used as a surrogate marker of response. The proportion of peripheral blood mononuclear cells (PBMC) secreting interleukin 2 (IL2), interferon gamma (IFNγ) and interleukin 4 (IL4) was measured by flow cytometry (FACS) before and after vaccination to assess whether the treatment induced a Th2 (predominantly humoral) to Th1 (predominantly cell-mediated) switch. Results There were no significant adverse events. In five patients the serum PSA declined during the trial and in two of these there was no concomitant change of therapy apart from vaccination with SRL172. Before vaccination with SRL172 patients had a low proportion of PBMC producing IFNγ and IL2 (all 10) and a higher proportion secreting IL4 (all three tested), suggesting a predominantly Th2 cytokine profile. After vaccination the proportion of IL4 secreting PBMC fell in all three patients tested. The proportion of IL2 secreting PBMC increased in three patients whose PSA fell. The proportion of IFNγ-secreting cells remained depressed in nine of 10 patients. Conclusion Two patients with advanced hormone-refractory prostate cancer had a PSA response to the vaccination with SRL172. The proportion of PBMC secreting IL2 is a potential marker of response to immunotherapy.

Long‐term treatment with desmopressin in children with primary monosymptomatic nocturnal enuresis: an open multicentre study

Abstract: Objective To study the long-term efficacy and safety of desmopressin treatment in children with primary monosymptomatic nocturnal enuresis. Patients and methods Children (aged 6–12 years) with nocturnal enuresis were recruited into an open multicentre trial. All children underwent an observation period of 4 weeks before starting a 6-week dose-titration period with desmopressin. If the number of wet nights decreased by more than half during medication, they began long-term treatment on 20–40 μg desmopressin. To test for cure and avoid overtreatment, the medication was interrupted for one week every third month. Results Of the 399 children forming the intention-to-treat cohort, 245 halved their number of wet nights and started long-term treatment. During the periods off medication, 77 children were dry and at the end of the study another 73 (still on medication) reduced the number of wet nights to ≤10% of that during the observation period. A further 51 children halved the number of wet nights compared with the observation period. No serious adverse events occurred. Conclusion Long-term treatment with nasal desmopressin at a main dose of 40 μg is an effective and safe treatment for monosymptomatic nocturnal enuresis.

Urinary levels of monocyte chemo-attractant protein-1 correlate with tumour stage and grade in patients with bladder cancer.

Abstract: Objective To determine if the chemokine monocyte chemo-attractant protein-1 (MCP-1) is produced locally in patients with bladder cancer and to analyse a possible correlation between tumour stage, grade and metastatic spread. and the urinary and systemic levels of MCP-1. Patients, subjects and methods Urine and serum samples were obtained from 60 patients with bladder cancer and 20 control subjects. Tumour stage. grade. metastasis and nodal status were assessed. MCP-I levels in serum and urine were determined using a sandwich enzyme-linked immunosorbent assay. Two transitional cell cancer cell lines (grade I and grade III) were analysed for MCP-1 production under normal and nutritive-stress cell culture. Results The correlation of urinary MCP-1 levels with tumour stage, grade and distant metastasis was highly significant. Patients with stage T2-T4 bladder cancer had three to fourfold higher mean MCP-1 concentrations (pg/mL) in their urine than those with T1 stage tumours or than the controls (controls 260; T1 359: T2 967: T3 917: T4 1829: P GI and the existence of distant metastasis (M1) also correlated significantly with higher urinary MCP-1 levels (GI 373; GII 661: GIII 1111:MO 644: M1 1379: P<0.05). No differences in circulating serum MCP-1 level were detected between controls and patients. The low-grade (GI) RT4 bladder cancer cell line produced only traces of MCP-1, which did not change under nutritional stress: in contrast. the highly malignant T24 bladder cancer cell line (GIII) spontaneously secreted large amounts of MCP-1 (7000 pg/mL) which increased under nutritive stress to 13 000 pg/mL. Conclusion MCP-1, as a potent monocyte chemo-attractant to tumour sites, is probably produced by bladder cancer cells: MCP-1 levels in the vicinity of the tumour (i.e. urine) correlate significantly with TNM stage and grade. As has already been shown in other neoplasms, the resulting monocyte/macrophage infiltrate possibly facilitates tumour neovascularization and tissue invasion. Therefore, MCP-1 levels in the urine of patients with bladder cancer may be a prognostic marker for the natural course of the disease. and modulation of this chemokine might be a future therapeutic approach for adjuvant treatment of bladder cancer.

Congenital reflux nephropathy : a follow-up of 108 cases diagnosed perinatally

Abstract: Objectives To determine: (i) the proportion of vesico-ureteric reflux (VUR) associated with congenital renal damage and whether it can be severe enough to cause renal impairment from birth; (ii) to evaluate the distribution of males and females affected; and (iii) to describe the course of congenital damage in the first years of life. Patients and methods A total of 108 children (76 male and 32 female, M:F 2.3:1), whose VUR was diagnosed before any infection, were followed from birth for a mean (range) of 4.3 (1–10) years. Renal damage was defined by serum creatinine concentration, creatinine clearance and renal imaging (ultrasonography and renal scintigraphy) performed within the first month of life and periodically thereafter. Results Of the 108 children, 58 had bilateral and 50 unilateral reflux (total number of refluxing units, 166). High-grade VUR (grade ≥4) was found in 96 (58%) refluxing renal units (RRUs). Males had a prevalence of bilateral severe (≥grade 4) reflux (M:F 5.2:1), while in those with unilateral VUR, the M:F ratio was 1.5:1. At birth, mild to moderate damage was present in 56 (36%) RRUs and only associated with VUR of grade ≥3. Bilateral reflux of grade ≥4 was associated with congenital moderate/severe renal failure in nine neonates (seven males). In infants with grade ≥4 VUR who underwent surgical correction, VUR resolved in 92% of cases. In infants with VUR of grade ≥4 followed medically, the reflux spontaneously resolved in 42% and ameliorated in 16% after 18 months. Serial renal scans during the follow-up showed no progression of renal damage. Conclusions VUR diagnosed at birth on prenatal ultrasonography is associated with congenital damage, with males affected more often than females. The damage involves both kidneys in a consistent proportion and is an important cause of chronic renal impairment from birth. It does not progress in the first years of life if infections are prevented. It is suggested that males with this condition may constitute a major group at risk of developing chronic renal failure in later life.

Histological and ultrastructural alterations in an animal model of Peyronie's disease.

Abstract: Objective To determine the role of transforming growth factor beta (TGF-β), one of the cytokines known to induce tissue fibrosis, in the induction of a Peyronie’s-like condition, and to produce an animal model for the further study of Peyronie’s disease. Materials and methods Twenty-four adult male Sprague-Dawley rats were divided into two groups: in group 1, different concentrations of cytomodulin, a synthetic heptapeptide with TGF-β-like activity, were injected into the tunica of each of 18 rats and six rats group 2 received saline injections as a control. The tunical tissues were taken after 3 days, 2 and 6 weeks and were examined histologically using Hart and trichrome stains. Electron microscopy was used to examine the ultrastructural changes in the same tissue samples. Results There were histological and ultrastructural alterations in 15 of 18 rats in group 1 (cytomodulin-injected), especially in tissue examined after 6 weeks. The most prominent histological changes were chronic inflammatory cellular infiltration, focal and diffuse elastosis, thickening, disorganization and clumping of the collagen bundles. The ultrastructural changes were in the form of densely packed collagen, fragmented and scarce elastic fibres, separation of neuronal fibres by interposing clumps of packed collagen, and perivascular collagen deposition as a part of the reorganization of the interstitial matrix. Conclusion Cytomodulin can induce a Peyronie’s-like condition in the rat penis, which may explain the role of TGF-β in the pathogenesis of Peyronie’s disease. With further refinement, such rats may be used as an experimental model for studies of Peyronie’s disease.

Functional rat bladder regeneration through xenotransplantation of the bladder acellular matrix graft.

Abstract: Objective To determine the decreased antigenicity of the bladder acellular matrix graft (BAMG) through xenotransplantation and to assess the in vivo and in vitro functional properties of the rat urinary bladder thus regenerated. Materials and methods After partial cystectomy (>50%), BAMGs prepared from hamster, rabbit and dog urinary bladders were grafted to male and female Sprague-Dawley rats; 10 control rats underwent partial cystectomy only. Urinary storage and voiding function were monitored in 15 animals using a specially designed ‘micturition cage’ and cystometry. After 4 months, organ-bath studies and histological techniques were used to evaluate bladder regeneration in vitro in the grafted animals. Results Clinically relevant antigenicity was not evident; no animal died from rejection and all bladder wall components regenerated in all BAMG xenografts. However, the degree and quality of regeneration varied. Muscularization, peak pressure, and bladder capacity were higher in the hamster BAMG-grafted animals, whereas in vitro contractility and compliance were best in the dog BAMG-regenerated bladders. All grafted bladders had significantly better capacity and compliance than the autoregenerated bladders after partial cystectomy alone. Conclusions The present in vivo and in vitro studies show that BAMG-augmentation cystoplasty can lead to morphological and functional regeneration of the rat bladder, preserving its low-pressure reservoir function. Because BAMG-regenerated bladders show functional innervation that is similar to normal bladders, they can work in coordination with the host bladder components, thus generating adequate intravesical pressure to produce sustained voiding. The decreased antigenicity makes heterologous BAMG transplants feasible without immunosuppression.