Quantifying the effect of urodynamic catheters on urine flow rate measurement.

INTRODUCTION: The effect of urodynamic catheters on urine flow rate (Q(max) ) is well documented but under-researched. Several studies show reduced Q(max) but methodologies and patient demographics differ. The aims of this study were to further quantify the effect of urodynamic catheters on Q(max) and to explore if this was consistent across different urodynamic diagnoses. METHODS: Four groups of 50 consecutive men attending for urodynamic studies (UDS) were retrospectively analyzed: Group 1 comprised 50 men with normal UDS, Group 2 was 50 men with BOO, and Group 3 contained 50 men with detrusor underactivity. Groups 1-3 had UDS performed using both 10 Fr filling and 4 Fr measuring catheters in situ. Group 4 comprised 50 men who had UDS performed with a smaller catheter assembly (8 Fr dual-lumen). Values of Q(max) with and without catheters present were compared using paired Student's t-tests. Differences between groups were compared using ANOVA. RESULTS: Q(max) measured during UDS in men from Groups 1-3 showed a mean reduction of 38% compared to Q(max) from "free" uroflowmetry. ANOVA indicated this reduction was significantly greater among men with normal UDS. Interestingly the group who underwent UDS with a smaller catheter assembly showed no significant reduction in Q(max) measured with catheters in situ. CONCLUSION: Our findings are in line with previous work suggesting that smaller calibre urethral catheters do not cause a significant obstructive effect during voiding. In addition it would appear that the reduction in Q(max) with larger urethral catheters in situ is greatest in those with normal urodynamics.

Is low bladder compliance predictive of detrusor overactivity?

AIMS: Bladder compliance (BC) expresses the relationship between bladder volume and bladder pressure and is generally regarded as a measure of bladder stiffness or distensibility. Many types of voiding dysfunction have been associated with low BC such as detrusor overactivity (DO). It has previously been reported that the presence of DO is an independent predictor of low BC. The aim of this study was to assess the predictive value of low BC for the diagnosis of idiopathic DO using ambulatory urodynamics as the gold standard investigation for comparison. METHODS: All patients with LUTS attending a single center for both conventional and ambulatory urodynamics over a 5-year period were reviewed. The predictive value of various set levels of BC was compared using a receiver-operator characteristics (ROC) curve in an attempt to find the optimal threshold of BC for the diagnosis of DO. RESULTS: 162 patients were identified and following exclusions 143 (88%) data sets were suitable for analysis. The mean (s.d.) BC in the 99 patients with DO was 92 (80) ml/cm H(2)O compared to 112 (91) ml/cm H(2)O in those who did not show DO on ambulatory urodynamics. This difference was not statistically significant according to a non-parametric Mann-Whitney test (P = 0.22). Furthermore no set threshold of BC was able to provide sufficient accuracy for the diagnosis of DO. The area under the curve was less than 0.5 (0.47) indicating a level of accuracy less than "chance". CONCLUSIONS: Low bladder compliance is not predictive of DO in our series. It is imperative to note that our results are obtained from a cohort comprising predominantly female patients without BOO and is therefore different to previous reports concentrating on male patients with BOO.

FGF8 over-expression in prostate cancer is associated with decreased patient survival and persists in androgen independent disease.

Identification of prostate cancers at high risk of progression is difficult and a better understanding of how peptide growth factors influence cellular function might be useful. Fibroblast growth factors (FGFs) have been implicated in prostate cancer development. FGF8 was identified in the Shionogi mouse mammary carcinoma SC-3 cell line as an androgen-induced mitogen. We tested if FGF8 was over-expressed in human prostate cancer and if its expression correlated with clinical data and outcome. One hundred and six cases of prostate cancer and ten cases of BPH were examined. In situ hybridization was employed to detect FGF8 mRNA expression, which was identified within the malignant prostatic epithelium in 85/106 (80.2%) cases. Increased expression of FGF8 correlated significantly with higher Gleason scores (P=0.0004) and advanced tumour stage (P=0.0016). Using immunohistochemistry, we confirmed over-expression of the FGF8b isoform. Men with tumours which expressed high levels of FGF8 had worse survival (P=0.034), although FGF8 mRNA was not able to provide additional prognostic information in a multivariate analysis. Additionally, FGF8 expression was shown to persist in androgen independent prostate cancer. Using a range of normal adult tissues, FGF8 expression was restricted to neurones and the germinal epithelium in addition to the prostate. In vitro studies demonstrated that in the presence of neutralizing antibody to FGF8b there was significant inhibition of prostate cancer cell growth, confirming the biological significance of FGF8 in prostate carcinogenesis.

Role of transition zone sampling by TURP in patients with raised PSA and multiple negative transrectal ultrasound-guided prostatic biopsies.

The purpose of the study was to determine the role of transurethral resection of the prostate (TURP) to detect prostate cancer in patients with consistently negative transrectal ultrasound-guided biopsies of the prostate. We retrospectively identified and analysed the patients who also had at least two sets of transrectal ultrasound guided sextant prostate biopsies before their TURP during the period between 1998 and 2002. A total of 14 such patients were identified and the outcome of TURP was analysed. Three patients were found to have cancer in the resected specimen (3/14 = 21%). All three cancers were significant (Gleason scores between 6 and 8) and required further treatment. In patients who have rising levels of prostate-specific antigen and who have had multiple negative peripheral zone biopsies, the presence of biologically important transition zone cancers needs to be considered. This can be detected by transurethral resection of the prostate that samples the transition zone of the prostate.

A prospective audit of hypospadias correction in a regional paediatric surgery centre.

AIM: To prospectively review the management and treatment of hypospadias in a single regional centre, and in particular, to assess the spectrum of cases treated, techniques used and to determine the nature of the complications. METHODS: One hundred and fifty-three consecutive boys undergoing hypospadias repair during a 36-month period were included in the study. Information was collected prospectively and included the site of the urethral meatus, presence of chordee, surgical technique employed, use of urinary diversion, and the prescription of postoperative antibiotics and analgesics. Patients were assessed in the clinic following surgery at which time information on outcome and complications was obtained. RESULTS: One hundred and fifty-seven procedures for hypospadias were performed. Single-stage reconstruction was performed in 145 boys. GRAP (glanular reconstruction and preputioplasty) repair was the most common operation employed (n=112). The overall fistula rate was 11.7 % with the majority of patients having a satisfactory functional and cosmetic outcome following surgery. CONCLUSION: A variety of techniques can be employed to provide satisfactory correction of hypospadias with an increasing emphasis on single-stage day case procedures. GRAP repair is the favoured option for distal hypospadias and incorporates preservation of the prepuce.

Basic science aspects of prostate cancer.

Prostate cancer carries significant morbidity and mortality, but its outcome is difficult to predict in the individual. Androgen ablation delays progression in men, but hormone resistance soon develops and much basic science research has focused on how prostate cancer 'escapes' hormonal control. Stem cell models of prostate development and homeostasis have been proposed, but have not yet been fully characterized. Some androgen-regulated signalling pathways and abnormalities that affect them have been defined recently. It is apparent that locally produced growth factors, often regulated by androgens, exert an effect both physiologically and pathologically and these too will be discussed.

The molecular pathology of urological malignancies.

Urological malignancies kill over 16,000 people annually in England and Wales. There have been exciting recent developments in our understanding of the molecular pathogenesis of these diseases, although many questions remain unanswered. Three separate genes (WT1, WT2, and WT3) have been implicated in Wilms' tumour development. Patients with von Hippel-Lindau (VHL) syndrome develop renal cell carcinoma and it has been shown that VHL protein inhibits elongin, a cellular transcription factor which controls RNA elongation. Use of molecular markers to identify superficial bladder tumours likely to progress to muscle invasive disease has met with some success. Increased epidermal growth factor receptor (EGFR) and p53 expression, and decreased E-cadherin expression all correlate with tumour progression. Tumours in patients with carcinoma in situ have distinct molecular features. Androgen ablation delays disease progression in men with prostate cancer, but relapse is inevitable. Research has been directed towards elucidating the mechanisms by which prostate cancer 'escapes' hormonal control. Mutations in the androgen receptor have been identified. It is apparent that locally produced growth factors mediate androgen-dependent processes and these too have been implicated in prostate carcinogenesis.

Laparoscopic radical nephrectomy in first-trimester pregnancy.

We present a case of a 30-year-old pregnant woman with renal cell carcinoma who underwent successful laparoscopic radical nephrectomy at 11 weeks of gestational age. The remainder of the pregnancy was uncomplicated, and the patient gave birth to a healthy baby boy at term. Although previous cases of successful nephrectomy performed in pregnancy for renal cell carcinoma have been reported, we believe this is the first case in which it has been performed laparoscopically. We suggest that when the expertise is available, laparoscopic nephrectomy is a safe alternative to open surgery, with the additional benefits of minimal access surgery.

aFGF immunoreactivity in prostate cancer and its co-localization with bFGF and FGF8.

Fibroblast growth factors (FGFs) have been implicated in the development of numerous malignancies including prostate cancer. In a pilot study it has been shown that FGF8 mRNA is up-regulated in prostate cancer. The aim of the present study was to determine whether aFGF and bFGF were co-expressed with FGF8 in human prostate cancer. Twenty-nine cases of prostate cancer of different histological grades were examined. Immunohistochemical analysis was employed to study aFGF and bFGF expression. In the light of the results, aFGF immunoreactivity was studied in a further 43 cases. aFGF and bFGF immunoreactivity was identified in the cytoplasm of the malignant prostatic epithelium. aFGF was overexpressed in 62/72 (86.1 per cent) cases and bFGF in 19/29 (65.5 per cent). High levels of aFGF immunoreactivity were noted in areas of high-grade prostatic intraepithelial neoplasia (PIN). In this series, aFGF immunoreactivity was most commonly observed and correlated closely with Gleason score and tumour stage ( p=0.007 and 0.007, respectively). Co-localization of aFGF, bFGF, and FGF8 was detected in 9/29 (31.0 per cent) cases. There was a significant correlation between aFGF and FGF8 expression. In conclusion, aFGF, bFGF, and FGF8 are co-localized in human prostate cancer; they may have a synergistic effect in prostate cancer growth and progression.