British Association of Urological Surgeons (BAUS) consensus document: Management of female voiding dysfunction.

OBJECTIVES: To report the British Association of Urological Surgeon's (BAUS) guidance on the assessment and management of female voiding dysfunction. METHODS: A contemporary literature search was conducted to identify the evidence base. The BAUS Section of Female, Neurological and Urodynamic Urology (FNUU) Executive Committee formed a guideline development group to draw up and review the recommendations. Where there was no supporting evidence, expert opinion of the BAUS FNUU executive committee, FNUU Section and BAUS members, including urology consultants working in units throughout the UK, was used. RESULTS: Female patients with voiding dysfunction can present with mixed urinary symptoms or urinary retention in both elective and emergency settings. Voiding dysfunction is caused by a wide range of conditions which can be categorized into bladder outlet obstruction (attributable to functional or anatomical causes) or detrusor underactivity. Guidance on the assessment, investigation and treatment of women with voiding dysfunction and urinary retention, in the absence of a known underlying neurological condition, is provided. CONCLUSION: Wa have produced a BAUS approved consensus on the management pathway for female voiding dysfunction with the aim to optimize assessment and treatment pathways for patients.

The past, present and future of augmentation cystoplasty.

What's known on the subject? And what does the study add? There is a wealth of evidence on the development, indications, outcomes and complications of augmentation cystoplasty (AC). Over the last decade, new evidence has been emerging to influence our clinical practice and application of this technique. AC is indicated as part of the treatment pathway for both neurogenic and idiopathic detrusor overactivity, usually where other interventions have failed or are inappropriate. The most commonly used technique remains augmentation with a detubularised patch of ileum (ileocystoplasty). Controversy persists over the role of routine surveillance following ileocystoplasty for the detection of subsequent bladder carcinoma; however the indication for surveillance after gastrocystoplasty is clearer due to a rising incidence of malignancy in this group. Despite a reduction in the overall numbers of AC operations being performed, it clearly still has a role to play, which we re-examine with contemporary studies from the last decade.

Does laser ablation prostatectomy lead to oncological compromise?

OBJECTIVE: To assess the incidence and outcome of incidental prostate cancer detected at transurethral resection of the prostate (TURP), and to evaluate whether laser ablation prostatectomy would miss significant cancer by failing to provide tissue for histopathological analysis. PATIENTS AND METHODS: Information on TURP-detected prostate cancer was gathered from 1996 to 2006, from The South-west Cancer Intelligence Service, hospital-operating and coding records, histopathology databases and The British Association of Urological Surgeons Cancer Registry. We recorded the total number of prostate cancers diagnosed per year, number of TURPs performed, Gleason scores and patients outcomes. RESULTS: TURP-detected prostate cancer has declined since the relatively high rates (22%) recorded locally in 1996-97. Between 2001 and 2006, a mean (range) of 124 (111-135) prostate cancers were detected per year. Incidental cancers accounted for only 1.5-5.6% of all newly diagnosed prostate cancers per year. Incidental cancers had a mean (sem) Gleason score of 5.7 (0.3) compared to 8.0 (0.3) in known cancers (P < 0.01) undergoing TURP. Of newly diagnosed patients, 82% were allocated to active surveillance, whilst 18% were started on hormone therapy, with no prostate cancer-related deaths over a mean (sem, range) follow-up of 49.7 (2.4, 11-81) months. CONCLUSIONS: TURP mainly samples transitional-zone tissue where tumours are relatively uncommon, and have a good prognosis. Our series of incidental TURP-detected cancers showed an incidence in keeping with published data, and favourable histological and clinical outcomes. We suggest the lack of tissue should not discourage the use of laser prostatectomy surgery.

Case report: differential diagnosis of isolated iliac lymphadenopathy following Bacillus Calmette-Guérin treatment for high-risk superficial bladder cancer.

We report the unusual case of a patient with G3 pT1 transitional cell carcinoma (TCC) of the bladder, which was treated with repeated transurethral resection and maintenance intravesical Bacillus Calmette-Guérin (BCG) therapy. At 30 months follow-up, a symptomatic, solitary iliac lymph node mass was identified and biopsied. Histology demonstrated granulomatous tissue only, in the absence of any intravesical bladder tumour recurrence. Following 6 months of anti-tuberculous medication, the mass had progressed, and repeat biopsy revealed undifferentiated carcinoma (of a bladder primary). This is a rare case of metastatic superficial bladder cancer progression without local recurrence after BCG therapy. As such, it can be viewed as a diagnostic challenge.

The effects of a new selective beta3-adrenoceptor agonist (GW427353) on spontaneous activity and detrusor relaxation in human bladder.

OBJECTIVE: To examine the effects of a new selective beta3-adrenoceptor agonist, GW427353 on human detrusor function, as beta2- and beta3-adrenoceptors have been identified in the bladder, and can mediate detrusor relaxation, but beta3-adrenoceptors are less widely distributed and beta3-adrenoceptor agonists should have the therapeutic advantage of producing fewer treatment side-effects. PATIENTS AND METHODS: 'Normal' human detrusor was retrieved from 12 patients (mean age 56 years) at cystectomy and from organ donors. Detrusor strips (4 x 1 x 1 mm) were mounted in superfused organ baths. Tone was induced with carbachol (5 x 10(-7)m) before applying either a nonselective beta-adrenoceptor agonist (isoprenaline) or GW427353 (with or without the beta3-adrenoceptor antagonist, SR59230A). In addition, the effect of GW427353 was tested on intrinsic nerve-evoked smooth muscle contraction over time. Effects on spontaneous activity were also recorded. RESULTS: GW427353 produced significant relaxation at concentrations of >10(-7)m; isoprenaline produced a significant effect from 10(-6)m, but otherwise both agonists had similar effects. The addition of SR59230A (10(-7)m), produced partial inhibition of the GW427353 response. GW427353 at 10(-6)m significantly reduced spontaneous activity within 10 min of incubation, and at higher concentrations (>5 x 10(-6)m) inhibited detrusor contractions evoked by electrical field stimulation. CONCLUSION: Neuropathic bladder dysfunction is characterized by increased spontaneous activity and involuntary detrusor contractions, which can result in urinary frequency, urgency, nocturia and incontinence. The novel feature of GW427353 is the ability to suppress spontaneous activity and produce significant relaxation in human detrusor tissue at low concentrations, whilst also inhibiting evoked detrusor contractions at higher concentrations.

The functional effects of a c-kit tyrosine inhibitor on guinea-pig and human detrusor.

OBJECTIVE: To describe the effect of a specific c-kit receptor inhibitor (imatinib mesylate) on human detrusor strips in vitro and guinea-pig cystometry in vivo, and to show histological data suggesting differences in the distribution of interstitial cells of Cajal (ICC)-like cells in 'normal' and overactive human detrusor, as these cells have been identified as possible mediators of spontaneous activity and excitability in bladder smooth muscle. MATERIALS AND METHODS: Specimens of human detrusor were stained immunohistochemically with a c-kit antibody. Human detrusor strips were mounted in a superfused organ-bath apparatus, and smooth muscle contraction was evoked with carbachol and electrical field stimulation in the presence and absence of imatinib mesylate. Also, guinea-pig urodynamic studies were conducted before and after i.v. administration of imatinib mesylate, and changes in bladder variables and spontaneous activity were recorded. RESULTS: Imatinib mesylate (10(-6)M) inhibited evoked smooth muscle contraction and spontaneous activity in overactive human detrusor, with less effect on normal human tissue. Imatinib mesylate (10(-5)M) improved bladder capacity, compliance, voided volumes, urinary frequency, and reduced contraction thresholds and spontaneous activity during guinea-pig cystometry. c-kit labelling showed significantly more ICC-like cells in overactive human detrusor than in normal specimens. CONCLUSION: c-kit receptor blockers have inhibitory effects on guinea-pig and overactive human detrusor, possibly via c-kit receptors on bladder ICC-like cells. This and the possibility that there are more ICC-like cells in overactive bladder suggest that the c-kit receptor may provide a novel target for treating detrusor overactivity.

Effects of imatinib mesylate (Glivec) as a c-kit tyrosine kinase inhibitor in the guinea-pig urinary bladder.

AIMS: In the gastrointestinal tract, slow wave activity in smooth muscle is generated by the interstitial cells of Cajal (ICC). Detrusor smooth muscle strips of most species show spontaneous contractions which are triggered by action potential bursts, however, the pacemaker mechanisms for the detrusor are still unknown. Recently, ICC-like cells have been found in guinea-pig bladder, using antibodies to the c-kit receptor. We have investigated the effects of Glivec, a c-kit tyrosine kinase inhibitor, on spontaneous action potentials in guinea-pig detrusor and intravesical pressure of isolated guinea-pig bladders. METHODS: Changes in the membrane potential were measured in guinea-pig detrusor smooth muscle using conventional microelectrode techniques. Pressure changes in the bladder were recorded using whole organ bath techniques. RESULTS: Smooth muscle cells in detrusor muscle bundles exhibited spontaneous action potentials, and spontaneous pressure rises occurred in isolated bladders. Glivec (10 microM) converted action potential bursts into continuous firing with no effects on the shape of individual action potentials. Glivec (>50 microM) reduced the amplitude of spontaneous pressure rises in the whole bladder in a dose dependent manner and abolished spontaneous action potentials in detrusor smooth muscle cells. CONCLUSIONS: The results suggest that ICC-like cells may be responsible for generating bursts of action potentials and contractions in detrusor smooth muscle. Drugs inhibiting the c-kit receptor may prove useful for treating the overactive bladder.

Investigation of the effect of the c-kit inhibitor Glivec on isolated guinea-pig detrusor preparations.

In order to assess the possible role of the c-kit positive cells in the bladder, the effects of c-kit tyrosine kinase inhibitor, Glivec, on spontaneous excitation and ion channel activity in detrusor smooth muscles of the guinea-pig bladder were investigated using intracellular microelectrodes, isometric muscle tension recordings and patch clamp techniques. Glivec (10 microM) converted action potential bursts into continuous firing without affecting their shape but at 50 microM abolished spontaneous action potentials. It had little effect on inward and outward currents at <10 microM, but inhibited them at >50 microM. Glivec decreased the amplitude of spontaneous contractions dose dependently. These results suggest that c-kit positive cells may play a role in modulating spontaneous electrical and mechanical activities. Drugs inhibiting the c-kit receptor may provide a new approach for treating the overactive bladder.

Thrombotic microangiopathy in advanced prostatic carcinoma.

We report a case of acute renal failure in a man with medically treated advanced prostate carcinoma. Imaging suggested renal tract obstruction as the cause; however, the patient failed to respond to treatment with dialysis and bilateral nephrostomy insertion. Postmortem examination revealed the renal failure to have been due to severe thrombotic microangiopathy.

Nerve regeneration: might this be the only solution for functional problems of the urinary tract?

PURPOSE OF REVIEW: To assess the potential role of nerve regeneration in restoring urinary tract function, the rapidly developing and exciting area of central and peripheral nerve repair and regeneration is reviewed, with particular reference to papers in which animal models of nerve damage resulting in urogenital dysfunction have been used. The difficulties and potential of these techniques for therapeutic application to human subjects with functional problems of the urinary tract are discussed. RECENT FINDINGS: Methods for encouraging regeneration of cut axons and directed growth in the inhibitory environment of the central nervous system are being extensively explored. The recent discovery of the potential of olfactory ensheathing cells has proved a significant advance. Olfactory ensheathing cells are a type of glial cell which can be harvested from the olfactory mucosa. Transplantation of these cells, in conjunction with a biodegradable synthetic nerve guide or conduit, has been shown to restore urinary tract function after spinal cord injury. Artificial, biodegradable conduits have also restored bladder and spermatic duct function after sympathetic nerve damage. Other adjuvants facilitating the process of axonal recovery include the use of neurotrophins to accelerate and guide the formation of new nerve-fibre growth. SUMMARY: These revolutionary technologies may, in the future, provide a means of treating urinary tract dysfunction with some types of aetiology, including acute spinal cord injury, and injury to nerves following pelvic surgery. It is, however, less likely that these treatments will be used successfully in the near future in patients in which the neural damage is long term, or associated with death of post-ganglionic neurons.