Management of recurrent stress urinary incontinence and urinary retention following midurethral sling insertion in women.

INTRODUCTION: Synthetic midurethral slings are the most common operations performed for women with stress urinary incontinence (SUI). However, there is only very scarce evidence regarding the management of complications from these operations. The aim of this survey was to canvass expert opinion regarding the management of recurrent SUI and urinary retention following insertion of these slings. METHODS: Expert urologists and urogynaecologists in the UK with an interest in SUI were identified. Three clinical scenarios on recurrent SUI and one on urinary retention following midurethral sling placements were emailed twice to the experts. RESULTS: The majority of the experts chose a repeat synthetic midurethral retropubic transvaginal tape (TVT) as the procedure of choice for recurrent SUI in patients who had had a previous TVT or midurethral transobturator tape inserted. In patients who continued to suffer SUI after a failed second TVT, there were mixed results with experts choosing fascial slings, colposuspension and bulking agents as their preferred method of treatment. In women who develop urinary retention following a TVT, tape pull-down within two weeks was the preferred method among the experts. However, division of the tape within two to six weeks following the procedure was also popular. CONCLUSIONS: Based on expert opinion, it is difficult to make a recommendation as to the best method of treating recurrent SUI or urinary retention following tape insertion. There is an urgent requirement for well conducted, multicentre, randomised clinical trials to look at the management of these complications and also the tools used to assess the patient before salvage surgical management.

The development of a supraregional network for the management of penile cancer.

INTRODUCTION: Although its incidence is increasing, penile cancer remains a rare disease in the UK. In view of this low volume, the National Institute for Clinical Excellence recommended that treatment is centralised in a limited number of centres arranged as supraregional networks. The aim of this centralisation is to allow the best standardised treatment for the primary tumours and nodal disease, thereby avoiding under or overtreatment. In this paper we review the formation and functioning of our network in the East Midlands. METHODS: Data were collected up to August 2010 from our prospective penile network database since its inception in 2005. These data were analysed to see our workload, patterns of referral and surgeries performed over this time period. RESULTS: The structure and function of the East Midlands network are described. There has been an increase in the number of cases discussed since its formation. There has also been a trend towards more conservative surgery, both of the primary tumour and of nodal management. Between September 2009 and August 2010, 16 glansectomies were performed versus 5 total and 9 partial penectomies. The same period saw 18 dynamic sentinel lymph node biopsies against 7 bilateral and 3 unilateral superficial groin dissections. There was a very high patient satisfaction rate, with patients feeling they had good support and information. CONCLUSIONS: On reviewing the literature it can be clearly seen that supraregional networks have led to a decrease in overtreatment and better recognition of the need to manage lymph node status optimally. Our network has demonstrated the trend toward conservative surgery and sentinel node biopsy. The formation of supraregional networks with a multidisciplinary approach will facilitate high volume centres that will offer optimal surgical therapy and also allow recruitment into studies and new chemotherapeutic regimens. It will also allow better data collection to aid clinical studies that hopefully will also demonstrate better outcomes.

Urethral venous malformation: an unusual cause of recurrent post-coital gross haematuria in association with haematospermia.

Three cases of recurrent post-coital haematuria are described. Extensive protracted investigations pinpointed urethral varicosities as the likely cause. All patients were successfully treated with diathermy fulguration.

A variant epidermal growth factor receptor protein is similarly expressed in benign hyperplastic and carcinomatous prostatic tissues in black and white men.

BACKGROUND AND OBJECTIVE: Anti-epidermal growth factor receptor strategies are now established in cancer treatment We have recently described the presence of EGFRvIII (a variant EGFR) in prostatic tumours from UK white men and this is now a target for anti-prostate cancer treatments. However, there has been no report on the expression of this abnormal protein in black men. MATERIALS AND METHODS: We determined EGFRvIII expression in sections of normal, benign hyperplastic (BPH) and carcinomatous (CaP) prostatic archival tissues from Nigerian men and UK white men using streptavidin immunohistochemical techniques. The EGFRvIII immunoreactivity was scored visually using a semi-quantitative method and the results compared statistically. RESULTS: EGFRvIII expression increased with increasing malignancy in both study populations (CaP > BPH > Normal p, <0.0001). Furthermore, EGFRvIII expression was similar in both BPH and CaP tissues in black and white men (p, 0.86 and 0.31 respectively). CONCLUSION: These results demonstrate that EGFRvIII immunoreactivity in prostatic tumours in black men is similar to that in white men. Anti-cancer treatments directed at the EGFRvIII should be equally effective in men from both subpopulations.

Testicular prostheses: development and modern usage.

INTRODUCTION: Testicular prostheses produced from various materials have been in use since 1941. The absence of a testicle has been shown to be a psychologically traumatic experience for males of all ages. The indications for insertion of a prosthesis include absence or following orchidectomy from a number of causes such as malignancy, torsion and orchitis. The most common substance used around the world in the manufacture of these implants is silicone; however, in the US, this material is currently banned because of theoretical health risks. This has led to the development of saline-filled prostheses as an alternative. PATIENTS AND METHODS: A Medline search was carried out on all articles on testicular prosthesis between 1966 and 2006. CONCLUSIONS: This review highlights the controversies regarding prosthetic materials, the complications of insertion and the potential benefits of this commonly performed procedure.

Penile prosthetic surgery and its role in the treatment of end-stage erectile dysfunction - an update.

The treatment of erectile dysfunction has been revolutionised with the introduction of orally active phosphodiesterase inhibitors which are successful in 70-80% of men. However, there remain a group of men in whom conservative treatment fails and surgical insertion of a penile prosthesis is required. This type of surgery has in the past been associated with technical difficulties and a high complication rate. This has spurred numerous developments in prosthesis design and surgical technique with the field changing at a rapid pace. Perhaps the most significant is the use of antimicrobial coatings on prostheses that have been shown to reduce the infection rate significantly. This review highlights those developments reported in the last 5 years.

Well leg compartment syndrome after pelvic and perineal surgery in the lithotomy position.

OBJECTIVE: Lower limb compartment syndrome after prolonged surgical procedures performed in the lithotomy position is a rare but potentially devastating complication. It is recognised after urological, colorectal, and gynaecological procedures. Sixteen cases of compartment syndrome after urological surgery have been reported. The objective of this study was to estimate the incidence of this complication in urological practice and identify risk factors for its development. DESIGN: A postal survey of UK consultant urologists was conducted. RESULTS: Replies were received from 261 consultants. In total there were 65 cases of compartment syndrome. Compartment syndrome occurred after radical cystectomy and urinary diversion in 51 cases and was rare in procedures lasting less than four hours. The incidence of compartment syndrome after cystectomy was estimated at around 1 in 500 cases. Risk factors for its development included perioperative blood loss, peripheral vascular disease, and obesity. CONCLUSIONS: Compartment syndrome after use of the lithotomy position may be more common than is generally appreciated and has been underreported in the past. All staff should be aware of this serious complication and adopt strategies for its avoidance.

Alterations in the expression of androgen receptor, wild type-epidermal growth factor receptor and a mutant epidermal growth factor receptor in human prostate cancer.

Prostatic carcinogenesis has been associated with alterations in the expression of the androgen receptor (AR) and the epidermal growth factor receptor (WT-EGFR), and over-expression of the constitutively active variant epidermal growth factor receptor (EGFRvIII). Changes in the expression of AR, WT-EGFR and EGFRvIII were evaluated in serial sections from 26 normal and 26 benign hyperplastic and 50 prostate cancer tissues using specific immunostaining techniques. The loss of AR expression in peri-epithelial stroma as prostatic tissues de-differentiated correlated strongly with the depletion of WT-EGFR and with increasing expression of the EGFRvIII in the adjacent epithelium. In contrast, changes in epithelial AR immunopositivity in these tissues correlated weakly with the changes in normal and variant EGFR levels. This is the first report correlating the changes in the expression of these three proteins in archival material from the different human prostatic tissue histotypes. The loss of expression of proteins that contribute to the regulation of prostatic homeostasis (AR and WT-EGFR) correlates strongly with the expression of a constitutively active variant EGF receptor (EGFRvIII) in human prostate cancer. These changes occur at an early stage of neoplastic transformation and may contribute to the progression of the disease to hormone independence.

Inhibition of the contractile responses of isolated human and rat bladders by clenbuterol.

PURPOSE: We investigated the inhibition of the contractile responses of human continent and unstable detrusor muscle by the beta2 agonist clenbuterol as well as the inhibition of electrical field stimulation evoked contractile responses of isolated rat bladder muscle strips by orally administered clenbuterol. MATERIALS AND METHODS: The contractile responses of human continent and unstable detrusor muscle strips to electrical field stimulation (0.05 milliseconds, 0.5 to 80 Hz.) were measured before and after adding 10(-9) to 10(-4) M. clenbuterol in vitro. In addition, 6 rats per group were dosed orally with 2 microg x kg(-1) clenbuterol daily acutely (1 dose) or chronically (1 dose daily for 8 days), or with distilled water to serve as controls. The contractile response to electrical field stimulation of strips of isolated detrusor muscle was then measured. Serum clenbuterol levels were analyzed in duplicate by enzyme-linked immunosorbent assay and high performance liquid chromatography. RESULTS: In vitro clenbuterol significantly inhibited the electrical field stimulation evoked contractile responses of detrusor muscle strips from unstable but not continent human bladders. A significant inhibitory effect of clenbuterol on the electrical field stimulation evoked contractile response of rat detrusor muscle was observed after chronic but not acute oral dosing (p <0.01). Serum clenbuterol levels measured by enzyme-linked immunosorbent assay and high performance liquid chromatography were not significantly different. CONCLUSIONS: Clenbuterol or related beta2-adrenoceptor agonists may represent a useful therapeutic strategy for detrusor muscle overactivity.

Further characterization of storage-related alterations in immunoreactivity of archival tissue sections and its implications for collaborative multicenter immunohistochemical studies.

Storage of unstained paraffin slides may lead to the deterioration of specimens and failure to detect cellular proteins immunohistochemically. Although the implication of age-induced alterations on multicenter immunohistochemical studies would be considerable, they have not been investigated previously. The current study was undertaken to examine the effect of this factor further and to explore new ways of overcoming the resultant shortcomings. The authors now report on the immunodetection of a host of antigens in similarly preserved unstained serial paraffin slides obtained from three centers using a panel of eight antibodies. Staining of recently prepared sections from the authors' centers resulted in similar strong patterns in seven of eight antibodies, with one antibody demonstrating variable immunoreactivity. However, storage of unstained paraffin sections at room temperature resulted in a variable but progressive decrease in expression of several tissue antigens. Although the loss in antigenicity was proportional to the length of storage, the effect was reversible if super antibody concentrations were used. The authors conclude that recently prepared paraffin sections from centers with similar fixation protocols have similar immunoreactivity and are suitable for use in comparative multicenter studies. However, in view of the delays that may attend tissue transportation during these projects, the authors suggest that test systems should be checked for age-induced antigen degradation by incubating sections with higher antibody concentrations.

Evidence for the differential expression of a variant EGF receptor protein in human prostate cancer.

Earlier studies have demonstrated an unexplained depletion of the epidermal growth factor receptor (EGFR) protein expression in prostatic cancer. We now attribute this phenomenon to the presence of a variant EGFR (EGFRvIII) that is highly expressed in malignant prostatic neoplasms. In a retrospective study, normal, benign hyperplastic and malignant prostatic tissues were examined at the mRNA and protein levels for the presence of this mutant receptor. The results demonstrated that whilst EGFRvIII was not present in normal prostatic glands, the level of expression of this variant protein increased progressively with the gradual transformation of the tissues to the malignant phenotype. The selective association of high EGFRvIII levels with the cancer phenotype underlines the role that this mutant receptor may maintain in the initiation and progression of malignant prostatic growth, and opens the way for new approaches in the management of this disease including gene therapy.

The role of penile prosthetic surgery in the modern management of erectile dysfunction.

The management of erectile dysfunction looks set to be revolutionised with the introduction of effective oral therapies. There will remain, however, some men who do not respond to conservative measures. This article reviews the important role of penile prosthetic surgery as a treatment option in these patients.

Malignant transformation of human prostatic epithelium is associated with the loss of androgen receptor immunoreactivity in the surrounding stroma.

The cellular pathways involved in the pathogenesis of hormone resistance remain unclear. Studies evaluating the role of changes in human androgen receptor (hAR) expression in the progression of prostatic tumors have been inconclusive. Androgenic influence over prostatic growth is mediated via the regulation of interactions between stromal and epithelial cells. We hypothesized that neoplastic transformation of the prostate would be associated with alterations in hAR expression in the adjacent stroma. Using immunohistochemical techniques, we determined hAR positivity in the epithelium and adjacent stroma of sections from 17 benign and 39 malignant prostatic glands. We found that whereas the expression of the receptor decreased in both cellular compartments as the tissues dedifferentiated, the depletion was more pronounced in the stromal nuclei (P<0.0001). However, in sections from both untreated and hormone-resistant prostate cancer tissues, although heterogeneity of hAR expression in malignant epithelia was increased, there appeared to be a unique field effect around the cancerous prostate glands that resulted in a decreased expression of the receptor in the adjacent benign glands and its total loss in the surrounding stroma. The loss of hAR in the stroma adjacent to malignant prostatic epithelium may play an important role in prostate cancer progression. Furthermore, the similarity of the lack of stromal hAR expression in newly diagnosed and hormone-resistant prostate cancer (P = 0.85) may be an indication that the mechanisms responsible for the acquisition of hormone independence are established early in the malignant transformation process.

Transversely tubularized ileal segments for the Mitrofanoff or Malone antegrade colonic enema procedures: the Monti principle.

OBJECTIVE: To assess the use of a transverse tubularized segment(s) of ileum in the Mitrofanoff or Malone antegrade colonic enema (MACE) procedures. PATIENTS AND METHODS: Eleven patients in three centres underwent the formation of a continent conduit to bowel (MACE, eight patients) and/or bladder (Mitrofanoff, four) using either a single segment of transverse tubularized ileum (10 patients) or two segments of ileum anastomosed and tubularized into a single conduit (two). RESULTS: Within a follow-up of 8 weeks to 6 months, all conduits were continent and catheterized easily. One stomal stenosis required a revision procedure. CONCLUSION: This method for forming a continent catheterizing conduit, based on the Mitrofanoff principle, appears to be effective and is recommended in cases where the appendix cannot be used or where a second conduit is required.

UK studies on suramin therapy in hormone resistant prostate cancer.

New insights regarding the biology of hormone resistant CaP have shown that major growth factors other than testosterone are responsible for cellular proliferation of androgen resistant prostate cancer cells. In vitro studies have confirmed the efficacy of growth factor inhibitors such as suramin in reducing cellular proliferation of androgen dependent LNCaP and independent PC-3 CaP cell lines as well as CaP cells obtained by primary culture. Initial clinical trials using high dose suramin (peak serum concentration 250-300 micrograms/ml) as monotherapy in patients with hormone resistant CaP have shown some promise, but the duration of response to therapy has been short lived and suramin toxicity is a problem. To minimize toxicity without reducing anti-tumour activity, studies evaluating its use in combination with other cytotoxic drugs are attractive in CaP. Suramin and doxorubicin, tumour necrosis factor and EMP have shown synergy in vitro. However, in a phase II clinical trial using combination therapy with low dose suramin (140 micrograms/ml) and mitomycin C in 32 patients, there was one complete response and six partial responses, and in 15 patients, the disease had stabilized. The median time to treatment failure was 103 days, and the median survival was 209 days. This regimen caused significant toxicities. The present study has shown that the combination of EMP 280 mg twice a day and suramin 1 g weekly infusions for 6 weeks, compared to EMP 280 mg alone, showed a statistically significant difference in the rate of depression of PSA levels after 3 and 6 months of treatment (p < 0.01) and a statistically significant reduction in bone pain and requirement for analgesics in patients on combination therapy-100% compared to 0% for patients on EMP alone.

Percutaneous nephrostomies.

A review was made of 127 percutaneous nephrostomies (PCN) in 106 patients with benign (74 patients) and malignant (32 patients) urinary tract obstruction. Data on underlying aetiology, complications, subsequent management and long-term management are presented. The study confirms that PCN is an effective and safe method of providing temporary or prolonged urinary diversion in obstruction. Its use in pelvic malignancy should be determined by the likelihood of obtaining worthwhile prolonged palliation in individual patients.