Identification of degradome components associated with prostate cancer progression by expression analysis of human prostatic tissues.

Extracellular proteases of the matrix metalloproteinase (MMP) and serine protease families participate in many aspects of tumour growth and metastasis. Using quantitative real-time RT-PCR analysis, we have undertaken a comprehensive survey of the expression of these enzymes and of their natural inhibitors in 44 cases of human prostate cancer and 23 benign prostate specimens. We found increased expression of MMP10, 15, 24, 25 and 26, urokinase plasminogen activator-receptor (uPAR) and plasminogen activator inhibitor-1 (PAI1), and the newly characterised serine proteases hepsin and matriptase-1 (MTSP1) in malignant tissue compared to benign prostate tissue. In contrast, there was significantly decreased expression of MMP2 and MMP23, maspin, and the protease inhibitors tissue inhibitor of metalloproteinase 3 (TIMP3), TIMP4 and RECK (reversion-inducing cysteine-rich protein with Kazal motifs) in the cancer specimens. The expression of MMP15 and MMP26 correlated positively with Gleason score, whereas TIMP3, TIMP4 and RECK expression correlated negatively with Gleason score. The cellular localisation of the expression of the deregulated genes was evaluated using primary malignant epithelial and stromal cell cultures derived from radical prostatectomy specimens. MMP10 and 25, hepsin, MTSP1 and maspin showed predominantly epithelial expression, whereas TIMP 3 and 4, RECK, MMP2 and 23, uPAR and PAI1 were produced primarily by stromal cells. These data provide the first comprehensive and quantitative analysis of the expression and localisation of MMPs and their inhibitors in human prostate cancer, leading to the identification of several genes involved in proteolysis as potential prognostic indicators, in particular hepsin, MTSP1, MMP26, PAI1, uPAR, MMP15, TIMP3, TIMP4, maspin and RECK.

Banking of fresh-frozen prostate tissue: methods, validation and use.

OBJECTIVE: To describe the establishment, methods, validation and use of a bank of fresh-frozen human prostate tissue. MATERIALS AND METHODS: On obtaining informed patient consent, protocols were followed for banking prostate tissue from any type of prostatectomy or cystoprostatectomy. A pseudobanking procedure was devised to determine the accuracy of assessing the histopathological status of the banked tissue. RNA was extracted, its quality assessed and used for quantitative real-time reverse transcription-polymerase chain reaction for the serine protease hepsin. RESULTS: To date prostate tissue from 112 patients has been banked, with pseudobanking in 58. The histopathological assessment showed pseudobanked tissue matched adjacent unbanked tissue in 98% of cases for benign vs malignant diagnoses, and in 92% of carcinomas for the Gleason score. Hepsin expression was significantly higher in malignant than in benign tissues (P < 0.0001). CONCLUSION: We established a validated method for banking human fresh-frozen prostate tissue and applied it successfully. Hepsin expression can be used to differentiate malignant and benign prostate tissue, and as an indicator of tissue heterogeneity.

Surgical technique for the conservative management of distal urethral melanoma.

Urethral melanoma is very rare and pathological diagnosis is important. The prognosis remains poor irrespective of the treatment modality. Rare cases of long-term survival have been reported, one of them following conservative management. An initial attempt at conservative resection is worth considering to offer a better quality of life to the patient for as long as possible. We describe a technique of organ-sparing resection in the management of urethral melanoma along with the follow-up protocol that we adapted.

Imaging assessment of uncomplicated bladder outflow obstruction.

To assess the impact of the use of plain X-ray films and ultrasound examinations on clinical decision-making in patients referred with symptoms of bladder outflow obstruction. Patients with symptoms of bladder outflow obstruction were recruited prospectively. After clinical assessment they underwent standard investigations of plain X-ray of the kidneys, ureters and bladder, and upper and lower urinary tract ultrasound. A management decision was made on the basis of all results. These decisions were then reviewed with specific reference to radiological findings to assess the role of imaging in the decision-making process. A total of 320 men were recruited for the study. X-ray of the kidneys, ureters and bladder detected 10 upper tract calculi, none of which has required active intervention to date. Four bladder calculi were detected. Two of these were also seen on ultrasound scan: one was small and insignificant, the other had caused microscopic haematuria, necessitating cystoscopy regardless of the X-ray findings. Upper tract ultrasound revealed abnormalities and anatomical variants which did not affect management. Four patients had upper tract dilatation but these had already had surgery planned on the basis of other investigations, including residual urine volume determination by lower tract ultrasound. Lower urinary tract ultrasound should be the only routine imaging used in the initial assessment of patients with bladder outflow obstruction, with consequent implications of reduced patient stress and reduced investigation cost.

Maximisation of the erectile response in the investigation of impotence.

UNLABELLED: The aim of this study was to assess whether redosing with a combination of intracavernosal (IC) vasoactive agents could produce a complete erectile response, thereby providing a reliable and reproducible method of dynamic investigation of erectile dysfunction. Forty-one impotent men were redosed with a combination intracavernosal agents until a constant penile rigidity was achieved. They were then shown audiovisual sexual stimulation (VES) by means of a videotape. The erectile responses were monitored continuously by RigiScan (Dacomed). RESULTS: Despite a constant rigidity with intracavernous injection (ICI), 16 men (39%) still had an improved response with VES that was clinically detectable. CONCLUSION: Dynamic investigation of erectile dysfunction with a combination and redosing of IC agents may still lead to an incomplete erectile response. This may potentially lead to patients being incorrectly labelled and confirms the limitations of follow-up studies using dynamic tests of erectile function.

Reproducibility of penile arterial colour duplex ultrasonography.

OBJECTIVE: To assess the reproducibility of penile arterial colour duplex ultrasonography (CDU) in patients with impotence. PATIENTS AND METHODS: Fifty-eight patients underwent CDU of their penile arteries on two occasions 2 weeks apart. Group A (n = 34) received 60 mg of papaverine intracavernosally before CDU and group B (n = 24) received a combination of papaverine, prostaglandin E1 and phentolamine. The variables measured during CDU were peak systolic velocity (PSV) and the end diastolic velocity (EDV), with the systolic rise-time (SRT) also recorded in group B. RESULTS: In both groups of patients the reproducibility between the first and second recordings was poor for all variables. The mean variation in PSV was 31.5% and 40.2%, and in EDV was 44.9% and 50.1%, for groups A and B, respectively. For the SRT, measured only in group B, the mean variation was 25.7%. CONCLUSIONS: These results show that CDU is a poorly reproducible technique for assessing vascular status in patients with impotence. Therefore, it is not reliable in the long-term follow-up of patients and single measurements should be interpreted with caution.

Erectile function following transurethral prostatectomy.

OBJECTIVE: To determine the true incidence and possible aetiology of impotence following transurethral prostatectomy. PATIENTS AND METHODS: Over a 9-month-period 268 patients who were about to undergo transurethral prostatectomy were interviewed about their sexual function. Full details of each operation were recorded including size of prostate, operative time, grade of surgeon and the occurrence of capsular perforation. The interviews were repeated by letter or telephone 3 months after operation. RESULTS: Of the 268 men interviewed, 246 (91.8%) were suitable for inclusion in the study. Pre-operatively, 137 (55.7%) were fully potent, 43 (17.5%) could achieve a partial erection and 66 (26.8%) were impotent. Of the fully potent patients, 20 (14.6%) became partially potent and four (2.9%) became impotent post-operatively. Of those who were partially potent before operation, 16 (37.2%) became impotent post-operatively. Overall, the risk of impotence was 28.1% if the prostate capsule was breached at operation but only 10.0% if it was not (P < 0.01). CONCLUSION: In fully potent men the risk of impotence after transurethral prostatectomy is fairly low, but it is higher in men who already have a degree of erectile failure. The risk of impotence is related to the incidence of capsular perforation at the time of surgery.

Gangrenous cystitis: case report and review of the literature.

A case of gangrenous cystitis in a 67-year-old woman is reported. Associated etiological factors include invasive recurrent carcinoma of the cervix, radiotherapy and atherosclerosis. Primary infection was not a feature. The patient was treated with antibiotics, bladder drainage and total cystectomy with complete recovery. The etiology and management of this unusual condition are discussed.

The role of colour duplex ultrasonography in the diagnosis of vasculogenic impotence.

Colour duplex ultrasonography was used to obtain peak systolic velocity (PSV) readings from cavernosal arteries at rest and during papaverine-induced tumescence. Results from 31 men with vasculogenic impotence were compared with those from 17 men with non-vasculogenic impotence and a control group of 6 potent men. In the flaccid state no significant differences in PSV readings were found between the vasculogenic and control groups. Following the injection of papaverine, men from the vasculogenic group without venous leakage were alone in having significantly lower PSV readings compared with the potent controls. All 23 men with normal penile haemodynamics had a mean PSV greater than or equal to 20 cm/s during tumescence. This was also the case for 19 (61%) of the vasculogenic group, including 9 (69%) of the 13 patients with venous leakage. The remaining 12 men in the vasculogenic group (39%) had a mean PSV less than 20 cm/s, this being diagnostic of an inadequate arterial inflow. Colour duplex ultrasonography can identify patients who have marked arterial insufficiency as the major cause of their impotence and hence allows more rational selection for angiography and revascularisation. Lesser degrees of arterial deficit are difficult to characterise using mean PSV readings alone.

Urodynamic study of ileocystoplasty in the treatment of idiopathic detrusor instability.

Enterocystoplasty is being used with increasing frequency in the treatment of patients with idiopathic detrusor instability. We have performed a prospective clinical and urodynamic study of this procedure in 11 patients using both conventional (CMG) and ambulatory monitoring techniques (AM). Nine of 11 patients were satisfied with the symptomatic outcome, but 7 relied on clean intermittent self-catheterisation (CISC) to achieve a good result. Urodynamic studies demonstrated a significant increase in residual urine volume from 48 +/- 72 ml before to 347 +/- 298 ml after operation, but there was only a small and statistically insignificant increase in cystometric capacity. Detrusor instability, present before operation in all patients, could still be demonstrated in over half of them after operation. However, a significant decrease in the severity of instability was found after operation as assessed by an increased volume at first unstable contraction. The bladder volume before operation at which the first unstable contraction occurred was smaller in those who still had persistent instability after enterocystoplasty compared with those in whom instability could not be identified after operation. These results suggest that all patients about to undergo ileocystoplasty should be trained in the use of CISC. In selected patients with idiopathic detrusor instability refractory to other treatment, this procedure can yield satisfactory results.

An animal model of non-obstructive bladder instability.

Eight minipigs with proven normal bladder function have undergone a circumferential supratrigonal bladder transection. Urodynamic studies were performed before, and at various times up to eight months after operation. Over the same period biopsies were taken for physiological and histological studies. By three weeks after transection all animals had developed bladder instability, the abnormal contractions being maintained for the duration of the study. Concomitant with this change was the development, in vitro, of a non-specific detrusor smooth muscle supersensitivity similar to that which occurs in obstructed animals. By contrast with the latter group there was, however, no loss of cholinergic nerve from the transected bladder muscle. The transected (decentralised) minipig may be a useful model for the study of bladder instability not associated with outflow obstruction. The findings suggest that anatomical denervation is not a prerequisite for unstable contractions although a functional loss of nerve may be of importance. Supersensitivity, however, appears to occur in both obstructed and nonobstructed instability.

Changing pattern of scrotal exploration for testicular torsion.

A total of 201 urgent scrotal explorations for unilateral painful testis was performed over a six-year period. Seventy-two (36%) testicular torsions were identified. Fifty-seven (79%) testes were salvaged and fifteen (21%) orchiectomies were done. Although the annual number of scrotal explorations increased over the years of study, no benefit in terms of increased testicular salvage could be identified.

The effect of pH and lignocaine on detrusor instability.

The effects of intravesical alkaline solution and lignocaine have been studied in 42 patients with detrusor instability, eight patients with low bladder compliance and eight with stable bladders. Filling the bladder with alkaline solution instead of saline resulted in a significant increase in bladder capacity in the unstable and low compliance bladders (35.9 and 27.5% respectively). The addition of lignocaine to the alkaline solution further increased bladder capacity in patients without bladder outflow obstruction. In all patients with flow rates of less than 10 ml/s, lignocaine reduced bladder capacity. There was a qualitative improvement in instability on using an alkaline filling medium. However, in three patients with outflow obstruction lignocaine caused the instability to worsen. Possible mechanisms for these findings are discussed.

Prospective randomized controlled trial of urethral versus suprapubic catheterization.

Sixty-six patients requiring catheterization in the course of general surgical operations were randomly allocated into two groups. Of the 34 patients catheterized urethrally 16 developed urinary tract infections whereas of the 32 suprapubically catheterized patients only 2 developed an infection (P less than 0.001). Five patients required recatheterization after removal of their urethral catheters. There were no major complications associated with the use of suprapubic catheters. We propose that, when catheterization is required during a general surgical procedure, the suprapubic route is to be preferred.

A study of the pathogenesis, urodynamic assessment and outcome of detrusor instability associated with bladder outflow obstruction.

One hundred patients awaiting surgery for bladder outflow obstruction were studied prospectively. All patients completed a symptom score and had urodynamic studies pre-operatively. These results were not known to the urologist and did not therefore influence the course of surgery. There was a good positive correlation between both the severity and the duration of irritative symptoms and the presence of detrusor instability. Eighty per cent of patients were significantly improved 3 months post-operatively. Patients with detrusor instability or low compliance were four times more likely to have an unsatisfactory outcome than those with stable bladders. The outcome could have been predicted in half of the unsuccessful patients on the basis of their pre-operative symptom score and urodynamic studies. Whilst a full urodynamic evaluation is usually unnecessary, all patients should have a flow rate estimation and those with a high urgency symptom score and an unexpectedly high flow rate require full urodynamic assessment. These patients should be considered for alternative treatment or warned pre-operatively of the likely outcome.