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To understand functional consequences of genetic and transcriptional aberrations in prostate cancer, the proteomic changes during disease formation and progression need to be revealed. Here we report high-throughput mass spectrometry on clinical tissue samples of benign prostatic hyperplasia (BPH), untreated primary prostate cancer (PC) and castration resistant prostate cancer (CRPC). Each sample group shows a distinct protein profile. By integrative analysis we show that, especially in CRPC, gene copy number, DNA methylation, and RNA expression levels do not reliably predict proteomic changes. Instead, we uncover previously unrecognized molecular and pathway events, for example, several miRNA target correlations present at protein but not at mRNA level. Notably, we identify two metabolic shifts in the citric acid cycle (TCA cycle) during prostate cancer development and progression. Our proteogenomic analysis uncovers robustness against genomic and transcriptomic aberrations during prostate cancer progression, and significantly extends understanding of prostate cancer disease mechanisms., Understanding of molecular events in cancer requires proteome-level characterisation. Here, proteome profiling of patient samples representing primary and progressed prostate cancer enables the authors to identify pathway alterations that are not reflected at the genomic and transcriptomic levels.

International audience; BACKGROUND: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial.METHODS: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov, number NCT01310894.FINDINGS: Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24-0·46; p

The palliative efficacy and toxicity of single-ifosfamide chemotherapy were investigated in patients with progressive metastatic hormone-refractory prostate cancer (HRPC). Thirty patients were randomised to receive ifosfamide by a 24-hour infusion on day 1 or a 3-hour infusion on days 1-4 at three week intervals until renewed disease progression or a total of six chemotherapy cycles. Response was analyzed according to the guidelines of the Prostate-Specific Antigen Working Group (1999). All 30 patients were included in the final analysis. 1 (3%) PSA normalization, 8 (27%) partial responses, 3 (10%) stabile diseases and 18 (60%) progressive diseases. The mean time to progression was 2.4 months, (range 0 -17) months and the median survival time was 13.6+ months, (range 2 -52). The treatment was well tolerated. No severe gr III-IV hematotoxicities were observed. In conclusion ifosfamide is effective and well tolerated as a single-agent in the treatment of HRPC. Further studies including ifosfamide in combination chemotherapy of HRPC are in progress.

To assess the effects of different approaches to decision-making on the treatment chosen for prostate cancer and on the patients' quality of life in prostate cancer.A multicentre randomized trial was conducted, including all histologically confirmed cases of prostate cancer diagnosed between September 1993 and November 1994 in four Finnish hospitals. In the intervention group, the role of the patient in the choice of treatment was actively emphasized. In the control group, the treatment was chosen using standardized treatment protocols. The first intermediate endpoint was the patient's participation in decision-making and the next will be the treatment chosen in the intervention and control groups. The main outcome will be the quality of life. Clinical data on prognostic factors including age, tumour grade, stage, functional status and serum prostate-specific antigen (PSA) concentration was collected for comparison between the arms, and between those enrolled or not.In all, 210 of 251 eligible patients were randomized into the two arms. Patients were randomized before obtaining informed consent, which led to four patients already randomized refusing to participate. The 41 patients not enrolled were of similar age and grade distribution, but more frequently had extensive disease than had those enrolled in the trial. Three patients were unable to participate because of rapid deterioration in their general condition after randomization. There were no clear differences in baseline characteristics (including age, functional status, tumour grade and stage) of the patients between the arms. The distribution of PSA level differed slightly between the arms, which may require adjustment in the analyses. Patients in the intervention arm participated in decision-making more actively than those in the control arm.Randomized studies on ethical issues such as the patient's role in choosing treatment are feasible and likely to provide important information.

In local or metastatic cancer, a prognostic tumour marker could be a valuable tool in the selection of different treatments. In renal cell cancer (RCC) no such markers have been available. We therefore evaluated the association between several pretreatment serum markers, tumour classification and short term survival in RCC patients. Serum samples were collected before surgery and three months thereafter from 24 RCC patients. Interleukin-6 (IL-6), IL- 12, soluble IL-2 receptor (sIL-2R) and intercellular adhesion molecule-1 (sICAM-1) were measured in serum samples using specific commercial enzyme immunoassay kits. Serum IL-6, sIL-2R and sICAM-1 levels before nephrectomy were significantly higher in non-local tumours than in local ones (mean IL-6 53 pg/ml versus 6.3 pg/ml, and sICAM-1 443 ng/ml versus 290 ng/ml, sIL-2R 3779 pg/ml versus 1796 pg/ml). In contrast, IL-12 levels were higher in local tumours (148 versus 102 pg/ml) and the levels increased significantly (P0.005) after removal of the primary tumour in patients with local disease. All patients with local tumours had normal IL-6 values, while only one with a non-local tumour had IL-6 levels below 10 pg/ml. In addition, IL-6 and sICAM-1 levels before operation were significantly higher in patients with short (less than one year) survival (p=0.007 to IL-6 and p=0.006 to sICAM-1). In contrast, patients with shorter survival had significantly lower IL-12 (p=0.03) levels. Our findings suggest that RCC induces changes in several immunological parameters. These soluble immunological factors, IL-6, IL-12, sIL-2R and sICAM-1, might have a role as prognostic factors in RCC.

The BTA stat is a rapid, non-invasive, qualitative urine test that detects bladder tumor-associated antigen (human complement factor H related protein) in urine. The sensitivity of this test is superior to that of urine cytology in detecting primary and recurrent tumors of the urinary bladder. Intravesical instillations are widely used to avoid recurrences and even progression. The objective of this study was to evaluate the effect of intravesical treatments on the BTA stat Test.501 consecutive patients followed up for bladder cancer were studied, of which 490 were eligible for analysis. Three hundred and twenty-seven (66.7%) of the patients had no history of intravesical treatments, whereas the remaining 163 (33.3%) had received treatments: 66 (40.5%) at the time of evaluation. A voided urine sample was obtained prior to cystoscopy and split for culture and BTA stat testing. The overall sensitivity and specificity were calculated and compared to the patients with no, past and present instillations.The overall sensitivity for the BTA stat Test was 56.6%, and the specificity was 76.4%. The specificity of the BTA stat Test was 80.7, 70.7 and 65.3% in those with no, past or present intravesical instillation treatments, respectively. The difference in specificity between those with no and present instillations was significant (p = 0.023), whereas the notable difference between those with no and past instillations did not reach significance (p = 0.076), nor was the difference between patients with past and present instillations significant (p = 0.558). Present instillation of mitomycin C had the strongest adverse effect on the test as the specificity was only 25.0%, whereas past treatment did not interfere with testing. The adverse effect of BCG treatment on testing extended.The overall specificity of the test is decreased in patients receiving intravesical treatments, whereas past treatments did not interfere with testing in general. However, the adverse effect of BCG on testing seems to extend, and therefore it is suggested that the BTA stat Test should not be used in patients having received BCG, and in those with present instillation of any type.

Five to ten percent of prostate cancers may be caused by inherited genetic defects. In order to explore the nature of inherited cancer risks in the genetically homogeneous Finnish population, we investigated the incidence of prostate cancer and other cancers in first-degree relatives of prostate cancer patients by linking the population-based parish records on relatives with the Finnish Cancer Registry (FCR) data.The study population was composed of first-degree relatives of two groups of prostate cancer patients diagnosed in Finland during 1988-1993: (1) all early-onset (60 years) patients (n = 557) from the entire country, (2) a sample (n = 989) of prostate cancer patients diagnosed at an age of60 years. A total of 11,427 first-degree relatives were identified through parish records, and their cancer incidence was determined based on a total of 299,970 person-years. Standardized incidence ratios (SIR) were calculated based on expected cancer rates in the general population.The SIR of prostate cancer was increased in both Cohort 1 (2.5, 95% CI 1.9-3.2) and Cohort 2 (1.7, 95% CI 1.4 2.1). The risk of prostate cancer was high for relatives of patients diagnosed at an early age, and then leveled off for patients in the median age of prostate cancer diagnosis (70-79 years). However, the prostate cancer risk for relatives of patients diagnosedor = 80 years was again statistically significantly elevated (SIR 1.8, 95% CI 1.3-2.6), suggesting a contribution of genetic factors to prostate cancer also at a late age of onset. Gastric cancer was the only other cancer type with a significantly elevated risk among the relatives. Increased risk of gastric cancer was seen only in male relatives of prostate cancer patients diagnosed at an early age, with the highest risk detected for the male relatives of prostate cancer patients diagnosed at an age of 55 years or less (SIR 5.0, 95% CI 2.8-8.2).Our population-based study indicates that hereditary factors may play an important role in the development of prostate cancer among the relatives of men diagnosed both at younger and older ages. This finding is relevant in the context of our observations that HPCX (hereditary prostate cancer susceptibility locus on Xq27-28) linkage in Finland is found exclusively among families with late age of onset. The association of gastric cancer with prostate cancer has not been reported previously, and may reflect the effects of a novel predisposition locus, which increases the risk to both of these common tumor types.

To evaluate changes in protein leakage in the glomerular filtration barrier, and in the ability of the tubule to reabsorb proteins during and after acute urinary retention (AUR).Glomerular and tubular function was investigated in 24 men during AUR (mean age 68 years, mean retention time 31 h and mean retention volume 1140 mL) who were then followed for 6 months by measuring the urinary excretion of glomerular and tubular proteins, and the glomerular filtration rate (GFR). Retention was relieved by inserting a suprapubic catheter and the cause of retention treated one month later. No patient had a previous renal disease or diabetes.During AUR, and after 1 and 6 months, albuminuria was detected in 100%, 92% and 54% of patients, and increased excretion of alpha1-microglobulin in 52%, 36% and 58%, of IgG in 79%, 58% and 40%, and of IgG4 in 67%, 42% and 20%, respectively. The mean GFR was normal during retention and during the follow-up.AUR causes disturbances in both the glomerular filtration and tubular reabsorption of proteins. Albuminuria and increased excretion of IgG, IgG4 and alpha1-microglobulin occurred in most patients during AUR. After relieving retention, the albuminuria and elevated alpha1-microglobulin excretion persisted, indicating slight glomerular dysfunction and a permanent defect in the proximal tubule to reabsorb proteins. This could be caused partly by previous chronic obstruction. AUR should be relieved immediately and the basic cause treated effectively to prevent further deterioration of renal function.

To determine whether ofloxacin coating has any effect on bacterial adherence to bioresorbable self-reinforced L-lactic acid polymer (SR-PLLA) urological stents.SR-PLLA stents were coated with epsilon-caprolactone/L-lactide copolymer blended with ofloxacin at three different concentrations of ofloxacin (0.5, 2 and 5% w/w). The adherence of five bacterial strains (Pseudomonas aeruginosa, Enterococcus faecalis, Proteus mirabilis and two strains of Escherichia coli) to the coated SR-PLLA stents was analysed. Uncoated stent pieces were used as controls. The effect of ofloxacin coating on bacterial growth in the microenvironment of the stent pieces was also analysed.Ofloxacin coating prevented bacterial adherence to SR-PLLA stent material; this effect correlated significantly with the ofloxacin concentration of the caprolactone coating. Ofloxacin coating reduced the amount of bacteria in the microenvironment of the stent, but because of natural resistance, ofloxacin coating had little effect on E. faecalis.Except for E. faecalis, ofloxacin coating may reduce stent-associated infections. However, further studies are needed to confirm its biocompatibility and efficacy in clinical use.

We assess whether the complex between prostate specific antigen (PSA) and alpha1-protease inhibitor in serum can be used to reduce further the number of false-positive PSA screen results independent of total and free PSA.Sera from 304 consecutive screen positive subjects, including 78 with and 226 without prostate cancer, and serum PSA of 4 to 10 microg./l. or higher in the Finnish, randomized, population based prostate cancer screening trial were analyzed for PSA-alpha-protease inhibitor, and total and free PSA. Main outcome measures were specificity, sensitivity and area under receiver operating characteristics curve for proportions of free PSA and PSA-alpha 1-protease inhibitor, and for a combination of these among screen positive cases.The proportion of serum PSA-alpha 1-protease inhibitor of total PSA was lower in cancer cases than in controls (0.9% versus 1.6%, p0.001). Logistic regression analysis of total PSA, free PSA and PSA-alpha 1-protease inhibitor showed that PSA-alpha 1-protease inhibitor in serum was an independent variable for discrimination between subjects with and without prostate cancer (p = 0.006) in the PSA range of 4 to 10 microg./l. The proportion of PSA-alpha 1-protease inhibitor alone improved specificity less than the proportion of free PSA but when these were combined by logistic regression they performed better than the proportion of free PSA alone at sensitivities of 85% to 95% (p0.001).Serum PSA-alpha 1-protease inhibitor improves the specificity of total and free PSA in a screening population with total PSA 4 to 10 microg./l.

Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide monotherapy or castration.Data from 2 open label, multicenter studies of identical design were pooled according to protocol. Patients with stage T3/4 prostate cancer were randomized to receive 150 mg. bicalutamide daily or castration (orchiectomy or 3.6 mg. goserelin acetate every 28 days) in a 2:1 ratio.A total of 480 patients with locally advanced prostate cancer were randomized to treatment. After a median followup of 6.3 years mortality was 56%. There was no statistically significant difference between the 2 groups in overall survival (hazard ratio 1.05, upper 1-sided 95% confidence limit 1.31, p = 0.70) or time to progression (1.20, 1.45, p = 0.11). There were statistically significant benefits in the bicalutamide monotherapy group in the 2 quality of life parameters of sexual interest (p = 0.029) and physical capacity (p = 0.046). The highest incidences of adverse events were the pharmacological side effects of hot flashes in the castration group, and breast pain and gynecomastia in the bicalutamide group. The incidences of other types of adverse events were low. Bicalutamide was well tolerated, with few drug related withdrawals from study, and no new safety issues were identified during this longer followup.Monotherapy with 150 mg. bicalutamide is an attractive alternative to castration in patients with locally advanced prostate cancer for whom immediate hormone therapy is indicated.

Recently a first X-ray-positive bioabsorbable urethral stent was developed by our group. The stent is made from self-reinforced poly-L,D-lactic acid (SR-PLA 96/4) blended with barium sulfate. The aim of this study was to evaluate the biocompatibility properties of the new stent materials.Rods made from pure SR-PLA 96/4 and SR-PLA 96/4 blended with barium sulfate were inserted into the dorsal muscles of a rabbit. Rods made from latex and silicone were used as positive and negative controls. To evaluate the long-term effect of BASO4 after the bioabsorption of the polymer, fast degrading SR-PGA (self-reinforced polyglycolic acid) and SR-PLA + BASO4 rods were used as controls. Urethral stents made from SR-PLA 96/4 and X-ray-positive SR-PLA 96/4 stents were inserted cystoscopically into the rabbit urethra. Metal stents were used as controls. The animals were sacrificed after 1 week, 1 month or 6 months.In the muscle implantation samples acute tissue reactions due to operative trauma were seen in all specimens at 1 week. After 6 months chronic inflammatory changes and foreign body reaction were seen only in the positive controls. The stent worked well in the rabbit urethra, its biocompatibility was good and there was less encrustation than in the metal stents.This first X-ray-positive bioabsorbable urethral stent showed no toxic tissue effects.

To assess the long-term effects of finasteride on pressure-flow parameters in men with urodynamically documented bladder outflow obstruction (BOO).One hundred twenty-one men with benign prostatic enlargement (BPE) and lower urinary tract symptoms (LUTS) underwent a pressure-flow study (PFS) at 1 of 11 clinical centers. The PFS technique was standardized, and all tracings were read by a single reader unaware of the treatment group. Patients who were obstructed according to a modified Abrams-Griffiths nomogram were randomized to 5 mg finasteride (n = 81) or placebo (n = 40) for 12 months; all patients continuing into an open extension received finasteride during the second 12 months of therapy. Results of the initial 12-month study demonstrated the benefit of finasteride treatment on PFS parameters. To examine the continuing effects over time, an analysis of the data from 54 patients who completed 24 months of treatment with finasteride is provided.Detrusor pressure at maximum flow (PdetQmax) continued to decrease during the second 12 months of therapy (decreases of 5.3 and 11.7 cm H2O at months 12 and 24, respectively). The percentage of patients obstructed by Abrams-Griffiths classification decreased from 76.2% at baseline to 66.7% at month 12 and 59.6% at month 24. An intention-to-treat analysis yielded similar results.Finasteride improves urodynamic measures of obstruction in men with BPE and LUTS, with continued improvement during the second 12 months of therapy.

Test-retest reliability of repeated voids in pressure-flow studies and the influence on maximum flow rate (Q(max)pQ), detrusor pressure at maximum flow rate (p(det)Qmax), voided volume, and residual urine were studied. Also the agreement in interpretation of pressure-flow tracings between investigators and a single blinded central reader acting as a quality control center (QCC) were assessed. In addition, correlations between p(det)Qmax and patient age, International Prostate Symptom Score (IPSS), free maximum flow rate (Qmax), and prostate volume were calculated. Using suprapubic pressure recording, 216 men with lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE) were investigated in 11 centers. In each pressure-flow study, three sequential voids were performed, and quality controlled recordings were analyzed for Q(max)pQ and p(det)Qmax by the QCC. Trans rectal ultrasound was used to measure the prostate volume. Mean Q(max)pQ did not change, but p(det)Qmax decreased significantly in the second and third sequential voids. Using the Abrams-Griffiths nomogram definition of obstruction, 125 patients (67%) were classified as obstructed from the first void, but only 111 patients (59%) from the third void. The agreement between the investigator assessment and that of a single blinded reader was good. There was no significant correlation between p(det)Qmax and patient age, IPSS, and Qmax, whereas a modest correlation was found between p(det)Qmax and prostate volume. In summary, there was no significant change in Q(max)pQ, but p(det)Qmax decreased for the three consecutive voids, which can be explained by a decrease in outlet resistance. The agreement between the investigator and QCC interpretations shows the value of a standardized technique, supporting the feasibility of multicenter urodynamic studies. There is a modest, but statistically significant, correlation between detrusor pressure and prostate size, supporting the hypothesis that prostate size is a contributing factor in symptomatic BPH.

The alterations in deoxyribonucleic acid (DNA) ploidy and p53 expression during progression of bladder cancer were determined.p53 Expression and DNA ploidy were studied in 51 patients with transitional cell carcinoma of the bladder (mean followup 5 years). Of 29 primarily superficial tumors (stages Ta and T1) 17 became subsequently invasive (greater than stage T2) within an average of 4 years (group 2) and 12 recurred superficially with no sign of progression during a mean followup of 10.8 years (group 1). Of the patients 22 had metastatic disease (group 3). Samples of tumors at diagnosis and recurrence or progression were analyzed by immunohistochemistry and flow cytometry.p53 Accumulation was detected at diagnosis in 29 of the 51 patients (57%), including 3 of 12 (25%) in group 1, 5 of 17 (29%) in group 2 and 14 of 22 (64%) in group 3. The p values for the differences between groups 1 and 3, and 2 and 3 were 0.07 and 0.054, respectively. Abnormal DNA contents were noted in 3 of 12 (25%), 11 of 17 (65%) and 16 of 22 (73%) patients in groups 1 to 3, respectively, and the differences between groups 1 and 2, and 1 and 3 were statistically significant. Using these 2 genetic markers, we found genetic progression to be uncommon in groups 1 and 3, whereas in group 2 an initially negative p53 staining became positive at invasion into the muscle in 5 of 12 patients (42%).The tumors in patients with superficial recurrences are mostly diploid and negative for p53, and those with metastasis are nondiploid and positive for p53 from the beginning, while further genetic progression is uncommon. However, p53 tends to accumulate frequently when the tumor begins to invade the muscle. There seems to be a need for caution against under staging an apparent stage T1 tumor that is positive for p53.

Our aim was to ascertain whether the short-term results and the frequency of complications of corrective surgery in hypospadias correlate with patients' opinions on their sexual life and voiding ability as adults, as well as to establish what kind of problems underlie dissatisfaction with the result of surgery.Between 1963 and 1975, 64 hypospadias patients, had been operated and their treatment completed in the Division of Paediatric Surgery at Tampere University Hospital. Their patient records were analyzed retrospectively, and a detailed questionnaire was mailed to 61 of them.43 (70.5%) patients returned the questionnaire. Of the respondees, 62.8% expressed satisfaction with the result of the operation. Among those who were satisfied, 22.2% had had complications after the operation, whereas 57.1% of those expressing dissatisfaction with the result had had complications (p0.05). Satisfied subjects had fewer problems in voiding and erection than those who were unsatisfied. They were also more often satisfied with the appearance of their penis and their sexual life. Fifteen patients would have preferred a longer follow-up.There is a correlation between the frequency of complications following hypospadias surgery and long-term results. Good short-term results also predict good long-term ones. There is no straight correlation between the presence of voiding abnormalities and overall satisfaction with the result. It seems that the overall appearance as perceived by the patient and patients' satisfaction with their sexual function are more important. This study shows that the 1-stage methods currently used, represented here by the Mathieu technique, give superior results compared to older methods, at least partly because complications occur less often.

We assess the long-term effects of finasteride on bladder outlet obstruction and symptoms in the treatment of patients with benign prostatic hyperplasia.Of the original 36 patients assigned to treatment with 5 mg. finasteride daily (group 1) or placebo (group 2) for 6 months 27 completed an open extension study of 5 mg. finasteride for 4 more years. The possible relief of bladder outlet obstruction was monitored with repeated pressure-flow studies at baseline, 6 months and 4.5 years.The treatment resulted in a further slight decrease in detrusor pressure at maximum flow rate in group 1 and a significant decrease in group 2 during the 4-year period, whereas improvement in maximum flow rate did not achieve statistical significance. Concomitantly, there was a significant improvement in obstructive and irritative symptoms.Finasteride decreases bladder outlet obstruction moderately and only occasionally relieves it completely. However, the decrease in obstruction achieved in many patients is sufficient to improve the symptoms significantly. The beneficial effect is long-lasting.

A permanent open shunt as a cause of impotence or impaired potency after a shunt operation for priapism is an unusual situation. In this series we studied the persistence of an open shunt in 26 patients who had developed impotence or impaired potency after operative treatment for priapism. All patients had been examined by cavernosography on the suspicion of an open shunt, giving a positive finding in five of 26 cases, in all of which impotence was cured by closure of the shunt. In five patients without a permanent open shunt potency returned to normal only after 6-12 months.

Studies were done to compare the acute effects of streptozotocin-induced diabetes and sucrose consumption on micturition, bladder mass and contractile responses of bladder strips to field stimulation and contractile agonists. Micturition changes occurred gradually in diabetic rats, reached maximal values within 7 to 14 days, and were accompanied by significant increases in bladder mass after 7 days. Bladder strips from diabetics responded to field stimulation, carbachol and KCl with significantly greater contractions than did those from controls within 7 days. Sucrose-drinking rats had maximal increases in fluid consumption and micturition frequency on the first night after starting treatment. Increases in micturition volumes were slower to develop than in diabetics. Bladder mass was significantly increased 30 and 60 days after starting sucrose treatment. Bladder strips from sucrose-drinking rats responded to field stimulation and carbachol with significantly greater contractions than did those from controls only after 60 days. Monitoring of drinking and micturition patterns established that diabetic rats drink and urinate during both the dark and light cycles. In contrast, control and sucrose-drinking rats drink and urinate principally at night. The results demonstrate that differences in bladder function between diabetic and sucrose drinking rats are apparent during the first month after treatment begins. The data suggest that the effects of diabetes and sucrose consumption on contractile bladder function are related to the diuresis-induced increases in bladder mass.

The recurrence rate and the time interval until the first recurrence were analysed in 169 consecutive conservatively treated patients with transitional cell carcinoma of the urinary bladder, in relation to initial tumour grade, number, size and stage, sex and smoking habits, at least five years after the diagnosis of the disease. The recurrence rate was higher among patients with more than three tumours and among patients with an invasive disease, while tumour size, histological grade and sex had no effect on the recurrence rate. The time until the first recurrence was found to be shorter among patients with an invasive disease and those with more than three tumours, and also among females. Smoking did not have any impact on the disease-free interval or on recurrence. We suggest that patients with multiple tumours are at great risk of recurrent disease. If invasion into muscle is found, the risk of recurrences will be high, and transurethral electroresection might not be an adequate form of therapy.

Although osteosclerotic metastases are characteristic of prostate cancer, bone resorption is also accelerated. Clodronate is a specific inhibitor of osteoclastic bone resorption and relieves bone pain of osteolytic lesions in myelomatosis and breast cancer. The present open study included 16 prostate cancer patients who had painful bone metastases and who had failed hormonal therapy. Clodronate was given intravenously for six days (300 mg/day) followed by oral treatment for 21 days (3200 mg/day). A clear pain relief was found in nine of the 16 (56%) patients after intravenous administration. During the next three weeks with oral administration there was still pain reduction in five patients, while in three patients the pain increased. The treatment had no effect on conventional tumour markers but urinary hydroxyproline excretion decreased, indicating reduced bone resorption. Clodronate offers an alternative for treating patients with painful metastases from prostate cancer.

Although endoscopic optical urethrotomy is the primary treatment for urethral stricture, it is associated with a high recurrence rate, and the essential problem is how to stop the scar from shrinking after cutting. In a controlled study the effect of treatment of recurrent urethral stricture by internal urethrotomy followed by clean intermittent self-catheterization (CIC) for 6 or 12 months was compared in 25 and 24 patients, respectively. Patients learnt easily how to perform CIC: only one patient was not able to do it at home. All patients were evaluated by uroflowmetry before and immediately after urethrotomy, and 3, 6, 9 and 12 months later. Recurrence was defined as the need for further treatment. There was no difference in the recurrence rate between the two groups, but the maximum flow rate was significantly lower at 12 months in the patients who had ceased catheterization at six months. Complications included in two patients asymptomatic bacteriuria and in 10 patients symptomatic urinary infection. CIC is a very satisfactory method of managing patients with recurrent stricture, it is easy to learn, it prevents a decrease in the maximum flow rate and can thus be applied to most patients instead of regular bouginage. On the basis of the present study we could not determine any optimal time for the duration of CIC after urethrotomy, or whether it has any effect on the natural course of the disease.

Polyorchidism is a rare urological anomaly with less than 60 cases reported in the literature. We report a case of right-sided polyorchidism with normal spermatogenesis diagnosed preoperatively by ultrasound imaging. Because of the high accuracy of ultrasound, surgical explorations are unnecessary if there are no signs of testicular torsion or other anomalies requiring operation.