| 1. |
- Vallbo, Christina, 1964, et al.
(author)
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The expression of thrombospondin-1 in benign prostatic hyperplasia and prostatic intraepithelial neoplasia is decreased in prostate cancer.
- 2004
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In: BJU Int. - : Wiley. ; 93:9, s. 1339-1343
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Journal article (peer-reviewed)abstract
- OBJECTIVE To evaluate the immunohistochemical expression of thrombospondin (TSP), a potent inhibitor of angiogenesis, in human benign prostatic hyperplasia (BPH) and prostate cancer. MATERIALS AND METHODS The expression of TSP-1, TSP-2 and CD36 receptor was assessed in 73 tissue specimens using immunohistochemistry; specimens were from 32 patients with BPH, seven with prostatic intraepithelial neoplasia (PIN) and 34 with cancer. RESULTS Immunohistochemistry showed that all 39 patients with BPH and PIN had TSP-1-positive glands. In contrast, none of the 34 patients with cancer had positive TSP-1 staining in the cancer tissue. All 73 patients were positive for TSP receptor CD36 and negative for TSP-2. CONCLUSIONS TSP is expressed in BPH, down-regulated in PIN and absent in prostate cancer tissue. This may indicate that TSP is important in prostate cancer progression. Further studies are needed to understand the significance of these findings for the malignant transformation of the prostate gland.
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| 2. |
- Benigni, F, et al.
(author)
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Oral treatment with a vitamin D3 analogue (BXL628) has anti-inflammatory effects in rodent model of interstitial cystitis
- 2006
-
In: BJU International. - : Blackwell Publishing Ltd. - 1464-4096 .- 1464-410X. ; 97:3, s. 617-624
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Journal article (peer-reviewed)abstract
- To investigate the effects of a vitamin D3 analogue (BXL628) in a model of chronic cystitis, as calcitriol analogues might be an interesting new therapeutic option for interstitial cystitis, for although the cause of the disease remains unclear, the increase in mast cells in the mucosa and detrusor muscle are significant. We devised a mouse model of allergen-induced allergic cystitis that is associated with the up-regulation of genes for interleukin-13, Fc epsilon RI alpha and mast cells-derived proteases, a massive inflammatory reaction in the bladder tissue, and augmented levels of mast cell-derived protease 1 (MMCP1) detected in mouse sera. Oral administration of BXL628 significantly reduced the expression of interleukin-13, Fc epsilon RI alpha and MMCP1 in the bladder. Furthermore, histological analysis showed a decrease in oedema and leukocyte infiltration in the bladder wall. BXL628 treatment reduced serum MMCP1 levels, indicating an effect on mast cell degranulation in vivo. Vitamin D3 analogues may successfully be used as anti-inflammatory agents in allergen-mediated inflammatory reactions. Moreover, the modulatory effect shown on mast cell activation by the BXL628 analogue strongly supports its potential therapeutic use in a possibly mast cell-dependent disease such as human interstitial cystitis.
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| 3. |
- Bivalacqua, Trinity J., et al.
(author)
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Dysregulation of cGMP-dependent protein kinase 1 (PKG-1) impairs erectile function in diabetic rats: influence of in vivo gene therapy of PKG1 alpha
- 2007
-
In: BJU International. - 1464-4096 .- 1464-410X. ; 99:6, s. 1488-1494
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Journal article (peer-reviewed)abstract
- To investigate the expression of cGMP-dependent protein kinase 1 (PKG1)alpha and PKG1 beta in the corpus cavernosum, and to evaluate the effect of adenoviral gene transfer of PKG1 alpha to the erectile compartment on erectile function in a rat model of diabetes. Diabetic (DM; induced by streptozotocin) male Sprague Dawley rats were transfected with adenoviruses (AdCMV beta gal or AdCMVPKG1 alpha, in 10 rats each) 2 months after the induction of DM. Intracavernosal pressure (ICP) during stimulation of the cavernosal nerve (CN) was assessed, and compared with mean arterial pressure (MAP). Erectile tissue was harvested for Western blot analysis, immunohistochemistry and total PKG activity. Ten age-matched rats without DM served as the control. Compared to controls, AdCMV beta gal-transfected DM rats had significantly lower peak ICP responses, ICP/MAP ratios, and filling rates during CN stimulation. In DM rats transfected with AdCMVPKG1 alpha, peak ICP, ICP/MAP ratios and filling rates were significantly better than in DM rats transfected with the reporter gene. As assessed by Western blot and immunohistochemistry, expression of PKG1 alpha and PKG1 beta was lower in corporal tissue from DM AdCMV beta gal-transfected rats than in controls. PKG1 alpha expression was improved after AdCMVPKG1 alpha gene therapy. Total PKG activity was lower in DM rat corporal tissue than in controls, and PKG1 alpha gene transfer significantly improved DM corporal PKG activity to a value greater than in the control. PKG1 alpha and PKG1 beta activities are reduced in the erectile tissue of the diabetic rat, and gene transfer of PKG1 alpha to the penis restored PKG activity and erectile function in vivo in diabetic rats. Gene therapy procedures targeting PKG1 alpha might be an interesting future therapeutic approach to overcome diabetic erectile dysfunction resistant to oral pharmacotherapy.
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| 4. |
- Björk, Thomas, et al.
(author)
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The prognostic value of different forms of prostate specific antigen and their ratios in patients with prostate cancer
- 1999
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In: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 84:9, s. 1021-1027
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To assess the prognostic value for patient survival of different forms of PSA and ratios thereof, before treatment for prostate cancer, by considering the forms and ratios both as independent markers and by comparing them with other commonly used prognostic markers, e.g. tumour grade, local stage (T-stage) and absence or presence of skeletal metastases (M-stage). PATIENTS AND METHODS: Blood samples were collected consecutively from men diagnosed with prostate cancer at our department in 1988. From this group, 66 men were followed until death, or for >/=9 years. Twenty-five patients died from their prostate cancer and 21 from other causes during the follow-up period. Forty-eight patients received hormonal treatment, whereas 18 remained untreated or received no treatment for their cancer before they died from other causes. Assays measuring the serum levels of free prostate specific antigen (fPSA), PSA complexed to alpha1-antichymotrypsin (PSA-ACT), and total PSA (tPSA) were used to calculate the percentage of free to total PSA (f/tPSA) fPSA/ACT and ACT/tPSA at diagnosis. Based on the initial levels or ratios of the PSA forms, the patients were divided into three numerically comparable groups (tertiles) for survival analysis. Prognostic factors predicting patient survival were evaluated using univariate (Kaplan-Meier life-tables with the log-rank test) and multivariate techniques (Cox proportional hazards regression model). RESULTS: Univariate analysis using the log-rank test showed that the serum level of each molecular form of PSA, i.e. tPSA (P=0.001), PSA-ACT (P<0.001) and fPSA (P<0.001), as well as grade (P<0.001), T-stage (P=0.00355) and M-stage (P<0.001), provided statistically significant prognostic information. Log-rank tests showed that none of the ratios, i.e. f/tPSA, fPSA/ACT and ACT/tPSA, were informative of prognosis (P>0.05). However, in a multivariate analysis regression model, not only M-stage (risk ratio 4.2; P=0. 026) and grade (risk ratio 2.6; P=0.022), but also f/tPSA (risk ratio 1.8; P=0.037), provided significant prognostic information. CONCLUSION: The values of tPSA, fPSA and PSA-ACT, as well as grade and T- and M-stage, are all independent prognostic factors of prostate cancer survival. In a multivariate analysis, not only M-stage and grade but also f/tPSA provided significant prognostic information.
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| 5. |
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| 6. |
- CARLSSON, STEFAN, 1987, et al.
(author)
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Age at surgery, educational level and long-term urinary incontinence after radical prostatectomy
- 2011
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In: BJU International. - 1464-4096 .- 1464-410X. ; 108:10, s. 1572-1577
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Journal article (peer-reviewed)abstract
- OBJECTIVE To identify predictors for long-term urinary leakage after radical prostatectomy. PATIENTS AND METHODS A consecutive series of 1411 patients who underwent radical prostatectomy (open surgery or robot-assisted laparoscopic surgery) at Karolinska University Hospital between 2002 and 2006 were invited to complete a study-specific questionnaire. Urinary leakage was defined as use of two or more pads per day. RESULTS Questionnaires were received from 1288 (91%) patients with a median follow-up of 2.2 years. Age at surgery predicts in an exponential manner long-term urinary incontinence at follow-up with an estimated relative increase of 6% per year. Among the oldest patients, 19% had urinary incontinence compared with 6% in the youngest age group, translating to a prevalence ratio of 2.4 (95% confidence interval [CI], 1.5-8.1). Low educational level, as compared with high, yielded an increased age-adjusted prevalence ratio of 2.5 (95% CI, 1.7-3.9). Patients who had undergone salvage radiation therapy had an increased prevalence of urinary incontinence (2.5; 95% CI, 1.6-3.8), as did those with respiratory disease (2.4; 95% CI, 1.3-4.4). Body mass index, prostate weight, presence of diabetes or previous transurethral resection did not appear to influence the prevalence of urinary incontinence. CONCLUSIONS In this series, a patient's age at radical prostatectomy influenced, in an exponential manner, his risk of long-term urinary incontinence. Other predictors are low educational level, salvage radiation therapy and respiratory disease. Intervention studies are needed to understand if these data are relevant to the prevalence of urinary leakage if a radical prostatectomy is postponed in an active monitoring programme.
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| 7. |
- Carlsson, Sigrid V., et al.
(author)
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Can one blood draw replace transrectal ultrasonography-estimated prostate volume to predict prostate cancer risk?
- 2013
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In: BJU International. - 1464-4096 .- 1464-410X. ; 112:5, s. 602-609
-
Journal article (peer-reviewed)abstract
- Objective To explore whether a panel of kallikrein markers in blood: total, free and intact prostate-specific antigen (PSA) and kallikrein-related peptidase 2, could be used as a non-invasive alternative for predicting prostate cancer on biopsy in a screening setting. Subjects and Methods The study cohort comprised previously unscreened men who underwent sextant biopsy owing to elevated PSA (3 ng/mL) in two different centres of the European Randomized Study of Screening for Prostate Cancer, Rotterdam (n = 2914) and Gteborg (n = 740). A statistical model, based on kallikrein markers, was compared with one based on established clinical factors for the prediction of biopsy outcome. Results The clinical tests were found to be no better than blood markers, with an area under the curve in favour of the blood measurements of 0.766 vs. 0.763 in Rotterdam and 0.809 vs. 0.774 in Gteborg. Adding digital rectal examination (DRE) or DRE plus transrectal ultrasonography (TRUS) volume to the markers improved discrimination, although the increases were small. Results were similar for predicting high-grade cancer. There was a strong correlation between the blood measurements and TRUS-estimated prostate volume (Spearman's correlation 0.60 in Rotterdam and 0.57 in Gteborg). Conclusions In previously unscreened men, each with indication for biopsy, a statistical model based on kallikrein levels was similar to a clinical model in predicting prostate cancer in a screening setting, outside the day-to-day clinical practice. Whether a clinical approach can be replaced by laboratory analyses or used in combination with decision models (nomograms) is a clinical judgment that may vary from clinician to clinician depending on how they weigh the different advantages and disadvantages (harms, costs, time, invasiveness) of both approaches.
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| 8. |
- Ekman, Mari, et al.
(author)
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Receptor-induced phasic activity of newborn mouse bladders is inhibited by protein kinase C and involves T-type Ca channels.
- 2009
-
In: BJU International. - 1464-4096 .- 1464-410X. ; 104:5, s. 690-697
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Journal article (peer-reviewed)abstract
- OBJECTIVE To investigate the mechanisms involved in the phasic contractile activity after muscarinic receptor activation of newborn urinary bladders and to compare neonatal and adult bladders. MATERIALS AND METHODS Detrusor muscle strips were isolated from newborn mice (aged 0-2 days) and compared with preparations from adult mice (aged 10-12 weeks). The effects of an activator (phorbol 12,13-dibutyrate, PDBu) and an inhibitor (GF109203X) of protein kinase C (PKC) on contractions were investigated. T-type Ca(2+) channels were blocked with NiCl(2). RESULTS The newborn urinary bladders responded with prominent phasic contractile activity in response to carbachol (1 microm). GF109203X (3 microm) reduced carbachol-induced force by approximately 60% in the newborn, compared with 30% in the adult. PDBu (1 microm) enhanced the muscarinic receptor-mediated contraction in adult bladder muscle, whereas it completely abolished the responses in the newborn. There was no inhibition after activation with depolarization (high-K(+)) or purinergic agonists (ATP, alpha,beta-methylene ATP). NiCl(2) (>30 microm) inhibited the peak responses to carbachol in the newborn and at 300 microm it completely abolished the phasic contractile response. The responses of the adult bladder muscle were only marginally affected by NiCl(2). CONCLUSIONS Muscarinic receptor stimulation recruits the PKC signalling pathway in both the adult and neonatal urinary bladder. Potent PKC activation is inhibitory on carbachol-induced activation in the newborn and stimulatory in the adult bladder. Furthermore, muscarinic receptor stimulation activates T-type Ca(2+) channels in the newborn, but not the adult bladder.
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| 9. |
- Ekman, Mari, et al.
(author)
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Signal transduction pathways of muscarinic receptor mediated activation in the newborn and adult mouse urinary bladder.
- 2009
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In: BJU International. - 1464-4096. ; 103:1, s. 90-97
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Journal article (peer-reviewed)abstract
- OBJECTIVE To study the role of M(2) and M(3) muscarinic receptor subtypes, sources of activator Ca(2+), and mechanisms involved in increased force oscillations in muscarinic contractions in the bladders of newborn and adult mice, as in the adult bladder muscarinic M(3) receptors are considered to mediate the main part of bladder contraction, and this has not been established in the newborn bladder. MATERIALS AND METHODS Bladder preparations from newborn (0-2 days) and adult (10-12 weeks) mice were mounted for in vitro force registration and activated with carbachol and high-K(+) solution in the presence of M(3) (4-DAMP 30 nm) or M(2) (methoctramine, 100 nm) receptor antagonists. Thapsigargin (1 microm) or ryanodine (10 microm) were used to inhibit sarcoplasmic reticulum Ca(2+) release. L-NAME (300 microm) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 microm) were used to inhibit nitric oxide synthase and guanylyl cyclase, respectively. Gap-junction function was inhibited with by 18-beta-glycyrrhetinic acid (18-beta-GA; 0.1-100 microm). Big-conductance (BK) and small-conductance (SK) K(+) channels were inhibited by apamine and charybdotoxin (0.3 microm), respectively. RESULTS Concentration-response relations for carbachol in the presence of 4-DAMP and methoctramine showed that M(3) receptors are the main activating pathway also in the newborn bladder. Neither thapsigargin nor ryanodine influenced the muscarinic responses of the newborn and adult bladders. Carbachol-induced contractions were not influenced by L-NAME or ODQ. The 18-beta-GA inhibited carbachol-induced contractions in both newborn and adult tissue in a similar manner. Apamine and charybdotoxin slightly increased the amplitude of the contractile responses. CONCLUSION These results suggest that in the newborn mouse bladder, as in adult bladders, the M(3) muscarinic receptor subtype is mainly responsible for carbachol-induced contractile responses. The main mechanism for muscarinic receptor-induced activation is influx of Ca(2+) from the extracellular medium, and there seems to be no major contribution of Ca(2+) release from intracellular stores. The phasic contractile activity induced by carbachol in the newborn bladder is not influenced by gap junction inhibition and does not involve SK and BK channels.
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| 10. |
- Gudjonsson, Sigurdur, et al.
(author)
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The value of bladder mapping and prostatic urethra biopsies for detection of carcinoma in situ (CIS)
- 2012
-
In: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 110:2B, s. E41-E45
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Journal article (peer-reviewed)abstract
- OBJECTIVES To assess the value of bladder mapping and prostatic urethra biopsies for detection of urothelial carcinoma in situ (CIS). CIS of the urinary bladder is a flat high-grade lesion of the mucosa associated with a significant risk of progression to muscle-invasive disease. CIS is difficult to identify on cystoscopy, and definite diagnosis requires histopathology. Traditionally, if CIS is suspected, multiple cold-cup biopsies are taken from the bladder mucosa, and resection biopsies are obtained from the prostatic urethra in males. This approach is often called bladder mapping (BMAP). The accuracy of BMAP as a diagnostic tool is not known. PATIENTS AND METHODS Male patients with bladder cancer scheduled for cystectomy underwent cold-cup bladder biopsies (sidewalls, posterior wall, dome, trigone), and resection biopsies were taken from the prostatic urethra. After cystectomy, the surgical specimen was investigated in a standardised manner and subsequently compared with the BMAP biopsies for the presence of CIS. RESULTS The histopathology reports of 162 patients were analysed. CIS was detected in 46% of the cystoprostatectomy specimens, and multiple (greater than= 2) CIS lesions were found in 30%. BMAP (cold-cup bladder biopsies + resection biopsies from the prostatic urethra) provided sensitivity of 51% for any CIS, and 55% for multiple CIS lesions. The cold-cup biopsies for CIS in the bladder mucosa showed sensitivity and specificity of 46% and 89%, respectively. CONCLUSION Traditional cold-cup biopsies are unreliable for detecting CIS in bladder mucosa and negative findings must be interpreted with caution.
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| 11. |
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| 12. |
- Kobelt, G., et al.
(author)
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The cost of feedback microwave thermotherapy compared with transurethral resection of the prostate for treating benign prostatic hyperplasia.
- 2004
-
In: BJU International. - 1464-4096 .- 1464-410X. ; 93:4, s. 543-548
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To compare the efficacy of a new microwave thermotherapy for treating benign prostatic hyperplasia (BPH), the ProstaLund Feedback Treatment (PLFT, ProstaLund Operations AB, Lund, Sweden) and transurethral resection of the prostate (TURP) in a clinical trial to their effectiveness in clinical practice over 1 year, to estimate their cost over 1 year, and to evaluate the cost of re-interventions over a longer period (2-3 years). PATIENTS AND METHODS: In a large randomized international 1-year clinical trial PLFT was as effective as TURP in improving symptoms of BPH and urinary flow. Because PLFT is an outpatient procedure it was less costly than TURP. However, the cost-effectiveness of the new procedure depends on its long-term effectiveness in clinical practice. All 146 patients in the randomized clinical trial were included in the present analysis. The outcome was based on the International Prostate Symptom Score (IPSS) and the bother score, and costs were estimated from treatment-related adverse events and hospitalization. To validate the estimates based on the clinical trial 1-year data on effectiveness and complete resource use in clinical practice were collected in a retrospective observational study from hospital charts and patient questionnaires of 88 patients who had undergone either TURP or PLFT. To assess the number of re-interventions after TURP after the first year information was obtained from hospital and surgical procedure data in the Swedish inpatient registry. The 3-year data for a total of 52,010 patients who had an index hospitalization for TURP between 1990 and 1995 were available for the analysis. The estimate of long-term consequences of PLFT was based on complication and re-intervention data for 87 patients who had undergone PLFT between 1997 and 1999. RESULTS: The mean 1-year costs in the clinical trial were estimated at [symbol: see text] 1763 for PLFT and [symbol: see text] 3209 for TURP. When all treatment-related resource use in clinical practice for 88 patients was included the costs were estimated at [symbol: see text] 1924 and [symbol: see text] 3264 for PLFT and TURP, respectively. The IPSS and bother scores were not significantly different between the groups in both datasets. Using the registry data the cost of TURP including re-interventions (TURP and bladder neck incisions) was estimated at [symbol: see text] 3159 over 2 years and [symbol: see text] 3185 over 3 years; the respective costs for PLFT were [symbol: see text] 2121 and at [symbol: see text] 2151. CONCLUSIONS: In the 1-year clinical trial PLFT was as effective but less costly than TURP, but long-term data are still lacking. However, the preliminary analysis over 3 years indicates that the average cost of the procedure remains lower than the total cost of TURP for the same period.
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| 13. |
- Ladjevardi, Sam, et al.
(author)
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Treatment with curative intent and survival in men with high-risk prostate cancer. A population-based study of 11 380 men with serum PSA level 20-100 ng/mL
- 2013
-
In: BJU International. - : Wiley-Blackwell. - 1464-4096 .- 1464-410X. ; 111:3, s. 381-388
-
Journal article (peer-reviewed)abstract
- Objective less thanbrgreater than less thanbrgreater thanTo investigate the influence of curative treatment on cause-specific mortality in men diagnosed with prostate cancer (PCa) with serum prostate-specific antigen (PSA) levels between 20 and 100 ng/mL. less thanbrgreater than less thanbrgreater thanMaterials and Methods less thanbrgreater than less thanbrgreater thanPatients with PCa (T1-4, N0/N1/NX, M0/MX), PSA 20-100 ng/mL and age andlt;= 75 years were identified in the National Prostate Cancer Register of Sweden. less thanbrgreater than less thanbrgreater thanData on co-morbidity diagnoses were obtained from the National Patient Register and cause of death from the Cause of Death Register. less thanbrgreater than less thanbrgreater thanFollowing adjustment for age at diagnosis, co-morbidity burden, Gleason score, T-category, PSA level and cause-specific mortality in relation to treatment were estimated using Cox regression analysis. less thanbrgreater than less thanbrgreater thanResult less thanbrgreater than less thanbrgreater thanA total of 11 380 men were diagnosed with PCa between 1996 and 2008 and fulfilled the inclusion criteria. less thanbrgreater than less thanbrgreater thanThe cumulative 10-year PCa-specific mortality was 36% for patients receiving only palliative treatment and 13% for those treated with curative intent. less thanbrgreater than less thanbrgreater thanFor the 8462 (74%) patients with PSA levels from 20 to 50 ng/mL at diagnosis, the hazard ratio for death from PCa was 0.23 (95% confidence interval 0.19-0.27) for those treated with curative intent compared with those given palliative treatment after adjusting for age, co-morbidity, T category, PSA level and Gleason score. The corresponding hazard ratio was 0.22 (95% confidence interval 0.17-0.30) for patients with PSA levels from 51 to 100 ng/mL. less thanbrgreater than less thanbrgreater thanConclusion less thanbrgreater than less thanbrgreater thanTreatment with curative intent for men with high-risk PCa was associated with reduced cause-specific mortality and should be considered even when serum PSA exceeds 20 ng/mL. Keywords prostate cancer, prostate-specific antigen, high-risk tumours, curative treatment, palliative treatment, population-based study
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| 14. |
- Lagou, M, et al.
(author)
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Location of interstitial cells and neurotransmitters in the mouse bladder
- 2006
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In: BJU International. - : Blackwell Publishing Ltd. - 1464-4096 .- 1464-410X. ; 97:6, s. 1332-1337
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Journal article (peer-reviewed)abstract
- To investigate whether interstitial cells (ICs) are present in the adult mouse bladder, and what transmitters characterize adjacent nerve fibres, as ICs in human and guinea-pig bladder lie close to nerve fibres but transmitters present in these nerves have not yet been reported. Sections of the bladder wall from 12 adult male mice (six each, aged 3-4 or 18-24 months) were incubated in carboxygenated Krebs' solution containing isobutyl-methyl-xanthene (1 mM), followed by the nitric oxide (NO) donor diethylamino-NONOate; control tissues remained in Krebs' solution. Samples were fixed in 4% paraformaldehyde and processed for immunofluorescence histochemistry for cGMP, neuronal NO synthase (nNOS), vesicular acetylcholine transferase (VAChT), calcitonin gene-related polypeptide (CGRP) and protein gene product (PGP) 9.5. ICs were identified as non-neuronal cells of appropriate morphology manifesting an increase in cGMP after exposure to the NO donor. ICs were apparent in the outer muscle, but not the inner muscle or suburothelial region. nNOS- and CGRP-immunoreactive fibres were close to and alongside IC processes. In contrast, nerve fibres containing VAChT were only occasionally found close to ICs and rarely running alongside them. ICs showed no immunoreactivity to c-kit. There was no overt difference in IC cell distribution between young and aged adult specimens. Older mice showed patchy denervation of the detrusor, but ICs were not specifically affected. ICs are confined to the outer part of the bladder wall in the mouse and may receive peptidergic and nitrergic innervation, which might serve to modulate their putative functional role. Alterations in the overall IC population do not appear to underlie ageing-related changes in lower urinary tract function.
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| 15. |
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| 16. |
- Streng, Tomi, et al.
(author)
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Phasic non-micturition contractions in the bladder of the anaesthetized and awake rat
- 2006
-
In: BJU International. - : Blackwell Publishing Ltd. - 1464-4096 .- 1464-410X. ; 97:5, s. 1094-1101
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To characterize the contractile activity that occurs in the bladder during the filling phase of the micturition cycle (non-micturition contractions, NMCs), which generate transient rises in intravesical pressure not associated with urine flow.MATERIALS AND METHODS: The experiments were conducted using anaesthetized (chloral hydrate) and un-anaesthetized rats. In un-anaesthetized rats bladder contractile activity was measured using an intravesical cannula implanted under full surgical anaesthesia 3 days previously. In the anaesthetized rats the bladder was exteriorized and a cannula inserted through the dome. In these experiments electrical activity within the detrusor was also measured with a suction electrode on the bladder surface. For each rat, the experimental protocol involved filling the bladder at a constant rate (10 mL/h) to evoke micturition cycles, or infusion of a fixed volume and recording made under effective isovolumetric conditions.RESULTS: In both anaesthetized and un-anaesthetized rats there were transient rises in bladder pressure (0.5-3 cmH2O). In the anaesthetized rats the amplitude of the transients increased throughout the filling phase, with little change in frequency. The phasic NMCs generating these pressure transients were accompanied by electrical changes in the detrusor. In the middle phase of bladder filling the slow pressure changes were accompanied by slow waves of electrical activity which changed in the pressure cycles immediately before micturition to high-frequency low-amplitude signals. In the un-anaesthetized rats there was a period immediately after voiding where there was no activity. As filling proceeded, low-amplitude low-frequency NMCs appeared that gradually increased in frequency and amplitude during the filling phase. However, the frequency of the transients decreased immediately before micturition despite an increase in amplitude. Similar responses were seen during isovolumetric recording.CONCLUSION: The present results show the presence of NMCs in the rat bladder, identify volume-dependent changes in the pattern of this activity during the micturition cycle, and show that NMCs are accompanied by electrical changes in the detrusor. The physiological significance of NMCs is not known but it might be linked to the generation of afferent discharge from mechanoreceptors in the wall, so contributing to sensations related to bladder volume.
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| 17. |
- Streng, Tomi, et al.
(author)
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The role of the rhabdosphincter in female rat voiding
- 2004
-
In: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 94:1, s. 138-142
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Journal article (peer-reviewed)abstract
- Objectves To obtain information on the mechanisms of female rat micturition using a model in which pressure was measured in the bladder and distal part of the urethra corresponding to the location of the rhabdosphincter, providing information on the role of the sphincter in opening and closing the urethral lumen. Materials and Methods A micturition reflex was induced in adult anaesthetized (chloral hydrate and urethane) female rats by filling the bladder with saline. Bladder pressure (BP), urethral pressure (UP), electromyography (EMG) of the middle part of the rhabdosphincter, and urinary flow rate in the distal urethra were simultaneously recorded. Results There were four phases of the micturition contraction, the second characterized by intraluminal pressure high-frequency oscillations (IPHFOs) of BP. When a non-oscillatory micturition contraction started, the BP increased and exceeded UP for the rest of the micturition contraction. Even though the BP increased during this first phase, the urethral lumen stayed closed. Its opening was indicated by a simultaneous decrease in BP and increase of UP as the fluid flowed from the bladder to the urethra. When the rhabdosphincter closed, as indicated by an EMG-burst of the muscle, the UP declined, bladder pressure increased and the flow ceased. Because of momentary contractions of the rhabdosphincter, the UP and urine flow rate had the same periodicity as the IPHFOs of BP. Conclusions The simultaneous recording of the BP, UP, EMG of the rhabdosphincter and urinary flow rate showed the sequence of events during micturition. The rhabdosphincter acts as an 'on-off' switch, causing interruptions in the urinary flow rate.
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| 18. |
- Vande Walle, Johan GJ, et al.
(author)
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A new fast-melting oral formulation of desmopressin : A pharmacodynamic study in children with primary nocturnal enuresis
- 2006
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In: BJU International. - 1464-4096 .- 1464-410X. ; 97:3, s. 603-609
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine the pharmacodynamic properties of a new oral lyophilisate formulation of desmopressin (in single doses of 30, 60, 120, 240, 360 or 480 μg) in children with known primary nocturnal enuresis (PNE) and thus identify those dosages that could provide a duration of action corresponding to a typical length of night-time sleep in children with PNE, additional objectives were to determine the safety and tolerability of desmopressin in this population. PATIENTS AND METHODS: Children with PNE (mean three or more wet nights/week), aged 6-12 years, were randomized into a double-blind, placebo-controlled study. An overhydration technique was used before dosing to suppress endogenous vasopressin production and thereby ensure that any antidiuresis could be attributed to treatment. Dosing with desmopressin or placebo occurred when urinary production was >0.13 mL/min/kg. Urinary volume, osmolality and duration of urinary-concentrating action (above three threshold levels: 125, 200 and 400 mOsm/kg) were determined as endpoints. RESULTS: All 72 participants receiving desmopressin had a pharmacodynamic response to the drug, while there was no change in urinary output in the 12 placebo-treated patients. There was a clear relationship between desmopressin dose and duration of action and osmolality during action, although the three highest-dose groups had similar results. The mean duration of action of desmopressin at the lowest osmolality threshold level was 3.6-10.6 h, according to dose, for the highest threshold, the values were 1.3-8.6 h. CONCLUSION: Desmopressin, as the oral lyophilisate, causes a marked decrease in urinary output in hydrated children with PNE. A small dose range (120-240 μg) is likely to control diuresis for a period corresponding to a night's sleep (7-11 h) in most children with PNE. However, some patients might require a higher dose to obtain antidiuresis for the complete night. © 2006 BJU International.
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| 19. |
- Waldkirch, Eginhard, et al.
(author)
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Non-genomic effects of androgens on isolated human vascular and nonvascular penile erectile tissue
- 2008
-
In: BJU International. - : Blackwell Publishing Ltd. - 1464-4096 .- 1464-410X. ; 101:1, s. 71-74
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Journal article (peer-reviewed)abstract
- OBJECTIVES To evaluate non-genomic effects of testosterone and dihydrotestosterone (DHT) on isolated human cavernosal arteries (HCA) and corpus cavernosum (HCC) using organ-bath studies and radio-immunoassays (RIA), as non-genomic effects of androgens are reported for vascular smooth musculature and there is evidence that the relaxant response involves a modulation of cyclic nucleotide tissue levels. MATERIALS AND METHODS The relaxation induced by the cumulative addition of testosterone and DHT (0.01-10 mu M) was studied using circular segments of HCA and strip preparations of HCC. To evaluate the effects of testosterone and DHT on tissue levels of cAMP and cGMP, specimens were exposed to increasing concentrations of the hormones. Forskolin and sodium nitroprusside (SNP) served as reference compounds. RESULTS Testosterone and DHT dose-dependently reversed the noradrenaline-induced tension of vascular segments and HCC strips. At the maximum concentration, testosterone and DHT reduced the mean (SD) tension to 79.8 (4.43)% and 83.9 (10.94)%, respectively. SNP and forskolin significantly stimulated the production of cGMP and cAMP. No effects of testosterone and DHT on cGMP and cAMP levels were detected. CONCLUSION Rapid androgen-induced relaxation of HCA and HCC occurs via non-genomic mechanisms. In penile erectile tissue, non-genomic relaxant effects of testosterone and DHT are not mediated via modulation of cyclic nucleotide tissue levels. Additional studies are required to establish if non-genomic relaxant effects are important in ensuring a basal level of perfusion to maintain overall penile function.
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| 20. |
- Werkström, Viktoria, et al.
(author)
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Phosphodiesterase 5 in the female pig and human urethra : morphological and functional aspects
- 2006
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In: BJU International. - : Blackwell Publishing Ltd. - 1464-4096 .- 1464-410X. ; 98:2, s. 414-423
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To characterize the distribution of phosphodiesterase 5 (PDE-5), cGMP and cGMP-dependent protein kinase I (PKG1), and to evaluate the effect of pharmacological inhibition of PDE-5 in isolated preparations of pig and human urethra, as the nitric oxide (NO)/cGMP pathway generates the main inhibitory signals to reduce resistance in the bladder outlet and urethra during emptying of the bladder.MATERIALS AND METHODS: After obtaining ethics committee approval, urethral specimens were obtained from three female patients during cystectomy, and from young female pigs. The specimens were prepared for immunohistochemical investigations and for functional studies in organ baths. Effects of sildenafil, vardenafil and tadalafil (1 nm to 30 microm) were studied in l-noradrenaline (1 microm)-activated or spontaneously contracted preparations, and on relaxations induced by electrical-field stimulation (EFS). Levels of cGMP were determined by radioimmunoassay.RESULTS: After stimulation with the NO donor, DETA NONO-ate (1 mm), there was greater cGMP-immunoreactivity (IR) in urethral and vascular smooth muscles. There was a wide distribution of cGMP- and vimentin-positive interstitial cells between pig urethral smooth muscle bundles. There was also cGMP-IR within NO-synthase-IR endothelium. There was PDE-5 IR within the urethral and vascular smooth muscle cells, but also in vascular endothelial cells that expressed cGMP-IR. In pig and human sections, there was strong PKG1-IR in alpha-actin-IR urethral smooth muscle cells that also contained IR for cGMP. Sildenafil, vardenafil and tadalafil caused mean (sem) concentration-dependent relaxations of the pig urethra which, at 30 microm, were 80 (3)% (11 samples), 81 (5)% (12 samples) and 64 (4)% (10 samples) of the spontaneous tone. The relaxation of L-noradrenaline-contracted female human urethra was 100% in response to 10 microm sildenafil, and 85 (15)% and 47 (13)% for 30 microm of vardenafil and tadalafil, respectively (three samples). Vardenafil or sildenafil (30 microm) doubled cGMP levels in pig specimens. There were no effects on cGMP levels with tadalafil. EFS (1-32 Hz) caused l-NG-nitroarginine-sensitive relaxations of pig urethral muscle that were increased in amplitude and duration by PDE-5 inhibition. At 0.1 microm, sildenafil, vardenafil or tadalafil significantly prolonged the mean (sem) duration of the relaxation at 4 Hz by 55 (19)%, 45 (14)% and 51 (12)%, respectively.CONCLUSIONS: PDE-5-, cGMP- and PKG1-IR is widely distributed in human and pig urethral tissues. Nerve-induced relaxations of urethral preparations were enhanced at low concentrations of sildenafil, vardenafil and tadalafil, whereas there were direct smooth muscle-relaxant actions of the PDE-5 inhibitors at high concentrations. Inhibition of PDE-5 might be an interesting option to facilitate cGMP-mediated relaxation of the outflow region.
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| 21. |
- Abd-El-Gawad, G, et al.
(author)
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Early and late metabolic alterations in children and adolescents with a kock urinary reservoir.
- 1999
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In: BJU international. - : Wiley. - 1464-4096 .- 1464-410X. ; 83:3, s. 285-9
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Journal article (peer-reviewed)abstract
- To assess the early and late metabolic effects of urinary diversion in children and adolescents with a Kock urinary reservoir.Thirteen children (aged 10.8- 16 years) and seven adolescents (aged 16-18 years; 10 girls and 10 boys), underwent surgery for congenital urinary incontinence. They were followed for 3-10 years (mean 6.5), divided into an early (3 months to 2 years) and a late (2-10 years) period, and assessed for renal function and any metabolic effects.At the early and late follow-up, one of 19 and three of 16 patients, respectively, had metabolic acidosis. Hyperchloraemia was present in four of 20 patients at the early and in eight of 18 at the late follow-up. Serum creatinine was increased in four of 20 patients at the early and eight of 18 at the late follow-up. In patients with infrequent reservoir emptying (
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| 22. |
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| 23. |
- Andersson, S O, et al.
(author)
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Prevalence of lower urinary tract symptoms in men aged 45-79 years : a population-based study of 40,000 Swedish men
- 2004
-
In: BJU International. - Karolinska Inst, Natl Inst Environm Med, SE-17177 Stockholm, Sweden. Univ Hosp Orebro, Dept Urol, Orebro, Sweden. Univ Hosp Orebro, Ctr Assessment Med Technol, Orebro, Sweden. Vasteras Hosp, Dept Urol, Vasteras, Sweden. : WILEY. - 1464-4096 .- 1464-410X. ; 94:3, s. 327-331
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Journal article (peer-reviewed)abstract
- OBJECTIVE To estimate the age-specific prevalence and severity of lower urinary tract symptoms (LUTS) among Swedish men, the intercorrelations between different symptoms, and to assess quality of life and health-seeking behaviour among men with LUTS. SUBJECTS AND METHODS In 1997, an International Prostate Symptom Score (IPSS) questionnaire, together with other questions about lifestyle, was mailed to all men aged 45-79 years living in two counties in Sweden; the analyses included 39 928 men. RESULTS Overall, 18.5% and 4.8% of the men were moderately and severely symptomatic; the prevalence of at least one symptom was 83%. LUTS were strongly age-dependent, with 1.8% of severe symptoms among men aged 45-49 years and increasing to 9.7% among those 75-79 years old. Frequent urination was the most common symptom among men aged <70 years and nocturia among those aged >70 years. Symptoms like hesitancy, poor flow and intermittency were highly correlated with each other (Spearman coefficients 0.56-0.60). There was a high correlation between the IPSS and a poor score for quality of life resulting from the bothersomeness of LUTS (r = 0.70). Among symptomatic subjects, 36% reported a poor quality of life (fairly bad, very bad or terrible). Only 29% of symptomatic subjects (IPSS >7) reported that they had been diagnosed previously for their urinary problems, and only 11% received medication for that. CONCLUSION Although the prevalence of LUTS in Sweden is high, the percentage of men whose quality of life is substantially affected is much lower.
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| 24. |
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| 25. |
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| 26. |
- Asplund, Ragnar, et al.
(author)
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Nocturia in relation to somatic health, mental health and pain in adult men and women
- 2005
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In: BJU International. - 1464-4096 .- 1464-410X. ; 95:6, s. 816-819
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To assess the relationship of nocturia to somatic health, mental health and bodily pain. SUBJECTS AND METHODS: A randomly selected group of men and women aged 20-64 years, living in three small municipalities in northern Sweden, or in the city of Ostersund or in Stockholm, were sent a postal questionnaire containing questions on somatic and mental health, satisfaction with life, pain, nocturnal voiding, work and sick-listing from work. RESULTS: Reports (from 1948 respondents) on poor somatic and mental health and on pain all increased in parallel with increasing frequency of nocturnal voids. In a multiple logistic regression analysis with sex, age, somatic health, mental health and bodily pain as the independent variables, significant independent correlates (odds ratios, confidence intervals) of nocturnal micturition (two or more episodes vs none or one) were: age 45-59 vs 20-44 years, 1.9 (1.3-2.7), > or =60 vs 20-44 years, 3.8 (2.4-6.0); somatic health, poor vs good, 2.3 (1.4-3.7); mental health, poor vs good, 1.9 (1.2-3.0); pain, rather mild vs very mild or none, 1.5 (1.0-2.3); rather severe vs very mild or none, 1.9 (1.1-3.2); and very severe vs very mild or none, 6.0 (2.5-14.0). Gender was deleted by the logistic model. Sick-listing for > or = 60 days during the past year was reported by 4.9%, 10.6%, 5.6% and 38.9% of the men with none, one, two or > or = three nocturnal voids, respectively, and by 10%, 12.4%, 23% and 46.7% (both P < 0.001) of the corresponding women, respectively. Life satisfaction decreased in parallel with increased nocturia. CONCLUSION: The impairment of both somatic and mental health was associated with increased nocturnal voiding. Pain was associated with a substantial increase in nocturia after adjusting for age and somatic and mental health. Sick-leave was more common in association with more nocturnal voids.
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| 27. |
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| 28. |
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| 29. |
- Brehmer, M, et al.
(author)
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Heat-induced apoptosis in human prostatic stromal cells
- 2000
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In: BJU International. - 1464-4096 .- 1464-410X. ; 85:4, s. 535-541
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Journal article (peer-reviewed)abstract
- Objective. To determine whether heat, used in transurethral microwave thermotherapy (TUMT) for benign prostatic hyperplasia and which causes necrotic lesions within the adenoma, induces apoptosis in benign human prostatic stromal cells. Materials and methods. Prostatic stromal cells were cultured from benign human prostatic tissue. The origin of the cells was identified by immunohistochemical staining and transmission electron microscopy. Cell cultures were exposed to moderate hyperthermia (47░C) for 1 h and any apoptosis detected by light microscopy, transmission electron microscopy and the measurement of induced caspase-3-like activity. Results. The cultures contained a mixed population of smooth muscle cells and myofibroblasts. Twenty-four hours after heat exposure, 76% of the cells were apoptotic and the caspase activity had increased, whereas only 14% of the cells were necrotic. Conclusion. Moderate hyperthermia induces apoptosis in cultured human prostatic stromal cells.
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| 30. |
- De Koning, HJ, et al.
(author)
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Monitoring the ERSPC trial
- 2003
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In: BJU international. - : Wiley. - 1464-4096 .- 1464-410X. ; 9292 Suppl 2, s. 112-114
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Journal article (peer-reviewed)
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| 31. |
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| 32. |
- Englund, Gunnar
(author)
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Optimizing the therapeutic approach of transurethral alprostadil
- 2000
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In: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 86:1, s. 68-74
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Journal article (peer-reviewed)abstract
- Objective To investigate the efficacy and safety of two different starting doses of transurethral alprostadil (250 mu g and 500 mu g, MUSE(R), Vivus Inc., Menlo Park, CA, USA, and Astra Lakemedel AB, Sodertalje, Sweden) and the need for dose titration in a general population with erectile dysfunction. Patients and methods In a 12-week randomized and open multicentre study with parallel groups, 166 patients were randomised to a starting dose of either 250 or 500 mu g of MUSE and evaluated for safety. Of these patients, 142 were included in the analysis of efficacy. MUSE marked in four doses (125, 250, 500 and 1000 mu g) was supplied and during the trial the dose could be increased or decreased step-wise until a satisfactory response was attained. The efficacy was assessed using the Erection Assessment Scale (EAS), as coitus (by diary) and the International Index of Erectile Function. Results The lowest dose of MUSE with which the patients achieved at least one EAS score of 4 or 5 was 125 mu g for 1% of participants, 250 mu g for 27%, 500 mu g for 32%. 1000 mu g for 6%, and finally 1000 mu g plus a pubic band for 8%. Thirty-five of the 142 patients (25%) did not report an EAS of 4 or 5. Most patients ( > 60%) achieved an EAS of 4 or 5 on the lower doses (125, 250 and 500 mu g). Almost all patients who had an EAS score of 4 or 5 also had intercourse. In all, 68% reported sexual intercourse at least once in course of the study. More patients reported penile pain while treated with 500 mu g than with 250 mu g (P < 0.05) during the first 4 weeks, However, the penile pain was severe in very few men and it was a minor problem. Hypotensive symptoms were reported six times, independently of dose level. The administration of MUSE was generally rated as comfortable. No patients reported urethral stricture, penile fibrosis, or priapism either in the clinic or at home. Conclusion Recommending 500 mu g as a starting dose increased the percentage of patients reporting at least one EAS of 4-5, with or without sexual intercourse, from 28% to 60%. No serious dose-related systemic effects were seen. When starting on 500 mu g, patients were more likely to find directly the dose that gave sufficient response and treatment satisfaction. We suggest that the appropriate starting dose of MUSE should be 500 mu g.
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| 33. |
- Fagerström, Tim, et al.
(author)
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Bipolar transurethral resection of the prostate causes less bleeding than the monopolar technique : a single-centre randomized trial of 202 patients
- 2010
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In: BJU International. - : Wiley-Blackwell. - 1464-4096 .- 1464-410X. ; 105:11, s. 1560-1564
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To compare bipolar with the conventional monopolar transurethral resection of the prostate (TURP) for blood loss and speed of resection.PATIENTS AND METHODS: In all, 202 consecutive patients from the hospital waiting list were randomized to undergo TURP using either a bipolar system (Surgmaster TURis, Olympus, Tokyo, Japan) or a monopolar system (24 F, Storz, Tübingen, Germany). The blood loss during and after surgery was measured using a photometer. Other variables compared included indices of resection speed and transfusion rate.RESULTS: There were no statistically significant differences in operative duration, resection weight, resection speed or radicality of resection. However, the median blood loss was 235 mL for the bipolar and 350 mL for monopolar TURP (P < 0.001). The decrease in blood haemoglobin concentration during the day of surgery was smaller in the bipolar group (5.5% vs 9.6%P < 0.001). Fewer patients were transfused with erythrocytes (4% vs 11%, P < 0.01), which can be explained by the much lower 75th percentile for blood loss in the bipolar group (at 472 vs 855 mL, respectively).CONCLUSIONS: Bipolar TURP using the TURis system was performed with the same speed as monopolar TURP but caused 34% less bleeding, the difference being greatest (81%) for the largest blood losses. Bipolar TURP also required fewer erythrocyte transfusions than the conventional monopolar technique.
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| 34. |
- Gladh, Gunilla, 1943-, et al.
(author)
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Anogenital electrical stimulation as treatment of urge incontinence in children
- 2001
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In: BJU International. - 1464-4096 .- 1464-410X. ; 87:4, s. 366-371
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Journal article (peer-reviewed)abstract
- Objectives To evaluate retrospectively the result of anogenital afferent stimulation (AGAS) in neurological healthy children with therapy-resistant urge incontinence.Patients and method The study included 48 children (24 girls and 24 boys, 5–14 years old) with a diagnosis of bladder instability verified by cystometry in all. Anogenital afferent stimulations were applied using a battery-powered dual constant-current stimulator. The children were stimulated continuously at 10 Hz for 20 min once or twice daily and if required the children and/or the parents continued to apply the treatment at home. For home stimulation a single (anal) channel stimulator was used. The patients were instructed to stimulate for 20 min at maximum intensity two to three times a week until the effects were optimal. The outcome was evaluated retrospectively by comparing voiding/incontinence diaries obtained before and at the follow-up 6–12 months after the end of treatment.Results AGAS was applied at the clinic for a median (range) of 9 (4–20) times. Thirty-one children continued with home stimulation for another 25 (5–96) sessions. At the follow-up, 18 children were cured and another seven improved, with a leakage score of less than half that before treatment. The treatment was well tolerated by most children.Conclusions Anogenital afferent stimulation is an effective, potentially curative treatment in children with severe urge incontinence. Home stimulation is a well accepted adjuvant to treatment at the clinic and improves the outcome.
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| 35. |
- Gustavsson, Helene, 1977, et al.
(author)
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ADAMTS1, a putative anti-angiogenic factor, is decreased in human prostate cancer.
- 2009
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In: BJU international. - 1464-410X .- 1464-4096. ; 104:11, s. 1786-90
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the expression of 'ADAM metallopeptidase with thrombospondin type I motif, 1' (ADAMTS1) in human prostate cancer, and to study its relationship to microvessel density (MVD) and metastasis. ADAMTS1 has been described as an anti-angiogenic and antitumour factor, but its function in prostate cancer is unknown. PATIENTS AND METHODS: ADAMTS1 expression was evaluated by immunohistochemistry in specimens obtained by transurethral resection of the prostate from patients with hormone-naïve and hormone-refractory prostate tumours, including adjacent benign tissue. A semiquantitative scoring system was used for evaluating the staining. MVD was quantified by counting the number of CD34-positive blood vessels. RESULTS: ADAMTS1 was strongly expressed in the luminal epithelial cells in benign prostate glands, whereas expression was significantly lower in prostate cancer cells. There was no obvious difference between hormone-naïve and hormone-refractory tumours, and ADAMTS1 expression did not correlate with Gleason score. However, in hormone-refractory tumours from patients with metastatic disease, the expression of ADAMTS1 was significantly lower than in tumours from patients without metastases. Furthermore, the MVD was higher in hormone-refractory than in hormone-naïve tumours and benign tissue, and MVD correlated with Gleason score. There was no association between ADAMTS1 and MVD in the hormone-naïve tumours, while hormone-refractory tumours with low ADAMTS1 expression had a higher MVD than those with moderate/high expression. CONCLUSION: ADAMTS1 expression is decreased in prostate cancer, and might be involved in the early steps of prostate cancer development. Further, ADAMTS1 might have an anti-angiogenic and antimetastatic role in hormone-refractory prostate cancer, where low ADAMTS1 expression is associated with a high MVD and metastasis.
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| 36. |
- Gårdmark, Truls, et al.
(author)
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Analysis of HER2 expression in primary urinary bladder carcinoma and corresponding metastases
- 2005
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In: BJU International. - 1464-4096 .- 1464-410X. ; 95:7, s. 982-986
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate the expression of HER2 receptors (previously reported to be over-expressed in malignant urothelium) in both primary tumours and metastases of transitional cell cancer, using two different staining methods and two different scoring techniques, considering the potential use of these receptors as targets for planned systemic anti-HER2 nuclide-based treatment. MATERIALS AND METHODS: HER2 expression was evaluated with two different immunohistochemical methods in 90 patients with primary urinary bladder cancer tumours and corresponding metastases. Sections were first stained with the commercially available breast cancer test kit (HercepTest, Dako, Glostrup, Denmark). Parallel sections were then stained with a modified HercepTest procedure. Two different evaluation criteria were compared; the HercepTest score that requires > or = 10% stained tumour cells (as for breast cancer) and a proposed 'Target score' that requires > 67% stained tumour cells. The latter score is assumed to be preferable for HER2-targeted radionuclide therapy. RESULTS: Using the HercepTest kit, the Target score gave lower fractions of positive primary tumours and metastases than the HercepTest score. The modified HercepTest staining procedure and Target score gave high HER2 values in 80% of primary tumours and 62% of metastases, which is considerably more than that obtained with the HercepTest staining and score. There was a significant decrease in HER2 positivity with increasing distance from the primary tumour. In nine sentinel-node metastases assessed, all but one were HER2-positive. Considering all regional metastases, 74% were positive, and of distant metastases, 47%; 72% of the patients with positive primary tumours also expressed HER2 in their metastases. CONCLUSIONS: When combining the modified HercepTest with customised evaluation criteria, more HER2-positive tumours were diagnosed. The degree of HER2 down-regulation was significantly higher in distant than in regional metastases. HER2-targeted therapy may be an alternative or complementary to other methods in the future treatment of metastatic urinary bladder carcinoma.
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| 37. |
- Gårdmark, Truls, et al.
(author)
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Analysis of progression and survival after 10 years of a randomized prospective study comparing mitomycin-C and bacillus Calmette-Guérin in patients with high-risk bladder cancer
- 2007
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In: BJU International. - 1464-4096 .- 1464-410X. ; 99:4, s. 817-820
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Journal article (peer-reviewed)abstract
- Objective: To report the 10-year follow-up of a study randomizing between instillations of bacillus Calmette-Guérin (BCG) and mitomycin-C (MMC) for treating high-risk and not muscle-invasive urinary bladder cancer to assess progression, the need for more aggressive treatment and survival (cancer-specific and overall), as many of the published studies comparing different treatments for disease that is not muscle-invasive have a short follow-up. Patients and methods: Between 1987 and 1992, 261 patients were included; they had frequently recurring Ta/T1G1–G2, T1G3 or primary Tis-dysplasia. The patients were randomized to treatment with either 40 mg of MMC or 120 mg of BCG (Danish strain 1331) given weekly for 6 weeks, then monthly up to a year and finally every third month for a further year. The 250 evaluable patients were followed using hospital files and national registers on causes of death. Results: The median follow-up for survivors was 123 months. The disease progressed in 58 (23%) of the patients, 34 in the MMC group and 24 in the BCG group (P = 0.26). Of the 140 patients who died, 68 were in the BCG and 72 in the MMC group (log-rank P = 0.98); most (95, 68%) died from other causes. Conclusion: Based on the follow-up of the present patients it cannot be concluded that the drugs originally administered, MMC or BCG, differed in their effect on progression, need for subsequent treatment or survival.
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| 38. |
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| 39. |
- Hahn, Robert G., et al.
(author)
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Blood loss and postoperative complications associated with transurethral resection of the prostate after pretreatment with dutasteride
- 2007
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In: BJU International. - : Wiley-Blackwell. - 1464-4096 .- 1464-410X. ; 99:3, s. 587-594
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine whether pretreatment with dutasteride, a dual 5alpha-reductase inhibitor (5ARI), reduces surgical blood loss or postoperative complications in patients with benign prostatic hyperplasia (BPH) who undergo transurethral resection of the prostate (TURP).PATIENTS AND METHODS: This double-blind, randomized, placebo-controlled, multicentre study comprised 214 patients with BPH. Placebo was compared with dutasteride 0.5 mg/day 2 weeks before and after TURP, or 4 weeks before and 2 weeks after TURP. Surgical blood loss was measured using a haemoglobin photometer (HemoCue AB, Angelholm, Sweden) and postoperative adverse events were recorded. Microvessel density (MVD) was calculated by immunostaining and light microscopy of the prostatic chips.RESULTS: Although dutasteride reduced serum dihydrotestosterone (DHT) by 86-89% in 2-4 weeks, and intraprostatic DHT was approximately 10 times lower than in the placebo group, the (adjusted) mean haemoglobin (Hb) loss during surgery was 2.15-2.55 g Hb/g resectate with no significant difference in blood loss between the groups either during or after TURP. Clot retention occurred in 6-11% and urinary incontinence in 14-15% of patients during the 14 weeks after TURP, with no difference between the groups. The MVD at TURP was also similar for all groups.CONCLUSION: There were no significant reductions in blood loss during or after TURP or complications afterward with dutasteride compared with placebo, despite significant suppression of intraprostatic DHT. Blood loss and transfusion rates in the placebo group were lower than those previously reported in studies where there was a beneficial effect of a 5ARI, relative to placebo, on bleeding during TURP.
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| 40. |
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| 41. |
- Hennenberg, Martin, et al.
(author)
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α1-adrenoceptor activation induces phosphorylation of β2-adrenoceptors in human prostate tissue
- 2011
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In: BJU International. - 1464-4096 .- 1464-410X. ; 108:6, s. 922-928
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Journal article (peer-reviewed)abstract
- OBJECTIVE:• To test whether β1-adrenoceptor activation leads to phosphorylation of the β2-adrenoceptor in human prostate tissue.PATIENTS AND METHODS:• Prostate tissue from patients undergoing radical prostatectomy was stimulated in vitro with the α1-adrenergic agonist phenylephrine (10 µM).• α2-adrenoceptor phosphorylation at serines 345/346 was studied using Western blot analysis with a phospho-specific antibody.• The role of second messenger kinases was assessed by studying the effects of the protein kinase C (PKC) inhibitor Ro 31-8425 and the protein kinase A (PKA) inhibitor H89 on phenylephrine-induced phosphorylation.• The expression of G protein-coupled receptor kinases (GRKs) 2/3 was analysed using quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry.RESULTS:• Stimulation of prostate tissue with phenylephrine resulted in phosphorylation of the β2-adrenoceptor (5, 10 and 20 min after stimulation).• This α1-adrenoceptor-induced phosphorylation of β2-adrenoceptors was resistant to inhibition of PKC and PKA.• Changes in phosphorylation levels were not attributable to changes in receptor levels, as these remained constant during stimulation.• RT-PCR and Western blot analysis showed expression of GRK2/3 in human prostate tissues.• Immunohistochemical staining showed that GRK2/3 expression in human prostate tissue is located to stromal and smooth muscle cells.CONCLUSIONS:• Activation of α1-adrenoceptors causes phosphorylation of β2-adrenoceptors in the human prostate. This may enhance α1-adrenergic contraction and is possibly mediated by GRK2, which is expressed in prostate smooth muscle.• Mutual regulation between different adrenergic receptors might be involved in the therapeutic effects of α1-blockers in patients with benign prostate hyperplasia.
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| 42. |
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| 43. |
- Henningsohn, L, et al.
(author)
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Time after surgery, symptoms and well-being in survivors of urinary bladder cancer
- 2003
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In: BJU International. - 1464-4096 .- 1464-410X. ; 91:4, s. 325-330
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To evaluate how an increasing burden of symptoms influences well-being, anxiety and depression at different intervals after a radical cystectomy with urostomy for bladder cancer, as this therapy can induce long-term distressful symptoms. PATIENTS AND METHODS: Patients with bladder cancer undergoing radical cystectomy in Stockholm between 1969 and 1995 were matched with 434 controls from the normal population, all 404 patients operated on between 1985 and 1995 at three other hospitals in Sweden were invited to enter the study. The final analysis included 306 patients and 310 controls, all assessed for symptoms and well-being. RESULTS: A low or moderate level of well-being was reported by 35% of the patients having none or one of the symptoms studied, by 39% with two symptoms, by 45% with three symptoms and by 66% of those with four or more symptoms. The values, irrespective of symptom burden, were 45% after 2-5 years of follow-up, 58% after 6-10 years and 38% at > 10 years after surgery. The total symptom burden also influenced the risk of anxiety and depression. Symptom prevalence remained largely unaffected by the duration of follow-up, except for defecation urgency. CONCLUSIONS: The number of long-term symptoms after radical surgery with a urostomy for urinary bladder cancer affects the risk of anxiety, depression and low or moderate well-being.
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| 44. |
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| 45. |
- Jiang, Chong-He, et al.
(author)
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Prolonged increase in micturition threshold volume by anogenital afferent stimulation in the rat
- 1998
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In: British Journal of Urology International. - : Wiley. - 1464-4096. ; 82:3, s. 483-487
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Journal article (peer-reviewed)abstract
- Objective To determine whether induced bladder contractions influence the modulation by intravesical electrical stimulation (IVES) of the micturition reflex in anaesthetized rats, and to identify the optimal IVES frequency and duration. Materials and methods Seventy-six adult female rats, anaesthetized by α-chloralose, were divided into four groups to study the effect of: (i) IVES in combination with bladder contractions; (ii) bladder contractions alone; (iii) IVES frequency; and (iv) IVES duration. IVES was administered using a catheter electrode in the bladder. The effect of various IVES procedures was evaluated by determining the micturition threshold volume obtained from repeated cystometries before and after stimulation. Results Administering IVES with standard parameters induced a significant decrease in the micturition threshold volume for about an hour. There was no difference in outcome between IVES with the bladder filled and contracting during the stimulation or empty and not contracting. Imposed bladder contractions per se had no effect on the micturition threshold volume. IVES at low frequencies (≤20 Hz) had a better modulatory effect than higher frequencies and the optimum duration of IVES was 5 min. Conclusions Evoked bladder contractions did not improve the IVES-induced modulation of the micturition reflex. These findings might help to improve the clinical application of the IVES procedure.
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| 46. |
- Johansson, Anna, et al.
(author)
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Targeting castration-induced tumour hypoxia enhances the acute effects of castration therapy in a rat prostate cancer model
- 2011
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In: BJU International. - 1464-4096 .- 1464-410X. ; 107:11, s. 1818-1824
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Journal article (peer-reviewed)abstract
- OBJECTIVE: • To explore the effects of castration therapy, the standard treatment for advanced prostate cancer, in relation to tumour hypoxia and to elicit its importance for the short- and long-term therapeutic response. MATERIAL AND METHODS: • We used the androgen-sensitive rat Dunning H prostate tumour model that transiently responds to castration treatment followed by a subsequent relapse, much like the scenario in human patients. • Tumour tissues were analysed using stereological methods in intact, 1 and 7 days after castration therapy. RESULTS: • Hypoxia was transiently up-regulated after castration therapy and correlated with the induction of tumour cell apoptosis. • When castration therapy was combined with tirapazamine (TPZ), a drug that targets hypoxic cells and the vasculature, the effects on tumour cell apoptosis and tumour volume were enhanced in comparison to either castration or TPZ alone. CONCLUSION: • The present study suggests that castration-induced tumour hypoxia is a novel target for therapy.
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| 47. |
- Kirrander, Peter, 1978-, et al.
(author)
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Dynamic sentinel node biopsy in penile cancer : initial experiences at a Swedish referral centre
- 2013
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In: BJU International. - 1464-4096 .- 1464-410X. ; 111:3B, s. E48-E53
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Journal article (peer-reviewed)abstract
- Study Type Therapy (case series) Level of Evidence4 What's known on the subject? and What does the study add? According to the current European Association of Urology Guidelines, dynamic sentinel node biopsy is the recommended approach to assess lymph node status in men with cN0 intermediate and high risk penile cancer. Nevertheless, most encouraging results derive from a limited number of studies. The present study shows a false-negative rate of 15%, comparable with or better than several previous studies. Nevertheless, the aim should be a false-negative rate of no more than 5%. We conclude that increased overall experience and the use of the complete modern dynamic sentinel node biopsy protocol are paramount to improve results.OBJECTIVE center dot To evaluate the false-negative rate and complication rate of dynamic sentinel node biopsy (DSNB) in penile cancer.PATIENTS AND METHODS center dot In this retrospective study, 58 unilaterally or bilaterally clinically lymph node negative (cN0) patients with penile cancer (57 squamous cell carcinomas and one malignant melanoma), scheduled for DSNB at the orebro University Hospital, Sweden, between 1999 and 2011, were analysed. center dot Preoperative ultrasonography and fine-needle aspiration cytology of suspicious nodes were not introduced until 2008. center dot Patients were assessed by lymphoscintigraphy using 99mtechnetium nanocolloid on the day before surgery and the dissection of sentinel nodes was aided by the lymphoscintigraphic images and intraoperative detection of radiotracer and patent blue dye. center dot The false-negative rate and complication rate were calculated per groin.RESULTS center dot Of the 58 patients, 32 (55%) underwent preoperative ultrasonography. center dot Two patients had positive fine-needle aspiration cytology and discontinued further DSNB protocol. Of the remaining 56 patients, all but one were bilaterally cN0 and hence 111 cN0 groins were assessed by lymphoscintigraphy. center dot In the 55 bilaterally cN0 patients, lymphoscintigraphy visualized a bilateral sentinel node in 34 (62%). center dot At surgery, all excised sentinel nodes were radioactive while 43% were additionally blue. In total, at least one sentinel node was harvested in 96 (86%) of the DSNB staged groins. center dot A positive sentinel node was found in 11 groins (bilaterally in three patients). During a median follow-up of 21 months, two false-negative cases emerged, producing a false-negative rate of 15%. Both false-negative cases occurred during the first half of the study. The complication rate was 10%. The majority of complications were minor and transient.CONCLUSIONS center dot DSNB is a minimally invasive staging tool in men with cN0 penile cancer, enabling early detection of metastatic disease and thus optimal care. center dot Our false-negative rate of 15% is comparable or even favourable in comparison with several previous studies, but far from the 5% or less that we aim for. The complication rate found is somewhat higher than previously reported. center dot With increased overall experience and the continued use of the complete DSNB protocol, we believe our results will improve and the complication rate will decrease.
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| 48. |
- Kirrander, Peter, 1978-, et al.
(author)
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Human papillomavirus prevalence, distribution and correlation to histopathological parameters in a large Swedish cohort of men with penile carcinoma
- 2011
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In: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 108:3, s. 355-359
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To analyse the overall and type-specific human papillomavirus (HPV) prevalence and distribution in penile carcinoma and determine the correlation to histopathological parameters.PATIENTS AND METHODS: In this retrospective study, we analysed HPV status in 241 patients with penile carcinoma, treated at Örebro University Hospital, Örebro, Sweden, between 1984 and 2008. Age and date at diagnosis was recorded. The tumour specimens were categorized according to the UICC 2002 TNM classification. A subset of patients was operatively staged with regard to lymph node status. A commercially available Real Time PCR was used to detect 13 different types of HPV (6,11,16,18,31,33,35,45,51,52,56,58 and 59).RESULTS: We excluded 25 patients due to low DNA quality. Of the remaining 216, 179 (82.9%) tumour specimens were HPV infected. The majority of cases positive for HPV (70.4%) were infected by a single-type. The most frequent type was HPV 16 followed by HPV 18. No significant association between HPV status and pathological tumour stage, grade or lymph node status was found.CONCLUSION: The HPV prevalence found is higher than in most other studies, further strengthening HPV as an etiological agent in penile carcinoma. Furthermore, the high prevalence of HPV 16 and 18 raises the question of what potential impact current HPV vaccines that target these specific HPV types might have on penile carcinoma. No significant association between HPV status and histopathological parameters was found in the present study. Additional investigations are needed to draw final conclusions on the prognostic value of HPV status in penile carcinoma.
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| 49. |
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| 50. |
- Kvåle, Rune, et al.
(author)
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Concordance between Gleason scores of needle biopsies and radical prostatectomy specimens : a population-based study
- 2009
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In: BJU International. - 1464-4096 .- 1464-410X. ; 103:12, s. 1647-1654
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To study the concordance between the Gleason scores of needle biopsies and radical prostatectomy (RP) specimens in a population-based registry, to clarify whether the concordance depends on the annual number of RP specimens assessed in the pathology unit, and to identify preoperative clinical factors that predict upgrading from a Gleason score of or=7 in the RP specimen. PATIENTS AND METHODS: Through the Cancer Registry of Norway, we identified 1116 patients with available Gleason scores from biopsy and RP specimens. Concordance was evaluated using the kappa coefficient, and predictors of concordance were assessed in univariate and multivariate logistic regression analyses. RESULTS: The Gleason scores were identical in biopsy and RP specimens in 591 of the 1116 (53%) patients. The biopsy-based Gleason score more often under-graded (38%) than over-graded (9%) the RP-based Gleason score. Pathology units that examined >40 RP specimens annually had a higher concordance between the Gleason score in the biopsy and RP specimen than did lower-volume units. The rate of upgrading from a Gleason score of or=7 in the RP specimen increased with increasing preoperative prostate-specific antigen serum levels, and with increasing intervals between biopsy and RP. CONCLUSIONS: The concordance in Gleason score between biopsy and RP was highest among the pathology departments that regularly evaluated RP specimens. Careful consideration of clinical factors and biopsy grading might improve the identification of patients considered as suitable for active surveillance.
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