| 1. |
- Manni, Giovanni Li, et al.
(författare)
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The OpenMolcas Web : A Community-Driven Approach to Advancing Computational Chemistry
- 2023
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 19:20, s. 6933-6991
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Tidskriftsartikel (refereegranskat)abstract
- The developments of the open-source OpenMolcas chemistry software environment since spring 2020 are described, with a focus on novel functionalities accessible in the stable branch of the package or via interfaces with other packages. These developments span a wide range of topics in computational chemistry and are presented in thematic sections: electronic structure theory, electronic spectroscopy simulations, analytic gradients and molecular structure optimizations, ab initio molecular dynamics, and other new features. This report offers an overview of the chemical phenomena and processes OpenMolcas can address, while showing that OpenMolcas is an attractive platform for state-of-the-art atomistic computer simulations.
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| 2. |
- Mistretta, Francesco A., et al.
(författare)
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DFL23448, A Novel Transient Receptor Potential Melastin 8-Selective Ion Channel Antagonist, Modifies Bladder Function and Reduces Bladder Overactivity in Awake Rats
- 2016
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS. - 0022-3565 .- 1521-0103. ; 356:1, s. 200-211
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Tidskriftsartikel (refereegranskat)abstract
- The transient receptor potential melastin 8 ion channel (TRPM8) is implicated in bladder sensing but limited information on TRPM8 antagonists in bladder overactivity is available. This study characterizes a new TRPM8-selective antagonist (DFL23448 [5-(2-ethyl-2H-tetrazol-5-yl)-2-(3-fluorophenyl)-1,3-thiazol-4-ol]) and evaluates it in cold-induced behavioral tests and tests on bladder function and experimental bladder overactivity in vivo in rats. DFL23448 displayed IC50 values of 10 and 21 nM in hTRPM8 human embryonic kidney 293 cells activated by Cooling Agent 10 or cold, but it had limited activity (IC50 > 10 mu M) at transient receptor potential vanilloids TRPV1, TRPA1, or TRPV4 or at various G protein-coupled receptors. In rats, DFL23448 administered intravenously or orally had a half-life of 37 minutes or 4.9 hours, respectively. DLF23448 (10 mg/kg i.v.) reduced icilin-induced "wet dog-like" shakes in rats. Intravesical DFL23448 (10 mg/l), but not vehicle, increased micturition intervals, micturition volume, and bladder capacity. During bladder overactivity by intravesical prostaglandin E-2 (PGE(2)), vehicle controls exhibited reductions in micturition intervals, micturition volumes, and bladder capacity by 37%-39%, whereas the same parameters only decreased by 12%-15% (P < 0.05-0.01 versus vehicle) in DFL23448-treated rats. In vehicle-treated rats, but not in DFL23448-treated rats, intravesical PGE(2) increased bladder pressures. Intravenous DFL23448 at 10 mg/kg, but not 1 mg/kg DFL23448 or vehicle, increased micturition intervals, micturition volumes, and bladder capacity. During bladder overactivity by intravesical PGE(2), micturition intervals, micturition volumes, and bladder capacity decreased in vehicle- and 1 mg/kg DFL23448-treated rats, but not in 10 mg/kg DFL23448-treated rats. Bladder pressures increased less in rats treated with DFL23448 10 mg/kg than in vehicle-or 1 mg/kg DFL23448-treated rats. DFL23448 (10 mg/kg i.v.), but not vehicle, prevented cold stress-induced bladder overactivity. Our results support a role for bladder TRPM8-mediated signals in experimental bladder overactivity.
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| 3. |
- Mistretta, Francesco A, et al.
(författare)
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DFL23448, a novel TRPM8-selective ion channel antagonist, modifies bladder function and reduces bladder overactivity in awake rats.
- 2016
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 1521-0103. ; 356:1, s. 200-211
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Tidskriftsartikel (refereegranskat)abstract
- The transient receptor potential (TRP) melastin 8 ion channel (TRPM8) is implicated in bladder sensing but limited information on TRPM8 antagonists in bladder overactivity (BO) is available. This study characterizes a new TRPM8-selective antagonist (DFL23448) and evaluates it in cold-induced behavioral tests and on bladder function and experimental BO in vivo in rats. DFL23448 displayed IC50 values of 10 and 21nM in hTRPM8 HEK-293 cells activated by Cooling Agent 10 or cold, but had limited activity (IC50 > 10μM) at TRPV1, TRPA1, TRPV4, or at various G-protein-coupled receptors. In rats, DFL23448 had a half-life of 37 minutes (intravenous; i.v.) or 4.9 hours (oral). DLF23448 (10mg/kg, i.v) reduced icilin-induced wet-dog shakes in rats. Intravesical (i.ves.) DFL23448 (10mg/L) but not vehicle increased micturition intervals (MI), micturition volumes (MV) and bladder capacity (BC). During BO by i.ves. PGE2, vehicle controls exhibited reductions of MI, MV and BC by 37-39%, whereas the same parameters only decreased by 12-15% (p<0.05-0.01 vs. vehicle) in DFL23448-treated rats. In vehicle-treated rats but not in DFL23448-treated rats, i.ves. PGE2 increased bladder pressures. Intravenous DFL23448 at 10mg/kg, but not 1mg/kg DFL23448 or vehicle, increased MI, MV, and BC. During BO by i.ves. PGE2, MI, MV, and BC decreased in vehicle- and in DFL23448 1mg/kg-treated rats, but not in DFL23448 10mg/kg-treated rats. Bladder pressures increased less in rats treated with DFL23448 10mg/kg than in vehicle- or DFL23448 1mg/kg- treated rats. DFL23448 (10mg/kg, i.v.), but not vehicle, prevented cold-stress BO. Our results support a role for bladder TRPM8-mediated signals in experimental BO.
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| 4. |
- Pellegrino, Francesco, et al.
(författare)
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Predictive value of kallikrein forms and β-microseminoprotein in blood from patients with evidence of detectable levels of PSA after radical prostatectomy
- 2023
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Ingår i: World Journal of Urology. - 1433-8726. ; 41, s. 1489-1495
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To determine whether β-microseminoprotein or any of the kallikrein forms in blood-free, total or intact PSA or total hK2-predict metastasis in patients with evidence of detectable levels of PSA in blood after radical prostatectomy.METHOD: We determined marker concentrations in blood from 173 men treated with radical prostatectomy and evidence of detectable levels of PSA in the blood (PSA ≥ 0.05) after surgery between 2014 and 2015 and at least 1 year after any adjuvant therapy. We used Cox regression to determine whether any marker was associated with metastasis using both univariate and multivariable models that included standard clinical predictors.RESULTS: Overall, 42 patients had metastasis, with a median follow-up of 67 months among patients without an event. The levels of intact and free PSA and free-to-total PSA ratio were significantly associated with metastasis. Discrimination was highest for free PSA (c-index: 0.645) and free-to-total PSA ratio (0.625). Only free-to-total PSA ratio remained associated with overall metastasis (either regional or distant) after including standard clinical predictors (p = 0.025) and increased discrimination from 0.686 to 0.697. Similar results were found using distant metastasis as an outcome (p = 0.011; c-index increased from 0.658 to 0.723).CONCLUSION: Our results provide evidence that free-to-total PSA ratio can risk stratifying patients with evidence of detectable levels of PSA in blood after RP. Further research is warranted on the biology of prostate cancer markers in patients with evidence of detectable levels of PSA in blood after radical prostatectomy. Our findings on the free-to-total ratio for predicting adverse oncologic outcomes need to be validated in other cohorts.
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| 5. |
- Abrate, Alberto, et al.
(författare)
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Mesenchymal stem cells expressing therapeutic genes induce autochthonous prostate tumour regression
- 2014
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 50:14, s. 2478-2488
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stem cells (MSC) as vehicles of therapeutic genes represent a unique tool to activate drugs within a neoplastic mass due to their property to home and engraft into tumours. In particular, MSC expressing the cytosine deaminase:: uracil phosphoribosyltransferase (CD-MSC) have been previously demonstrated to inhibit growth of subcutaneous prostate cancer xenografts thanks to their ability to convert the non-toxic 5-fluorocytosine into the antineoplastic 5-fluorouracil. Since both the immune system and the tumour microenvironment play a crucial role in directing cancer progression, in order to advance towards clinical applications, we tested the therapeutic potential of this approach on animal models that develop autochthonous prostate cancer and preserve an intact immune system. As cell vectors, we employed adipose-tissue and bone-marrow MSC. CD-MSC toxicity on murine prostate cancer cells and tumour tropism were verified in vitro and ex-vivo before starting the preclinical studies. Magnetic Resonance Imaging was utilised to follow orthotopic tumour progression. We demonstrated that intravenous injections of CD-MSC cells, followed by intraperitoneal administration of 5-fluorocytosine, caused tumour regression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which develops aggressive and spontaneous prostate cancer. These results add new insights to the therapeutic potential of specifically engineered MSC in prostate cancer disease.
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| 6. |
- Ahmed, Kamran, et al.
(författare)
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Development of a standardised training curriculum for robotic surgery: a consensus statement from an international multidisciplinary group of experts
- 2015
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Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 116:1, s. 93-101
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To explore the views of experts about the development and validation of a robotic surgery training curriculum, and how this should be implemented. Materials and methods: An international expert panel was invited to a structured session for discussion. The study was of a mixed design, including qualitative and quantitative components based on focus group interviews during the European Association of Urology (EAU) Robotic Urology Section (ERUS) (2012), EAU (2013) and ERUS (2013) meetings. After introduction to the aims, principles and current status of the curriculum development, group responses were elicited. After content analysis of recorded interviews generated themes were discussed at the second meeting, where consensus was achieved on each theme. This discussion also underwent content analysis, and was used to draft a curriculum proposal. At the third meeting, a quantitative questionnaire about this curriculum was disseminated to attendees to assess the level of agreement with the key points. Results: In all, 150 min (19 pages) of the focus group discussion was transcribed (21 316 words). Themes were agreed by two raters (median agreement kappa 0.89) and they included: need for a training curriculum (inter-rater agreement kappa 0.85); identification of learning needs (kappa 0.83); development of the curriculum contents (kappa 0.81); an overview of available curricula (kappa 0.79); settings for robotic surgery training ((kappa 0.89); assessment and training of trainers (kappa 0.92); requirements for certification and patient safety (kappa 0.83); and need for a universally standardised curriculum (kappa 0.78). A training curriculum was proposed based on the above discussions. Conclusion: This group proposes a multi-step curriculum for robotic training. Studies are in process to validate the effectiveness of the curriculum and to assess transfer of skills to the operating room.
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| 7. |
- Aizawa, Naoki, et al.
(författare)
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URB937, a peripherally restricted inhibitor for fatty acid amide hydrolase, reduces prostaglandin E-2-induced bladder overactivity and hyperactivity of bladder mechano-afferent nerve fibres in rats
- 2016
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Ingår i: BJU International. - : WILEY-BLACKWELL. - 1464-4096 .- 1464-410X. ; 117:5, s. 821-828
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Tidskriftsartikel (refereegranskat)abstract
- Objective To determine if inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) can counteract the changes in urodynamic variables and bladder afferent activities induced by intravesical prostaglandin E-2 (PGE(2)) instillation in rats. Materials and methods In female Sprague-Dawley rats we studied the effects of URB937, a peripherally restricted FAAH inhibitor, on single-unit afferent activity (SAA) during PGE(2)-induced bladder overactivity (BO). SAA measurements were made in urethane-anaesthetised rats and Ad-and C-fibres were identified by electrical stimulation of the pelvic nerve and by bladder distention. Cystometry (CMG) in conscious animals and during SAA measurements was performed during intravesical instillation of PGE(2) (50 or 100 mu M) after intravenous administration of URB937 (0.1 and 1 mg/kg) or vehicle. In separate experiments, the comparative expressions of FAAH and cannabinoid receptors, CB1 and CB2, in microsurgically removed L6 dorsal root ganglion (DRG) were studied by immunofluorescence. Results During CMG, 1 mg/kg URB937, but not vehicle or 0.1 mg/kg URB937, counteracted the PGE(2)-induced changes in urodynamic variables. PGE(2) increased the SAAs of C-fibres, but not Ad-fibres. URB937 (1 mg/kg) depressed Ad-fibre SAA and abolished the facilitated C-fibre SAA induced by PGE(2). The DRG nerve cells showed strong staining for FAAH, CB1 and CB2, with a mean (SEM) of 77 (2)% and 87 (3)% of FAAH-positive nerve cell bodies co-expressing CB1 or CB2 immunofluorescence, respectively. Conclusion The present results show that URB937, a peripherally restricted FAAH inhibitor, reduces BO and C-fibre hyperactivity in the rat bladder provoked by PGE(2), suggesting an important role of the peripheral endocannabinoid system in BO and hypersensitivity.
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| 8. |
- Andriole, Gerald L, et al.
(författare)
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Effect of dutasteride on the risk of prostate cancer.
- 2010
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Ingår i: The New England journal of medicine. - 1533-4406. ; 362:13, s. 1192-202
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a study to determine whether dutasteride reduces the risk of incident prostate cancer, as detected on biopsy, among men who are at increased risk for the disease.
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| 9. |
- Artibani, Walter, et al.
(författare)
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EAU Policy on Live Surgery Events.
- 2014
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 66:1, s. 87-97
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Forskningsöversikt (refereegranskat)abstract
- Live surgery is an important part of surgical education, with an increase in the number of live surgery events (LSEs) at meetings despite controversy about their real educational value, risks to patient safety, and conflicts of interest.
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| 10. |
- Bastian, Patrick J., et al.
(författare)
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Insignificant Prostate Cancer and Active Surveillance: From Definition to Clinical Implications
- 2009
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 55:6, s. 1321-1332
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Forskningsöversikt (refereegranskat)abstract
- Context: Due to early detection strategies, prostate cancer is diagnosed early in its natural history. It remains unclear whether all patients diagnosed with prostate cancer warrant radical treatment or may benefit from delayed intervention following active surveillance. Objective: A systematic review of active surveillance protocols to investigate the inclusion criteria for active surveillance and the outcome of treatment. Evidence acquisition: Medline was searched using the following terms: prostate cancer, active surveillance and expectant management for dates up to October 2008. Further studies were chosen on the basis of manual searches of reference lists and review papers. Evidence synthesis: Numerous studies on active surveillance were identified. The recent inclusion criteria of the studies are rather similar. Keeping the short follow-up of all studies in mind, the majority of men stay on active surveillance, and the percentage of patients receiving active treatment is as high as 35% of all patients. Once a patients requires active treatment, most patients still present with curable prostate cancer. Furthermore, only few deaths due to prostate cancer have occurred. Conclusions: Active surveillance is an alternative option to immediate treatment of men with presumed insignificant prostate cancer. It seems that criteria used to identify men with low-risk prostate cancer are rather similar, and immediate treatment of men meeting these criteria may result in an unnecessary number of treatments in these highly selected patients. Data from randomised trials comparing active surveillance and active treatment will provide additional insight into outcome and follow-up strategies. (C) 2009 Published by Elsevier B.V. on behalf of European Association of Urology.
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| 11. |
- Bettiga, Arianna, et al.
(författare)
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Bladder cancer cell growth and motility implicate cannabinoid 2 receptor-mediated modifications of sphingolipids metabolism
- 2017
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The inhibitory effects demonstrated by activation of cannabinoid receptors (CB) on cancer proliferation and migration may also play critical roles in controlling bladder cancer (BC). CB expression on human normal and BC specimens was tested by immunohistochemistry. Human BC cells RT4 and RT112 were challenged with CB agonists and assessed for proliferation, apoptosis, and motility. Cellular sphingolipids (SL) constitution and metabolism were evaluated after metabolic labelling. CB1-2 were detected in BC specimens, but only CB2 was more expressed in the tumour. Both cell lines expressed similar CB2. Exposure to CB2 agonists inhibited BC growth, down-modulated Akt, induced caspase 3-activation and modified SL metabolism. Baseline SL analysis in cell lines showed differences linked to unique migratory behaviours and cytoskeletal re-arrangements. CB2 activation changed the SL composition of more aggressive RT112 cells by reducing (p amp;lt; 0.01) Gb3 ganglioside (-50 +/- 3%) and sphingosine 1-phosphate (S1P, -40 +/- 4%), which ended up to reduction in cell motility (-46 +/- 5%) with inhibition of p-SRC. CB2-selective antagonists, gene silencing and an inhibitor of SL biosynthesis partially prevented CB2 agonist-induced effects on cell viability and motility. CB2 activation led to ceramide-mediated BC cell apoptosis independently of SL constitutive composition, which instead was modulated by CB2 agonists to reduce cell motility.
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| 12. |
- Buono, Roberta, et al.
(författare)
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Silodosin and tadalafil have synergistic inhibitory effects on nerve-mediated contractions of human and rat isolated prostates
- 2014
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Ingår i: European Journal of Pharmacology. - : Elsevier. - 0014-2999 .- 1879-0712. ; 744, s. 42-51
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Tidskriftsartikel (refereegranskat)abstract
- Lower urinary tract symptoms (CUTS) in men with benign prostatic hyperplasia (BPH) are associated with erectile dysfunction. Alpha-1-adrenoceptor antagonists are effective drugs for treating symptomatic BPH. Clinical data show improvements in LUIS by phosphodiesterase 5 inhibitors. This study aimed to evaluate effects of siloclosin, a highly selective alpha(1A)-adrenoceptor antagonist, alone or in combination with the phosphocliesterase 5 inhibitor tadalafil on contractions of isolated human and rat prostates. In organbath studies, effects of increasing concentrations of siloclosin (1 nM-1 mu M) and tadalafil (100 nM-100 mu M) on contractions by electrical field stimulation or phenylephrine of human and rat prostate strip preparations were investigated. The combination silodosin and tadalafil reduced electrically-induced contractions of human prostate preparations better than single drugs alone. At any frequencies (1-32 Hz), inhibitory effects of combined therapy (P-values vs single drug) in human tissue were 26-42% (1 nM silodosin+100 nM tadalafil; P less than 0.05), 40-58% (10 nM silodosin+1 mu M tadalafil; P less than 0.001-0.05), 56-67% (100 nM silodosin+10 mu M tadalafil; P less than 0.01-0.05), and 33-55% (1 mu M silodosin+100 mu M tadalafil P less than 0.01-0.05), Similar findings were obtained in rat prostate preparations. In human and rat prostate tissue, the drug combination exerted similar inhibitory effect on phenylephrine contractions as silodosin alone. Silodosin plus tadalafil had greater potency than each drug alone to inhibit prostate contractions to electrical field stimulation but not to phenylephrine. This study supports the clinical application of a combination of an (alpha(1A)-adrenoceptor antagonist and a phosphodiesterase 5 inhibitor for symptomatic BPH and suggests that the drug combination requires endogenous nerve-activity for optimal effect.
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| 13. |
- Castiglione, Fabio, et al.
(författare)
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Adipose-derived Stem Cells Counteract Urethral Stricture Formation in Rats
- 2016
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 70:6, s. 1032-1041
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Tidskriftsartikel (refereegranskat)abstract
- Background: A medical treatment for urethral stricture (US) is not yet available. Objective: To evaluate if local injection of human adipose tissue-derived stem cells (hADSC) prevents urethral fibrosis in a rat model of US. Design, setting, and participants: Male rats were divided into three groups: sham, US, and hADSC (n = 12 each). Sham rats received a vehicle injection in the urethral wall. US and hADSCs were incised and injected with the fibrosis-inducer transforming growth factor-β1 in the urethral wall. Intervention: One day later, hADSCs were injected in the urethral wall of hADSC rats whereas sham and US rats were injected with the vehicle. After 4 wk, the rats underwent cystometries and tissues were then harvested for functional and molecular analyses. Outcome measurements and statistical analysis: Cystometry, microultrasound, histochemistry, organ bath studies, reverse transcription polymerase chain reaction, and western blot. Results and limitations: US rats exhibited 49-51% shorter micturition intervals, 35-51% smaller micturition volumes and bladder capacity, 33-62% higher threshold pressures and flow pressures, and 35-37% lower bladder filling compliance compared with hADSC-treated rats and sham rats (p
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| 14. |
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| 15. |
- Castiglione, Fabio, et al.
(författare)
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Inhibition of Phosphodiesterase 4 Enhances Clitoral and Vaginal Blood Flow Responses to Dorsal Clitoral Nerve Stimulation or PGE1 in Anesthetized Female Rats
- 2013
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Ingår i: Journal of Sexual Medicine. - : Wiley-Blackwell. - 1743-6095 .- 1743-6109. ; 10:4, s. 939-950
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. Cyclic adenosine 35 monophosphate (cAMP) is produced by adenylate cyclase after activation by, e.g., vasoactive intestinal polypeptide or prostaglandin E1 (PGE1). The cAMP-degrading phosphodiesterase 4 (PDE4) is expressed in the vagina and clitoris, but no information is available on the functional role for PDE4-related signals in the female neurovascular genital response. Aim. The aim of this study is to study the effect of inhibition of PDE4 with rolipram on nerve- and PGE1-induced vaginal and clitoral blood flow responses of rat. Methods. Measure of clitoral and vaginal blood flow and blood pressure in anesthetized rats during activation of the dorsal clitoral nerve (DCN) before and after intraperitoneal administration of rolipram or sildenafil (phosphodiesterase type 5 inhibitors [PDE5]) and nitro-L-arginine (L-NNA) (nitric oxide synthase inhibitor). Effect by topical administration of PGE1 on genital blood flow was also evaluated. Main Outcome Measure. Blood flow was recorded as tissue perfusion units (TPU) by a Laser Doppler Flowmeter. Mean arterial blood pressure (MAP) was recorded (cmH2O) in the carotid artery. Blood flow responses are expressed as TPU/MAP. Unpaired t-test and an analysis of variance were used. Results. Compared with control stimulations, rolipram (0.3mg/kg) caused a twofold increase in peak blood flow (Pandlt;0.05) and fourfold increase of the rate of clitoral blood flow during activation of the DCN (Pandlt;0.05). Simultaneously, a twofold increase in peak blood flow and threefold increase in rate of blood flow were noted in the vagina (Pandlt;0.05). Similar effects were noted for sildenafil (0.2mg/kg) (Pandlt;0.05). Inhibitory effects by L-NNA (60mg/kg) on blood flow responses to DCN activation were significantly lower for rats treated with rolipram than with sildenafil (Pandlt;0.05). PGE1-induced (10g) blood flow responses were significantly higher (Pandlt;0.05) in rats treated with rolipram than with sildenafil. Conclusions. These findings suggest that the cAMP/PDE4 system may be of similar functional importance as the nitric oxide/cyclic guanosine monophosphate/PDE5 pathway for neurovascular genital responses of the female rat. Castiglione F, Bergamini A, Russo A, La Croce G, Castagna G, Colciago G, Salonia A, Rigatti P, Montorsi F, and Hedlund P. Inhibition of phosphodiesterase 4 enhances clitoral and vaginal blood flow responses to dorsal clitoral nerve stimulation or PGE1 in anesthetized female rats. J Sex Med 2013; 10: 939-950.
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| 16. |
- Castiglione, Fabio, et al.
(författare)
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Intratunical Injection of Human Adipose Tissue-derived Stem Cells Prevents Fibrosis and Is Associated with Improved Erectile Function in a Rat Model of Peyronies Disease
- 2013
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 63:3, s. 551-560
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Tidskriftsartikel (refereegranskat)abstract
- Background: Peyronies disease (PD) is a connective tissue disorder of the tunica albuginea (TA). Currently, no gold standard has been developed for the treatment of the disease in its active phase. less thanbrgreater than less thanbrgreater thanObjective: To test the effects of a local injection of adipose tissue-derived stem cells (ADSCs) in the active phase of a rat model of PD on the subsequent development of fibrosis and elastosis of the TA and underlying erectile tissue. less thanbrgreater than less thanbrgreater thanDesign, setting, and participants: A total of 27 male 12-wk-old Sprague-Dawley rats were divided in three equal groups and underwent injection of vehicle (sham), 50-mu g transforming growth factor (TGF)-beta 1 in a 50-mu l vehicle in either a PD or a PD plus ADSC group in the dorsal aspect of the TA. less thanbrgreater than less thanbrgreater thanIntervention: The sham and PD groups were treated 1 d after TGF-beta 1 injection with intralesional treatment of vehicle, and the PD plus ADSC group received 1 million human-labeled ADSCs in the 50-mu l vehicle. Five weeks after treatment, six rats per group underwent erectile function measurement. Following euthanasia, penises were harvested for histology and Western blot. less thanbrgreater than less thanbrgreater thanOutcome measurements and statistical analysis: The ratio of intracavernous pressure to mean arterial pressure (ICP/MAP) upon cavernous nerve stimulation, elastin, and collagen III protein expression and histomorphometric analysis of the penis. Statistical analysis was performed by analysis of variance followed by the Tukey-Kramer test for post hoc comparisons or the Mann-Whitney test when applicable. less thanbrgreater than less thanbrgreater thanResults and limitations: Erectile function significantly improved after ADSC treatment (ICP/MAP 0.37 in PD vs 0.59 in PD plus ADSC at 5-V stimulation; p = 0.03). PD animals developed areas of fibrosis and elastosis with a significant upregulation of collagen III and elastin protein expression. These fibrotic changes were prevented by ADSC treatment. less thanbrgreater than less thanbrgreater thanConclusions: This study is the first to test stem cell therapy in an animal model of PD. Injection of ADSCs into the TA during the active phase of PD prevents the formation of fibrosis and elastosis in the TA and corpus cavernosum.
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| 17. |
- Castiglione, Fabio, et al.
(författare)
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Intratunical Injection of Human Adipose Tissue–Derived Stem Cells Restores Collagen III/I Ratio in a Rat Model of Chronic Peyronie's Disease
- 2019
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Ingår i: Sexual Medicine. - : Oxford University Press (OUP). - 2050-1161. ; 7:1, s. 94-103
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Previous studies have shown that the injection of adipose tissue–derived stem cells (ADSCs) into the tunica albuginea (TA) during the active phase of Peyronie's disease (PD) prevents the development of fibrosis. Aim: To investigate, using an animal model, whether local injection of human ADSCs (hADSCs) can alter the degree of fibrosis in the chronic phase of PD. Methods: 27 male, 12-week-old rats were divided into 3 equal groups: sham, PD without treatment, and PD treated with hADSCs 1 month after disease induction. Sham rats underwent 2 injections of vehicle into the TA 1 month apart. PD rats underwent transforming growth factor β1 (TGFβ1) injection and injection of vehicle 1 month later. PD-hADSC rats underwent TGFβ1 injection followed by 1 million hADSCs 1 month later. 1 week after treatment, n = 3 animals/group were euthanized, and the penises were harvested for quantitative polymerase chain reaction. 1 month after treatment, the other animals, n = 6 per group, underwent measurement of intracavernous pressure (ICP) and mean arterial pressure (MAP) during electrostimulation of the cavernous nerve. After euthanasia, penises were again harvested for histology and Western blot. Main Outcome Measure: The primary outcome measures included (a) gene expression at one week post-injection; (b) measurement of ICP/MAP upon cavernous nerve stimulation as a measure of erectile function; (c) elastin, collagen I and III protein expression; and (d) Histomorphometric analysis of the penis. Means where compared by analysis of variance (ANOVA) followed by a Student-Newman-Keuls test for post hoc comparisons or Mann-Whitney test when applicable. Results: No significant difference was noted in ICP or ICP/MAP in response to cavernous nerve electrostimulation between the 3 groups at 2.5, 5, and 7.5 V (P > .05 for all voltages). PD animals developed tunical and subtunical areas of fibrosis with a significant upregulation of collagen III protein. The collagen III/I ratio was higher in the PD (4.6 ± 0.92) group compared with sham (0.66 ± 0.18) and PD-hADSC (0.86 ± 0.06) groups (P < .05) These fibrotic changes were prevented when treated with hADSCs. Compared with PD rats, PD-hADSC rats demonstrated a decreased expression of several fibrosis-related genes. Conclusion: Injection of hADSCs reduces collagen III expression in a rat model of chronic PD. Castiglione F, Hedlund P, Weyne E, et al. Intratunical Injection of Human Adipose Tissue–Derived Stem Cells Restores Collagen III/I Ratio in a Rat Model of Chronic Peyronie's Disease. Sex Med 2018;XX:XX–XX.
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| 18. |
- Castiglione, Fabio, et al.
(författare)
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Intratunical injection of stromal vascular fraction prevents fibrosis in a rat model of Peyronies disease
- 2019
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Ingår i: BJU International. - : WILEY. - 1464-4096 .- 1464-410X. ; 124:2, s. 342-348
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate whether local injection of autologous adipose stromal vascular fraction (SVF) can prevent the development of fibrosis and elastosis in the tunica albuginea (TA) using a rat model of the acute phase of Peyronies disease (PD). Methods A total of 24 male 12-week-old Sprague-Dawley rats were divided into three equal groups: sham; PD without treatment (transforming growth factor-beta [TGF -beta]); and PD treated with SVF 1 day after disease induction. Sham rats received two injections of vehicle into the TA 1 day apart. TGF -beta rats received TGF- beta 1 injection and injection of vehicle 1 day later. SVF rats received TGF-beta 1 injection, followed by SVF 1 day later. One month after treatment, all rats underwent measurement of intracavernosal pressure and mean arterial pressure during electrostimulation of the cavernous nerve. The rats were then killed and penises were harvested for histology and Western blot analysis. Results Erectile function was moderately reduced in the TGF-beta group and was significantly improved after SVF treatment (P amp;lt; 0.05). PD rats developed areas of fibrosis with a significant upregulation of collagen III, collagen I and elastin protein expression. These fibrotic changes were prevented when treated with SVF. Conclusions Local injection of SVF may represent treatment for the acute phase of PD.
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| 19. |
- Castiglione, Fabio, et al.
(författare)
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Perioperative Betamethasone Treatment Reduces Signs of Bladder Dysfunction in a Rat Model for Neurapraxia in Female Urogenital Surgery
- 2012
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 62:6, s. 1076-1085
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Information on autonomic neurapraxia in female urogenital surgery is scarce, and a model to study it is not available.OBJECTIVE:To develop a model to study the impact of autonomic neurapraxia on bladder function in female rats, as well as to assess the effects of corticosteroid therapy on the recovery of bladder function in this model.DESIGN, SETTING, AND PARTICIPANTS:Female Sprague-Dawley rats were subjected to bilateral pelvic nerve crush (PNC) and perioperatively treated with betamethasone or vehicle. Bladder function and morphology of bladder tissue were evaluated and compared with sham-operated rats.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Western blot, immunohistochemistry, organ bath experiments, and cystometry.RESULTS AND LIMITATIONS:Sham-operated rats exhibited regular micturitions without nonvoiding contractions (NVCs). Crush of all nerve branches of the pelvic plexus or PNC resulted in overflow incontinence and/or NVCs. Betamethasone treatment improved recovery of regular micturitions (87.5% compared with 27% for vehicle; p<0.05), reduced lowest bladder pressure (8 ± 2 cm H(2)O compared with 21 ± 5 cm H(2)O for vehicle; p<0.05), and reduced the amplitude of NVCs but had no effect on NVC frequency in PNC rats. Compared with vehicle, betamethasone-treated PNC rats had less CD68 (a macrophage marker) in the pelvic plexus and bladder tissue. Isolated bladder from betamethasone-treated PNC rats exhibited better nerve-induced contractions, contained more cholinergic and sensory nerves, and expressed lower amounts of collagen III than bladder tissue from vehicle-treated rats.CONCLUSIONS:PNC causes autonomic neurapraxia and functional and morphologic changes of isolated bladder tissue that can be recorded as bladder dysfunction during awake cystometry in female rats. Perioperative systemic betamethasone treatment reduced macrophage contents of the pelvic plexus and bladder, partially counteracted changes in the bladder tissue, and had protective effects on micturition function.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Fallara, Giuseppe, et al.
(författare)
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Recurrence pattern in localized RCC : results from a European multicenter database (RECUR)
- 2022
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Ingår i: Urologic Oncology. - : Elsevier. - 1078-1439 .- 1873-2496. ; 40:11, s. 494.e11-494.e17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The impact of open versus minimally invasive surgery on recurrence pattern in the management of localized renal cell carcinoma (RCC) remains uncertain. We thus aimed to determine the impact of surgical approach on survival and recurrence pattern.Material and methods: This is a multi-institutional, matched cohort study on patients with pT1-3aN0M0 RCC from the RECUR database. After propensity score matching between open and minimally invasive surgery, disease-free (DFS) survival and risk of first recurrence according to recurrence site, namely local recurrence, abdominal/retroperitoneal, thoracic/mediastinal or uncommon site metastases were investigated with Cox regression analysis. Overall (OS) and Cancer Specific Survival (CSS) were also assessed.Results: After matching, 1,019 patients who underwent open and 1,019 who underwent minimally invasive surgery were included (of which 70 robot-assisted). At 5.2 years of median follow-up, 130 patients in open and 125 in minimally invasive group experienced disease progression. A higher risk of local recurrence (HR 2.06; 95% CI 1.18–3.58, P-value = 0.01) and uncommon site metastases (HR 1.09; 95% CI 1.01–1.16; P-value = .04) was found for minimally invasive surgery relative to open surgery, while no difference was found in terms of DFS (HR 0.83; 95% CI 0.64–1.06; P-value = .14). No differences were found in terms of OS and CSS. Main limitation is the retrospective nature of the study.Conclusions: The risk for local recurrence and uncommon site metastases was higher for minimally invasive surgery compared to open surgery, although no differences were found for OS, CSS, and DFS.
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| 25. |
- Fridriksson, Jon Örn, 1981-
(författare)
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Adverse effects of curative treatment of prostate cancer
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Screening for prostate cancer is debated, there is conflicting data on the net benefit of screening. Men who consider screening need to be informed on the pros and cons. Rehospitalization after surgery can be used as an indicator of general quality of care. For radical prostatectomy, little is known on the readmission rate after surgery. Men diagnosed with low- and intermediate-risk prostate cancer have low prostate-cancer specific mortality. However, adverse effects after curative treatment can be severe and decrease quality of life. Curative treatments for prostate cancer differ mainly in the pattern of adverse effects but detailed analysis of long-term adverse effects is lacking.The aim of this thesis was to assess the perioperative quality of radical prostatectomy and the risk of adverse effects after curative treatment for prostate cancer.Material and Methods In this thesis, data from the National Prostate Cancer Register (NPCR) and other nationwide Swedish registers were used. By use of the Swedish personal identity number, NPCR was cross-linked to other registers creating Prostate Cancer data Base Sweden (PCBaSe), a large dataset for research.Results The proportion of men who had received information on the pros and cons of screening for prostate cancer with PSA testing was low (14%) indicating that the majority of men who were screened did not make an informed decision. The risk of rehospitalization within 90 days after radical prostatectomy was approximately 10% and similar after retropubic and robot-assisted radical prostatectomy. Compared to controls, there was an increased risk of adverse effects after both radiotherapy and radical prostatectomy up to twelve years after treatment and the overall risk was quite similar after retropubic and robot-assisted radical prostatectomy.Conclusion Improved information to men on the pros and cons of PSA screening is warranted. The risk of adverse effects was elevated up to 12 years after curative treatment for prostate cancer. The pattern of adverse effects was different after radiotherapy and radical prostatectomy but quite similar after retropubic and robot-assisted radical prostatectomy.
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| 26. |
- Fuellhase, Claudius, et al.
(författare)
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Spinal Cord FAAH in Normal Micturition Control and Bladder Overactivity in Awake Rats
- 2013
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 189:6, s. 2364-2370
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We assessed whether spinal inhibition of the cannabinoid degrading enzyme FAAH would have urodynamic effects in normal rats and rats with bladder overactivity induced by partial urethral obstruction or prostaglandin E2. We also determined the expression of FAAH, and the cannabinoid receptors CB1 and CB2 in the sacral spinal cord. Materials and Methods: We used 44 rats for functional (cystometry) and Western blot experiments. The FAAH inhibitor oleoyl ethyl amide (3 to 300 nmol) was administered intrathecally (subarachnoidally) or intravenously. The expression of FAAH and CB1/CB2 receptors was determined by Western blot. Results: Oleoyl ethyl amide given intrathecally affected micturition in normal rats and rats with bladder overactivity but effects were more pronounced in the latter. In normal rats oleoyl ethyl amide only decreased micturition frequency, while it decreased frequency and bladder pressures in rats with bladder overactivity. Intravenous oleoyl ethyl amide (3 to 300 nmol) had no urodynamic effect. FAAH and CB1/CB2 receptors were expressed in the rat sacral spinal cord. The expression of CB1/CB2 receptors but not FAAH was higher in obstructed than in normal rats. Conclusions: FAAH inhibition in the sacral spinal cord by oleoyl ethyl amide resulted in urodynamic effects in normal rats and rats with bladder overactivity. The spinal endocannabinoid system may be involved in normal micturition control and it appears altered when there is bladder overactivity.
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| 27. |
- Fuellhase, Claudius, et al.
(författare)
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Spinal neuronal cannabinoid receptors mediate urodynamic effects of systemic fatty acid amide hydrolase (FAAH) inhibition in rats
- 2016
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Ingår i: Neurourology and Urodynamics. - : WILEY-BLACKWELL. - 0733-2467 .- 1520-6777. ; 35:4, s. 464-470
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Tidskriftsartikel (refereegranskat)abstract
- AimsTo test if urodynamic effects from systemic Fatty Acid Amide Hydrolase (FAAH) inhibition involve sacral spinal cannabinoid type 1 (CB1) or type 2 (CB2) receptors. MethodsMale rats with or without partial urethral obstruction were used for cystometry or immunohistochemistry. Urodynamic effects of intravenous (IV) 0.3mg/kg Oleoyl Ethyl Amide (OEtA; FAAH inhibitor), and intrathecal (IT) 5g rimonabant (CB1 antagonist) or 5g SR144528 (CB2 antagonist) were studied in awake rats. ResultsAfter administration of rimonabant or SR144528, non-obstructed rats with normal bladder function developed bladder overactivity (BO), which was counteracted by OEtA. OEtA also counteracted BO in obstructed rats. SR144528 did not affect bladder function in obstructed rats but counteracted the urodynamic effects of OEtA. Surprisingly, rimonabant (and AM251, another CB1 antagonist) reduced BO in obstructed rats, whereafter OEtA produced no additional urodynamic effects. CB1 expression increased in the sacral spinal cord of obstructed rats whereas no changes were observed for CB2 or FAAH. ConclusionsUrodynamic effects of systemic FAAH inhibition involve activities at spinal neuronal CB1 and CB2 receptors in normal and obstructed rats. Endogenous spinal CB receptor ligands seem to regulate normal micturition and BO. Altered spinal CB receptor functions may be involved in the pathogenesis of obstruction-induced BO. Neurourol. Urodynam. 35:464-470, 2016. (c) 2015 Wiley Periodicals, Inc.
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| 28. |
- Gandaglia, Giorgio, et al.
(författare)
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Structured Population-based Prostate-specific Antigen Screening for Prostate Cancer : The European Association of Urology Position in 2019
- 2019
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 76:2, s. 142-150
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PCa)is one of the first three causes of cancer mortality in Europe. Screening in asymptomatic men (aged 55–69 yr)using prostate-specific antigen (PSA)is associated with a migration toward lower staged disease and a reduction in cancer-specific mortality. By 20 yr after testing, around 100 men need to be screened to prevent one PCa death. While this ratio is smaller than for breast and colon cancer, the long natural history of PCa means many men die from other causes. As such, the nonselective use of PSA testing and radical treatments can lead to overdiagnosis and overtreatment. The European Association of Urology (EAU)supports measures to encourage appropriate PCa detection through PSA testing, while reducing overdiagnosis and overtreatment. These goals may be achieved using personalized risk-stratified approaches. For diagnosis, the greatest benefit from early detection is likely to come in men assessed using baseline PSA levels at the age of 45 yr to individualize screening intervals. Multiparametric magnetic resonance imaging as well as risk calculators based on family history, ethnicity, digital rectal examination, and prostate volume should be considered to triage the need for biopsy, thus reducing the risk of overdiagnosis. For treatment, the EAU advocates balancing patient's life expectancy and cancer's mortality risk when deciding an approach. Active surveillance is encouraged in well-informed patients with low-risk and some intermediate-risk cancers, as it decreases the risks of overtreatment without compromising oncological outcomes. Conversely, the EAU advocates radical treatment in suitable men with more aggressive PCa. Multimodal treatment should be considered in locally advanced or high-grade cancers. Patient summary: Implementation of prostate-specific antigen (PSA)-based screening should be considered at a population level. Men at risk of prostate cancer should have a baseline PSA blood test (eg, at 45 yr). The level of this test, combined with family history, ethnicity, and other factors, can be used to determine subsequent follow-up. Magnetic resonance imaging scans and novel biomarkers should be used to determine which men need biopsy and how any cancers should be treated.
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| 29. |
- Hakim, Lukman, et al.
(författare)
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Intratunical injection of autologous adipose stromal vascular fraction reduces collagen III expression in a rat model of chronic penile fibrosis
- 2019
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Ingår i: International Journal of Impotence Research. - : Springer Science and Business Media LLC. - 0955-9930 .- 1476-5489.
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that the injection of adipose stem cells and stromal vascular fraction(SVF) into the tunica albuginea (TA) during the inflammatory phase in a rat model of Peyronie’s disease(PD) prevented the development of TA fibrosis. Our aim was to investigate whether local injection of SVF can reduce established fibrosis in a rat model of chronic phase of PD. Eighteen-male 12-wk-old Sprague-Dawley rats were divided in three equal groups: sham, PD without treatment (PD) and PD treated with SVF(PD-SVF). Sham rats underwent 2 injections of vehicle into the TA one month apart. PD rats underwent TGF-β1 injection and injection of vehicle one month later. PD-SVF rats underwent TGF-β1 injection followed by SVF (1-million cells) one month later. One month after the last treatment, the animals, n = 6 rats per group, underwent measurement of intracorporal and mean arterial pressure during electrostimulation of the cavernous nerve. Following euthanasia, penises were harvested for in-vitro study. Erectile function was not statistically significantly different between groups. PD animals developed subtunical areas of fibrosis and elastosis with upregulation of collagen III protein. These fibrotic changes were reversed after injection of SVF. We provide evidence that local injection of SVF reverses TA fibrosis in a rat model of chronic phase of PD.
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| 30. |
- Heidenreich, Axel, et al.
(författare)
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Early Detection of Prostate Cancer: European Association of Urology Recommendation
- 2013
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 64:3, s. 347-354
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Tidskriftsartikel (refereegranskat)abstract
- Background: The recommendations and the updated EAU guidelines consider early detection of PCa with the purpose of reducing PCa-related mortality and the development of advanced or metastatic disease. Objective: This paper presents the recommendations of the European Association of Urology (EAU) for early detection of prostate cancer (PCa) in men without evidence of PCa-related symptoms. Evidence acquisition: The working panel conducted a systematic literature review and meta-analysis of prospective and retrospective clinical studies on baseline prostate-specific antigen (PSA) and early detection of PCa and on PCa screening published between 1990 and 2013 using Cochrane Reviews, Embase, and Medline search strategies. Evidence synthesis: The level of evidence and grade of recommendation were analysed according to the principles of evidence-based medicine. The current strategy of the EAU recommends that (1) early detection of PCa reduces PCa-related mortality; (2) early detection of PCa reduces the risk of being diagnosed and developing advanced and metastatic PCa; (3) a baseline serum PSA level should be obtained at 40-45 yr of age; (4) intervals for early detection of PCa should be adapted to the baseline PSA serum concentration; (5) early detection should be offered to men with a life expectancy >= 10 yr; and (6) in the future, multivariable clinical risk-prediction tools need to be integrated into the decision-making process. Conclusions: A baseline serum PSA should be offered to all men 40-45 yr of age to initiate a risk-adapted follow-up approach with the purpose of reducing PCa mortality and the incidence of advanced and metastatic PCa. In the future, the development and application of multivariable risk-prediction tools will be necessary to prevent over diagnosis and over treatment. (C) 2013 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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| 31. |
- Lue, Tom F., et al.
(författare)
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Summary of the recommendations on sexual dysfunctions in men
- 2004
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Ingår i: Journal of Sexual Medicine. - : Oxford University Press (OUP). - 1743-6109 .- 1743-6095. ; 1:1, s. 6-23
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Tidskriftsartikel (refereegranskat)abstract
- Introduction. There are few published guidelines for the management of sexual dysfunctions in men and women, despite the prevalence and lack of attention to these problems. Disorders of sexual function in men include erectile dysfunction, orgasm/ejaculation disorders, priapism, and Peyronie's disease. Aim. To provide evidence-based and expert-opinion consensus guidelines for the clinical management of men's sexual dysfunctions. Methods. An International Consultation in collaboration with major urological and sexual medicine societies assembled over 200 multidisciplinary experts from 60 countries into 17 consultation committees. Committee members established the scope and objectives for each chapter. Following intensive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measure. New algorithms and guidelines for assessment and treatment of men's sexual dysfunction were developed. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of the medical literature, in addition to cultural and ethical considerations. Results. Recommendations and guidelines for men's sexual dysfunction are presented. These guidelines were developed as evidence-based, patient-centered, and multidisciplinary in focus. For the clinical assessment and diagnosis of ED, a basic evaluation was recommended for all patients, with optional and specialized testing reserved for special cases. A new treatment algorithm is proposed. This algorithm provides a clinically relevant guideline for managing ED in the large majority of men. New treatment guidelines and algorithms are provided for men's orgasm and ejaculation disorders, including premature ejaculation, retrograde and delayed ejaculation. Finally, expert opinion-based guidelines for the clinical management of priapism and Peyronie's disease are provided. Conclusions. Additional research is needed to validate and extend these guidelines. Nonetheless, this summary encompasses the recommendations concerning men's sexual dysfunctions presented at the 2nd International Consultation on Sexual Medicine in Paris, France, June 28-July 1, 2003.
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| 32. |
- Murphy, Declan G., et al.
(författare)
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Downsides of Robot-assisted Laparoscopic Radical Prostatectomy: Limitations and Complications
- 2010
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 57:5, s. 735-746
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Tidskriftsartikel (refereegranskat)abstract
- Context: Robot-assisted laparoscopic radical prostatectomy (RALP) using the da Vinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) is now in widespread use for the management of localised prostate cancer (PCa). Many reports of the safety and efficacy of this procedure have been published. However, there are few specific reports of the limitations and complications of RALP. Objective: The primary purpose of this review is to ascertain the downsides of RALP by focusing on complications and limitations of this approach. Evidence acquisition: A Medline search of the English-language literature was performed to identify all papers published since 2001 relating to RALP. Papers providing data on technical failures, complications, learning curve, or other downsides of RALP were considered. Of 412 papers identified, 68 were selected for review based on their relevance to the objective of this paper. Evidence synthesis: RALP has the following principal downsides: (1) device failure occurs in 0.2-0.4% of cases; (2) assessment of functional outcome is unsatisfactory because of nonstandardised assessment techniques; (3) overall complication rates of RALP are low, although higher rates are noted when complications are reported using a standardised system; (4) long-term oncologic data and data on high-risk PCa are limited; (5) a steep learning curve exists, and although acceptable operative times can be achieved in <20 cases, positive surgical margin (PSM) rates may require experience with >80 cases before a plateau is achieved; (6) robotic assistance does not reduce the difficulty associated with obese patients and those with large prostates, middle lobes, or previous surgery, in whom outcomes are less satisfactory than in patients without such factors; (7) economic barriers prevent uniform dissemination of robotic technology. Conclusions: Many of the downsides of RALP identified in this paper can be addressed with longer-term data and more widespread adoption of standardised reporting measures. The significant learning curve should not be understated, and the expense of this technology continues to restrict access for many patients. (C) 2009 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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| 33. |
- Ploussard, Guillaume, et al.
(författare)
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The Contemporary Concept of Significant Versus Insignificant Prostate Cancer
- 2011
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 60:2, s. 291-303
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Forskningsöversikt (refereegranskat)abstract
- Context: The notion of insignificant prostate cancer (Ins-PCa) has progressively emerged in the past two decades. The clinical relevance of such a definition was based on the fact that low-grade, small-volume, and organ-confined prostate cancer (PCa) may be indolent and unlikely to progress to biologic significance in the absence of treatment. Objective: To review the definition of Ins-PCa, its incidence, and the clinical impact of Ins-PCa on the contemporary management of PCa. Evidence acquisition: A review of the literature was performed using the Medline, Scopus, and Web of Science databases with no restriction on language up to September 2010. The literature search used the following terms: insignificant, indolent, minute, microfocal, minimal, low volume, low risk, and prostate cancer. Evidence synthesis: The most commonly used criteria to define Ins-PCa are based on the pathologic assessment of the radical prostatectomy specimen: (1) Gleason score <= 6 without Gleason pattern 4 or 5, (2) organ-confined disease, and (3) tumour volume < 0.5 cm(3). Several preoperative criteria and prognostication tools for predicting Ins-PCa have been suggested. Nomograms are best placed to estimate the risk of progression on an individualised basis, but a substantial proportion of men with a high probability of harbouring Ins-PCa are at risk for pathologic understaging and/or undergrading. Thus, there is an ongoing need for identifying novel and more accurate predictors of Ins-PCa to improve the distinction between insignificant versus significant disease and thus to promote the adequate management of PCa patients at low risk for progression. Conclusions: The exciting challenge of obtaining the pretreatment diagnostic tools that can really distinguish insignificant from significant PCa should be one of the main objectives of urologists in the following years to decrease the risk of overtreatment of Ins-PCa. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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| 34. |
- Russo, Andrea, et al.
(författare)
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Effects of the Gonadotropin-Releasing Hormone Antagonist Ganirelix on Normal Micturition and Prostaglandin E-2-Induced Detrusor Overactivity in Conscious Female Rats
- 2011
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Ingår i: EUROPEAN UROLOGY. - : ELSEVIER SCIENCE BV, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS. - 0302-2838 .- 1873-7560. ; 59:5, s. 868-874
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gonadotropin-releasing hormone (GnRH) antagonists have been reported to have beneficial effects on lower urinary tract symptoms in patients with benign prostatic hyperplasia. Objective: Our aim was to investigate the effects of ganirelix, a GnRH receptor antagonist, on bladder function and detrusor overactivity (DO) in female rats. Design, setting, and participants: Female Sprague-Dawley rats received 2 wk of daily systemic (0.1 mg/kg) or acute intravesical administration (IVES; 0.14 mg/l or 1.4 mg/l) ganirelix or vehicle (controls). Measurements: Assessments were obtained using cystometry in awake rats, organ bath studies, enzyme-linked immunosorbent assay, and western blot (WB). Results and limitations: Luteinising hormone levels were lower in rats treated systemically with ganirelix than in controls. No differences were observed in body or bladder weights. Micturition interval (MI), micturition volume (MV), residual volume, and bladder capacity (BC) were similar in both groups at baseline. No differences in urodynamic pressure parameters were observed between groups at baseline. Intravesical prostaglandin E-2 reduced MI, MV, and BC, and it increased basal pressure (BP), threshold pressure (TP), flow pressure (FP), and maximum pressure (MP) in all rats. MI, MV, and BC were reduced by 43% +/- 4%, 50% +/- 4%, and 43% +/- 4% (controls) versus 22% +/- 3%, 23% +/- 3%, and 21% +/- 3% (ganirelix-treated rats; p andlt; 0.001). TP and FP increased by 38% +/- 8% and 30% +/- 4% (controls) versus 16% +/- 7% and 16% +/- 5% (ganirelix; p andlt; 0.05). The maximal force of contractions for carbachol was larger in detrusor from ganirelix-treated rats (231% vs 177% of 60 mM K+-induced contractions). At 0.14 mg/l, but not 0.14 mg/l, IVES ganirelix increased MI, MV, and BC and decreased BP, TP, FP, and MP. In vitro, ganirelix had no effect on detrusor function. The gonadotropin-releasing hormone receptor was expressed (by WB) in the bladder mucosa. Conclusions: Systemic treatment with ganirelix counteracted experimental DO in female rats. Because bladder preparations from these rats exhibited larger contractions to carbachol and because intravesical ganirelix affected both micturition intervals and urodynamic pressure profiles, a peripheral site of action of ganirelix in the urinary bladder cannot be excluded.
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| 35. |
- Russo, Andrea, et al.
(författare)
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Silodosin From Bench to Bedside: Selectivity, Safety, and Sustained Efficacy
- 2011
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Ingår i: European urology. Supplement. - : Elsevier. - 1569-9056 .- 1878-1500. ; 10:6, s. 445-450
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Tidskriftsartikel (refereegranskat)abstract
- Context: Silodosin is the alpha(1)-adrenoceptor (AR) antagonist with the highest selectivity for the alpha(1A)-AR subtype that is available for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). How do preclinical findings translate into clinical effect? less thanbrgreater than less thanbrgreater thanObjective: Analyse information on the preclinical selectivity profile of silodosin in relation to clinical efficacy and safety. less thanbrgreater than less thanbrgreater thanEvidence acquisition: A Medline search for published articles on silodosin in preclinical and clinical studies was conducted. Information was also acquired from documents published by the European Medicines Agency. less thanbrgreater than less thanbrgreater thanEvidence synthesis: Silodosin exhibits high selectivity for the alpha(1A) subtype of the adrenoceptor, and it also displays selectivity for the lower urinary tract and prostate versus vascular functions as assessed in studies of isolated tissues, animal models, and patients. Silodosin causes symptom relief within days and is superior to placebo and noninferior to tamsulosin in reducing symptoms in patients with BPH. The effects of silodosin were sustained for 40-52 wk in open-label extension studies of 1170 patients. The safety and tolerability of silodosin are excellent. Silodosin more frequently causes abnormal ejaculation than placebo or tamsulosin, although only a minority of the patients discontinues treatment due to this adverse event. less thanbrgreater than less thanbrgreater thanConclusions: Both preclinical and clinical studies support the contention that silodosin has high uroselectivity and a positive cardiovascular safety profile, likely related to its selectivity for the alpha(1A)-AR subtype. Silodosin has a rapid onset of action and a sustained efficacy on LUTS due to BPH.
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| 36. |
- Schroeder, Fritz H., et al.
(författare)
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Can dutasteride delay or prevent the progression of prostate cancer in patients with biochemical failure after radical therapy? Rationale and design of the Avodart after Radical Therapy for Prostate Cancer Study
- 2009
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Ingår i: BJU International. - 1464-4096. ; 103:5, s. 590-596
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Tidskriftsartikel (refereegranskat)abstract
- To describe the Avodart after Radical Therapy for prostate cancer Study (ARTS), investigating the use of dutasteride (a dual 5 alpha-reductase inhibitor that suppresses intraprostatic dihydrotestosterone, reduces tumour volume and improves other markers of tumour regression in prostate cancer) to prevent or delay disease progression in patients with biochemical recurrence after therapy with curative intent. An increasing serum prostate-specific antigen (PSA) level after radical prostatectomy (RP) or radiotherapy (RT) is indicative of recurrent prostate cancer and typically pre-dates clinically detectable metastatic disease by several years. ARTS is an ongoing European multicentre trial in which patients are stratified by previous therapy (RP with or without salvage RT vs primary RT) and randomized to double-blind treatment with dutasteride 0.5 mg or placebo once daily for 2 years. Eligible patients will have a PSA doubling time (DT) of 3-24 months. Biochemical recurrence is defined as three increases in PSA level from the nadir, with each increase >= 4 weeks apart and each PSA level >= 0.2 ng/mL, and a final PSA level of >= 0.4 ng/mL (after RP) or >= 2 ng/mL (after primary RT). Study endpoints include time to PSA doubling, time to disease progression, treatment response (PSA decrease or an increase of <= 15% from baseline), changes in PSA and PSADT, and changes in anxiety (Memorial Anxiety Scale for Prostate Cancer). ARTS will be the first study to evaluate the effects of dutasteride on PSADT, disease progression and treatment response in patients with biochemical failure after RP or RT, and should help to elucidate the potential role of dual 5 alpha-reductase inhibition in prostate cancer.
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| 37. |
- Ventimiglia, Eugenio, et al.
(författare)
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Long-term Outcomes Among Men Undergoing Active Surveillance for Prostate Cancer in Sweden.
- 2022
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Ingår i: JAMA network open. - : American Medical Association (AMA). - 2574-3805. ; 5:9
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Tidskriftsartikel (refereegranskat)abstract
- The long-term outcomes among men with prostate cancer (PC) whose disease is managed with active surveillance (AS) remains unknown.To develop a simulation model with a 30-year follow-up for men with PC managed with AS.In this cohort study, a state transition model was created using data from Prostate Cancer data Base Sweden (PCBaSe) on 23655 men diagnosed with PC and managed with deferred treatment to estimate treatment trajectories. A simulation was performed with 100000 men in each combination of age at diagnosis, Charlson Comorbidity Index, and PC risk with a follow-up of 30 years.Death from PC and death from other causes were estimated, and the proportion of time without active PC treatment was assessed until date of death or age 85 years.This study included 23655 men from PCBaSe with a median age at diagnosis of 69 years (IQR, 64-74 years). Of these, 16177 men underwent active surveillance for PC and 7478 underwent watchful waiting. The proportion of men who were diagnosed at age 55 years and died of PC before age 85 years was 9% for very low-risk PC, 13% for low-risk PC, and 15% for intermediate-risk PC. Among men with a Charlson Comorbidity Index of 0 who were diagnosed at age 70 years, the corresponding percentages were 3%, 6%, and 7%, respectively. The mean proportion of remaining life-years without active PC treatment for men diagnosed at age 55 years was 12 of 25 years (48%) for very low-risk PC, 9 of 25 years (36%) for low-risk PC, and 7 of 25 (29%) for intermediate-risk PC. For men aged 70 years, the corresponding numbers were 10 of 13 years (77%), 9 of 13 years (66%), and 8 of 13 years (60%), respectively. Men with intermediate-risk PC who were younger than 60 years at diagnosis had a high risk of PC death (12%-15%) and fewer remaining life-years without active PC treatment (29%-33%). In contrast, men with low-risk PC who were older than 65 years at diagnosis had a lower risk of PC death (3%-5%) and more remaining life-years without active PC treatment (62%-77%).The findings of this Swedish cohort study suggest that active surveillance may be a safe strategy for disease management among men with PC who were older than 65 years at diagnosis.
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| 38. |
- Ventimiglia, Eugenio, et al.
(författare)
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Nationwide, population-based study of post radical prostatectomy urinary incontinence correction surgery
- 2018
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Ingår i: Journal of Surgical Oncology. - : WILEY. - 0022-4790 .- 1096-9098. ; 117:2, s. 321-327
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesTo assess the use of post radical prostatectomy (RP) urinary incontinence (PPI) surgery and to investigate factors related to its use. MethodsCohort study in Prostate Cancer database Sweden (PCBaSe) of men who underwent primary RP between 1998 and 2012. PPI correction procedures were identified in the Patient Registry. Hazard ratios (HR) and 95% confidence intervals (CIs) of PPI surgeries were estimated. ResultsSeven hundred eighty-two out of 26280 (3%) men underwent PPI surgery at a median time of 3 years after RP. There was an eightfold increase in the absolute number of PPI surgeries during 2000-2014 and a threefold increase in the number per 1000 RPs performed. Factors associated with high use PPI surgery were age >70, HR 1.96 (1.54-2.50), and high hospital RP volume (>100 RPs/year), HR 0.81 (0.66-0.99). There was a 10-fold difference in use of PPI surgery per 1000 RPs between the county with the highest versus lowest use. In a subgroup of men with Patient-Reported Outcome Measures (PROM); severe PPI was reported by 7% of men and 24% of them underwent PPI surgery. ConclusionsThree percent of all men received PPI surgery, with a 10-fold variation among health care providers. Only a quarter of men with severe PPI underwent PPI surgery, suggesting that PPI surgery remains underutilized.
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| 39. |
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| 40. |
- Villa, Luca, et al.
(författare)
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The Rho-kinase inhibitor Y27632 promotes ureteral relaxation in an in vivo rat model for partial ureteral obstruction
- 2023
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Ingår i: World Journal of Urology. - : SPRINGER. - 0724-4983 .- 1433-8726. ; 41:9, s. 2541-2547
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Aim of this study was to evaluate the effect of intravenous Y27632 (a ROK inhibitor) on intra-ureteral pressures and on blood pressure in an in vivo rat model for unilateral partial ureteral obstruction (PUO). Methods: 15 Male Sprague Dawley rats were used. Under isofluran anesthesia, saline was continuously infused via polyethylene (PE)-10 catheters inserted in the ureters beneath the kidney pelvis. Left psoas muscle was sutured around the distal left ureter to create a partial obstruction. Carotid artery and femoral vein were cannulated with PE catheters for registration of mean arterial blood pressure (MAP) and for administration of drugs. Left and right ureter pressures and MAP were simultaneously recorded. Y27632 (0.03 and 0.1 mg/kg each n = 6–7) was given intravenously. T-test was used for comparisons. Results: Spontaneous peristaltic pressure waves were recorded at baseline for both ureters. After the obstruction, Y27632 reduced maximum pressure (MaxP) by 10.5 ± 1.9% (0.03 mg/kg; p = 0.004) and 29.1 ± 4.8% (0.1 mg/kg; p < 0.001), minimum pressure (MinP) by 5.2 ± 2.3% (0.03 mg/kg; p = 0.02) and 12.2 ± 3.4% (0.1 mg/kg; p = 0.009), the area under the curve (AUC) by 7.8 ± 2.4% (0.03 mg/kg; p = 0.008) and 16.5 ± 3.7% (0.1 mg/kg;p = 0.007), the waves amplitude by 23.4 ± 11.3% (0.03 mg/kg; p = 0.098) and 38.7 ± 7.5% (0.1 mg/kg; p < 0.001), with no effect on contraction frequency. During simultaneous recordings from the normal ureter at the investigated doses, Y27632 reduced MaxP, MinP, AUC and waves amplitude by 1–7%. The MAP was reduced by 12.5 ± 5.3% (0.03 mg/kg; p = 0.07) and 15.8 ± 1.8% (0.1 mg/kg; p < 0.001). Conclusions: Y27632 decreased intra-ureteral pressures of a partially obstructed ureter with limited effect on blood pressure in an animal model of unilateral PUO.
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| 41. |
- Weinhold, Philipp, et al.
(författare)
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The transient receptor potential A1 ion channel (TRPA1) modifies in vivo autonomous ureter peristalsis in rats
- 2021
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Ingår i: Neurourology and Urodynamics. - : Wiley. - 0733-2467 .- 1520-6777. ; 40:1, s. 147-157
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The current study aimed to explore the expression of transient receptor potential A1 ion channels (TRPA1) in the rat ureter and to assess if TRPA1-active compounds modulate ureter function. Methods: The expression of TRPA1 in rat ureter tissue was studied by immunofluorescence. The TRPA1 distribution was compared to calcitonin gene-related peptide (CGRP), α-actin (SMA1), anoctamin-1 (ANO1), and c-kit. For in vivo analyses, a catheter was implanted in the right ureter of 50 rats. Ureter peristalsis and pressures were continuously recorded by a data acquisition set-up during intraluminal infusion of saline (baseline), saline plus protamine sulfate (PS; to disrupt the urothelium), saline plus PS with hydrogen sulfide (NaHS) or cinnamaldehyde (CA). Comparisons were made between rats treated systemically with vehicle or a TRPA1-antagonist (HC030031). Results: TRPA1-immunoreactive nerves co-expressed CGRP and were mainly located in the suburothelial region of the ureter. Immunoreactivity for TRPA1 was also encountered in c-kit-positive but ANO1-negative cells of the ureter suburothelium and wall. In vivo, HC030031-treated rats had elevated baseline peristaltic frequency (p < 0.05) and higher intraluminal pressures (p < 0.01). PS increased the frequency of ureter peristalsis versus baseline in vehicle-treated rats (p < 0.001) but not in HC030031-treated rats. CA (p < 0.001) and NaHS (p < 0.001) decreased ureter peristalsis. This was counteracted by HC030031 (p < 0.05 and p < 0.01). Conclusions: In rats, TRPA1 is expressed on cellular structures considered of importance for peristaltic and mechanoafferent functions of the ureter. Functional data indicate that TRPA1-mediated signals regulate ureter peristalsis. This effect was pronounced after mucosal disruption and suggests a role for TRPA1 in ureter pathologies involving urothelial damage.
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| 42. |
- Witjes, J. Alfred, et al.
(författare)
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Hexaminolevulinate-Guided Fluorescence Cystoscopy in the Diagnosis and Follow-Up of Patients with Non-Muscle-Invasive Bladder Cancer : Review of the Evidence and Recommendations
- 2010
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 57:4, s. 607-614
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Forskningsöversikt (refereegranskat)abstract
- Context: Compared with standard white-light cystoscopy, photodynamic diagnosis with blue light and the photosensitiser hexaminolevulinate has been shown to improve the visualisation of bladder tumours, reduce residual tumour rates by at least 20%, and improve recurrence-free survival. There is currently no overall European consensus outlining specifically where hexaminolevulinate is or is not indicated. Objective: Our aim was to define specific indications for hexaminolevulinate guided fluorescence cystoscopy in the diagnosis and management of non-muscle invasive bladder cancer (NMIBC). Evidence acquisition: A European expert panel was convened to review the evidence for hexaminolevulinate-guided fluorescence cystoscopy in the diagnosis and management of NMIBC (identified through a PubMed MESH search) and available guidelines from across Europe. On the basis of this information and drawing on the extensive clinical experience of the panel, specific indications for the technique were then identified through discussion. Evidence synthesis: The panel recommends that hexaminolevulinate-guided fluorescence cystoscopy be used to aid diagnosis at initial transurethral resection following suspicion of bladder cancer and in patients with positive urine cytology but negative white-light cystoscopy for the assessment of tumour recurrences in patients not previously assessed with hexaminolevulinate, in the initial follow-up of patients with carcinoma in situ (CIS) or multifocal tumours, and as a teaching tool. The panel does not currently recommend the use of hexaminolevulinate-guided fluorescence cystoscopy in patients for whom cystectomy is indicated or for use in the outpatient setting with flexible cystoscopy. Conclusions: Evidence is available to support the use of hexaminolevulinate-guided fluorescence cystoscopy in a range of indications, as endorsed by an expert panel. (c) 2010 European Association of Urology.
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