| 1. |
- 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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| 2. |
- Beyer, Katharina, et al.
(författare)
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Diagnostic and prognostic factors in patients with prostate cancer : a systematic review
- 2022
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:4
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Forskningsöversikt (refereegranskat)abstract
- Objectives As part of the PIONEER Consortium objectives, we have explored which diagnostic and prognostic factors (DPFs) are available in relation to our previously defined clinician and patient-reported outcomes for prostate cancer (PCa). Design We performed a systematic review to identify validated and non-validated studies. Data sources MEDLINE, Embase and the Cochrane Library were searched on 21 January 2020. Eligibility criteria Only quantitative studies were included. Single studies with fewer than 50 participants, published before 2014 and looking at outcomes which are not prioritised in the PIONEER core outcome set were excluded. Data extraction and synthesis After initial screening, we extracted data following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of prognostic factor studies (CHARMS-PF) criteria and discussed the identified factors with a multidisciplinary expert group. The quality of the included papers was scored for applicability and risk of bias using validated tools such as PROBAST, Quality in Prognostic Studies and Quality Assessment of Diagnostic Accuracy Studies 2. Results The search identified 6604 studies, from which 489 DPFs were included. Sixty-four of those were internally or externally validated. However, only three studies on diagnostic and seven studies on prognostic factors had a low risk of bias and a low risk concerning applicability. Conclusion Most of the DPFs identified require additional evaluation and validation in properly designed studies before they can be recommended for use in clinical practice. The PIONEER online search tool for DPFs for PCa will enable researchers to understand the quality of the current research and help them design future studies. Ethics and dissemination There are no ethical implications.
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| 3. |
- 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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| 4. |
- Collins, Justin, et al.
(författare)
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Live streaming of robotic surgery from leading educational centres enables a global approach to surgical teaching
- 2016
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 195:4, s. E116-E116
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Following recently published EAU Policy on Live Surgical Events (LSE's) it is assured that live surgery will be ongoing at conferences in the immediate future. However, the panel reached >80% consensus view that performing at a home institution may be safer. The committee also identified issues with a ‘travelling surgeon’ performing complex surgery in an unfamiliar environment with a surgical team that is not experienced with the intricacies of surgeons techniques. LSE's from home institutions remove or minimize these negative aspects.
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| 5. |
- Cornford, Philip, et al.
(författare)
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EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer-2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent.
- 2024
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Ingår i: European urology. - 1873-7560.
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Tidskriftsartikel (refereegranskat)abstract
- The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines provide recommendations for the management of clinically localised prostate cancer (PCa). This paper aims to present a summary of the 2024 version of the EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on the screening, diagnosis, and treatment of clinically localised PCa.The panel performed a literature review of all new data published in English, covering the time frame between May 2020 and 2023. The guidelines were updated, and a strength rating for each recommendation was added based on a systematic review of the evidence.A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is considered, a combination of targeted and regional biopsies should be performed. Prostate-specific membrane antigen positron emission tomography imaging is the most sensitive technique for identifying metastatic spread. Active surveillance is the appropriate management for men with low-risk PCa, as well as for selected favourable intermediate-risk patients with International Society of Urological Pathology grade group 2 lesions. Local therapies are addressed, as well as the management of persistent prostate-specific antigen after surgery. A recommendation to consider hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term intensified hormonal treatment.The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. These PCa guidelines reflect the multidisciplinary nature of PCa management.This article is the summary of the guidelines for "curable" prostate cancer. Prostate cancer is "found" through a multistep risk-based screening process. The objective is to find as many men as possible with a curable cancer. Prostate cancer is curable if it resides in the prostate; it is then classified into low-, intermediary-, and high-risk localised and locally advanced prostate cancer. These risk classes are the basis of the treatments. Low-risk prostate cancer is treated with "active surveillance", a treatment with excellent prognosis. For low-intermediary-risk active surveillance should also be discussed as an option. In other cases, active treatments, surgery, or radiation treatment should be discussed along with the potential side effects to allow shared decision-making.
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| 6. |
- Gandaglia, Giorgio, et al.
(författare)
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Clinical Characterization of Patients Diagnosed with Prostate Cancer and Undergoing Conservative Management : A PIONEER Analysis Based on Big Data
- 2023
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Ingår i: European Urology. - 0302-2838.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics. Objective: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data. Design, setting, and participants: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146). Outcome measurements and statistical analysis: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data. Results and limitations: The most common comorbidities were hypertension (35–73%), obesity (9.2–54%), and type 2 diabetes (11–28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12–25%) and emergency department visits (10–14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent. Conclusions: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data. Patient summary: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis.
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| 7. |
- Gandaglia, Giorgio, et al.
(författare)
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Epidemiology and Prevention of Prostate Cancer
- 2021
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Ingår i: European Urology Oncology. - : Elsevier. - 2588-9311. ; 4:6, s. 877-892
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Worldwide, prostate cancer (PCa) represents the second most common solid tumor in men.OBJECTIVE: To assess the geographical distribution of PCa, epidemiological differences, and the most relevant risk factors for the disease.EVIDENCE ACQUISITION: Estimated incidence, mortality, and prevalence of PCa for the year 2020 in 185 countries were derived from the IARC GLOBOCAN database. A review of English-language articles published between 2010 and 2020 was conducted using MEDLINE, EMBASE, and Scopus to identify risk factors for PCa.EVIDENCE SYNTHESIS: In the year 2020, there were over 1414000 estimated new cases of PCa worldwide, with an age-standardized rate (ASR) incidence of 31 per 100000 (lifetime cumulative risk: 3.9%). Northern Europe has the highest all-age incidence ASR (83), while the lowest ASR was in South-Central Asia (6.3). In the year 2020, there were over 375000 estimated deaths worldwide, and the overall mortality ASR was 7.7 per 100000, with the highest ASR in the Caribbean (28) and the lowest in South-Central Asia (3.1). Family history, hereditary syndromes, and race are the strongest risk factors for PCa. Metabolic syndrome was associated with the risk of developing PCa, high-grade disease, and adverse pathology. Diabetes and exposure to ultraviolet rays were found to be inversely associated to PCa incidence. Cigarette smoking and obesity may increase PCa-specific mortality, while regular physical activity may reduce disease progression. Although 5-alpha reductase inhibitors are known to be associated with a reduced incidence of PCa, available studies failed to show an effect on overall mortality.CONCLUSIONS: Family history, race, and hereditary syndromes are well-established risk factors for PCa. Modifiable risk factors may impact the risk of developing PCa and that of dying from the disease, but little evidence exist for any clear indication for prevention other than early diagnosis to reduce PCa mortality.PATIENT SUMMARY: Prostate cancer (PCa) rates vary profoundly worldwide, with incidence and mortality rates being highest in Northern Europe and Caribbean, respectively. South-Central Asia has the lowest epidemiological burden. Family history, race, and hereditary syndromes are well-established risk factors for PCa. Modifiable risk factors may impact the risk of developing PCa and that of dying from the disease itself, but little evidence exist for any clear indication for prevention other than early diagnosis to reduce PCa mortality.
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| 8. |
- 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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| 9. |
- Lawlor, Ailbhe, et al.
(författare)
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Predictive Models for Assessing Patients’ Response to Treatment in Metastatic Prostate Cancer : A Systematic Review
- 2024
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Ingår i: European Urology Open Science. - 2666-1691. ; 63, s. 126-135
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Forskningsöversikt (refereegranskat)abstract
- Background and objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients’ response to treatment. Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria. Key findings and limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance. Conclusions and clinical implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa. Patient summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals.
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| 10. |
- Marra, Giancarlo, et al.
(författare)
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Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review.
- 2023
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Ingår i: European urology. - 0302-2838 .- 1873-7560. ; 84:1, s. 65-85
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Tidskriftsartikel (refereegranskat)abstract
- The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed.To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent.A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021.We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy.Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers.We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact.
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