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Sökning: L773:0302 2838 > (2010-2014)

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  • Abouassaly, Robert, et al. (författare)
  • Sequelae of Treatment in Long-term Survivors of Testis Cancer
  • 2011
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 60:3, s. 516-526
  • Forskningsöversikt (refereegranskat)abstract
    • Context: Testicular cancer patients are often diagnosed at a young age, and because of the advances in the treatment of this disease, the vast majority have a normal life expectancy after therapy. Thus, recognition of the long-term sequelae of treatment (ie, surgery, radiation therapy, and chemotherapy) is particularly important in these patients. Objective: To review the adverse effects and the risk of secondary malignancy in long-term survivors of testicular cancer. Evidence acquisition: We conducted a Medline search to identify original articles and reviews on the long-term effects of testicular cancer treatment. Although the search included articles from January 1948 to February 2011, the majority of the included articles were published in the last two decades. Evidence synthesis: All studies examining the long-term sequelae of treatment in testicular cancer are retrospective in nature, with most classified as cohort, case-control, and/or epidemiologic studies. Given that no standardized method of reporting long-term complications exists, evidence synthesis is limited. Conclusions: Recent evidence suggests an increased risk of cardiovascular disease, neurotoxicity, and mild reductions in renal function in survivors of testicular cancer. Treatment of testicular malignancy can also negatively affect gonadal function and fertility and has been shown to result in an increased risk of solid malignancy and leukemia. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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  • Abrahamsson, Per-Anders (författare)
  • Potential Benefits of Intermittent Androgen Suppression Therapy in the Treatment of Prostate Cancer: A Systematic Review of the Literature.
  • 2010
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 57, s. 49-59
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: The well-known side-effect profile of androgen-deprivation therapy (ADT) has significant quality-of-life (QoL) implications. Intermittent androgen deprivation (IAD) alternates androgen blockade with treatment cessation to allow hormonal recovery between treatment cycles, thus potentially improving tolerability and QoL. OBJECTIVE: To evaluate available evidence regarding the efficacy and tolerability of IAD and assess its value in the treatment of prostate cancer (PCa). EVIDENCE ACQUISITION: Key phase 2/3 clinical trials of IAD in PCa published within the last 10 yr were identified on Medline using the terms prostatic neoplasms [MeSH], intermittent androgen suppression, intermittent hormonal deprivation, intermittent androgen deprivation, and intermittent hormonal therapy. Abstracts from trials reported at 2008-2009 conferences were also included. EVIDENCE SYNTHESIS: Data from 19 phase 2 studies are discussed with respect to prostate-specific antigen values for treatment suspension/reinitiation, treatment regimens, cycle lengths, testosterone normalisation, and tolerability. Outcome data were promising: Most trials reported an improvement in QoL during the off-therapy periods. Interim data from eight phase 3 trials comparing IAD and continuous androgen deprivation (CAD) support the phase 2 results. IAD generally showed comparable efficacy to CAD with respect to various outcomes, including biochemical progression, progression-free survival, and overall survival. However, IAD was significantly better than CAD with respect to 3-yr risk of progression in one study, and it demonstrated tolerability benefits, particularly with respect to sexual function. Patients most likely to benefit from IAD and factors predictive of poor response are also discussed. CONCLUSIONS: IAD seems to be as effective as CAD while showing tolerability and QoL advantages, especially recovery of sexual potency; however, there are as yet insufficient data to determine whether IAD has the potential to prevent or reverse the long-term complications associated with ADT.
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  • Abrams, P, et al. (författare)
  • The future of urology
  • 2012
  • Ingår i: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 61:3, s. 534-540
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Akre, Olof, et al. (författare)
  • Mortality Among Men with Locally Advanced Prostate Cancer Managed with Noncurative Intent: A Nationwide Study in PCBaSe Sweden
  • 2011
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 60:3, s. 554-563
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There are limited prognostic data for locally advanced prostate cancer PCa to guide in the choice of treatment. Objective: To assess mortality in different prognostic categories among men with locally advanced PCa managed with noncurative intent. Design, setting, and participants: We conducted a register-based nationwide cohort study within the Prostate Cancer DataBase Sweden. The entire cohort of locally advanced PCa included 14 908 men. After the exclusion of 2724 (18%) men treated with curative intent, 12 184 men with locally advanced PCa either with local clinical stage T3 or T4 or with T2 with serum levels of prostate-specific antigen (PSA) between 50 and 99 ng/ml and without signs of metastases remained for analysis. Measurements: We followed up the patient cohort in the Cause of Death Register for <= 11 yr and assessed cumulative incidence of PCa -specific death stratified by age and clinical characteristics. Results and limitations: The PCa -specific mortality at 8 yr of follow-up was 28% (95% confidence interval [CI], 25-32%) for Gleason score (GS) 2-6, 41% (95% CI, 38-44%) for GS 7, 52% (95% CI, 47-57%) for GS 8, and 64% (95% CI, 59-69%) for GS 9-10. Even for men aged >85 yr at diagnosis with GS 8-10, PCa was a major cause of death: 42% (95% CI, 37-47%). Men with locally advanced disease and a PSA <4 ng/ml at diagnosis were at particularly increased risk of dying from PCa. One important limitation is the lack of bone scans in 42% of the patient cohort, but results remained after exclusion of patients with unknown metastasis status. Conclusions: The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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  • Altman, Daniel, et al. (författare)
  • The genetic and environmental contribution to the occurrence of bladder pain syndrome: an empirical approach in a nationwide population sample.
  • 2011
  • Ingår i: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 59:2, s. 280-5
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The aetiology of bladder pain syndrome (BPS) remains poorly understood, and a number of pathogenic mechanisms have been proposed. The importance of genetic factors for BPS is receiving growing attention, but data so far are of a preliminary nature. OBJECTIVE: To empirically assess the genetic and environmental contribution to BPS in a population-based sample of twins. DESIGN, SETTING, AND PARTICIPANTS: The study included >25 000 twins born between 1959 and 1985. Individuals with BPS were identified using latent class cluster analysis (LCCA) based on self-reported symptoms from a nationwide screening for complex diseases in the Swedish Twin Registry. By comparing monozygotic and dizygotic twins, we estimated twin similarity and the relative proportions of phenotypic variance resulting from genetic and environmental factors. MEASUREMENTS: Twin similarity was measured. RESULTS AND LIMITATIONS: The LCCA yielded an overall BPS prevalence of 1.1% and 2.4% for males and females, respectively. In males, the contribution of genetic effects to BPS could not be assessed because of the small number of concordant twin pairs. In women, twin similarity estimates indicated a genetic component for the aetiology of BPS, but genetic factors contributed less than one-third of the total variation in susceptibility to BPS. Nonshared environmental factors accounted for more than two-thirds of the variance, whereas early nongenetic factors shared within the family were of little or no consequence to the risk of developing BPS later in life. Use of self-reported symptoms to define the disease phenotype is a limitation of the study. CONCLUSIONS: The influence of environmental factors in the development of BPS in women is substantial, whereas genetic influences are of only modest importance for the possibility of developing the disease.
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  • Artibani, Walter, et al. (författare)
  • EAU Policy on Live Surgery Events.
  • 2014
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 66:1, s. 87-97
  • 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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  • Auprich, Marco, et al. (författare)
  • Contemporary Role of Prostate Cancer Antigen 3 in the Management of Prostate Cancer
  • 2011
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 60:5, s. 1045-1054
  • Forskningsöversikt (refereegranskat)abstract
    • Context: Newly discovered biomarkers ideally should prove clinical usefulness, provide additional detection, staging, and prognosis information to improve individual risk assessment, and potentially permit targeted cancer therapy. Objective: To review, display, and evaluate the current evidence regarding the biologic and analytic approach of urinary prostate cancer gene 3 (PCA3) in prostate cancer (PCa) detection, staging, and prognosis, and its therapeutic potential. Evidence acquisition: A systematic and comprehensive Medline search was performed using the Medical Subject Headings search terms PCA3, DD3, UPM3, prostate cancer, cell-lines, prostate tissue, prostate biopsy, detection, diagnosis, radical prostatectomy, staging, grading, progression, and gene therapy. Results were restricted to English-language papers published within the period 1999-2011. Evidence synthesis: The PCA3 gene is highly overexpressed in specific PCa cell lines and prostatic tumours. In 2006, a simple and robust urine test (Progensa) became commercially available. Despite its costs, prostate cancer antigen 3 (PCA3) is superior to prostate-specific antigen (PSA) and percent free PSA in the early detection of PCa. PCA3 improves the diagnostic accuracy of externally validated nomograms among men with an elevated PSA undergoing biopsy. PCA3 independently predicts low-volume disease and pathologically insignificant PCa but is not associated with locally advanced disease and is limited in the prediction of aggressive cancer. Preliminary data demonstrate that combining PCA3 with other new biomarkers further improves diagnostic and prognostic accuracy. Finally, findings of the first PCA3-Gene-ViroTherapy study suggest therapeutic potential by exploiting PCA3 overexpression. Conclusions: PCA3, integrated in novel biopsy nomograms or risk stratification tools, can be used to counsel or confirm biopsy indications. If confirmed in further studies, using PCA3 together with established staging risk factors could assist clinicians in specific pretreatment decision making. So far no evidence for the usefulness of PCA3 in active surveillance programs has been presented. Published by Elsevier B. V. on behalf of European Association of Urology.
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  • Barbieri, Christopher E., et al. (författare)
  • The Mutational Landscape of Prostate Cancer
  • 2013
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 64:4, s. 567-576
  • Forskningsöversikt (refereegranskat)abstract
    • Context: Prostate cancer (PCa) is a clinically heterogeneous disease with marked variability in patient outcomes. Molecular characterization has revealed striking mutational heterogeneity that may underlie the variable clinical course of the disease. Objective: In this review, we discuss the common genomic alterations that form the molecular basis of PCa, their functional significance, and the potential to translate this knowledge into patient care. Evidence acquisition: We reviewed the relevant literature, with a particular focus on recent studies on somatic alterations in PCa. Evidence synthesis: Advances in sequencing technology have resulted in an explosion of data regarding the mutational events underlying the development and progression of PCa. Heterogeneity is the norm; few abnormalities in specific genes are highly recurrent, but alterations in certain signaling pathways do predominate. These alterations include those in pathways known to affect tumorigenesis in a wide spectrum of tissues, such as the phosphoinositide 3-kinase/phosphatase and tensin homolog/Akt pathway, cell cycle regulation, and chromatin regulation. Alterations more specific to PCa are also observed, particularly gene fusions of ETS transcription factors and alterations in androgen signaling. Mounting data suggest that PCa can be subdivided based on a molecular profile of genetic alterations. Conclusions: Major advances have been made in cataloging the genomic alterations in PCa and understanding the molecular mechanisms underlying the disease. These findings raise the possibility that PCa could soon transition from being a poorly understood, heterogeneous disease with a variable clinical course to being a collection of homogenous subtypes identifiable by molecular criteria, associated with distinct risk profiles, and perhaps amenable to specific management strategies or targeted therapies. (C) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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  • Bekema, Hendrika J., et al. (författare)
  • Systematic Review of Adrenalectomy and Lymph Node Dissection in Locally Advanced Renal Cell Carcinoma
  • 2013
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 64:5, s. 799-810
  • Forskningsöversikt (refereegranskat)abstract
    • Context: Controversy remains over whether adrenalectomy and lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for locally advanced renal cell carcinoma (RCC) cT3-T4N0M0. Objective: To systematically review all relevant literature comparing oncologic, perioperative, and quality-of-life (QoL) outcomes for locally advanced RCC managed with RN with or without concomitant adrenalectomy or LND.Evidence acquisition: Relevant databases were searched up to August 2012. Randomised controlled trials (RCTs) and comparative studies were included. Outcome measures were overall survival, QoL, and perioperative adverse effects. Risks of bias (RoB) were assessed using Cochrane RoB tools. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.Evidence synthesis: A total of 3658 abstracts and 252 full-text articles were screened. Eight studies met the inclusion criteria: six LNDs (one RCT and five nonrandomised studies [NRSs]) and two adrenalectomies (two NRSs). RoB was high across the evidence base, and the quality of evidence from outcomes ranged from moderate to very low. Meta-analyses were not undertaken because of diverse study designs and data heterogeneity. There was no significant difference in survival between the groups, even though 5-yr overall survival appears better for the RN plus LND group compared with the no-LND group in one randomised study. There was no evidence of a difference in adverse events between the RN plus LND and no-LND groups. No studies reported QoL outcomes. There was no evidence of an oncologic difference between the RN with adrenalectomy and RN without adrenalectomy groups. No studies reported adverse events or QoL outcomes.Conclusions: There is insufficient evidence to draw any conclusions on oncologic outcomes for patients having concomitant LND or ipsilateral adrenalectomy compared with patients having RN alone for cT3-T4N0M0 RCC. The quality of evidence is generally low and the results potentially biased. Further research in adequately powered trials is needed to answer these questions.
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  • Bill-Axelson, Anna, et al. (författare)
  • Long-term Distress After Radical Prostatectomy Versus Watchful Waiting in Prostate Cancer : A Longitudinal Study from the Scandinavian Prostate Cancer Group-4 Randomized Clinical Trial
  • 2013
  • Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 64:6, s. 920-928
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Studies enumerating the dynamics of physical and emotional symptoms following prostate cancer (PCa) treatment are needed to guide therapeutic strategy. Yet, overcoming patient selection forces is a formidable challenge for observational studies comparing treatment groups.OBJECTIVE:To compare patterns of symptom burden and distress in men with localized PCa randomized to radical prostatectomy (RP) or watchful waiting (WW) and followed up longitudinally.DESIGN, SETTING, AND PARTICIPANTS:The three largest, Swedish, randomization centers for the Scandinavian Prostate Cancer Group-4 trial conducted a longitudinal study to assess symptoms and distress from several psychological and physical domains by mailed questionnaire every 6 mo for 2 yr and then yearly through 8 yr of follow-up.INTERVENTION:RP compared with WW.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:A questionnaire was mailed at baseline and then repeatedly during follow-up with questions concerning physical and mental symptoms. Each analysis of quality of life was based on a dichotomization of the outcome (yes vs no) studied in a binomial response, generalized linear mixed model.RESULTS AND LIMITATIONS:Of 347 randomized men, 272 completed at least five questionnaires during an 8-yr follow-up period. Almost all men reported that PCa negatively influenced daily activities and relationships. Health-related distress, worry, feeling low, and insomnia were consistently reported by approximately 30-40% in both groups. Men in the RP group consistently reported more leakage, impaired erection and libido, and fewer obstructive voiding symptoms. For men in the WW group, distress related to erectile symptoms increased gradually over time. Symptom burden and distress at baseline was predictive of long-term outlook.CONCLUSIONS:Cancer negatively influenced daily activities among almost all men in both treatment groups; health-related distress was common. Trade-offs exist between physiologic symptoms, highlighting the importance of tailored treatment decision-making. Men who are likely to experience profound long-term distress can be identified early in disease management.
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  • Bjartell, Anders (författare)
  • "A Robot Saved My Life": Is It a Myth?
  • 2012
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 62:5, s. 775-776
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • Brandt, Andreas, et al. (författare)
  • Age-Specific Risk of Incident Prostate Cancer and Risk of Death from Prostate Cancer Defined by the Number of Affected Family Members
  • 2010
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 58:2, s. 275-280
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The thorough assessment of familial prostate cancer (PCa) risk is as important as ever to provide a basis for clinical counselling and screening recommendations. Objective: Our aim was to determine the age-specific risks of PCa and the risk of death from PCa according to the number and the age of affected first-degree relatives. Design, setting, and participants: The nationwide Swedish Family-Cancer Database includes a record of >11.8 million individuals and their cancers from 1958 to 2006. All men from the database with identified parents (>3.9 million individuals) were followed between 1961 and 2006. The study included 26 651 PCa patients, of whom 5623 were familial. Measurements: The age-specific hazard ratios (HRs) of PCa and the HRs of death from PCa were calculated according to the number and age of affected fathers and brothers. Results and limitations: The HRs of PCa diagnosis increased with the number of affected relatives and decreased with increasing age. The highest HRs were observed for men <65 yr of age with three affected brothers (HR: approximately 23) and the lowest for men between 65 and 74 yr of age with an affected father (HR: approximately 1.8). The HRs increased with decreasing paternal or fraternal diagnostic age. The pattern of the risk of death from familial PCa was similar to the incidence data. Conclusions: The present results should guide clinical counselling and demonstrate the vast increases in risk when multiple first-degree relatives are affected. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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  • Bruins, Harman M, et al. (författare)
  • The impact of the extent of lymphadenectomy on oncologic outcomes in patients undergoing radical cystectomy for bladder cancer : a systematic review
  • 2014
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 66:6, s. 1065-1077
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Controversy exists regarding the therapeutic value of lymphadenectomy (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To systematically review the relevant literature assessing the impact of LND on oncologic and perioperative outcomes in patients undergoing RC for MIBC. EVIDENCE ACQUISITION: Medline, Medline In-Process, Embase, the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Center on Health Sciences Information (LILACS) were searched up to December 2013. Comparative studies reporting on no LND, limited LND (L-LND), standard LND (S-LND), extended LND (E-LND), superextended LND (SE-LND), and oncologic and perioperative outcomes were included. Risk-of-bias and confounding assessments were performed. EVIDENCE SYNTHESIS: Twenty-three studies reporting on 19 793 patients were included. All but one study were retrospective. Planned meta-analyses were not possible because of study heterogeneity; therefore, data were synthesized narratively. There were high risks of bias and confounding across most studies as well as extreme heterogeneity in the definition of the anatomic boundaries of LND templates. All seven studies comparing LND with no LND favored LND in terms of better oncologic outcomes. Seven of 14 studies comparing (super)extended LND with L-LND or S-LND reported a beneficial outcome for (super)extended LND in at least a subset of patients. No difference in outcome was reported in two studies comparing E-LND and S-LND. The comparative harms of different extents of LND remain unclear. CONCLUSIONS: Although the quality of the data was poor, the available evidence indicates that any kind of LND is advantageous over no LND. Similarly, E-LND appears to be superior to lesser degrees of dissection, while SE-LND offered no additional benefits. It is hoped that data from ongoing randomized clinical trials will clarify remaining uncertainties. PATIENT SUMMARY: The current literature suggests that removal of lymph nodes in bladder cancer surgery is beneficial and might result in better outcomes in terms of prolonging survival; however, the quality of the available studies is poor, and high-quality studies are needed.
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  • Budäus, Lars, et al. (författare)
  • Functional Outcomes and Complications Following Radiation Therapy for Prostate Cancer : A Critical Analysis of the Literature
  • 2012
  • Ingår i: European Urology. - Basel : Karger. - 0302-2838 .- 1873-7560. ; 61:1, s. 112-127
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Prostate cancer (PCa) patients have many options within the realms of surgery or radiation therapy (RT). Technical advancements in RT planning and delivery have yielded different approaches, such as external beam, brachytherapy, and newer approaches such as image-guided tomotherapy or volumetric-modulated arc therapy. The selection of the optimal RT treatment for the individual is still a point of discussion, and the debate centres on two important outcomes-namely, cancer control and reduction of side-effects. OBJECTIVE: To critically review and summarise the available literature on functional outcomes and rectal sequelae following RT for PCa treatment. EVIDENCE ACQUISITION: A review of the literature published between 1999 and 2010 was performed using Medline and Scopus search. Relevant reports were identified using the terms prostate cancer, radiotherapy, functional outcomes, external beam radiation, brachytherapy, IMRT, quality of life, and tomotherapy and were critically reviewed and summarised. EVIDENCE SYNTHESIS: Related to nonuniform definition of their assessed functional end points and uneven standards of reporting, only a minority of series retrieved could be selected for analyses. Moreover, patterns of patient selection for different types of RT, inherent differences in the RT modalities, and the presence or absence of hormonal treatment also limit the ability to synthesise results from different publications or perform meta-analyses across the different treatment types. Nonetheless, several studies agree that recent technical improvements in the field of RT planning and delivery enable the administration of higher doses with equal or less toxicity. Regardless of the type of RT, the most frequently considered functional end points in the published analyses are gastrointestinal (GI) complications and rectal bleeding. Established risk factors for acute or late toxicities after RT include advanced age, larger rectal volume, a history of prior abdominal surgery, the concomitant use of androgen deprivation, preexisting diabetes mellitus, haemorrhoids, and inflammatory bowel disease (IBD). Similarly, mild acute irritative urinary symptoms are reported in several studies, whereas total urinary incontinence and other severe urinary symptoms are rare. Pretreatment genitourinary complaints, prior transurethral resection of the prostate (TURP), and the presence of acute genitourinary toxicity are suggested as contributing to long-term urinary morbidity. Erectile dysfunction (ED) is not an immediate side-effect of RT, and the occurrence of spontaneous erections before treatment is the best predictor for preserving erections sufficient for intercourse. In addition, the use of magnetic resonance imaging (MRI) permits a reduction in the dose delivered to vascular structures critical for erectile function. CONCLUSIONS: In the future, further improvement in RT planning and delivery will decrease side-effects and permit administration of higher doses. Related to the anatomy of the prostate, these higher doses may favour rectal sparing while not readily sparing the urethra and bladder neck. As a consequence, there may be a future shift from dose-limiting long-term rectal morbidity towards long-term urinary morbidity. In the absence of prospective randomised trials comparing different types of surgical and RT-based treatments in PCa, the introduction of validated tools for reporting functional and clinical outcomes is crucial for evaluating and identifying each individual's best treatment choice.
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  • Bul, Meelan, et al. (författare)
  • Active Surveillance for Low-Risk Prostate Cancer Worldwide: The PRIAS Study
  • 2013
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 63:4, s. 597-603
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Overdiagnosis and subsequent overtreatment are important side effects of screening for, and early detection of, prostate cancer (PCa). Active surveillance (AS) is of growing interest as an alternative to radical treatment of low-risk PCa. Objective: To update our experience in the largest worldwide prospective AS cohort. Design, setting, and participants: Eligible patients had clinical stage T1/T2 PCa, prostate-specific antigen (PSA) <= 10 ng/ml, PSA density <0.2 ng/ml per milliliter, one or two positive biopsy cores, and Gleason score <= 6. PSA was measured every 3-6 mo, and volume-based repeat biopsies were scheduled after 1, 4, and 7 yr. Reclassification was defined as more than two positive cores or Gleason >6 at repeat biopsy. Recommendation for treatment was triggered in case of PSA doubling time <3 yr or reclassification. Outcome measurements and statistical analysis: Multivariate regression analysis was used to evaluate predictors for reclassification at repeat biopsy. Active therapy-free survival (ATFS) was assessed with a Kaplan-Meier analysis, and Cox regression was used to evaluate the association of clinical characteristics with active therapy over time. Results and limitations: In total, 2494 patients were included and followed for a median of 1.6 yr. One or more repeat biopsies were performed in 1480 men, of whom 415 men (28%) showed reclassification. Compliance with the first repeat biopsy was estimated to be 81%. During follow-up, 527 patients (21.1%) underwent active therapy. ATFS at 2 yr was 77.3%. The strongest predictors for reclassification and switching to deferred treatment were the number of positive cores (two cores compared with one core) and PSA density. The disease-specific survival rate was 100%. Follow-up was too short to draw definitive conclusions about the safety of AS. Conclusions: Our short-term data support AS as a feasible strategy to reduce overtreatment. Clinical characteristics and PSA kinetics during follow-up can be used for risk stratification. Strict monitoring is even more essential in men with high-risk features to enable timely recognition of potentially aggressive disease and offer curative intervention. Limitations of using surrogate end points and markers in AS should be recognized.
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  • Burger, Maximilian, et al. (författare)
  • ICUD-EAU International Consultation on Bladder Cancer 2012: Non-Muscle-Invasive Urothelial Carcinoma of the Bladder
  • 2013
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 63:1, s. 36-44
  • Forskningsöversikt (refereegranskat)abstract
    • Context: Our aim was to present a summary of the Second International Consultation on Bladder Cancer recommendations on the diagnosis and treatment options for non-muscle-invasive urothelial cancer of the bladder (NMIBC) using an evidence-based approach. Objective: To critically review the recent data on the management of NMIBC to arrive at a general consensus. Evidence acquisition: A detailed Medline analysis was performed for original articles addressing the treatment of NMIBC with regard to diagnosis, surgery, intravesical chemotherapy, and follow-up. Proceedings from the last 5 yr of major conferences were also searched. Evidence synthesis: The major findings are presented in an evidence-based fashion. We analyzed large retrospective and prospective studies. Conclusions: Urothelial cancer of the bladder staged Ta, T1, and carcinoma in situ (CIS), also indicated as NMIBC, poses greatly varying but uniformly demanding challenges to urologic care. On the one hand, the high recurrence rate and low progression rate with Ta low-grade demand risk-adapted treatment and surveillance to provide thorough care while minimizing treatment-related burden. On the other hand, the propensity of Ta high-grade, T1, and CIS to progress demands intense care and timely consideration of radical cystectomy. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.
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  • Carlsson, Sigrid, et al. (författare)
  • Predictive Value of Four Kallikrein Markers for Pathologically Insignificant Compared With Aggressive Prostate Cancer in Radical Prostatectomy Specimens: Results From the European Randomized Study of Screening for Prostate Cancer Section Rotterdam
  • 2013
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 64:5, s. 693-699
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Treatment decisions can be difficult in men with low-risk prostate cancer (PCa). Objective: To evaluate the ability of a panel of four kallikrein markers in blood-total prostate-specific antigen (PSA), free PSA, intact PSA, and kallikrein-related peptidase 2-to distinguish between pathologically insignificant and aggressive disease on pathologic examination of radical prostatectomy (RP) specimens as well as to calculate the number of avoidable surgeries. Design, setting, and participants: The cohort comprised 392 screened men participating in rounds 1 and 2 of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer. Patients were diagnosed with PCa because of an elevated PSA >= 3.0 ng/ml and were treated with RP between 1994 and 2004. Outcome measurements and statistical analysis: We calculated the accuracy (area under the curve [AUC]) of statistical models to predict pathologically aggressive PCa (pT3-T4, extracapsular extension, tumor volume >0.5 cm(3), or any Gleason grade >= 4) based on clinical predictors (age, stage, PSA, biopsy findings) with and without levels of four kallikrein markers in blood. Results and limitations: A total of 261 patients (67%) had significant disease on pathologic evaluation of the RP specimen. While the clinical model had good accuracy in predicting aggressive disease, reflected in a corrected AUC of 0.81, the four kallikrein markers enhanced the base model, with an AUC of 0.84 (p < 0.0005). The model retained its ability in patients with low-risk and very-low-risk disease and in comparison with the Steyerberg nomogram, a published prediction model. Clinical application of the model incorporating the kallikrein markers would reduce rates of surgery by 135 of 1000 patients overall and 110 of 334 patients with pathologically insignificant disease. A limitation of the present study is that clinicians may be hesitant to make recommendations against active treatment on the basis of a statistical model. Conclusions: Our study provided proof of principle that predictions based on levels of four kallikrein markers in blood distinguish between pathologically insignificant and aggressive disease after RP with good accuracy. In the future, clinical use of the model could potentially reduce rates of immediate unnecessary active treatment. (c) 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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34.
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35.
  • Castiglione, Fabio, et al. (författare)
  • 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
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 63:3, s. 551-560
  • 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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36.
  • Castiglione, Fabio, et al. (författare)
  • Perioperative Betamethasone Treatment Reduces Signs of Bladder Dysfunction in a Rat Model for Neurapraxia in Female Urogenital Surgery
  • 2012
  • Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 62:6, s. 1076-1085
  • 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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37.
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38.
  • Catto, James W. F., et al. (författare)
  • MicroRNA in Prostate, Bladder, and Kidney Cancer: A Systematic Review
  • 2011
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 59:5, s. 671-681
  • Forskningsöversikt (refereegranskat)abstract
    • Context: MicroRNAs (miRNA) are noncoding RNAs that post- transcriptionally regulate gene expression. Their altered expression and function have been observed in most urologic cancers. MiRNAs represent potential disease biomarkers and novel therapeutic targets. Objective: To review and evaluate the evidence implicating miRNAs in the pathogenesis of prostate cancer (PCa), bladder cancer (BCa), and renal cancer. Evidence acquisition: A systematic review was performed using PubMed and Embase to search for reports using strings for microRNA, non- coding RNA, cancer, prostate, bladder, and renal cancer. Identified manuscripts were retrieved and references searched. Selected studies were required to concentrate on the role of miRNA in these urologic cancers. Evidence synthesis: We reviewed articles that focus on this topic. More than 40 miRNAs have been implicated in urologic cancer and many target common carcinogenic pathways. In particular, apoptosis avoidance, cell proliferation, epithelial- to- mesenchymal transition, angiogenic signalling, and the generation of androgen independence are targeted or facilitated by more than one miRNA. Little work has been done to evaluate the translational applications for this knowledge to date. Novel therapeutic strategies have been developed and are under investigation to selectively modulate miRNAs; such work would potentially enable personalised tumour therapy. Conclusions: MiRNAs appear to be important modulators of urologic cancer. Their expression is frequently altered in these tumours, and many are functionally implicated in their pathogenesis. They require evaluation to determine the translational role and therapeutic potential for this knowledge. Crown Copyright (C) 2011 Published by Elsevier B. V. on behalf of European Association of Urology. All rights reserved.
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39.
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40.
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41.
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42.
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43.
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44.
  • Coyne, Karin S, et al. (författare)
  • Urinary Incontinence and its Relationship to Mental Health and Health-Related Quality of Life in Men and Women in Sweden, the United Kingdom, and the United States.
  • 2012
  • Ingår i: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 61:1, s. 88-95
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Differences in health burden associated with urinary incontinence (UI) subtypes have been previously described, but the majority of studies are in women. Additional research is needed to examine the prevalence and burden of UI subtype including postmicturition incontinence, nocturnal enuresis, coital incontinence, and incontinence for unspecified reasons. OBJECTIVE: Examine the burden of UI in men and women in Sweden, the United Kingdom, and the United States. DESIGN, SETTING, AND PARTICIPANTS: Secondary analyses of the Epidemiology of Lower Urinary Tract Symptoms (EpiLUTS), a cross-sectional Internet survey, were performed. Participants who reported UI were categorized as (1) urgency urinary incontinence (UUI) only, (2) stress urinary incontinence (SUI) only, (3) mixed urinary incontinence (MUI), (4) UUI plus other incontinence (OI), (5) SUI plus OI, or (6) OI. Differences in health outcomes across UI groups were explored by gender using descriptive statistics and general linear models. MEASUREMENTS: Outcomes included treatment seeking for urinary symptoms, perception of bladder condition, depression, anxiety, and health-related quality of life (HRQL). RESULTS AND LIMITATIONS: Of 14 140 men and 15 860 women, 6479 men (45.8%) and 10 717 women (67.6%) reported UI. The most prevalent UI subgroups were OI in men and SUI in women. MUI and SUI plus OI had the greatest treatment seeking among men, whereas MUI and UUI plus OI had the greatest treatment seeking among women. Men with MUI had the highest rates of anxiety, followed by those with UUI plus OI and SUI plus OI, and OI with a similar trend observed for depression. Anxiety and depression were highest in SUI plus OI and MUI women. MUI and UUI plus OI men and women had significantly lower HRQL compared with other UI groups. CONCLUSIONS: UI is common in men and women aged >40. Individuals with UUI combined with SUI or OI bear a greater mental health burden and report poorer HRQL.
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45.
  • de la Rosette, Jean J. M. C. H., et al. (författare)
  • Categorisation of Complications and Validation of the Clavien Score for Percutaneous Nephrolithotomy
  • 2012
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 62:2, s. 246-255
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although widely used, the validity and reliability of the Clavien classification of postoperative complications have not been tested in urologic procedures, such as percutaneous nephrolithotomy (PCNL). Objective: To validate the Clavien score and categorise complications of PCNL. Design, setting, and participants: Data for 528 patients with complications after PCNL were used to create a set of 70 unique complication-management combinations. Clinical case summaries for each complication-management combination were compiled in a survey distributed to 98 urologists, who rated each combination using the Clavien classification. Outcome measurements and statistical analysis: Interrater agreement for Clavien scores was estimated using Fleiss' kappa (kappa). The relationship between Clavien score and the duration of postoperative hospital stay was analysed using multivariate nonlinear regression models that adjusted for operating time, preoperative urine microbial culture, presence of staghorn stone, and use of postoperative nephrostomy tube. Results and limitations: Overall interrater agreement in grading postoperative complications was moderate (kappa = 0.457; p < 0.001). Agreement was highest for Clavien score 5 and decreased with lower Clavien scores. Higher agreement was found for Clavien scores 3 and 4 than in subcategories of these scores. Postoperative stay increased with higher Clavien scores and was unaffected by inherent differences between study centres. A standard list of post-PCNL complications and their corresponding Clavien scores was created. Conclusions: Although the Clavien classification demonstrates high validity, interrater reliability is low for minor complications. To improve the reliability and consistency of reporting adverse outcomes of PCNL, we have assigned Clavien scores to complications of PCNL. (C) 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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46.
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47.
  • Dev, HS, et al. (författare)
  • Single-Site Surgery: More oR-LESS?
  • 2010
  • Ingår i: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 58:6, s. 849-850
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
48.
  • Dohle, Gert R., et al. (författare)
  • European Association of Urology Guidelines on Vasectomy
  • 2012
  • Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 61:1, s. 159-163
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: The European Association of Urology presents its guidelines for vasectomy. Vasectomy is highly effective, but problems can arise that are related to insufficient preoperative patient information, the surgical procedure, and postoperative follow-up. Objective: These guidelines aim to provide information and recommendations for physicians who perform vasectomies and to promote the provision of adequate information to the patient before the operation to prevent unrealistic expectations and legal procedures. Evidence acquisition: An extensive review of the literature was carried out using Medline, Embase, and the Cochrane Database of Systematic Reviews from 1980 to 2010. The focus was on randomised controlled trials (RCTs) and meta-analyses of RCTs (level 1 evidence) and on well-designed studies without randomisation (level 2 and 3 evidence). A total of 113 unique records were identified for consideration. Non-English language publications were excluded as well as studies published as abstracts only or reports from meetings. Evidence synthesis: The guidelines discuss indications and contraindications for vasectomy, preoperative patient information and counselling, surgical techniques, postoperative care and subsequent semen analysis, and complications and late consequences. Conclusions: Vasectomy is intended to be a permanent form of contraception. There are no absolute contraindications for vasectomy. Relative contraindications may be the absence of children, age <30 yr, severe illness, no current relationship, and scrotal pain. Preoperative counselling should include alternative methods of contraception, complication and failure rates, and the need for postoperative semen analysis. Informed consent should be obtained before the operation. Although the use of mucosal cautery and fascial interposition have been shown to reduce early failure compared to simple ligation and excision of a small vas segment, no robust data show that a particular vasectomy technique is superior in terms of prevention of late recanalisation and spontaneous pregnancy after vasectomy. After semen analysis, clearance can be given in case of documented azoospermia and in case of rare nonmotile spermatozoa in the ejaculate at least 3 mo after the procedure. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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49.
  • Duchek, Milos, et al. (författare)
  • Bacillus Calmette-Guerin Is Superior to a Combination of Epirubicin and Interferon-alpha 2b in the Intravesical Treatment of Patients with Stage T1 Urinary Bladder Cancer. A Prospective, Randomized, Nordic Study
  • 2010
  • Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 57:1, s. 25-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Bacillus Calmette-Guerin (BCG) instillation is regarded as the most effective bladder-sparing treatment for patients with high-grade T1 tumours and carcinoma in situ (CIS). The major problem with this therapy is the side-effects, making maintenance therapy difficult, even impossible, in a proportion of patients. Thus, alternative schedules and drugs have been proposed. Objective: To compare BCG to the combination of epirubicin and interferon-alpha 2b as adjuvant therapy of T1 tumours. Design, setting, and participants: This is a Nordic multicenter, prospective, randomised trial in patients with primary T1 G2-G3 bladder cancer. Initial transurethral resection (TUR) was followed by a second-look resection. Patients were randomised to receive either regimen, given as induction for 6 wk followed by maintenance therapy for 2 yr. Measurements: The drugs were compared with respect to time to recurrence and progression. Also, side-effects were documented. Results and limitations: A total of 250 patients were randomised. At the primary end point, 62% were disease free in the combination arm as opposed to 73% in the BCG arm (p = 0.065). At 24 mo, there was a significant difference in favour of the BCG-treated patients (p = 0.012) regarding recurrence, although there was no difference regarding progression. The subgroup analysis showed that the superiority of BCG was mainly in those with concomitant CIS. In a multivariate analysis of association with recurrence/progression status, significant variables for outcome were type of drug, tumour size, multiplicity, status at second-look resection, and grade. A corresponding analysis was performed separately in the two treatment arms. Tumour size was the only significant variable for BCG-treated patients, while multiplicity, status at second-look resection, and grade were significant for patients treated with the combination. Conclusions: For prophylaxis of recurrence, BCG was more effective than the combination. There were no differences regarding progression and adverse events between the two treatments.
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50.
  • Fall, Magnus, 1941, et al. (författare)
  • EAU Guidelines on Chronic Pelvic Pain.
  • 2010
  • Ingår i: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 57:1, s. 35-48
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: These guidelines were prepared on behalf of the European Association of Urology (EAU) to help urologists assess the evidence-based management of chronic pelvic pain (CPP) and to incorporate the recommendations into their clinical practice. OBJECTIVE: To revise guidelines for the diagnosis, therapy, and follow-up of CPP patients. EVIDENCE ACQUISITION: Guidelines were compiled by a working group and based on a systematic review of current literature using the PubMed database, with important papers reviewed for the 2003 EAU guidelines as a background. A panel of experts weighted the references. EVIDENCE SYNTHESIS: The full text of the guidelines is available through the EAU Central Office and the EAU Web site (www.uroweb.org). This article is a short version of the full guidelines text and summarises the main conclusions from the guidelines on the management of CPP. CONCLUSIONS: A guidelines text is presented including chapters on chronic prostate pain and bladder pain syndromes, urethral pain, scrotal pain, pelvic pain in gynaecologic practice, neurogenic dysfunctions, the role of the pelvic floor and pudendal nerve, psychological factors, general treatment of CPP, nerve blocks, and neuromodulation. These guidelines have been drawn up to provide support in the management of the large and difficult group of patients suffering from CPP.
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