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Sökning: WFRF:(Witjes A)

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  • Horwich, A, et al. (författare)
  • EAU–ESMO consensus statements on the management of advanced and variant bladder cancer - an international collaborative multi-stakeholder effort : under the auspices of the EAU and ESMO Guidelines Committees
  • 2019
  • Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 30:11, s. 1697-1727
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.
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  • Kiemeney, Lambertus A, et al. (författare)
  • A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.
  • 2010
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 415-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
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  • Bhatt, Nikita R., et al. (författare)
  • Contemporary use of phytotherapy in patients with lower urinary tract symptoms due to benign prostatic hyperplasia : results from the EVOLUTION European registry
  • 2021
  • Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 0724-4983 .- 1433-8726. ; 39:7, s. 2661-2667
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To use the European Association of Urology Research Foundation (EAURF) registry data to determine the proportion of contemporary Lower Urinary Tract Symptoms associated with Benign Prostatic Enlargement (LUTS/BPE) patients prescribed phytotherapy, and to determine their subjective quality of life and clinical progression responses. Methods: This was a prospective multicenter multinational observational registry study, conducted over 2 years. Men ≥ 50 years seeking LUTS/BPE were divided at baseline into two cohorts, presently/recently untreated patients (PUP) commencing pharmacotherapy at baseline and presently/recently treated patients (c-PTP) continuing previously received pharmacotherapy, with 24-month follow-up (FU). Results: Overall, 2175 patients were enrolled with 1838 analyzed. Of the PUP cohort (n = 575), 92 (16%) received phytotherapy and 65 (71%, n = 65/92) completed 24-month FU, with France prescribing 34% (n = 30/89) the highest proportion of phytotherapy among all LUTS/BPE medications. In the c-PTP group (n = 1263), only 69 (5%) patients were using phytotherapy, falling to n = 35/69 (51%) at 24-month FU (highest in France 20% (n = 43/210)). Though defined disease progression occurred in ≤ 20%, with only 1% proceeding to surgical intervention, in both groups, clinically meaningful improvement was lower and symptom persistence was higher in PUP but similar in the treated (c-PTP) patients on phytotherapy compared to the other LUTS/BPE medication. Conclusion: Low heterogeneous prescribing rates for phytotherapy were reported in both PUP and c-PTP cohorts over the 24-month FU. Although phytotherapy led to subjective improvements, healthcare practitioners should prescribe them with caution until higher quality evidence and guideline recommendations supporting its use are available.
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  • Bhatt, Nikita R., et al. (författare)
  • Quality of life with pharmacological treatment in patients with benign prostatic enlargement : results from the Evolution European Prospective Multicenter Multi-National Registry Study
  • 2021
  • Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 0724-4983 .- 1433-8726. ; 39:2, s. 517-526
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lower urinary tract symptoms due to benign prostate enlargement (LUTS/BPE) can lead to significant disturbances to health-related quality of life (HRQoL) and psychological well-being. The aim of this study was to evaluate the effect of pharmacological treatment of LUTS/BPE on disease specific and generic QOL measures. Methods: Evolution was a European prospective, multicenter multi-national, observational registry collecting real-life clinical data over 2 years on the management of LUTS/BPE in primary and secondary care. This study investigated disease-specific QOL using questionnaires such as IPSS Q8, BPH Impact Index (BII) and generic QOL using questionnaires like EuroQOL Five Dimension (EQ5D) which encompassed EQ5D VAS and EQ5D health index. Results: The registry enrolled 1838 BPE patients and 1246 patients were evaluable at the end of 24 months. Nearly 70% of patients in the study were previously treated with medical therapy and 17% of these had already discontinued medical treatment previously for various reasons with lack of efficacy being the most common. The mean time since diagnosis of LUTS in the previously treated group was 4.7 years (0–26 years). Medical management produced statistically significant improvement in QOL (disease specific and generic) in previously untreated patients and an insignificant change in generic QOL in previously treated patients. Conclusions: After 5-years from the onset of symptoms, LUTS/BPE patients previously treated with medication had significantly impaired QOL in patients in a manner comparable to other chronic diseases. Earlier intervention with minimally invasive surgical techniques (MIT) should be considered in LUTS/BPE patients that do not show a significant improvement in QOL with medical therapy.
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  • Davis, Niall F., et al. (författare)
  • Medical therapy versus transurethral resection of the prostate (TURP) for the treatment of symptomatic benign prostatic enlargement (BPE) : a cost minimisation analysis
  • 2019
  • Ingår i: World Journal of Urology. - : Springer Science and Business Media LLC. - 0724-4983 .- 1433-8726. ; 37:5, s. 873-878
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: A cost minimisation analysis compares the costs of different interventions’ to ascertain the least expensive over time. We compared different prostate targeted drug treatments with TURP to identify the optimal cost saving duration of a medical therapy for symptomatic benign prostatic enlargement (BPE). Methods: The Evolution registry is a prospective, multicentre registry, conducted by the European Association of Urology Research Foundation (EAUrf) for 24 months in 5 European countries. Evolution was designed to register the management of symptomatic BPE in clinical practice settings in 5 European countries. Direct cost evaluation associated with prostate targeted medical therapies and TURP was also recorded and analysed. Results: In total, 1838 men were enrolled with 1246 evaluable at 24 months. Medical therapies were more cost saving than TURP for treatment durations ranging from 2.9 to 70.4 years. Cost saving depended on both medication class and individual country assessed. Daily tamsulosin monotherapy was more cost saving than TURP for ≤ 13.9 years in Germany compared to ≤ 32.7 years in Italy. Daily finasteride monotherapy was more cost saving for ≤ 5.9 years in France compared to ≤ 36.9 years in Spain. Combination therapy was more cost saving for ≤ 5.9 years for Italian patients versus ≤ 13.8 years in Germany. Conclusions: BPE medical management was more cost saving than TURP for different specific treatment durations. Information from this study will allow clinicians to convey medical and surgical costs over time, to both patients and payors alike, when considering BPE treatment.
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  • Rafnar, Thorunn, et al. (författare)
  • European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.
  • 2011
  • Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 20:21, s. 4268-81
  • Tidskriftsartikel (refereegranskat)abstract
    • Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.
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