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| 8. |
- Albers, P, et al.
(författare)
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Guidelines on testicular cancer
- 2005
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Ingår i: European urology. - : Elsevier BV. - 0302-2838. ; 48:6, s. 885-894
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Tidskriftsartikel (refereegranskat)
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| 11. |
- Aus, Gunnar, 1958
(författare)
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Current status of HIFU and cryotherapy in prostate cancer--a review.
- 2006
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Ingår i: Eur Urol. - : Elsevier BV. ; 50:5, s. 927-934
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To evaluate the current status of high-intensity focused ultrasound (HIFU) and cryosurgery as the primary treatment option in patients with prostate cancer. Method A MedLine search using specified search terms was done on February 28, 2005. This search rendered 150 papers related to HIFU and 566 papers related to cryosurgery. Very few of these papers presented original outcome data and are included in the present review. Results No controlled trial was available for analysis, and no survival data were presented. No validated biochemical, surrogate end point was available for any of the two therapies. HIFU showed progression-free survival (based on prostate-specific antigen ± biopsy data) of 63–87% (projected 3- to 5-yr data), but median follow-up in the studies ranged from 12–24 mo. Negative postoperative biopsies was seen in 82–94% of patients. Complications have been reduced by the combination of transurethral resection of the prostate and HIFU. Cryosurgery showed a progression-free survival of 36–92% (projected 1–7 yr data), depending on risk groups and definition of failure. Negative biopsies were seen in 72–87%, but no biopsy data were available for the currently used third-generation cryotherapy machines. Complications seem to be lower with the third-generation machines. Conclusions None of the evaluated therapies has enough data available to support their use as an alternative to established therapies (surgery, radiation) for localised prostate cancer. Until further data become available, the use of both treatments should be restricted to patients unfit for established therapies who still have the need for local therapy. Take Home Message Both HIFU and cryotherapy are used in the treatment of prostate cancer, but there is a profound lack of long-term follow-up data for the currently used treatment modalities. Their use should be limited to patients unfit for conventional therapies.
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| 12. |
- Aus, Gunnar, 1958, et al.
(författare)
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EAU Guidelines on Prostate Cancer.
- 2005
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Ingår i: Eur Urol. - : Elsevier BV. ; 48:4, s. 546-551
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The first summary of the European Association of Urology (EAU) guidelines on prostate cancer was published in 2001. These guidelines have been continuously updated since many important changes affecting the clinical management of patients with prostate cancer have occurred over the past years. The aim of this paper is to present a summary of the 2005 update of the EAU guidelines on prostate cancer. Methods: A literature review of the new data has been performed by the working panel. The guidelines have been updated and level of evidence/grade of recommendation added to the text. This enables readers to better understand the quality of the data forming the basis of the recommendations. Results: A full version is available at the EAU Office or at www.uroweb.org. Systemic prostate biopsies under ultrasound guidance is the preferred diagnostic method and the use of periprostatic injection of a local anaesthetic can significantly reduce pain/discomfort associated with the procedure. Active treatment (surgery or radiation) is mostly recommended for patients with localized disease and a long life expectancy with radical prostatectomy being the only treatment evaluated in a randomized controlled trial. Follow-up is at large based on prostate specific antigen (PSA) and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy has become an option for selected patients with hormone refractory prostate cancer. Conclusion: The knowledge in the field of prostate cancer is rapidly changing. These EAU guidelines on prostate cancer summarize the most recent findings and put them into clinical practice.
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| 13. |
- Aus, Gunnar, 1958
(författare)
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Editorial comment on: Additional Surgical Intervention after Radical Prostatectomy, Radiation Therapy, Androgen-Deprivation Therapy, or Watchful Waiting
- 2007
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 52:4
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Tidskriftsartikel (refereegranskat)abstract
- Editorial Comment Scott Eggener, Memorial Sloan-Kettering Cancer Center, New York, NY, United States eggeners@mskcc.org ‘‘Now that we’ve got PSA velocity, what are we going to do with it’’ Prostate-specific antigen velocity (PSAV) was introduced nearly 15 yr ago as men diagnosed with prostate cancer were found to exhibit more rapid rises in PSA years prior to their diagnosis compared to those without clinically evident prostate cancer [1]. Recently, interest in PSAV has been rekindled, because the rate of PSA change in the year prior to radical prostatectomy or radiation therapy has been directly associated with the likelihood of disease- specific death [2,3]. Although these and other studies have generated much ‘‘publicity’’ for PSAV, physicians still lack sound guidance on whether, or how, to use PSAV in clinical practice. For instance, debate exists whether PSAV is a valuable adjunct to PSA alone to determine prostate cancer risk [4,5] or prompt diagnostic procedures. Further, in men considering treatment options or, alternatively, following primary therapy, how should pretreatment PSAV be appropriately integrated into their care? Should a markedly elevated level prompt multimodal therapy, a lower threshold for instituting secondary therapies, or not be considered at all? Simply and concisely, we do not know. This article, similar to another publication [6], shows that formulas used to calculate PSAV are generally inconsistent and highlights that as we continue to decipher the appropriate role for PSAV, a uniform methodologic language is mandatory. Linear regression has been anointed the de facto ‘‘gold standard’’ to calculate PSAV. With adequate measurements over an adequate period of time (both yet to be definitively determined), linear regression is assumed to best control for shortterm physiologic fluctuations in serum PSA levels and most fairly represent the ‘‘big-picture’’ PSAV. However, as a point-of-care tool, not all physicians have the resources to quickly perform linear regression. This study suggests a simple arithmetic method that may suffice. Studies like this should trigger further work to explore how PSAV is affected by the absolute PSA
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| 15. |
- Aus, Gunnar, 1958, et al.
(författare)
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Prostate cancer screening decreases the absolute risk of being diagnosed with advanced prostate cancer--results from a prospective, population-based randomized controlled trial.
- 2007
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Ingår i: Eur Urol. - : Elsevier BV. ; 51:3, s. 659-664
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objectives Randomized controlled trials are currently conducted to assess whether the mortality from prostate cancer is reduced by early detection with the use of prostate-specific antigen (PSA) measurements in serum. To be effective, such a program should be able to reduce the absolute number of men diagnosed with metastatic prostate cancer (for which no cure is available). The aim of the present report is to evaluate whether PSA-based screening reduces the risk of being diagnosed with metastatic prostate cancer. Methods A population-based, prospective, randomized, controlled screening trial for prostate cancer started in 1995 (the Göteborg branch of the European Randomized Study of Screening for Prostate Cancer [ERSPC]). Ten thousand, randomly selected men aged 50–66 yr were invited for biennial PSA testing, with 10,000 men serving as passive controls for whom diagnosis of metastatic prostate cancer was monitored by using the Swedish Cancer Registry. Results After a follow-up of 10 yr, the risk of being diagnosed with metastatic prostate cancer was reduced by 48.9%—that is, decreasing from 47 cases in the control group to 24 cases in the group randomized to PSA-based screening (p = 0.0084). However, the risk of being diagnosed with prostate cancer increased 1.8-fold with PSA-based screening. Conclusions Biennial PSA screening reduces the risk of being diagnosed with metastatic prostate cancer, the first prerequisite for achieving decreased cancer mortality in younger men. This putative benefit is balanced by a 1.8-fold increased risk for diagnosis of prostate cancer. Take Home Message The present randomized, controlled study shows that men taking part in a PSA-based prostate cancer–screening program will have a 50% reduction in the risk of being diagnosed with advanced/metastatic, noncurable prostate cancer.
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| 18. |
- Basra, R., et al.
(författare)
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Design and Validation of a New Screening Instrument for Lower Urinary Tract Dysfunction: The Bladder Control Self-Assessment Questionnaire (B-SAQ)
- 2006
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Ingår i: Eur Urol. - 0302-2838.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To develop and validate a short patient self-assessment screening questionnaire: bladder control self-assessment questionnaire (B-SAQ) for the evaluation of lower urinary tract symptoms. This first validation study was undertaken amongst women. PATIENTS AND METHODS: Three hundred twenty-nine women attending general gynaecology and urogynaecology clinics completed both the B-SAQ and Kings Health questionnaire prior to medical consultation, and independent physician assessment of the presence of lower urinary tract symptoms (LUTS) and need for treatment. The psychometric properties of the B-SAQ were subsequently analysed. RESULTS: The B-SAQ was quick and easy to complete, with 89% of respondents completing all items correctly in less than 5min. The internal consistency (Cronbach's alpha score 0.90-0.91), criterion validity (Pearson's correlation values of 0.79 and 0.81, p<0.0001 with the incontinence impact domain of the Kings Health questionnaire), and test-retest reliability of the questionnaire were good. The sensitivity and specificity of the questionnaire to identify patients with bothersome LUTS was 98% and 79%, respectively. CONCLUSIONS: LUTS are commonly underreported. Empowering patients to self-assess their bladder symptoms and the need for treatment will improve treatment-seeking behaviour. The B-SAQ is a psychometrically robust, short screening questionnaire that offers patients the ability to assess their bladder symptoms and the bother they cause, and the potential benefit of seeking medical help.
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| 19. |
- Bastian, Patrick J., et al.
(författare)
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Insignificant Prostate Cancer and Active Surveillance: From Definition to Clinical Implications
- 2009
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 55:6, s. 1321-1332
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Forskningsöversikt (refereegranskat)abstract
- Context: Due to early detection strategies, prostate cancer is diagnosed early in its natural history. It remains unclear whether all patients diagnosed with prostate cancer warrant radical treatment or may benefit from delayed intervention following active surveillance. Objective: A systematic review of active surveillance protocols to investigate the inclusion criteria for active surveillance and the outcome of treatment. Evidence acquisition: Medline was searched using the following terms: prostate cancer, active surveillance and expectant management for dates up to October 2008. Further studies were chosen on the basis of manual searches of reference lists and review papers. Evidence synthesis: Numerous studies on active surveillance were identified. The recent inclusion criteria of the studies are rather similar. Keeping the short follow-up of all studies in mind, the majority of men stay on active surveillance, and the percentage of patients receiving active treatment is as high as 35% of all patients. Once a patients requires active treatment, most patients still present with curable prostate cancer. Furthermore, only few deaths due to prostate cancer have occurred. Conclusions: Active surveillance is an alternative option to immediate treatment of men with presumed insignificant prostate cancer. It seems that criteria used to identify men with low-risk prostate cancer are rather similar, and immediate treatment of men meeting these criteria may result in an unnecessary number of treatments in these highly selected patients. Data from randomised trials comparing active surveillance and active treatment will provide additional insight into outcome and follow-up strategies. (C) 2009 Published by Elsevier B.V. on behalf of European Association of Urology.
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| 25. |
- Ceder, Jens, et al.
(författare)
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Delta-Like 1 (Dlk-1), a Novel Marker of Prostate Basal and Candidate Epithelial Stem Cells, Is Downregulated by Notch Signalling in Intermediate/Transit Amplifying Cells of the Human Prostate.
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 54, s. 1344-1353
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is a lack of understanding of the processes that regulate differentiation in the prostate. OBJECTIVE: To determine localisation, activity, and regulation of cytodifferentiation-modulatory proteins in the human adult prostate. DESIGN, SETTINGS, AND PARTICIPANTS: Eighteen volunteering patients with organ-confined prostate cancer were prospectively enrolled at a single university hospital. INTERVENTION: All patients underwent radical prostatectomy, and normal/benign tissue was excised and obtained from the transition zone. MEASUREMENTS: Expression and activity of Notch-protein family members, including the Notch-homologous protein Delta-like 1 (Dlk-1/Pref1), were investigated immunohistochemically in normal/benign tissue and explant cultures. The effect of the Notch inhibitor L-685,458 on Dlk-1 expression and cell number was investigated in primary cell cultures, and data were analysed with Student t test. RESULTS AND LIMITATIONS: Mature luminal cells were found to co-express Notch-1 and its ligand Jagged1, but epithelia in normal/benign tissue showed no active Notch signalling. The basal cell layer, rare candidate epithelial stem cells, and a subpopulation of neuroendocrine cells expressed the differentiation protein Dlk-1. In explant cultures, luminal cells and Jagged1 expression were lost, whereas intermediate cells downregulated Dlk-1 concomitant with Notch-1 upregulation and activation. Notch inhibition in primary cell cultures led to lower cell densities (p<0.001) and suppressed downregulation of Dlk-1. This is a small study; current results need to be confirmed in larger investigations. CONCLUSIONS: We demonstrate that Notch-1 is upregulated in differentiation of prostate epithelia, and that the novel prostate progenitor marker Dlk-1 is downregulated by Notch signalling in intermediate cells. The identification of Dlk-1-expressing candidate stem and neuroendocrine cells suggests a hierarchical relationship.
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| 26. |
- Ceder, Jens, et al.
(författare)
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The characterization of epithelial and stromal subsets of candidate stem/progenitor cells in the human adult prostate.
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:3, s. 524-532
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Questions regarding the cell source and mechanisms in the initiation and progression of prostate cancer are today still open for debate. Indeed, our knowledge regarding prostate cell regulation, self-renewal, and cytodifferentiation is presently rather limited. In this study, we investigated these processes in the normal adult human prostate. METHODS: Dynamic expression patterns in prostate stem/progenitor cells, intermediate/transit-amplifying cells, and cell lineages were immunohistochemically identified in an in situ explant renewal model of the human normal/benign adult prostate (n=6). RESULTS: Cells with a basal phenotype proliferated significantly in explant cultures, whereas luminal cells went into apoptosis. Results further show down-regulation in tissue cultures of the basal and hypothetical stem cell marker Bcl-2 in the majority of cells, except in rare putative epithelial stem cells. Investigation of established (AC133) and novel candidate prostate stem/progenitor markers, including the cell surface receptor tyrosine kinase KIT and its ligand stem cell factor (SCF), showed that these rare epithelial cells are AC133(+)/CD133(low)/Bcl-2(high)/cytokeratin(+)/vimentin(-)/KIT(low)/SCF(low). In addition, we report on a stromal population that expresses the mesenchymal marker vimentin and that is AC133(-)/CD133(high)/Bcl-2(-)/cytokeratin(-)/KIT(high)/SCF(high). CONCLUSIONS: We provide evidence for epithelial renewal in response to tissue culture and for basal and epithelial stem/progenitor cell recruitment leading to an expansion of an intermediate luminal precursor phenotype. Data further suggest that SCF regulates prostate epithelial stem/progenitor cells in an autocrine manner and that all or a subset of the identified novel stromal phenotype represents prostate stromal progenitor cells or interstitial pacemaker cells or both.
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| 29. |
- Chi, Kim N., et al.
(författare)
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Castration-resistant Prostate Cancer: From New Pathophysiology to New Treatment Targets
- 2009
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 56:4, s. 594-605
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Tidskriftsartikel (refereegranskat)abstract
- Context: Castration-resistant prostate cancer (CRPC) refers to patients who no longer respond to surgical or medical castration. Standard treatment options are limited. Objective: To review the concepts and rationale behind targeted agents currently in late-stage clinical testing for patients with CRPC. Evidence acquisition: Novel targeted therapies in clinical trials were identified from registries. The MEDLINE database was searched for all relevant reports published from 1996 to October 2009. Bibliographies of the retrieved articles and major international meeting abstracts were hand-searched to identify additional studies. Evidence synthesis: Advances in our understanding of the molecular mechanisms underlying prostate cancer (PCa) progression has translated into a variety of treatment approaches. Agents targeting androgen receptor (AR) activation and local steroidogenesis, angiogenesis, immunotherapy, apoptosis, chaperone proteins, the insulin-like growth factor (IGF) pathway, RANK-ligand, endothelin receptors, and the Src family kinases are entering or have recently completed accrual to phase 3 trials for patients with CRPC. Conclusions: A number of new agents targeting mechanisms of PCa progression with early promising results are in clinical trials and have the potential to provide novel treatment options for CRPC in the near future. (C) 2009 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 30. |
- Crawford, E. David, et al.
(författare)
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PSA-based screening for prostate cancer: How does it compare with other cancer screening tests?
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 54:2, s. 262-273
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Forskningsöversikt (refereegranskat)abstract
- Context: Despite the substantive societal impact of prostate cancer, the medical community is currently divided on the balance between benefit and harm of screening for prostate cancer using prostate-specific antigen (PSA). Objective: To examine whether PSA-based screening for prostate cancer meets current guidelines on efficacy and effectiveness for screening, and how it compares with other currently implemented cancer-screening methods. Evidence acquisition: A literature search was conducted for reviews and individual studies that have examined the performance of screening for colorectal, cervical, breast, and prostate cancer. Each screening method was assessed using the United Kingdom National Screening Committee guidelines. Data on screening test performance (sensitivity, specificity, etc) were extracted from these articles for comparison. Evidence synthesis: In common with other cancers for which screening is conducted, prostate cancer represents a significant morbidity and mortality burden. The PSA test can be considered "simple" and "safe" within appropriate boundaries. The sensitivity/specificity profile of PSA is not optimal but has clinical validity: Cases missed at screening detected as interval cases do not have a poor outcome. Early prostate cancer intervention can be beneficial for long-term outcomes, although the benefits need to be weighed against the adverse effects of intervention. Early evidence from screening studies also suggests positive stage and grade shifts, although Level 1 mortality data are still awaited. Robust cost-effectiveness data are still lacking, although current evidence suggests that PSA screening may lie within acceptable limits. Conclusion: Until better markers become available, PSA can be regarded as an appropriate screening tool for prostate cancer at a population level. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 31. |
- Dizeyi, Nishtman, et al.
(författare)
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Expression of serotonin receptors 2B and 4 in human prostate cancer tissue and effects of their antagonists on prostate cancer cell lines.
- 2005
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 47:6, s. 895-900
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Overexpression of receptors to neuroendocrine (NE) cell products has been suggested to contribute to development of hormone-refractory prostate cancer (HRPC). In this study, we evaluated the expression of 5-HTR2B and 5-HTR4 in HRPC, and the effects of their antagonist on PC cell line growth. METHODS: Proteins and mRNA expression was determined by immunohistochemistry, western blot and RT-PCR. Growth inhibition of PC cell lines was determined in vitro using ELISA-BrdU proliferation assay and cell cycle was evaluated by flow cytometry. RESULTS: Immunostaining of 5-HTR2B was observed in low-grade and high-grade tumours, PIN and BPH cells, and in vascular endothelial cells, whereas 5-HTR4 was found predominantly in high-grade tumours. This result was confirmed by western blot analysis. At the mRNA level, 5-HTR4 mRNA was expressed in DU145 and LNCaP cells. Antagonists to both receptor subtypes inhibited proliferation of PC cells in a dose-dependent manner. CONCLUSIONS: The present result indicate that 5-HTRs are present at various tumour stages and that antagonists to these receptors can inhibit the proliferative activity of androgen-independent PC cell lines.
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| 32. |
- Egevad, L, et al.
(författare)
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Donald F. Gleason, 1920-2008 Obituary
- 2009
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Ingår i: EUROPEAN UROLOGY. - : Elsevier BV. - 0302-2838. ; 55:5, s. 1247-1249
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 33. |
- Eichelberg, Christian, et al.
(författare)
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Diagnostic and prognostic molecular markers for renal cell carcinoma : a critical appraisal of the current state of research and clinical applicability.
- 2009
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Ingår i: European urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 55:4, s. 851-63
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Earlier detection of renal cell carcinoma (RCC) and the recent expansion of treatment possibilities have positively influenced the outlook for patients with this disease. However, progression and treatment response are still not sufficiently predictable. Molecular markers could help to refine individual risk stratification and treatment planning, although they have not yet become clinically routine. OBJECTIVE: This review presents an overview of diagnostic and prognostic molecular markers for RCC and a subgrouping of these markers for different clinical issues. EVIDENCE ACQUISITION: Literature and recent meeting abstracts were searched using these terms: renal (cell) carcinoma, molecular/tumor markers, biopsy, blood, urine, disease progression/prognosis, immunohistochemistry, risk factors, and survival. Due to the resulting large number of articles, studies were subjectively selected according to the importance of a study on the field, number of investigated patients, originality, multivariate analyses performed, contrast with previously published data, actuality, and assumed clinical applicability of the described results. More then 90% of the selected studies originated from the past 10 yr; >50% of the articles were written in 2006 or later. EVIDENCE SYNTHESIS: These data were predominantly obtained via nonrandomized, retrospective, but often controlled studies. Thereby, the resulting level of evidence is 2A/2B. The broad spectrum of described molecular markers (MMs) for RCC consists of markers already extensively studied in other malignancies (eg, p53), as well as MMs typically associated with specific RCC-altered gene functions and pathways (eg, von Hippel-Lindau [VHL]). The main goal of using MMs is to refine the prediction of clinical end points like tumor progression, treatment response, and cancer-specific and/or overall survival. Further, MMs might facilitate the clinical work-up of undefined renal masses and prove to be more convenient tools for screening and follow-up in blood and urine. CONCLUSIONS: Presently, there are a number of promising MMs for diverse clinical questions, but the available data are not yet valid enough for routine, clinical application. We should comply with the demand for large multicenter prospective investigations, stratified for RCC type and treatment modalities, to lift the use of molecular markers in RCC to a practical level, thereby providing a better consultation for our patients regarding diagnosis, treatment, and follow-up.
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| 34. |
- Fall, Magnus, 1941, et al.
(författare)
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Treatment of Bladder Pain Syndrome/Interstitial Cystitis 2008: Can We Make Evidence-Based Decisions?
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 54:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Context Opinions on how to best treat bladder pain/interstitial cystitis are ambiguous. Objective To review previous and recent literature on this subject to assess the current state of evidence. Evidence acquisition With important previous papers reviewed for the 2003 European Association of Urology guidelines as background, the PubMed database was searched and articles published in 2003–2007 were reviewed and relevant ones were selected for detailed study. Evidence synthesis A large number of studies describing a variety of quite dissimilar therapeutic principles were retrieved. The various methods and level of evidence are summarised in tables. Only pentosan polysulfate sodium (oral and intravesical), amitriptyline, hydroxyzine, cyclosporin A, intravesical dimethyl sulfoxide, transurethral resection of visible Hunner lesions, and major reconstructive surgery reached a high degree of recommendation. However, a number of pitfalls hamper evaluation of the available information; a crucial one is that our understanding of basic mechanisms causing bladder pain is fragmentary. So far, we are faced with a large variety of hypotheses although it is difficult to identify the most relevant ones. In this respect, we are not much helped by the recent literature because many studies have poor descriptions of patients or are of a pilot character, with no follow-up by larger trials. Controlled studies are rather scarce. On the other hand, some good-quality studies following up positive pilot trials end up with negative results. Conclusion Perhaps the most significant problem concerns inclusion and exclusion criteria in bladder pain syndrome/interstitial cystitis studies. At this stage, it is not too easy to communicate the wide available expert knowledge to the general audience. More sophisticated standards, capable of being generally used, have to come. Take Home Message Evaluation of the rich literature on bladder pain syndrome/interstitial cystitis is difficult. The most significant problem concerns inclusion and exclusion criteria. It is not easy to communicate available expert knowledge, and more sophisticated standards, capable of being generally used, must come.
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| 35. |
- Frisk, Jessica, et al.
(författare)
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Two Modes of Acupuncture as a Treatment for Hot Flushes in Men with Prostate Cancer—A Prospective Multicenter Study with Long-Term Follow-Up
- 2009
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 55:1, s. 156-163
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hot flushes are common and distressing among men with castrational treatment for prostate cancer. Of the few treatments, most have side effects. Objective: Assess changes in hot flushes of electrostimulated (EA) and traditional acupuncture (TA). Design, Setting, and Participants: Thirty-one men with hot flushes due to prostate cancer treatment were recruited from three urological departments in Sweden, from 2001 to 2004. Intervention: Thirty-one men were randomized to EA (4 electrostimulated needle points) or TA (12 needle points) weekly for 12 wk. Measurements: Primary outcome: number of and distress from hot flushes in 24h and change in “hot flush score.” Secondary outcome: change in 24-h urine excretion of CGRP (calcitonin gene–related peptide). Results and Limitations: Twenty-nine men completed the treatment. Hot flushes per 24h decreased significantly, from a median of 7.6 (interquartile range [IQR], 6.0–12.3) at baseline in the EA group to 4.1 (IQR, 2.0–6.5) (p=0.012) after 12 wk, and from 5.7 (IQR, 5.1–9.5) in the TA group to 3.4 (IQR1.8–6.3) (p=0.001). Distress by flushes decreased from 8.2 (IQR, 6.5–10.7) in the EA group to 3.3 (IQR, 0.3–8.1) (p=0.003), and from 7.6 (IQR, 4.7–8.3) to 3.4 (IQR, 2.0–5.6) (p=0.001) in the TA group after 12 wk, (78% and 73% reduction in “hot flush score,” respectively). The effect lasted up to 9 mo after treatment ended. CGRP did not change significantly. Few, minor side effects were reported. Limitations: small number of patients; no placebo control, instead a small group controlled for 6 wk pretreatment. Conclusions: EA and TA lowered number of and distress from hot flushes. The hot flush score decreased 78% and 73%, respectively, in line with or better than medical regimens for these symptoms. Acupuncture should be considered an alternative treatment for these symptoms, but further evaluation is needed, preferably with a non- or placebo-treated control group.
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| 36. |
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| 37. |
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| 38. |
- Giwercman, Yvonne, et al.
(författare)
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The 5alpha-Reductase Type II A49T and V89L High-Activity Allelic Variants are More Common in Men with Prostate Cancer Compared with the General Population.
- 2005
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 48:Jul 20, s. 679-685
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare men with prostate disease with those from the general population regarding polymorphisms in the androgen receptor gene and in the 5 alpha-reductase II (SRD5A2) gene. Materials and methods: The SRD5A2 polymorphisms A49T, V89L and R227Q, the androgen receptor CAG and GGN repeats and sex hormone status was investigated in men with prostate cancer (CaP) (n = 89), benign prostate hyperplasia (n = 45) and healthy military conscripts (n = 223). Results: The SRD5A2 high-activity allele variants A49T AT and V89L LL were more frequent in CaP-patients compared to general population, p = 0.026 and p = 0.05, respectively. CaP progression was, however, independent of SRD5A2 variants. In contrary, men with GGN < 23 had a higher risk of dying from the disease than their counterparts with longer repeats. Conclusions: Men with CaP were more often genetically predisposed to a higher enzymatic activity in the turn over from T to DHT compared to the general population. In our population, androgen receptor genotype affected CaP outcome.
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| 41. |
- Gratzke, Christian, et al.
(författare)
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Transient Receptor Potential A1 (TRPA1) Activity in the Human Urethra-Evidence for a Functional Role for TRPA1 in the Outflow Region
- 2009
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Ingår i: EUROPEAN UROLOGY. - : Elsevier BV. - 0302-2838 .- 1873-7560. ; 55:3, s. 696-704
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Tidskriftsartikel (refereegranskat)abstract
- Background: A role for the transient receptor potential (TRP) A1 ion channel in rat lower urinary tract (LUT) sensation and disease has been proposed, but in the human LUT no information on TRPA1 activity is available. Objectives: To investigate the distribution of TRPA1 in the human urethra and to study the effect of TRPA1 agonists on isolated urethral strip preparations. Design, settings, and participants: Urethral specimens were obtained preoperatively from 10 patients and were freshly prepared for Western blot, immunohistochemistry, and functional in vitro investigations. Measurements: The expression patterns of TRPA1 were studied with Western blot and immunohistochemistry. The effects of allyl isothiocyanate (A1), cinnamaldehyde (CA), and NaHS (donor of H2S) on tension of urethral strips were investigated in tissue baths. Results and limitations: TRPA1 immunoreactivity (-IR) was found in nerve fibres in the suburothelial space and was also located to nerve fibres of the muscle layer. Single TRPA1-IR nerves extended into the urothelium. A majority, but not all TRPA1-IR nerves also expressed immunoreactivity for CGRP or TRPV1. In the urothelium, TRPV1 was located to the outer layers whereas TRPA1 was observed in basal urothelial cells. Interspersed between strands of smooth muscle cells of the urethral wall, TRPA1- and vimentin-IR cells containing central nuclei and slender cytoplasmatic extensions were observed. In functional experiments, TRPA1-agonists had no contractile effect in urethral preparations. After precontraction with phenylephrine, AI, CA, and NaHS caused concentration-dependent relaxations of urethral strip preparations.´ Conclusions: The localization of TRPA1 to nerves that also express TRPV1 and CGRP, and in urothelial cells and interstitial cells, as well as the findings that TRPA1 agonists can modify tone of urethral preparations, propose a role for TRPA1 in afferent and efferent sensory signaling of the human outflow region.
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| 42. |
- Gudjonsson, Sigurdur, et al.
(författare)
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Should All Patients with Non-Muscle-Invasive Bladder Cancer Receive Early Intravesical Chemotherapy after Transurethral Resection? The Results of a Prospective Randomised Multicentre Study.
- 2009
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 55, s. 773-780
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To decrease recurrences in non-muscle-invasive bladder cancer (NMIBC), the European Association of Urology (EAU) guidelines recommend immediate, intravesical chemotherapy after transurethral resection (TUR) for all patients with Ta/T1 tumours. OBJECTIVE: To study the benefits of a single, early, intravesical instillation of epirubicin after TUR in patients with low- to intermediate-risk NMIBC. DESIGN, SETTING, AND PARTICIPANTS: In this prospective randomised multicentre trial, 305 patients with primary as well as recurrent low- to intermediate-risk (Ta/T1, G1/G2) tumours were enrolled between 1997 and 2004. Patients were randomly allocated to receive 80mg of epirubicin in 50ml of saline intravesically within 24h of TUR or no further treatment after TUR. MEASUREMENTS: The primary end point was time to first recurrence. RESULTS AND LIMITATIONS: A total of 219 patients remained for analysis after exclusions. The median follow-up time was 3.9 yr. During the study period, 62% (63 of 102) of the patients in the epirubicin group and 77% (90 of 117) in the control group experienced recurrence (p=0.016). In a multivariate model, the hazard ratio (HR) for recurrence was 0.56 (p=0.002) for early instillation of epirubicin versus no treatment. In a subgroup analysis, the treatment had a profound recurrence-reducing effect on patients with primary, solitary tumours, whereas it provided no benefits in patients with recurrent or multiple tumours. Furthermore, patients with a modified European Organisation for Research and Treatment of Cancer (EORTC) risk score of 0-2 with and without single instillation had recurrence rates of 41% and 69%, respectively (p=0.003), whereas the corresponding rates for those with a risk score of >/=3 were 81% and 85%, respectively (p=0.35). CONCLUSIONS: A single, early instillation of epirubicin after TUR for NMIBC reduces the likelihood of tumour recurrence; however, the benefit seems to be minimal in patients at intermediate or high risk of recurrence. Future trials will determine the value of early instillation in addition to serial instillations in NMIBC.
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| 43. |
- Gudjonsson, Sigurdur, et al.
(författare)
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The Value of the UroVysion((R)) Assay for Surveillance of Non-Muscle-Invasive Bladder Cancer.
- 2008
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 54:2, s. 402-408
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Patients with non-muscle-invasive bladder cancer are traditionally followed by repeat cystoscopy and urine cytology. A fluorescence in situ hybridisation technique called UroVysion((R)) (UV) is now available for clinical diagnosis of urothelial cancer cells. The aim of the present study was to compare UV analysis with routine follow-up methods. METHODS: We studied an unselected cohort of patients undergoing cystoscopy follow-ups at two Swedish centres in 2004-2005. All patients were investigated by cystoscopy, cytology, and UV assay. The UV assay was evaluated with regards to sensitivity, specificity, and positive predictive value for tumour recurrence. RESULTS: In all, 159 cases were analysed. UV had a 30% overall sensitivity for the 27 biopsy-proven recurrences and 70% sensitivity for high-risk tumours (pT1 and carcinoma in situ [CIS]). The specificity of UV was 95%. UV detected all six CIS cases in the study and was predictive in two additional patients who developed CIS within 1 yr of inclusion. Cytology was positive in four of those eight CIS cases and atypical in the other four. CONCLUSIONS: The UV assay cannot replace cystoscopy for surveillance of patients with non-muscle-invasive bladder cancer, but it may be valuable as a supplement to traditional measures for detecting CIS. Before any conclusions can be drawn regarding the efficacy of novel markers of bladder cancer, they must be studied in bladder cancer patients undergoing endoscopic surveillance.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Hopfgarten, T., et al.
(författare)
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The choice between a therapy-induced long-term symptom and shortened survival due to prostate cancer
- 2006
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Ingår i: Eur Urol. - : Elsevier BV. - 0302-2838. ; 50:2, s. 280-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: A patient with newly diagnosed localized prostate cancer can choose from an array of therapies. A patient's willingness to trade life for freedom from therapy-induced long-term symptoms is poorly investigated. METHODS: In October 2002, we attempted to collect information from the 591 men who had been diagnosed and registered with prostate cancer in 1999 in Stockholm County. In a postal questionnaire, men were asked to balance absence or presence of certain therapy-induced long-term symptoms against varying lengths of survival gain as a consequence of the therapy. RESULTS: Information was provided by 511 (86%) of the 591 men. A large majority of the men participating in this study ended up in one of two extreme categories: either they accepted the therapy-induced symptom to gain survival or they did not. For fecal leakage, 78% of the men chose one of two extreme categories compared with 74% for urinary leakage, 71% for tender enlarged breasts, 73% for erectile dysfunction, and 78% for restricted diet. Thirty-seven percent of the men in the study were willing to accept fecal leakage if there was only the slightest chance to gain survival, comparing percentages for urinary leakage, tender enlarged breasts, restricted diet, and erectile dysfunction and were 48%, 53%, 55%, and 64%, respectively. CONCLUSION: Willingness to accept therapy-induced long-term symptoms to avoid a shortened survival due to prostate cancer varies dramatically among men with localized prostate cancer and a large majority of men are in one of two extreme categories. Among symptoms, long-term fecal leakage was the one fewest men were willing to accept to gain survival.
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| 49. |
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| 50. |
- Höglund, Mattias
(författare)
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On the Origin of Syn- and Metachronous Urothelial Carcinomas.
- 2007
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Ingår i: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 51:5, s. 1185-1193
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Forskningsöversikt (refereegranskat)abstract
- Objective: To evaluate existing models for the origin of meta- and synchronous urothelial carcinomas in light of the accumulated genetic data. Methods: Published studies on the clonal origin and genetic relationships of syn- and metachronous tumors, genetic aberrations in normal and premalignant urothelial lesions, as well as histologic and genetic mapping studies of cystectomized bladder samples are reviewed. Results: The most common models for the origin of syn- and metachronous tumors are found to conform less well to the accumulated genetic data. A new model is proposed, the field-first-turnor-later model, in which aberrant cells with a stem cell, or stem cell-like, origin spread in the urothelium by cellular displacement, creating fields of premalignant cells. Tumor growth is suggested to be initiated by critical genetic events occurring in individual cells in such fields. Hence, recurring tumors are proposed to originate from a shared field of premalignant cells and not from previous overt tumors. Conclusions: The proposed model can better account for the existing genetic and histological data on syn- and metachronous urothelial carcinomas. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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