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  • 101.
    Carlsson, Per
    et al.
    Linköping University, Department of Department of Health and Society, Center for Medical Technology Assessment. Linköping University, Faculty of Health Sciences.
    Hedbrant, Johan
    System Analysis Group, Linköping University.
    Pedersen, Knud
    The Department of Urology, Ryhov County Hospital in Jönköping, Sweden.
    Varenhorst, Eberhard
    The Department of Urology, Norrköping County Hospital, Sweden.
    Gray, Darryl
    Sector of Clinical Epidemiology, Mayo Clinic, Rochester, USA.
    An evaluation of prostate cancer screening using a decision analytic model1993Report (Other academic)
    Abstract [en]

    As early prostate cancer is often asymptomatic, the disease is often not diagnosed until it has reached an advanced, incurable stage. However, if diagnosed when it is still confined to the prostate, prostate caner is potentially curable. At present, there are no completed prospective evaluations or other scientific evidence to suggest that prostate cancer mortality is reduced or that quality of life is increased either by curative treatment or by screening programmes. However, the potential effects of a screening programme can be modelled using decision analytic computer software.

    The aim of this project was to develop a model for comparing the expected quality-adjusted life expectancy for a group of men subjected to a programme of screening for prostate cancer to that of a control group with conventional case-finding, given limited empirical data on the effectiveness of both strategies.

    Due to limitations of existing data, the analysis was developed during the early stages of evaluating a prostate cancer screening programme. We wish to illustrate how an analytic tool such as this model can be used in the future.

    The model was functionally separated into two parts. The first part, the observation submodel, covers the first 6 years of the programme and classifies the screened population into different quality of life states, based on observed outcomes. The second part, the simulation submodel, predicts quality adjusted life-years for healthy participants and for prostate cancer patients who receiving curative treatment or expectant management. Data for the model were obtained from a pilot programme on screening for prostate cancer in which a randomly selected population sample has been screened by digital rectal examination in Norrköping Sweden in 1987 and 1990. The outcome evaluated in the model was quality-adjusted life expectancy for individuals in the cohort invited to the screening programme, compared to results for population controls.

    While the preliminary results identify some health benefits associated with screening, more accurate empirical data for a number of key variables could improve the evaluation. One feature of this model is that it combines solid, empirical data from the observation submodel with simulated results. When better empirical data on the actual consequences of different strategies are available, they can easily be analysed by using this model.

  • 102. Carlsson, Sigrid
    et al.
    Berglund, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sjoberg, Daniel
    Khatami, Ali
    Stranne, Johan
    Bergdahl, Svante
    Lodding, Par
    Aus, Gunnar
    Vickers, Andrew
    Hugosson, Jonas
    Effects of surgeon variability on oncologic and functional outcomes in a population-based setting2014In: BMC Urology, ISSN 1471-2490, E-ISSN 1471-2490, Vol. 14, p. 25-Article in journal (Refereed)
    Abstract [en]

    Background: Oncologic and functional outcomes after radical prostatectomy (RP) can vary between surgeons to a greater extent than is expected by chance. We sought to examine the effects of surgeon variation on functional and oncologic outcomes for patients undergoing RP for prostate cancer in a European center. Methods: The study comprised 1,280 men who underwent open retropubic RP performed by one of nine surgeons at an academic institution in Sweden between 2001 and 2008. Potency and continence outcomes were measured preoperatively and 18 months postoperatively by patient-administered questionnaires. Biochemical recurrence (BCR) was defined as a prostate-specific antigen (PSA) value > 0.2 ng/mL with at least one confirmatory rise. Multivariable random effect models were used to evaluate heterogeneity between surgeons, adjusting for case mix (age, PSA, pathological stage and grade), year of surgery, and surgical experience. Results: Of 679 men potent at baseline, 647 provided data at 18 months with 122 (19%) reporting potency. We found no evidence for heterogeneity of potency outcomes between surgeons (P = 1). The continence rate for patients at 18 months was 85%, with 836 of the 979 patients who provided data reporting continence. There was statistically significant heterogeneity between surgeons (P = 0.001). We did not find evidence of an association between surgeons' adjusted probabilities of functional recovery and 5-year probability of freedom from BCR. Conclusions: Our data support previous studies regarding a large heterogeneity among surgeons in continence outcomes for patients undergoing RP. This indicates that some patients are receiving sub-optimal care. Quality assurance measures involving performance feedback, should be considered. When surgeons are aware of their outcomes, they can improve them to provide better care to patients.

  • 103. Carlsson, Sigrid
    et al.
    Drevin, Linda
    Loeb, Stacy
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Franck Lissbrant, Ingela
    Robinson, David
    Johansson, Eva
    Stattin, Pär
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Nursing.
    Population-based study of long-term functional outcomes after prostate cancer treatment2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, no 6B, p. E36-E45Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate long-term urinary, sexual and bowel functional outcomes after prostate cancer treatment at a median follow-up of 12 years (IQR 11-13).

    PATIENTS AND METHODS: In this nationwide, population-based study, we identified from the National Prostate Cancer Register, Sweden, 6,003 men diagnosed with localized prostate cancer (clinical local stage T1-2, any Gleason score, prostate specific antigen < 20 ng/mL, NX or N0, MX or M0) between 1997 and 2002 who were ≤70 years at diagnosis. 1,000 prostate cancer-free controls were selected, matched for age and county of residence. Functional outcomes were evaluated with a validated self-reported questionnaire.

    RESULTS: Responses were obtained from 3,937/6,003 cases (66%) and 459/1,000 (46%) controls. Twelve years post diagnosis, at a median age of 75 years, the proportion of cases with adverse symptoms was 87% for erectile dysfunction or sexually inactive, 20% for urinary incontinence and 14% for bowel disturbances. The corresponding proportions for controls were 62%, 6% and 7%, respectively. Men with prostate cancer, except those on surveillance, had an increased risk of erectile dysfunction, compared to control men. Radical prostatectomy was associated with increased risk of urinary incontinence (odds ratio; OR 2.29 [95% CI 1.83-2.86] and radiotherapy increased the risk of bowel dysfunction (OR 2.46 [95% CI 1.73-3.49]) compared to control men. Multi-modal treatment, in particular including androgen deprivation therapy (ADT), was associated with the highest risk of adverse effects; for instance radical prostatectomy followed by radiotherapy and ADT was associated with an OR of 3.74 [95 CI 1.76-7.95] for erectile dysfunction and OR 3.22 [95% CI 1.93-5.37] for urinary incontinence.

    CONCLUSION: The proportion of men who suffer long-term impact on functional outcomes after prostate cancer treatment was substantial.

  • 104.
    Carlsson, Sigrid
    et al.
    Mem Sloan Kettering Canc Ctr, Dept Surg, Urol Serv, New York, NY 10021 USA.;Univ Gothenburg, Sahlgrenska Acad, Dept Urol, Gothenburg, Sweden..
    Drevin, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Loeb, Stacy
    NYU, New York, NY USA.;Manhattan Vet Affairs Med Ctr, New York, NY USA..
    Widmark, Anders
    Umea Univ, Oncol, Dept Radiat Sci, Umea, Sweden..
    Lissbrant, Ingela Franck
    Univ Gothenburg, Sahlgrenska Acad, Dept Oncol, Gothenburg, Sweden..
    Robinson, David
    Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umea, Sweden.;Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden..
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Stattin, Par
    Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, S-90185 Umea, Sweden..
    Fransson, Per
    Umea Univ, Dept Nursing, Umea, Sweden..
    Population-based study of long-term functional outcomes after prostate cancer treatment2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 117, no 6B, p. E36-E45Article in journal (Refereed)
    Abstract [en]

    Objective To evaluate long-term urinary, sexual and bowel functional outcomes after prostate cancer treatment at a median (interquartile range) follow-up of 12 (11-13) years. Patients and Methods In this nationwide, population-based study, we identified 6 003 men diagnosed with localized prostate cancer (clinical local stage T1-2, any Gleason score, prostate-specific antigen <20 ng/mL, NX or N0, MX or M0) between 1997 and 2002 from the National Prostate Cancer Register, Sweden. The men were aged <= 70 years at diagnosis. A control group of 1 000 men without prostate cancer were also selected, matched for age and county of residence. Functional outcomes were evaluated with a validated self-reported questionnaire. Results Responses were obtained from 3 937/6 003 cases (66%) and 459/1 000 (46%) controls. At 12 years after diagnosis and at a median age of 75 years, the proportion of cases with adverse symptoms was 87% for erectile dysfunction/sexual inactivity, 20% for urinary incontinence and 14% for bowel disturbances. The corresponding proportions for controls were 62, 6 and 7%, respectively. Men with prostate cancer, except those on surveillance, had an increased risk of erectile dysfunction compared with the men in the control group. Radical prostatectomy was associated with an increased risk of urinary incontinence (odds ratio [OR] 1.89, 95% confidence interval [CI] 1.36-2.62) and radiotherapy increased the risk of bowel dysfunction (OR 2.46, 95% CI 1.73-3.49) compared with men in the control group. Multimodal treatment, in particular treatment including androgen deprivation therapy (ADT), was associated with the highest risk of adverse effects; for instance, radical prostatectomy followed by radiotherapy and ADT was associated with an OR of 3.74 (95% CI 1.76-7.95) for erectile dysfunction and an OR of 3.22 (95% CI 1.93-5.37) for urinary incontinence. Conclusion The proportion of men who experienced a long-term impact on functional outcomes after prostate cancer treatment was substantial.

  • 105. Carlsson, Stefan
    et al.
    Bratt, Ola
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Egevad, Lars
    Current routines for transrectal ultrasound-guided prostate biopsy: A web-based survey by the Swedish Urology Network2012In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, no 6, p. 405-410Article in journal (Refereed)
    Abstract [en]

    Objective. This study aimed to survey current Swedish practices for performing and handling transrectal ultrasound-guided prostate biopsies. Material and methods. A Swedish Urology Network (SUNe) was organized for the distribution of information, survey studies and research collaborations. A web-based questionnaire was distributed to the members in 2011. Results. In this first SUNe survey, 137 (91%) of the 151 members replied. All used antibiotic prophylaxis (84% ciprofloxacin, 12% trimethoprim-sulfamethoxazole), most commonly (63%) as a single dose of ciprofloxacin. Local anaesthesia was used by 87%. Half of the respondents only used a "side-fire" probe, whereas 17% always used an "end-fire" probe. Most (84%) routinely took 10 or more biopsy cores. About three-quarters started with the right base of the prostate and did not routinely take midline biopsies. More than one-third never or rarely sampled the anterior part of the prostate. There was great variability in how biopsy location was reported, but 71% considered a national standardized coordinate system desirable. Fine-needle aspiration was used occasionally by 39%, in more than 10% of cases by 6% and always by 2%. Most urologists mounted the biopsy cores on paper before fixation (78%), put only one core per jar (75%) and used flat-bottomed jars (70%). Conclusions. Most routines for handling of prostate biopsies, antibiotic prophylaxis, local anaesthesia and number of cores were uniform. However, there is still a need for standardization of the performance of ultrasound-guided biopsies. Although the method used to specify biopsy location varied greatly, most urologists would prefer a national standardized system.

  • 106.
    Carrero, Juan J.
    et al.
    Karolinska Inst, Renal Med, Stockholm, Sweden..
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jensevik, Karin
    Szummer, Karolina
    Karolinska Inst, Cardiol, Stockholm, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Evans, Marie
    Karolinska Inst, Renal Med, Stockholm, Sweden..
    Spaak, Jonas
    Karolinska Inst, Clin Sci, Stockholm, Sweden..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Karolinska Inst, Cardiol, Stockholm, Sweden..
    Clinical Outcomes Associated With The Duration Of Dual Antiplatelet Therapy With Clopidogrel And Aspirin In Chronic Kidney Disease Patients With Acute Coronary Syndrome2016In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, p. 1441-1441Article in journal (Other academic)
  • 107.
    Carrero, Juan Jesus
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Grams, Morgan E.
    Johns Hopkins Univ, Sch Med, Div Nephrol, Baltimore, MD USA.;Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA..
    Sang, Yingying
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Gasparini, Alessandro
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Matsushita, Kunihiro
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA..
    Qureshi, Abdul R.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Evans, Marie
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Barany, Peter
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Lindholm, Bengt
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Stockholm, Sweden..
    Ballew, Shoshana H.
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA..
    Levey, Andrew S.
    Tufts Med Ctr, Div Nephrol, Boston, MA USA..
    Gansevoort, Ron T.
    Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands..
    Elinder, Carl G.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Renal Med & Baxter Novum, Stockholm, Sweden.;Stockholm Cty Council, Publ Healthcare Serv Comm, Stockholm, Sweden..
    Coresh, Josef
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA..
    Albuminuria changes are associated with subsequent risk of end-stage renal disease and mortality2017In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 91, no 1, p. 244-251Article in journal (Refereed)
    Abstract [en]

    Current guidelines for chronic kidney disease (CKD) recommend using albuminuria as well as estimated glomerular filtration rate (eGFR) to stage CKD. However, CKD progression is solely defined by change in eGFR with little regard to the risk implications of change in albuminuria. This is an observational study from the Stockholm CREAtinine Measurements (SCREAM) project, a health care utilization cohort from Stockholm, Sweden, with laboratory measures from 2006-2011 and follow-up through December 2012. Included were 31,732 individuals with two or more ambulatory urine albumin to creatinine ratio (ACR) tests. We assessed the association between change in ACR during a baseline period of 1, 2, or 3 years and end-stage renal disease (ESRD) or death. Using a 2-year baseline period, there were 378 ESRD events and 1712 deaths during a median of 3 years of follow-up. Compared to stable ACR, a 4-fold increase in ACR was associated with a 3.08-times (95% confidence interval 2.59 to 3.67) higher risk of ESRD while a 4-fold decrease in ACR was associated with a 0.34-times (0.26 to 0.45) lower risk of ESRD. Similar associations were found in people with and without diabetes mellitus, with and without hypertension, and also when adjusted for the change in eGFR during the same period. The association between change in ACR and mortality was weaker: ACR increase was associated with mortality, but the relationship was largely flat for ACR decline. Results were consistent for 1-, 2-, and 3-year ACR changes. Thus, changes in albuminuria are strongly and consistently associated with the risk of ESRD and death.

  • 108. Carter, H Ballentine
    et al.
    Albertsen, Peter C
    Barry, Michael J
    Etzioni, Ruth
    Freedland, Stephen J
    Greene, Kirsten Lynn
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Kantoff, Philip
    Konety, Badrinath R
    Murad, Mohammad Hassan
    Penson, David F
    Zietman, Anthony L
    Early detection of prostate cancer: AUA Guideline2013In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 190, no 2, p. 419-426Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    The guideline purpose is to provide the urologist with a framework for the early detection of prostate cancer in asymptomatic average risk men.

    MATERIALS AND METHODS:

    A systematic review was conducted and summarized evidence derived from over 300 studies that addressed the predefined outcomes of interest (prostate cancer incidence/mortality, quality of life, diagnostic accuracy and harms of testing). In addition to the quality of evidence, the panel considered values and preferences expressed in a clinical setting (patient-physician dyad) rather than having a public health perspective. Guideline statements were organized by age group in years (age <40; 40 to 54; 55 to 69; ≥ 70).

    RESULTS:

    Except prostate specific antigen-based prostate cancer screening, there was minimal evidence to assess the outcomes of interest for other tests. The quality of evidence for the benefits of screening was moderate, and evidence for harm was high for men age 55 to 69 years. For men outside this age range, evidence was lacking for benefit, but the harms of screening, including over diagnosis and overtreatment, remained. Modeled data suggested that a screening interval of two years or more may be preferred to reduce the harms of screening.

    CONCLUSIONS:

    The Panel recommended shared decision-making for men age 55 to 69 years considering PSA-based screening, a target age group for whom benefits may outweigh harms. Outside this age range, PSA-based screening as a routine could not be recommended based on the available evidence.

  • 109.
    Castiglione, Fabio
    et al.
    University of Leuven, Belgium; IRCCS Osped San Raffaele, Italy.
    Dewulf, Karel
    University of Leuven, Belgium.
    Hakim, Lukman
    University of Leuven, Belgium; Airlangga University, Indonesia.
    Weyne, Emmanuel
    University of Leuven, Belgium.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, Italy.
    Russo, Andrea
    IRCCS Osped San Raffaele, Italy.
    Boeri, Luca
    IRCCS Osped San Raffaele, Italy.
    Bivalacqua, Trinity J.
    Johns Hopkins Medical Institute, MD 21205 USA.
    De Ridder, Dirk
    University of Leuven, Belgium.
    Joniau, Steven
    University of Leuven, Belgium.
    Albersen, Maarten
    University of Leuven, Belgium.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Lund University, Sweden.
    Adipose-derived Stem Cells Counteract Urethral Stricture Formation in Rats2016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 70, no 6, p. 1032-1041Article in journal (Refereed)
    Abstract [en]

    Background: A medical treatment for urethral stricture (US) is not yet available. Objective: To evaluate if local injection of human adipose tissue-derived stem cells (hADSC) prevents urethral fibrosis in a rat model of US. Design, setting, and participants: Male rats were divided into three groups: sham, US, and hADSC (n = 12 each). Sham rats received a vehicle injection in the urethral wall. US and hADSCs were incised and injected with the fibrosis-inducer transforming growth factor-beta 1 in the urethral wall. Intervention: One day later, hADSCs were injected in the urethral wall of hADSC rats whereas sham and US rats were injected with the vehicle. After 4 wk, the rats underwent cystometries and tissues were then harvested for functional and molecular analyses. Outcome measurements and statistical analysis: Cystometry, microultrasound, histochemistry, organ bath studies, reverse transcription polymerase chain reaction, and western blot. Results and limitations: US rats exhibited 49-51% shorter micturition intervals, 35-51% smaller micturition volumes and bladder capacity, 33-62% higher threshold pressures and flow pressures, and 35-37% lower bladder filling compliance compared with hADSC-treated rats and sham rats (p amp;lt; 0.05). By ultrasound, US rats had hyperechogenic and thick urethral walls with narrowed lumen compared with sham rats, whereas hADSC rats displayed less extensive urethral changes. Isolated detrusor from US rats exhibited 34-55% smaller contractions than detrusor from sham rats (p amp;lt; 0.05). Corresponding values were 11-35% for isolated detrusors from hADSC rats. Collagen and elastin protein expression were increased in the penile urethras of US rats compared with sham and hADSC groups (p amp;lt; 0.05). Endothelial and inducible nitric oxide synthase expressions were higher (p amp;lt; 0.05) in the hADSC group. Compared with US rats, hADSC rats demonstrated decreased expression of several fibrosis-related genes. Administration of hADSCs was performed at an early stage of US development, which we consider a limitation of the study. Conclusions: Local injection of hADSCs prevents stricture formation and urodynamic complications in a new rat model for US. Patient summary: Stem cell therapy is effective for preventing urethral stricture in an experimental setting. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  • 110.
    Catto, James W. F.
    et al.
    Univ Sheffield, Acad Urol Unit, Sheffield, S Yorkshire, England..
    Blazeby, Jane M.
    Univ Bristol, Bristol Ctr Surg Res, Bristol, Avon, England..
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Kings Coll London, Fac Life Sci & Med, London, England..
    Hamdy, Freddie C.
    Univ Oxford, Nuffield Dept Surg Sci, Oxford, England..
    Brown, Julia
    Univ Leeds, Leeds Inst Clin Trials Res, Leeds, W Yorkshire, England..
    In Defense of Randomized Clinical Trials in Surgery: Let Us Not Forget Archie Cochrane's Legacy2017In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, no 5, p. 820-821Article in journal (Refereed)
  • 111.
    Cazzaniga, Walter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. IRCCS Osped San Raffaele, Unit Urol URI, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Garmo, Hans
    Uppsala Univ Hosp, Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden;Kings Coll London, Div Canc Studies, Canc Epidemiol Grp, London, England.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 (SPCG-4) study2019In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 123, no 3, p. 421-428Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate if results in terms of absolute risk in mature randomised trials are relevant for contemporary decision-making. To do so, we compared the outcome for men in the radical prostatectomy (RP) arm of the Scandinavian Prostate Cancer Group Study number 4 (SPCG-4) randomised trial with matched men treated in a contemporary era before and after compensation for the grade migration and grade inflation that have occurred since the 1980s.

    PATIENTS AND METHODS: A propensity score-matched analysis of prostate cancer mortality and all-cause mortality in the SPCG-4 and matched men in the National Prostate Cancer Register (NPCR) of Sweden treated in 1998-2006 was conducted. Cumulative incidence of prostate cancer mortality and all-cause mortality was calculated. Cox proportional hazards regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for a matching on original Gleason Grade Groups (GGG) and second, matching with GGG increased one unit for men in the NPCR.

    RESULTS: Matched men in the NPCR treated in 2005-2006 had half the risk of prostate cancer mortality compared to men in the SPCG-4 (HR 0.46, 95% CI 0.19-1.14). In analysis of men matched on an upgraded GGG in the NPCR, this difference was mitigated (HR 0.73, 95% CI 0.36-1.47).

    CONCLUSIONS: Outcomes after RP for men in the SPCG-4 cannot be directly applied to men in the current era, mainly due to grade inflation and grade migration. However, by compensating for changes in grading, similar outcomes after RP were seen in the SPCG-4 and NPCR. In order to compare historical trials with current treatments, data on temporal changes in detection, diagnostics, and treatment have to be accounted for.

  • 112.
    Cazzaniga, Walter
    et al.
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Ventimiglia, Eugenio
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Alfano, Massimo
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Lissbrant, Ingela Franck
    Univ Goteborg, Sahlgrenska Acad, Dept Oncol, Inst Clin Sci, Gothenburg, Sweden.
    Carlsson, Stefan
    Karolinska Univ Hosp, Div Urol, Stockholm, Sweden;Karolinska Inst, Dept Mol Med & Surg MMK, Stockholm, Sweden.
    Styrke, Johan
    Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
    Montorsi, Francesco
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Salonia, Andrea
    IRCCS Osped San Raffaele, URI, Unit Urol, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Mini Review on the Use of Clinical Cancer Registers for Prostate Cancer: The National Prostate Cancer Register (NPCR) of Sweden2019In: FRONTIERS IN MEDICINE, ISSN 2296-858X, Vol. 6, article id 51Article, review/survey (Refereed)
    Abstract [en]

    Given the increasing prevalence of cancer, it is vital to systematically collect data in order to monitor disease trends and quality of cancer care. For this purpose, clinical cancer registries have been developed in some countries. These registers are intended to be used as a basis for quality assurance and quality improvement, but they also constitute a rich resource of real world data for research. The aim of thismini-review was to describe the structure and the organization of the National Prostate Cancer Register (NPCR) with some examples on how data in NPCR have affected prostate cancer care in Sweden.

  • 113.
    Cederblad, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Sarkadi, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Engvall, Gunn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Infrequent enuresis, the uninvestigated majority: comparisons between children with enuresis of varying severity.2015In: Journal of Pediatric Urology, ISSN 1477-5131, E-ISSN 1873-4898, Vol. 11, no 1, p. 24.e1-24.e6Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The main objective was to compare children with frequent enuresis (FE) and children with infrequent enuresis (IE) using anamnestic data and variables related to bladder and kidney function. A secondary aim was to look at the group of children who wet their beds every single night, a phenomenon we chose to call constant enuresis (CE).

    SUBJECTS AND METHODS: The parents recorded the number of wet and dry nights for a period of 14 days, and measured the voided volumes as well as nocturnal urine production for 48 h. History data relevant to bladder and bowel function was also recorded.

    RESULTS: The children could be grouped as follows: IE, n = 14; FE, n = 18; and CE, n = 22. The children with IE were slightly older than the other groups, IE mean 7.57; FE mean 6.22; CE, mean 6.56 (p = 0.004). When comparing the groups in terms of the measured parameters, only one significant difference was found: the FE group had larger average daytime voided volumes, but only when the first morning void was included. The only significantly differing anamnestic variable was previous daytime incontinence, which was more common among the children in the IE group.

    CONCLUSIONS: When comparing children with varying enuresis severity, no major differences regarding bladder function and urine production were found. Furthermore, children with infrequent enuresis tend to be slightly older when they seek medical help.

  • 114. Chang, Alex R
    et al.
    Grams, Morgan E
    Ballew, Shoshana H
    Bilo, Henk
    Correa, Adolfo
    Evans, Marie
    Gutierrez, Orlando M
    Hosseinpanah, Farhad
    Iseki, Kunitoshi
    Kenealy, Timothy
    Klein, Barbara
    Kronenberg, Florian
    Lee, Brian J
    Li, Yuanying
    Miura, Katsuyuki
    Navaneethan, Sankar D
    Roderick, Paul J
    Valdivielso, Jose M
    Visseren, Frank L J
    Zhang, Luxia
    Gansevoort, Ron T
    Hallan, Stein I
    Levey, Andrew S
    Matsushita, Kunihiro
    Shalev, Varda
    Woodward, Mark
    Ärnlöv, Johan (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lannfelt, Lars (Contributor)
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium2019In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 364, article id k5301Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality.

    DESIGN: Individual participant data meta-analysis.

    SETTING: Cohorts from 40 countries with data collected between 1970 and 2017.

    PARTICIPANTS: Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607).

    MAIN OUTCOME MEASURES: GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m2) and all cause mortality.

    RESULTS: Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index.

    CONCLUSIONS: Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR.

  • 115.
    Chen, Hui
    et al.
    Guangzhou Med Univ, Peoples R China; Jinan Univ, Peoples R China.
    Zeng, Jianwen
    Guangzhou Med Univ, Peoples R China.
    Zeng, Peng
    Guangzhou Med Univ, Peoples R China.
    Jiang, Chonghe
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Guangzhou Med Univ, Peoples R China.
    Xie, Keji
    Guangzhou First Peoples Hosp, Peoples R China.
    Lindström, Sivert
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Repeat periods of electrical stimulation prolong the modulation of the micturition reflex in the rat2018In: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 37, no 8, p. 2480-2486Article in journal (Refereed)
    Abstract [en]

    AimsMethodsThe aim of this study was to determine if the duration of the micturition reflex modulation could be prolonged by repeated periods of afferent stimulation in the decorticated rat. Eighteen female Sprague-Dawley rats were used for the study, 10 for intravesical electrical stimulation (IVES), and 8 for Ano-genital pudendal afferents stimulation. Repeated constant flow cystometries were performed with body-warm saline (0.06-0.1mL/min) at about 10min interval. The selected afferents were stimulated continuously for 5min at maximal intensity. The same stimulation was repeated six times with a pause of 5min between the stimulations. The mean threshold volume of cystometries performed during one hour before and each hour after the stimulation were compared. ResultsConclusionsAfter six periods of IVES, the micturition threshold volume decreased to its lowest value (62% of control) during the first hour and remained at 80% 4h later (n=10, Pamp;lt;0.01). Ano-genital afferent stimulation produced a corresponding increase in the micturition threshold volume. The long-lasting poststimulation effect was again observed for more than 5h. During the first hour the mean threshold volume increased to 211% of controls and it remained at about this level for the entire observation period (n=8, Pamp;lt;0.01). Repeated short periods of stimulation prolonged the modulatory effect well beyond the stimulation period. The findings provide experimental evidence supporting the clinical application of IVES and ano-genital stimulation for treatment of neurogenic urinary bladder dysfunction.

  • 116.
    Chen, Yun
    et al.
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden, Department of Physiology, University of Gothenburg, Box 432, SE 405 30 Gothenburg, Sweden.
    Lasaitiene, Daina
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
    Gabrielsson, Britt G.
    RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Carlsson, Lena M. S.
    RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Billig, Håkan
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
    Carlsson, Björn
    RCEM, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Marcussen, Niels
    Institute of Pathology, Aarhus Kommunehospital, Aarhus, Denmark.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, KC - Kirurgi- och onkologicentrum, Onkologiska kliniken.
    Friberg, Peter
    Department of Physiology, University of Gothenburg, Gothenburg, Sweden.
    Neonatal Losartan Treatment Suppresses Renal Expression of Molecules Involved in Cell-Cell and Cell-Matrix Interactions2004In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 15, no 5, p. 1232-1243Article in journal (Refereed)
    Abstract [en]

    Lack of neonatal angiotensin II type I receptor (AT1) stimulation produces renal abnormalities characterized by papillary atrophy and impaired urinary concentrating ability, but the mechanisms involved are still unclear. DNA microarray was used to identify genes that are differentially expressed in renal medulla in response to neonatal treatment with AT 1 receptor antagonist losartan (30 mg/kg per d), which commenced within 24 h after birth. The data showed that losartan treatment for 48 h downregulated 68 genes, ~30% of which encode various components of cytoskeleton and cytoskeleton-associated proteins, extracellular matrix, and enzymes involved in extracellular matrix maturation or turnover. With the use of immunohistochemistry and Western immunoblot, the microarray data were confirmed and it was demonstrated that losartan suppressed renal expression of syndecan 2, a-smooth muscle actin, MHC class II, and leukocyte type 12-lipoxygenase by day 4. In addition, losartan inhibited medullary expression of integrin a6 and caused relocalization of integrins a6 and a3. Moreover, losartan inhibited cell proliferation in medullary tubules by day 9, as detected by Ki-67 immunostaining. This study provides new data supporting the contention that a lack of AT1 receptor stimulation results in abnormal matrix assembly, disturbed cell-cell and cell-matrix interactions, and subsequent abnormal tubular maturation. Moreover, regulation of the expression of leukocyte type 12-lipoxygenase and a-smooth muscle actin by the renin-angiotensin system in the immature kidney adds new knowledge toward the understanding of renal vascular development.

  • 117. Chua, Horng-Ruey
    et al.
    Schneider, Antoine G.
    Sherry, Norelle L.
    Lotfy, Nadiah
    Chan, Matthew J.
    Galtieri, Jonathan
    Wong, Geoffrey R.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Matte, Caue de Araujo
    Collins, Allison
    Garcia-Alvarez, Mercedes
    Bellomo, Rinaldo
    Initial and Extended Use of Femoral Versus Nonfemoral Double-Lumen Vascular Catheters and Catheter-Related Infection During Continuous Renal Replacement Therapy2014In: American Journal of Kidney Diseases, ISSN 0272-6386, E-ISSN 1523-6838, Vol. 64, no 6, p. 909-917Article in journal (Refereed)
    Abstract [en]

    Background: The risk of catheter-related infection or bacteremia, with initial and extended use of femoral versus nonfemoral sites for double-lumen vascular catheters (DLVCs) during continuous renal replacement therapy (CRRT), is unclear. Study Design: Retrospective observational cohort study. Setting & Participants: Critically ill patients on CRRT in a combined intensive care unit of a tertiary institution. Factor: Femoral versus nonfemoral venous DLVC placement. Outcomes: Catheter-related colonization (CRCOL) and bloodstream infection (CRBSI). Measurements: CRCOL/CRBSI rates expressed per 1,000 catheter-days. Results: We studied 458 patients (median age, 65 years; 60% males) and 647 DLVCs. Of 405 single-site only DLVC users, 82% versus 18% received exclusively 419 femoral versus 82 jugular or subclavian DLVCs, respectively. The corresponding DLVC indwelling duration was 6 +/- 4 versus 7 +/- 5 days (P = 0.03). Corresponding CRCOL and CRBSI rates (per 1,000 catheter-days) were 9.7 versus 8.8 events (P = 0.8) and 1.2 versus 3.5 events (P = 0.3), respectively. Overall, 96 patients with extended CRRT received femoral-site insertion first with subsequent site change, including 53 femoral guidewire exchanges, 53 new femoral venipunctures, and 47 new jugular/subclavian sites. CRCOL and CRBSI rates were similar for all such approaches (P = 0.7 and P = 0.9, respectively). On multivariate analysis, CRCOL risk was higher in patients older than 65 years and weighing >90 kg (ORs of 2.1 and 2.2, respectively; P < 0.05). This association between higher weight and greater CRCOL risk was significant for femoral DLVCs, but not for nonfemoral sites. Other covariates, including initial or specific DLVC site, guidewire exchange versus new venipuncture, and primary versus secondary DLVC placement, did not significantly affect CRCOL rates. Limitations: Nonrandomized retrospective design and single-center evaluation. Conclusions: CRCOL and CRBSI rates in patients on CRRT are low and not influenced significantly by initial or serial femoral catheterizations with guidewire exchange or new venipuncture. CRCOL risk is higher in older and heavier patients, the latter especially so with femoral sites.

  • 118. Collins, Justin
    et al.
    Mottrie, Alexander
    Hosseini, Abolfazl
    Challacombe, Benjamin
    Adding, Christofer
    Dasgupta, Prokar
    Artibani, Walter
    Gaston, Richard
    Piechaud, Thierry
    Sooriakumaran, Prasanna
    Pini, Giovannalberto
    Nilsson, Andreas
    Fragkiadis, Evangelos
    Tewari, Ashutosh
    Badani, Ketan
    Gill, Inderbir
    Desai, Mihir
    Patel, Vipul
    Ahlawat, Rajesh
    Murphy, Declan
    Coelho, Rafael
    Rha, Koon
    Gandaglia, Giorgio
    Verhagen, Harko
    Stockholm University, Faculty of Social Sciences, Department of Computer and Systems Sciences.
    Wiklund, Peter
    Live streaming of robotic surgery from leading educational centres enables a global approach to surgical teaching2016In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 195, no 4, p. e116-Article in journal (Refereed)
    Abstract [en]

    Following recently published EAU Policy on Live Surgical Events (LSE's) it is assured that live surgery will be ongoing at conferences in the immediate future. However, the panel reached >80% consensus view that performing at a home institution may be safer. The committee also identified issues with a ‘travelling surgeon’ performing complex surgery in an unfamiliar environment with a surgical team that is not experienced with the intricacies of surgeons techniques. LSE's from home institutions remove or minimize these negative aspects.

  • 119. Collins, Justin W.
    et al.
    Verhagen, Harko
    Stockholm University, Faculty of Social Sciences, Department of Computer and Systems Sciences.
    Mottrie, Alexander
    Wiklund, Peter N.
    Application and Integration of Live Streaming from Leading Robotic Centres Can Enhance Surgical Education2015In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 68, no 5, p. 747-749Article in journal (Refereed)
    Abstract [en]

    Internet-based video-streaming enables us to share surgical knowledge and to study leading surgeons while they operate in their home institutions, and is widely accessible to trainees. Planned developments include enriched learning experiences with improved user friendliness, interactivity, and real-time feedback.

  • 120.
    Coomans, Marijke
    et al.
    Leiden Univ, Netherlands.
    Dirven, Linda
    Leiden Univ, Netherlands; Haaglanden Med Ctr, Netherlands.
    Aaronson, Neil K.
    Netherlands Canc Inst, Netherlands.
    Baumert, Brigitta G.
    Univ Hosp Bonn, Germany; Maastricht Univ, Netherlands; Maastricht Univ, Netherlands.
    van den Bent, Martin
    Erasmus MC Canc Inst, Netherlands.
    Bottomley, Andrew
    European Org Res Treatment Canc, Belgium.
    Brandes, Alba A.
    Azienda USL IRCCS Inst Neurol Sci, Italy.
    Chinot, Olivier
    Aix Marseille Univ, France.
    Coens, Corneel
    European Org Res and Treatment Canc Headquarters, Belgium.
    Gorlia, Thierry
    Univ Bonn, Germany; Univ Bonn, Germany.
    Herrlinger, Ulrich
    Grp Hop Pitie Salpetriere, France.
    Keime-Guibert, Florence
    Groupe Hôpital Pitié-Salpetrière, Paris, France.
    Malmström, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Advanced Home Care in Linköping.
    Martinelli, Francesca
    Northwestern Univ, IL 60611 USA.
    Stupp, Roger
    Azienda Osped San Giovanni Addolorata, Italy.
    Talacchi, Andrea
    Univ Hosp, Switzerland; Univ Zurich, Switzerland.
    Weller, Michael
    Univ Hosp Heidelberg, Germany; German Consortium Translat Canc Res DKTK, Germany.
    Wick, Wolfgang
    Univ Amsterdam, Netherlands.
    Reijneveld, Jaap C.
    Leiden Univ, Netherlands; Haaglanden Med Ctr, Netherlands.
    Taphoorn, Martin J. B.
    Leiden University Medical Center, Leiden, Netherlands; Haaglanden Medical Center, Den Haag, Netherlands.
    The added value of health-related quality of life as a prognostic indicator of overall survival and progression-free survival in glioma patients: a meta-analysis based on individual patient data from randomised controlled trials2019In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 116, p. 190-198Article in journal (Refereed)
    Abstract [en]

    Objective: Prognostic value of health-related quality of life (HRQoL) data may be important to inform patients in clinical practice and to guide clinical decision-making. Our study investigated the added prognostic value of HRQoL for overall survival (OS) and progression-free survival (PFS) in a large heterogeneous sample of glioma patients, besides known prognostic factors. Methods: We included individual baseline data from previously published randomised controlled trials (RCTs) in glioma patients in which HRQoL was assessed through the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BN20 questionnaires. Multivariable Cox regression models (stratified for newly diagnosed versus recurrent disease) were constructed, first with clinical variables (age, sex, tumour type, performance status, allocated treatment and extent of resection) only and subsequently with HRQoL variables added, separately for OS and PFS. The added prognostic value of HRQoL was calculated using C-indices. Results: Baseline HRQoL and clinical data from 15 RCTs were included, comprising 5217 patients. In the model including both clinical and HRQoL variables, better cognitive and role functioning and less motor dysfunction were independently associated with longer OS, whereas better role and cognitive functioning, less nausea and vomiting and more appetite loss were independently associated with prolonged PFS. However, C-indices indicated only a small prognostic improvement of the models for OS and PFS when adding HRQoL to the clinical prognostic variables (+1.1% for OS and +.7% for PFS). Conclusion: Our findings demonstrate that several baseline HRQoL variables are independently prognostic for OS and PFS, yet the added value of HRQoL to the known clinical prognostic variables was small. (C) 2019 Elsevier Ltd. All rights reserved.

  • 121.
    Coppo, Rosanna
    et al.
    Regina Margherita Hosp, Fdn Ric Molinette Nephrol Dialysis & Transplantat, Turin, Italy..
    Lofaro, Danilo
    Annunziata Hosp, Cosenza, Italy..
    Camilla, Roberta R.
    Regina Margherita Hosp, Fdn Ric Molinette Nephrol Dialysis & Transplantat, Turin, Italy..
    Bellur, Shubha
    Oxford Univ Hosp, Oxford, England..
    Cattran, Daniel
    Toronto Gen Hosp, Univ Hlth Network, Toronto, ON, Canada..
    Cook, H. Terence
    Imperial Coll, Hammersmith Hosp, London, England..
    Roberts, Ian S. D.
    Oxford Univ Hosp, Oxford, England..
    Peruzzi, Licia
    Regina Margherita Hosp, Fdn Ric Molinette Nephrol Dialysis & Transplantat, Turin, Italy..
    Amore, Alessandro
    Regina Margherita Hosp, Fdn Ric Molinette Nephrol Dialysis & Transplantat, Turin, Italy..
    Emma, Francesco
    Bambino Gesu Pediat Hosp, Rome, Italy..
    Fuiano, Laura
    Bambino Gesu Pediat Hosp, Rome, Italy..
    Berg, Ulla
    Karolinska Univ Hosp, Huddinge, Sweden..
    Topaloglu, Rezan
    Hacettepe Univ, Ankara, Turkey..
    Bilginer, Yelda.
    Hacettepe Univ, Ankara, Turkey..
    Gesualdo, Loreto
    Univ Bari & Foggia, Bari, Italy..
    Polci, Rosaria
    Belcolle Hosp, Viterbo, Italy..
    Mizerska-Wasiak, Malgorzata
    Univ Warsaw, Warsaw, Poland..
    Caliskan, Yasar
    Istanbul Univ, Istanbul, Turkey..
    Lundberg, Sigrid
    Karolinska Inst, Stockholm, Sweden..
    Cancarini, Giovanni
    Spedali Civili Univ Hosp, Brescia, Italy..
    Geddes, Colin
    Western Infirm Glasgow, Glasgow, Lanark, Scotland..
    Wetzels, Jack
    Radboud Univ Nijmegen, Nijmegen, Netherlands..
    Wiecek, Andrzej
    Silesian Univ, Katowice, Poland..
    Durlik, Magdalena
    Med Univ Warsaw, Warsaw, Poland..
    Cusinato, Stefano
    Borgomanero Hosp, Borgomanero, Italy..
    Rollino, Cristiana
    San Giovanni Bosco Hosp, Turin, Italy..
    Maggio, Milena
    Hosp Maggiore Lodi, Lodi, Italy..
    Praga, Manuel
    Hosp 12 Octubre, Madrid, Spain..
    Smerud, Hilde Kloster
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tesar, Vladimir
    Gen Univ Hosp, Prague, Czech Republic..
    Maixnerova, Dita
    Gen Univ Hosp, Prague, Czech Republic..
    Barratt, Jonathan
    Leicester Gen Hosp, Leicester, Leics, England..
    Papalia, Teresa
    Annunziata Hosp, Cosenza, Italy..
    Bonofiglio, Renzo
    Annunziata Hosp, Cosenza, Italy..
    Mazzucco, Gianna
    Univ Turin, Turin, Italy..
    Giannakakis, Costantinos
    Univ Rome, Rome, Italy..
    Söderberg, Magnus
    Karolinska Univ Hosp, Huddinge, Sweden..
    Orhan, Diclehan
    Hacettepe Univ, Ankara, Turkey..
    Di Palma, Anna Maria
    Univ Bari & Foggia, Bari, Italy..
    Maldyk, Jadwiga
    Univ Warsaw, Warsaw, Poland..
    Ozluk, Yasemin
    Istanbul Univ, Istanbul, Turkey..
    Sudelin, Birgitta
    Karolinska Inst, Stockholm, Sweden..
    Tardanico, Regina
    Spedali Civili Univ Hosp, Brescia, Italy..
    Kipgen, David
    Western Infirm Glasgow, Glasgow, Lanark, Scotland..
    Steenbergen, Eric
    Radboud Univ Nijmegen, Nijmegen, Netherlands..
    Karkoszka, Henryk
    Silesian Univ, Katowice, Poland..
    Perkowska-Ptasinska, Agnieszka
    Med Univ Warsaw, Warsaw, Poland..
    Ferrario, Franco
    Monza Hosp, Monza, Italy..
    Gutierrez, Eduardo
    Hosp 12 Octubre, Madrid, Spain..
    Honsova, Eva
    Gen Univ Hosp, Prague, Czech Republic..
    Risk factors for progression in children and young adults with IgA nephropathy: an analysis of 261 cases from the VALIGA European cohort2017In: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 32, no 1, p. 139-150Article in journal (Refereed)
    Abstract [en]

    There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease. Data on 261 young patients [age < 23 years; mean follow-up of 4.9 (range 2.5-8.1) years] enrolled in VALIGA, a study designed to validate the Oxford Classification of IgAN, were assessed. Renal biopsies were scored for the presence of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1-2) (MEST score) and crescents (C1). Progression was assessed as end stage renal disease and/or a 50 % loss of estimated glomerular filtration rate (eGFR) (combined endpoint) as well as the rate of renal function decline (slope of eGFR). Cox regression and tree classification binary models were used and compared. In this cohort of 261 subjects aged < 23 years, Cox analysis validated the MEST M, S and T scores for predicting survival to the combined endpoint but failed to prove that these scores had predictive value in the sub-group of 174 children aged < 18 years. The regression tree classification indicated that patients with M1 were at risk of developing higher time-averaged proteinuria (p < 0.0001) and the combined endpoint (p < 0.001). An initial proteinuria of ae<yen>0.4 g/day/1.73 m(2) and an eGFR of < 90 ml/min/1.73 m(2) were determined to be risk factors in subjects with M0. Children aged < 16 years with M0 and well-preserved eGFR (> 90 ml/min/1.73 m(2)) at presentation had a significantly high probability of proteinuria remission during follow-up and a higher remission rate following treatment with corticosteroid and/or immunosuppressive therapy. This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.

  • 122.
    Corsonello, Andrea
    et al.
    INRCA Ancona, Ancona, Italy;INRCA, Fermo, Italy;INRCA, Cosenza, Italy.
    Tap, Lisanne
    Erasmus Univ, Geriatr Med Sect, Dept Internal Med, Med Ctr Rotterdam, Rotterdam, Netherlands.
    Roller-Wirnsberger, Regina
    Med Univ Graz, Dept Internal Med, Auenbruggerpl 15, A-8036 Graz, Austria.
    Wirnsberger, Gerhard
    Med Univ Graz, Dept Internal Med, Auenbruggerpl 15, A-8036 Graz, Austria.
    Zoccali, Carmine
    Osped Riuniti Reggio Calabria, CNR, IFC, Clin Epidemiol & Pathophysiol Hypertens & Renal D, Reggio Di Calabria, Italy.
    Kostka, Tomasz
    Med Univ Lodz, Dept Geriatr, Hlth Ageing Res Ctr, Lodz, Poland.
    Guligowska, Agnieszka
    Med Univ Lodz, Dept Geriatr, Hlth Ageing Res Ctr, Lodz, Poland.
    Mattace-Raso, Francesco
    Erasmus Univ, Geriatr Med Sect, Dept Internal Med, Med Ctr Rotterdam, Rotterdam, Netherlands.
    Gil, Pedro
    Hosp Clin San Carlos, Dept Geriatr Med, Madrid, Spain.
    Guardado Fuentes, Lara
    Hosp Clin San Carlos, Dept Geriatr Med, Madrid, Spain.
    Meltzer, Itshak
    Ben Gurion Univ Negev, Fac Hlth Sci, Recanati Sch Community Hlth Profess, Beer Sheva, Israel.
    Yehoshua, Ilan
    Maccabi Healthcare Serv Southern Reg, Tel Aviv, Israel.
    Formiga-Perez, Francesc
    Bellvitge Univ Hosp, Internal Med Dept, IDIBELL, Geriatr Unit, Barcelona, Spain;Bellvitge Univ Hosp, Nephrol Dept, IDIBELL, Barcelona, Spain.
    Moreno-Gonzalez, Rafael
    Bellvitge Univ Hosp, Internal Med Dept, IDIBELL, Geriatr Unit, Barcelona, Spain;Bellvitge Univ Hosp, Nephrol Dept, IDIBELL, Barcelona, Spain.
    Weingart, Christian
    Friedrich Alexander Univ Erlangen Nurnberg, Krankenhaus Barmherzige Bruder Regensburg, Dept Gen Internal Med & Geriatr, Erlangen, Germany;Friedrich Alexander Univ Erlangen Nurnberg, Inst Biomed Aging, Erlangen, Germany.
    Freiberger, Ellen
    Friedrich Alexander Univ Erlangen Nurnberg, Krankenhaus Barmherzige Bruder Regensburg, Dept Gen Internal Med & Geriatr, Erlangen, Germany;Friedrich Alexander Univ Erlangen Nurnberg, Inst Biomed Aging, Erlangen, Germany.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Stockholm, Sweden.
    Carlsson, Axel C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Stockholm, Sweden.
    Bustacchini, Silvia
    INRCA Ancona, Ancona, Italy;INRCA, Fermo, Italy;INRCA, Cosenza, Italy.
    Lattanzio, Fabrizia
    INRCA Ancona, Ancona, Italy;INRCA, Fermo, Italy;INRCA, Cosenza, Italy.
    Design and methodology of the screening for CKD among older patients across Europe (SCOPE) study: a multicenter cohort observational study2018In: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 19, article id 260Article in journal (Refereed)
    Abstract [en]

    Background: Decline of renal function is common in older persons and the prevalence of chronic kidney disease (CKD) is rising with ageing. CKD affects different outcomes relevant to older persons, additionally to morbidity and mortality which makes CKD a relevant health burden in this population. Still, accurate laboratory measurement of kidney function is under debate, since current creatinine-based equations have a certain degree of inaccuracy when used in the older population. The aims of the study are as follows: to assess kidney function in a cohort of 75+ older persons using existing methodologies for CKD screening; to investigate existing and innovative biomarkers of CKD in this cohort, and to align laboratory and biomarker results with medical and functional data obtained from this cohort. The study was registered at ClinicalTrials.gov, identifier NCT02691546, February 25th 2016. Methods/design: An observational, multinational, multicenter, prospective cohort study in community dwelling persons aged 75 years and over, visiting the outpatient clinics of participating institutions. The study will enroll 2450 participants and is carried out in Austria, Germany, Israel, Italy, the Netherlands, Poland and Spain. Participants will undergo clinical and laboratory evaluations at baseline and after 12 and 24 months-follow-up. Clinical evaluation also includes a comprehensive geriatric assessment (CGA). Local laboratory will be used for 'basic' parameters (including serum creatinine and albumin-to-creatinine ratio), whereas biomarker assessment will be conducted centrally. An intermediate telephone follow-up will be carried out at 6 and 18 months. Discussion: Combining the use of CGA and the investigation of novel and existing independent biomarkers within the SCOPE study will help to provide evidence in the development of European guidelines and recommendations in the screening and management of CKD in older people.

  • 123. Crawley, Danielle
    et al.
    Garmo, Hans
    Rudman, Sarah
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala.
    Zethelius, Björn
    Holmberg, Lars
    Adolfsson, Jan
    Van Hemelrijck, Mieke
    Association between type 2 diabetes, curative treatment and survival in men with intermediate- and high-risk localized prostate cancer2018In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 121, no 2, p. 209-216Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate whether curative prostate cancer (PCa) treatment was received less often by men with both PCa and Type 2 diabetes mellitus (T2DM) as little is known about the influence of T2DM diagnosis on the receipt of such treatment in men with localized PCa.

    Subjects and Methods: The Prostate Cancer database Sweden (PCBaSe) was used to obtain data on men with T2DM and PCa (n = 2210) for comparison with data on men with PCa only (n = 23 071). All men had intermediate-(T1-2, Gleason score 7 and/or prostate-specific antigen [PSA] 10-20 ng/mL) or high-risk (T3 and/or Gleason score 8-10 and/or PSA 20-50 ng/mL) localized PCa diagnosed between 1 January 2006 and 31 December 2014. Multivariate logistic regression was used to calculate the odds ratios (ORs) for receipt of curative treatment in men with and without T2DM. Overall survival, for up to 8 years of follow-up, was calculated both for men with T2DM only and for men with T2DM and PCa.

    Results: Men with T2DM were less likely to receive curative treatment for PCa than men without T2DM (OR 0.78, 95% confidence interval 0.69-0.87). The 8-year overall survival rates were 79% and 33% for men with T2DM and high-risk PCa who did and did not receive curative treatment, respectively.

    Conclusions: Men with T2DM were less likely to receive curative treatment for localized intermediate-and high-risk PCa. Men with T2DM and high-risk PCa who received curative treatment had substantially higher survival times than those who did not. Some of the survival differences represent a selection bias, whereby the healthiest patients received curative treatment. Clinicians should interpret this data carefully and ensure that individual patients with T2DM and PCa are not under-nor overtreated.

  • 124. Dabestani, Saeed
    et al.
    Beisland, Christian
    Stewart, Grant D.
    Bensalah, Karim
    Gudmundsson, Eirikur
    Lam, Thomas B.
    Gietzmann, William
    Zakikhani, Paimaun
    Marconi, Lorenzo
    Fernandez-Pello, Sergio
    Monagas, Serenella
    Williams, Samuel Paul
    Torbrand, Christian
    Powles, Thomas
    Van Werkhoven, Erik
    Meijer, Richard
    Volpe, Alessandro
    Staehler, Michael
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Bex, Axel
    Intensive Imaging-based Follow-up of Surgically Treated Localised Renal Cell Carcinoma Does Not Improve Post-recurrence Survival: Results from a European Multicentre Database (RECUR)2019In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, no 2, p. 261-264Article in journal (Refereed)
    Abstract [en]

    The optimal follow-up (FU) strategy for patients treated for localised renal cell carcinoma(RCC) remains unclear. Using the RECUR database, we studied imaging intensity utilised in contemporary FU to evaluate its association with outcome after detection of disease recurrence. Consecutive patients with nonmetastatic RCC (n = 1612) treated with curative intent at 12 institutes across eight European countries between 2006 and 2011 were included. Recurrence occurred in 336 patients. Cross-sectional (computed tomography, magnetic resonance imaging) and conventional (chest X-ray, ultrasound) methods were used in 47% and 53%, respectively. More intensive FU imaging (more than twofold) than recommended by the European Association of Urology (EAU) was not associated with improved overall survival (OS) after recurrence. Overall, per patient treated for recurrence remaining alive with no evidence of disease, the number of FU images needed was 542, and 697 for high-risk patients. The study results suggest that use of more imaging during FU than that recommended in the 2017 EAU guidelines is unlikely to improve OS after recurrence. Prospective studies are needed to design optimal FU strategies for the future.

    Patient summary: After curative treatment for localised kidney cancer, follow-up is necessary to detect any recurrence. This study illustrates that increasing the imaging frequency during follow-up, even to double the number of follow-up imaging procedures recommended by the European Association of Urology guidelines, does not translate into improved survival for those with recurrence.

  • 125. Dabestani, Saeed
    et al.
    Beisland, Christian
    Stewart, Grant D.
    Bensalah, Karim
    Gudmundsson, Eirikur
    Lam, Thomas B.
    Gietzmann, William
    Zakikhani, Paimaun
    Marconi, Lorenzo
    Fernandéz-Pello, Sergio
    Monagas, Serenella
    Williams, Samuel P.
    Powles, Thomas
    Van Werkhovenn, Erik
    Meijer, Richard
    Volpe, Alessandro
    Staehler, Michael
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Bex, Axel
    Increased use of cross-sectional imaging for follow-up does not improve post-recurrence survival of surgically treated initially localized RCC: results from a European multicenter database (RECUR)2019In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, no 1, p. 14-20Article in journal (Refereed)
    Abstract [en]

    Objective: Modality and frequency of image-based renal cell carcinoma (R.C.C.) follow-up strategies are based on risk of recurrence. Using the R.E.C.U.R.-database, frequency of imaging was studied in regard to prognostic risk groups. Furthermore, it was investigated whether imaging modality utilized in contemporary follow-up were associated with outcome after detection of recurrence. Moreover, outcome was compared based on whether the assessment of potential curability was a pre-defined set of criteria's (per-protocol) or stated by the investigator. Materials and methods: Consecutive non-metastatic R.C.C. patients (n = 1,612) treated with curative intent at 12 institutes across eight European countries between 2006 and 2011 were included. Leibovich or U.I.S.S. risk group, recurrence characteristics, imaging modality, frequency and survival were recorded. Primary endpoints were overall survival (O.S.) after detection of recurrence and frequency of features associated with favourable outcome (non-symptomatic recurrences and detection within the follow-up-programme). Results: Recurrence occurred in 336 patients. Within low, intermediate and high risk for recurrence groups, the frequency of follow-up imaging was highest in the early phase of follow-up and decreased significantly over time (p < 0.001). However, neither the image modality for detection nor >= 50% cross-sectional imaging during follow-up were associated with improved O.S. after recurrence. Differences between per protocol and investigator based assessment of curability did not translate into differences in O.S. Conclusions: As expected, the frequency of imaging was highest during early follow-up. Cross-sectional imaging use for detection of recurrences following surgery for localized R.C.C. did not improve O.S. post-recurrence. Prospective studies are needed to determine the value of imaging in follow-up.

  • 126. Dabestani, Saeed
    et al.
    Beisland, Christian
    Stewart, Grant D.
    Bensalah, Karim
    Gudmundsson, Eirikur
    Lam, Thomas B.
    Gietzmann, William
    Zakikhani, Paimaun
    Marconi, Lorenzo
    Fernandéz-Pello, Sergio
    Monagas, Serenella
    Williams, Samuel P.
    Torbrand, Christian
    Powles, Thomas
    Van Werkhoven, Erik
    Meijer, Richard
    Volpe, Alessandro
    Staehler, Michael
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Bex, Axel
    Long-term Outcomes of Follow-up for Initially Localised Clear Cell Renal Cell Carcinoma: RECUR Database Analysis.2018In: European urology focus, ISSN 2405-4569, article id S2405-4569(18)30072-5Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Optimal follow-up (FU) strategy to detect potentially curable (PC) recurrences after treatment of localised clear cell renal cell carcinoma (ccRCC) is unclear. This study retrospectively analysed a large international database to determine recurrence patterns and overall survival (OS), as part of a wider project to issue recommendations on FU protocols.

    OBJECTIVE: To analyse associations between RCC recurrences in patients with ccRCC, their risk group stratifications, treatments, and subsequent outcomes.

    DESIGN, SETTING, AND PARTICIPANTS: Nonmetastatic ccRCC patients treated with curative intent between 1 January 2006 and 31 December 2011, with at least 4 yr of FU, were included. Patient, tumour and recurrence characteristics, Leibovich score, and management and survival data were recorded. Isolated local, solitary, and oligometastatic (three or fewer lesions at a single site) recurrences were considered PC, while all others were probably incurable (PI).

    INTERVENTION: Primarily curative surgical treatment of ccRCC while at recurrence detection metastasectomy, systemic therapy, best supportive care, or observation.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incidence, time to recurrence (TTR), and OS were measured. Competing risk analysis, Kaplan-Meier, and Cox regression models were used.

    RESULTS AND LIMITATION: Of 1265 patients with ccRCC, 286 had a recurrence, with 131 being PC and 155 PI. Five-year cumulative risks of recurrence for low- (n=53), intermediate- (n=105), and high-risk (n=128) patients were, respectively, 7.2%, 23.2%, and 61.6%, of whom 52.8%, 37.1%, and 30.5% were PC, respectively. Median TTR was 25.0 for PC patients versus 17.3 mo for PI patients (p=0.004). Median OS was longer in PC compared with that in PI patients (p<0.001). Competing risk analysis showed highest risk of ccRCC-related death in younger and high-risk patients. Limitations were no data on comorbidities, retrospective cohort, and insufficient data excluding 12% of cohort.

    CONCLUSIONS: Low-risk group recurrences are rare and develop later. Treatment of recurrences with curative intent is disappointing, especially in high-risk patients. An age- and risk score-dependent FU approach is suggested.

    PATIENT SUMMARY: We analysed data from eight European countries, and found that the incidence of the kidney cancer recurrence and patient survival correlated with clinical factors known to predict cancer recurrence reliably and age. We conclude that these factors should be used to design follow-up strategies.

  • 127.
    Dabestani, Saeed
    et al.
    Department of Urology, Skåne University Hospital, Malmö, Sweden.
    Thorstenson, Andreas
    Section of Urology, Department of Molecular Medicine and Surgery, Karolinska Institute Solna, Stockholm, Sweden.
    Lindblad, Per
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Harmenberg, Ulrika
    Department of Oncology, Karolinska University Hospital, Solna, Stockholm, Sweden.
    Ljungberg, Börje
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Lundstam, Sven
    Department of Urology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Renal cell carcinoma recurrences and metastases in primary non-metastatic patients: a population-based study2016In: World journal of urology, ISSN 0724-4983, E-ISSN 1433-8726, Vol. 34, no 8, p. 1081-1086Article in journal (Refereed)
    Abstract [en]

    Purpose: To present the occurrence of metastases and local recurrences in primary non-metastatic patients with renal cell carcinoma (RCC) in a contemporary Swedish population-based cohort.

    Methods: Between 2005 and 2009, a total of 4527 patients were included in the prospective National Swedish Kidney Cancer Register accounting for nearly all RCC patients in Sweden. Among M0 patients, 472 (13 %) had no follow-up data registered within 5-year follow-up time and were excluded from the analysis.

    Results: In total, 939 (21 %) had distant metastases at presentation with a decrease from 23 to 18 % during the inclusion period. Of 3107 patients with follow-up data and with M0 disease, 623 (20 %) were diagnosed with a tumor recurrence during 5-year follow-up. Mean time to recurrence was 24 months (SD ± 20 months). Among these, 570 patients (92 %) were at primary diagnosis treated with radical nephrectomy, 23 patients (3.7 %) with partial nephrectomy and 12 patients (1.9 %) with minimally invasive treatments. The most frequent sites of metastases were lung (54 %), lymph nodes (22 %) and bone (20 %). The treatment of recurrence was in 50 % systemic treatments, while metastasectomy was performed in 17 % of the patients, out of which 68 % were with a curative intention.

    Conclusions: In this population-based study, 21 % of the patients had metastatic disease at presentation, with a decreasing trend over the study period. During 5-year follow-up, 20 % of the primary non-metastatic patients had recurrent disease. Of the patients with recurrence, half were given systemic oncological treatment and 17 % underwent metastasectomy.

  • 128. Dahle, Dag Olav
    et al.
    Jenssen, Trond
    Holdaas, Hallvard
    Åsberg, Anders
    Soveri, Inga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Holme, Ingar
    Mjøen, Geir
    Eide, Ivar A
    Pihlstrøm, Hege
    Dörje, Christina
    Halden, Thea A S
    Hartmann, Anders
    Uric acid and clinical correlates of endothelial function in kidney transplant recipients2014In: Clinical Transplantation, ISSN 0902-0063, E-ISSN 1399-0012, Vol. 28, no 10, p. 1167-1176Article in journal (Refereed)
    Abstract [en]

    Uric acid is associated with increased mortality in kidney transplant recipients (KTRs), but it is uncertain if this involves endothelial dysfunction. We hypothesized, first, that there was an association between uric acid and endothelial function, and second, that there were associations between endothelial function and cardiac and mortality risk scores.

    METHODS: One hundred and fifty-two patients were examined 10 wk after kidney transplantation by two measures of endothelial function, the brachial artery flow-mediated dilatation (FMD) expressed as percent dilatation (FMD%), and fingertip peripheral arterial tone (PAT) expressed as log-reactive hyperemia index (LnRHI). Risk scores were calculated from a recently validated formula. Other clinical correlates of endothelial function were described in stepwise linear regression models.

    RESULTS: Uric acid was associated negatively with FMD% in an age- and gender-adjusted model, while not in the multivariable model. No association was shown between uric acid and LnRHI. FMD% was associated negatively with risk scores in both crude and age- and gender-adjusted models (p < 0.01). LnRHI was associated negatively with risk scores in the latter model only (p < 0.05).

    CONCLUSIONS: Uric acid was neither associated with FMD% nor LnRHI in KTRs. There were significant associations between endothelial function indices and cardiac and mortality risk scores.

  • 129.
    Dahlin, Britt-Inger
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Preoperative carbohydrate drink in a randomized study improves postoperative quality of life after urological surgery.2009In: International Journal of Urological Nursing, ISSN 1749-771X, Vol. 3, no 2, p. 64-68Article in journal (Other academic)
    Abstract [en]

    Recently, fast track treatment in surgery has been advocated. Fasting time has been cut down to attenuate preoperative discomfort as irritable and preoperative thirst. We accessed effects of preoperative carbohydrate drink on preoperative quality of life (QOL) including hospitalization time, drinking first day, gut emptying, and return to work. A total of 170 patients scheduled for nephrectomy or prostatectomy were randomized to carbohydrate drink or overnight fasting. Responses a modified QLQ-C30 questionnaire were collected before and one month after surgery.

    In patients treated with prostatectomy to the variables: did you worry, total health and total QOL improved, while most (19 of 30) variables were impaired. Nephrectomy patients had significantly fewer parameters with impaired QOL than prostatectomy (p = 0.01). There was significant weight loss despite surgical procedure (p < 0.001). When comparing the carbohydrate and control groups, there was no difference concerning age, sex and stages. After prostatectomy, only the QOL variable “worry” improved (p = 0.027) in the carbohydrate group. After nephrectomy, the carbohydrate group had less weight loss (p = 0.035) than controls and had improved QOL as: “short of breath” (p = 0.038), “feel tense” (p = 0.057), “worry” (p = 0.035), and “interfered social activities” (p = 0.024). There was no difference in hospitalization time, drinking 1st day, time to gut emptying, and return to normal activities between the groups, despite surgical procedure.

    Carbohydrate drink before surgery significantly improved QOL variables such as “worry”, “tense”, and “social activities”. Weight loss was significantly reduced compared with controls after nephrectomy. Thus, carbohydrate drinking before elective surgery improves postoperative QOL parameters, but not postoperative drinking and hospitalization time.

  • 130. Damoiseaux, Jan
    et al.
    Heijnen, Ingmar
    Van Campenhout, Christel
    Eriksson, Catharina
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
    Fabien, Nicole
    Herold, Manfred
    van der Molen, Renate G.
    Egner, William
    Patel, Dina
    Plaza-Lopez, Aresio
    Radice, Antonella
    Rego de Sousa, Marie Jose
    Viander, Markku
    Shoenfeld, Yehuda
    An international survey on anti-neutrophil cytoplasmic antibodies (ANCA) testing in daily clinical practice2018In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 56, no 10, p. 1759-1770Article in journal (Refereed)
    Abstract [en]

    Background: Detection of anti-neutrophil cytoplasmic antibodies (ANCA) is important for the diagnosis of the ANCA-associated vasculitides (AAV). For AAV, especially ANCA directed against myeloperoxidase (MPO) and proteinase 3 (PR3) are most relevant. ANCA with less well-defined specificities may, however, also be detected in other inflammatory and non-inflammatory conditions.

    Methods: A questionnaire, initiated by the European Autoimmunity Standardisation Initiative (EASI), was used to gather information on methods and testing algorithms used for ANCA in clinical laboratories of 12 European countries (EASI survey).

    Results: Four hundred and twenty-nine responses were included in the EASI survey analysis which revealed differences within countries and between countries. Laboratories overall were poor in adherence to international consensus on ANCA testing. Substantial variation was observed with respect to the use of ANCA indirect immunofluorescence (IIF) in the algorithm, application of distinct methods for MPO- and PR3-ANCA, the daily availability of new ANCA results, and interpretation of test results.

    Conclusions: Awareness of these differences may stimulate further harmonization and standardization of ANCA testing. This may be promoted by an update of the international ANCA consensus and the introduction of international standards.

  • 131.
    Danielsson, Gun
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Malmstrom, Per-Uno
    Uppsala Univ, Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Wijkstrom, Hans
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Nyberg, Tommy
    Karolinska Inst, Sweden; Univ Cambridge, England.
    Thulin, Helena
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Bladder health in patients treated with BCG instillations for T1G2-G3 bladder cancer - a follow-up five years after the start of treatment2018In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, no 5-6, p. 377-384Article in journal (Refereed)
    Abstract [en]

    Objective: Investigate symptoms and how they affect daily life in patients with Non-Muscle Invasive Bladder Cancer (NMIBC) treated with Bacillus Calmette-Guerin (BCG) instillations. Materials and methods: Patients treated with BCG were included. After an initial transurethral resection (TURB) followed by a second-look resection, the patients were given an induction course with BCG for 6 weeks followed by maintenance therapy for 2 years. The patients answered a questionnaire before, during and after the treatment. The questionnaire contained questions about specific symptoms combined with bother questions on how each symptom affected patients life. Results: In total, 113 of 116 patients responded to the first questionnaire. Thirty per cent of all patients were bothered by disease-specific symptoms before the start of BCG. Few patients reported fever, haematuria, illness or urinary tract symptoms. No difference in symptoms was found between patients with or without concomitant CIS (carcinoma in situ). Patients younger than 65 years of age reported a greater worry about the symptom burden in the future than those who were older. Patients younger than 65 years reported a decreased level of mental well-being. Conclusion: Patients with bladder cancer T1G2-G3 had disease-specific symptoms present already before the start of the BCG. The burden of symptoms was reduced over time and showed that the bladder might recover. BCG instillations had side-effects that negatively affected the patients well-being. It is important to record the patients baseline bladder and voiding status before as well as during the BCG-instillation period in order to understand symptoms caused by the treatment.

  • 132.
    Danielsson, Gun
    et al.
    Karolinska Univ Hosp, Patient Area Pelv Canc, Canc Theme, Stockholm, Sweden; Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Jahnson, Staffan
    Linköping Univ Hosp, Dept Urol, IKE, Linköping, Sweden.
    Wijkström, Hans
    Karolinska Univ Hosp, Patient Area Pelv Canc, Canc Theme, Stockholm, Sweden; Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Nyberg, Tommy
    Karolinska Inst, Dept Oncol Pathol, Clin Canc Epidemiol, Stockholm, Sweden; Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
    Thulin, Helena
    Karolinska Univ Hosp, Patient Area Pelv Canc, Canc Theme, Stockholm, Sweden; Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Bladder health in patients treated with BCG instillations for T1G2-G3 bladder cancer - a follow-up five years after the start of treatment2018In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, no 5-6, p. 377-384Article in journal (Refereed)
    Abstract [en]

    Objective: Investigate symptoms and how they affect daily life in patients with Non-Muscle Invasive Bladder Cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) instillations.

    Materials and methods: Patients treated with BCG were included. After an initial transurethral resection (TURB) followed by a second-look resection, the patients were given an induction course with BCG for 6 weeks followed by maintenance therapy for 2 years. The patients answered a questionnaire before, during and after the treatment. The questionnaire contained questions about specific symptoms combined with bother questions on how each symptom affected patients’ life.

    Results: In total, 113 of 116 patients responded to the first questionnaire. Thirty per cent of all patients were bothered by disease-specific symptoms before the start of BCG. Few patients reported fever, haematuria, illness or urinary tract symptoms. No difference in symptoms was found between patients with or without concomitant CIS (carcinoma in situ). Patients younger than 65 years of age reported a greater worry about the symptom burden in the future than those who were older. Patients younger than 65 years reported a decreased level of mental well-being.

    Conclusion: Patients with bladder cancer T1G2–G3 had disease-specific symptoms present already before the start of the BCG. The burden of symptoms was reduced over time and showed that the bladder might recover. BCG instillations had side-effects that negatively affected the patient’s well-being. It is important to record the patients’ baseline bladder and voiding status before as well as during the BCG-instillation period in order to understand symptoms caused by the treatment.

  • 133.
    Danneman, Daniela
    et al.
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
    Drevin, Linda
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Delahunt, Brett
    Univ Otago, Wellington Sch Med & Hlth Sci, Wellington, New Zealand..
    Samaratunga, Hemamali
    Aquesta Pathol, Brisbane, Qld, Australia.;Univ Queensland, Sch Med, Brisbane, Qld, Australia..
    Robinson, David
    Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden..
    Bratt, Ola
    Cambridge Univ Hosp, Dept Urol, Cambridge, England.;Lund Univ, Dept Translat Med, Lund, Sweden..
    Loeb, Stacy
    NYU, Dept Urol & Populat Hlth, New York, NY USA.;Manhattan Vet Affairs Med Ctr, New York, NY USA..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umea, Sweden..
    Egevad, Lars
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Pathol, Stockholm, Sweden..
    Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000-20122017In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 119, no 1, p. 50-56Article in journal (Refereed)
    Abstract [en]

    Objectives To investigate how well the Gleason score in diagnostic needle biopsies predicted the Gleason score in a subsequent radical prostatectomy (RP) specimen before and after the 2005 International Society of Urological Pathology (ISUP) revision of Gleason grading, and if the recently proposed ISUP grades 1-5 (corresponding to Gleason scores 6, 3 + 4, 4 + 3, 8 and 9-10) better predict the RP grade. Patients and Methods All prostate cancers diagnosed in Sweden are reported to the National Prostate Cancer Register (NPCR). We analysed the Gleason scores and ISUP grades from the diagnostic biopsies and the RP specimens in 15 598 men in the NPCR who: were diagnosed between 2000 and 2012 with clinical stage T1-2 M0/X prostate cancer on needle biopsy; were aged <= 70 years; had serum PSA concentration of < 20 ng/mL; and underwent a RP < 6 months after diagnosis as their primary treatment. Results Prediction of RP Gleason score increased from 55 to 68% between 2000 and 2012. Most of the increase occurred before 2005 (nine percentage points; P < 0.001); however, when adjusting for Gleason score and year of diagnosis in a multivariable analysis, the prediction of RP Gleason score decreased over time (odds ratio [OR] 0.98; P < 0.002). A change in the ISUP grades would have led to a decreasing agreement between biopsy and RP grades over time, from 68% in 2000 to 57% in 2012, with an OR of 0.95 in multivariable analysis (P < 0.001). Conclusion Agreement between biopsy and RP Gleason score improved from 2000 to 2012, with most of the improvement occurring before the 2005 ISUP grading revision. Had ISUP grades been used instead of Gleason score, the agreement between biopsy and RP grade would have decreased, probably because of its separation of Gleason score 7 into ISUP grades 2 and 3 (Gleason score 3 + 4 vs 4 + 3).

  • 134. Danneman, Daniela
    et al.
    Drevin, Linda
    Delahunt, Brett
    Samaratunga, Hemamali
    Robinson, David
    Bratt, Ola
    Loeb, Stacy
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Egevad, Lars
    Accuracy of prostate biopsies for predicting Gleason score in radical prostatectomy specimens: nationwide trends 2000-20122017In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 119, no 1, p. 50-56Article in journal (Refereed)
    Abstract [en]

    Objectives To investigate how well the Gleason score in diagnostic needle biopsies predicted the Gleason score in a subsequent radical prostatectomy (RP) specimen before and after the 2005 International Society of Urological Pathology (ISUP) revision of Gleason grading, and if the recently proposed ISUP grades 1-5 (corresponding to Gleason scores 6, 3 + 4, 4 + 3, 8 and 9-10) better predict the RP grade. Patients and Methods All prostate cancers diagnosed in Sweden are reported to the National Prostate Cancer Register (NPCR). We analysed the Gleason scores and ISUP grades from the diagnostic biopsies and the RP specimens in 15 598 men in the NPCR who: were diagnosed between 2000 and 2012 with clinical stage T1-2 M0/X prostate cancer on needle biopsy; were aged <= 70 years; had serum PSA concentration of < 20 ng/mL; and underwent a RP < 6 months after diagnosis as their primary treatment. Results Prediction of RP Gleason score increased from 55 to 68% between 2000 and 2012. Most of the increase occurred before 2005 (nine percentage points; P < 0.001); however, when adjusting for Gleason score and year of diagnosis in a multivariable analysis, the prediction of RP Gleason score decreased over time (odds ratio [OR] 0.98; P < 0.002). A change in the ISUP grades would have led to a decreasing agreement between biopsy and RP grades over time, from 68% in 2000 to 57% in 2012, with an OR of 0.95 in multivariable analysis (P < 0.001). Conclusion Agreement between biopsy and RP Gleason score improved from 2000 to 2012, with most of the improvement occurring before the 2005 ISUP grading revision. Had ISUP grades been used instead of Gleason score, the agreement between biopsy and RP grade would have decreased, probably because of its separation of Gleason score 7 into ISUP grades 2 and 3 (Gleason score 3 + 4 vs 4 + 3).

  • 135. Danneman, Daniela
    et al.
    Drevin, Linda
    Robinson, David
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Egevad, Lars
    Gleason inflation 1998-2011: a registry study of 97 168 men2015In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 115, no 2, p. 248-255Article in journal (Refereed)
    Abstract [en]

    Objectives: To study long-term trends in Gleason grading in a nationwide population and to assess the impact of the International Society of Urological Pathology (ISUP) revision in 2005 of the Gleason system on grading practices, as in recent years there has been a shift upwards in Gleason grading of prostate cancer. Patients and Methods: All newly diagnosed prostate cancers in Sweden are reported to the National Prostate Cancer Register (NPCR). In 97 168 men with a primary diagnosis of prostate cancer on needle biopsy from 1998 to 2011, Gleason score, clinical T stage (cT) and serum levels of prostate-specific antigen (s-PSA) at diagnosis were analysed. Results: Gleason score, cT stage and s-PSA were reported to the NPCR in 97%, 99% and 99% of cases. Before and after 2005, Gleason score 7-10 was diagnosed in 52% and 57%, respectively (P < 0.001). After standardisation for cT stage and s-PSA with 1998 as baseline these tumours increased from 59% to 72%. Among low-risk tumours (stage cT1 and s-PSA 4-10 ng/mL) Gleason score 7-10 increased from 16% in 1998 to 40% in 2011 (P trend < 0.001), mean 19% and 33% before and after 2005 (P < 0.001). Among high-risk tumours (stage T3 and s-PSA 20-50 ng/mL) Gleason score 7-10 increased from 65% in 1998 to 94% in 2011 (P trend < 0.001), mean 78% and 90% before and after 2005 (P < 0.001). A Gleason score of 2-5 was reported in 27% in 1998 and 1% in 2011. Gleason score 5 decreased sharply after 2005 and Gleason score 2-4 was almost abandoned. Conclusions: There has been a gradual shift towards higher Gleason grading, which started before 2005 but became more evident after the ISUP 2005 revision. Among low-stage tumours reporting of Gleason score 7-10 was more than doubled during the study period. When corrected for stage migration upgrading is considerable over recent decades. This has clinical consequences for therapy decisions such as eligibility for active surveillance. Grading systems need to be as stable as possible to enable comparisons over time and to facilitate the interpretation of the prognostic impact of grade.

  • 136. Danneman, Daniela
    et al.
    Drevin, Linda
    Robinson, David
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Egevad, Lars
    Gleason inflation 1998-2011: a registry study of 97,168 men2015In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 115, no 2, p. 248-55Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To study long-term trends in Gleason grading in a nationwide population and to assess the impact of the International Society of Urological Pathology (ISUP) revision in 2005 of the Gleason system on grading practices, as in recent years there has been a shift upwards in Gleason grading of prostate cancer.

    PATIENTS AND METHODS: All newly diagnosed prostate cancers in Sweden are reported to the National Prostate Cancer Register (NPCR). In 97 168 men with a primary diagnosis of prostate cancer on needle biopsy from 1998 to 2011, Gleason score, clinical T stage (cT) and serum levels of prostate-specific antigen (s-PSA) at diagnosis were analysed.

    RESULTS: Gleason score, cT stage and s-PSA were reported to the NPCR in 97%, 99% and 99% of cases. Before and after 2005, Gleason score 7-10 was diagnosed in 52% and 57%, respectively (P < 0.001). After standardisation for cT stage and s-PSA with 1998 as baseline these tumours increased from 59% to 72%. Among low-risk tumours (stage cT1 and s-PSA 4-10 ng/mL) Gleason score 7-10 increased from 16% in 1998 to 40% in 2011 (P trend < 0.001), mean 19% and 33% before and after 2005 (P < 0.001). Among high-risk tumours (stage T3 and s-PSA 20-50 ng/mL) Gleason score 7-10 increased from 65% in 1998 to 94% in 2011 (P trend < 0.001), mean 78% and 90% before and after 2005 (P < 0.001). A Gleason score of 2-5 was reported in 27% in 1998 and 1% in 2011. Gleason score 5 decreased sharply after 2005 and Gleason score 2-4 was almost abandoned.

    CONCLUSIONS: There has been a gradual shift towards higher Gleason grading, which started before 2005 but became more evident after the ISUP 2005 revision. Among low-stage tumours reporting of Gleason score 7-10 was more than doubled during the study period. When corrected for stage migration upgrading is considerable over recent decades. This has clinical consequences for therapy decisions such as eligibility for active surveillance. Grading systems need to be as stable as possible to enable comparisons over time and to facilitate the interpretation of the prognostic impact of grade.

  • 137. Daouacher, Georgios
    et al.
    von Below, Catrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Gestblom, Charlotta
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Grzegorek, Rafael
    Wassberg, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Waldén, Mauritz
    Laparoscopic extended pelvic lymph node (LN) dissection as validation of the performance of [(11) C]-acetate positron emission tomography/computer tomography in the detection of LN metastasis in intermediate- and high-risk prostate cancer2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, no 1, p. 77-83Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the accuracy of the radiopharmaceutical [(11) C]-acetate combined with positron emission tomography/computer tomography (acetate-PET/CT) in lymph node (LN) staging in newly diagnosed prostate cancer cases. A second aim was to evaluate the potential discriminative properties of acetate-PET/CT in clinical routine.

    PATIENTS AND METHODS: In a prospective comparative study, from July 2010 to June 2013, 53 men with newly histologically diagnosed intermediate- or high-risk prostate cancer underwent acetate-PET/CT investigation at one regional centre before laparoscopic extended pelvic LN dissection (ePLND) at one referral centre. The sensitivity, specificity and accuracy of acetate-PET/CT were calculated. Comparisons were made between true-positive and false-negative PET/CT cases to identify differences in the clinical parameters: PSA level, Gleason status, lymph metastasis burden and size, calculated risk of LN involvement, and curative treatment decisions.

    RESULTS: In all, 26 patients had surgically/histologically confirmed LN metastasis (LN+). Acetate-PET/CT was true positive in 10 patients, false positive in one, false negative in 16, and true negative in 26. The individual sensitivity was 38%, specificity 96%, and accuracy 68%. The acetate-PET/CT positive cases had significantly more involved LNs (mean 7.9 vs 2.4, P < 0.001) with larger cancer diameters (14.1 vs 4.9 mm, P = 0.001) and fewer eventually had treatment with curative intent (40% vs 94%, P <0.005), although we lack long-term outcome data.

    CONCLUSION: Acetate-PET/CT has too low a sensitivity for routine LN staging but the specificity is high. The acetate-PET/CT positive cases have a very high burden of LN spread.

  • 138.
    Davidsson, Sabina
    et al.
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ohlson, Anna-Lena
    Department of Laboratory Medicine, Pathology, University Hospital Örebro, Örebro, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Swen-Olof
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Giunchi, Francesca
    Department of Hematology-Oncology, Molecular Pathology Laboratory, Addarii Institute of Oncology, University of Bologna, Bologna, Italy.
    Rider, Jennifer R.
    Department of Epidemiology, Boston University School of Public Health, Boston MA, USA.
    Fiorentino, Michelangelo
    Department of Hematology-Oncology, Molecular Pathology Laboratory, Addarii Institute of Oncology, University of Bologna, Bologna, Italy.
    FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer2018In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, no 1, p. 40-47Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (Tregs ). In the present study we evaluated the prevalence of Treg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer.

    METHODS: Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4+ Tregs and CD8+ Tregs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of Tregs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area.

    RESULTS: In men with prostate cancer, similarly high numbers of stromal CD4+ Tregs were identified in PAH and tumor, but CD4+ Tregs were less common in PIN. Greater numbers of epithelial CD4+ Tregs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4+ Tregs in the normal prostatic tissue counterpart.

    CONCLUSIONS: Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4+ Tregs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established.

  • 139.
    Davidsson, Sabina
    et al.
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Giunchi, Francesca
    Molecular Pathology Laboratory, Addarii Institute of Oncology, Department of Specialist Diagnostic and Experimental Medicine, University of Bologna, Bologna, Italy.
    Harlow, Alyssa
    Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
    Kirrander, Peter
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Rider, Jennifer
    Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
    Fiorentino, Michelangelo
    Molecular Pathology Laboratory, Addarii Institute of Oncology, Department of Specialist Diagnostic and Experimental Medicine, University of Bologna, Bologna, Italy.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology.
    PD-L1 Expression in Men with Penile Cancer and its Association with Clinical Outcomes2019In: European Urology Oncology, E-ISSN 2588-9311, Vol. 2, no 2, p. 214-221Article in journal (Refereed)
    Abstract [en]

    Background: It has been hypothesized that PD-L1 expression in tumor cells and tumor-infiltrating immune (TII) cells may contribute to tumor progression by inhibiting antitumor immunity.

    Objective: To investigate the association between PD-L1 expression in tumor cells and TII cells and clinical outcomes in penile cancer.

    Design, setting, and participants: A cohort of 222 men treated for penile squamous cell carcinoma (SqCC) at Örebro University Hospital between 1984 and 2008 with long-term follow-up (median 34 mo) was evaluated for PD-L1 expression in tumor cells and TII cells via immunohistochemistry.

    Outcome measurements and statistical analysis: Association between clinicopathological features and PD-L1 expression was estimated using χ2 and Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used.

    Results and limitations: We found that 32.1% of the tumors and 64.2% of the TII cells expressed PD-L1. Our data demonstrate that penile SqCC patients with PD-L1–positive tumor cells or TII cells are at significant risk of lower cancer-specific survival and that the prognostic value of PD-L1 expression was strongest for tumor cell positivity. The use of tissue microarrays rather than whole sections may be viewed as a limitation.

    Conclusions: Tumor PD-L1 expression independently identifies penile SqCC patients at risk of poor clinical outcomes.

    Patient summary: We investigated how many patients with penile cancer had tumors that manufactured PD-L1, a protein that decreases the ability of the immune system to fight cancer. We found that up to one-third of penile tumors make this protein. Patients whose tumors make PD-L1 have more aggressive penile cancer and worse clinical outcomes.

  • 140.
    Davidsson, Sabina
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fiorentino, Michelangelo
    Mol Pathol Lab, Addarii Inst Oncol, Dept Hematol Oncol, Univ Bologna, Bologna, Italy; Sch Med, Dana Farber Canc Inst, Dept Pathol, Brigham & Womens Hosp & Adult Oncol, Harvard Univ, Boston MA, USA.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fang, Fang
    Sch Med, Channing Lab, Dept Med, Brigham & Womens Hosp, Harvard Univ, Boston MA, USA; Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden.
    Mucci, Lorelei A.
    Sch Publ Hlth, Dept Epidemiol, Harvard Univ, Boston MA, USA; Sch Med, Channing Lab, Dept Med, Brigham & Womens Hosp, Harvard Univ, Boston MA, USA.
    Varenhorst, Eberhard
    Dept Urol, Linköping Univ Hosp, Linköping, Sweden.
    Fall, Katja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Rider, Jennifer R.
    Dept Urol, Örebro Univ Hosp, Örebro, Sweden; Sch Med, Dana Farber Canc Inst, Dept Pathol, Brigham & Womens Hosp & Adult Oncol, Harvard Univ, Boston MA, USA.
    Inflammation, focal atrophic lesions, and prostatic intraepithelial neoplasia with respect to risk of lethal prostate cancer2011In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, no 10, p. 2280-2287Article in journal (Refereed)
    Abstract [en]

    Background: A challenge in prostate cancer (PCa) management is identifying potentially lethal disease at diagnosis. Inflammation, focal prostatic atrophy, and prostatic intraepithelial neoplasia (PIN) are common in prostate tumor specimens, but it is not clear whether these lesions have prognostic significance. Methods: We conducted a case-control study nested in a cohort of men diagnosed with stage T1a-b PCa through transurethral resection of the prostate in Sweden. Cases are men who died of PCa (n = 228). Controls are men who survived more than 10 years after PCa diagnosis without metastases (n = 387). Slides were assessed for Gleason grade, inflammation, PIN, and four subtypes of focal prostatic atrophy: simple atrophy (SA), postatrophic hyperplasia (PAH), simple atrophy with cyst formation, and partial atrophy. We estimated OR and 95% CI for odds of lethal PCa with multivariable logistic regression. Results: Chronic inflammation and PIN were more frequently observed in tumors with PAH, but not SA. No specific type of atrophy or inflammation was significantly associated with lethal PCa overall, but there was a suggestion of a positive association for chronic inflammation. Independent of age, Gleason score, year of diagnosis, inflammation, and atrophy type, men with PIN were 89% more likely to die of PCa (95% CI: 1.04-3.42). Conclusion: Our data show that PIN, and perhaps presence of moderate or severe chronic inflammation, may have prognostic significance for PCa. Impact: Lesions in tumor adjacent tissue, and not just the tumor itself, may aid in identification of clinically relevant disease. Cancer Epidemiol Biomarkers Prev; 20(10); 2280-7. (C) 2011 AACR.

  • 141.
    Davidsson, Sabina
    et al.
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Rider, Jennifer R.
    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA.
    Unemo, Magnus
    Örebro University, School of Health Sciences. Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Pathology, Örebro University Hospital, Örebro, Sweden; Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden .
    Andersson, Swen-Olof
    Örebro University, School of Health Sciences. Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Elgh, Fredrik
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer2016In: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 11, article id 26Article in journal (Refereed)
    Abstract [en]

    Background: Prostate cancer is the most common cancer among men in Western countries but the exact pathogenic mechanism of the disease is still largely unknown. An infectious etiology and infection-induced inflammation has been suggested to play a role in prostate carcinogenesis and Propionibacterium acnes has been reported as the most prevalent microorganism in prostatic tissue. We investigated the frequency and types of P. acnes isolated from prostate tissue samples from men with prostate cancer and from control patients without the disease.

    Methods: We included 100 cases and 50 controls in this study. Cases were men diagnosed with prostate cancer undergoing radical prostatectomy and controls were men undergoing surgery for bladder cancer without any histological findings of prostate cancer. Six biopsies taken from each patient's prostate gland at the time of surgery were used for cultivation and further characterization of P. acnes.

    Results: The results revealed that P. acnes was more common in men with prostate carcinoma than in controls, with the bacteria cultured in 60 % of the cases vs. 26 % of the controls (p = 0.001). In multivariable analyses, men with P. acnes had a 4-fold increase in odds of a prostate cancer diagnosis after adjustment for age, calendar year of surgery and smoking status (OR: 4.46; 95 % CI: 1.93-11.26). To further support the biologic plausibility for a P. acnes infection as a contributing factor in prostate cancer development, we subsequently conducted cell-based experiments. P. acnes- isolates were co-cultured with the prostate cell line PNT1A. An increased cell proliferation and cytokine/chemokine secretion in infected cells was observed.

    Conclusion: The present study provides further evidence for a role of P. acnes in prostate cancer development.

  • 142.
    Davidsson, Sabina
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Mölling, Paula
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Rider, Jennifer R.
    Karlsson, Mats G.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Elgh, Fredrik
    Andrén, Ove
    Örebro University, School of Medicine, Örebro University, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden.
    Prevalence and typing of Propionibacterium acnes in prostate tissue obtained from men with prostate cancer and from health controlsManuscript (preprint) (Other academic)
  • 143. Delanaye, Pierre
    et al.
    Ebert, Natalie
    Melsom, Toralf
    Gaspari, Flavio
    Mariat, Christophe
    Cavalier, Etienne
    Björk, Jonas
    Christensson, Anders
    Nyman, Ulf
    Porrini, Esteban
    Remuzzi, Giuseppe
    Ruggenenti, Piero
    Schaeffner, Elke
    Soveri, Inga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Sterner, Gunnar
    Eriksen, Bjørn Odvar
    Bäck, Sten-Erik
    Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1 How to measure glomerular filtration rate with iohexol?2016In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 9, no 5, p. 682-699Article in journal (Refereed)
    Abstract [en]

    While there is general agreement on the necessity to measure glomerular filtration rate (GFR) in many clinical situations, there is less agreement on the best method to achieve this purpose. As the gold standard method for GFR determination, urinary (or renal) clearance of inulin, fades into the background due to inconvenience and high cost, a diversity of filtration markers and protocols compete to replace it. In this review, we suggest that iohexol, a non-ionic contrast agent, is most suited to replace inulin as the marker of choice for GFR determination. Iohexol comes very close to fulfilling all requirements for an ideal GFR marker in terms of low extra-renal excretion, low protein binding and in being neither secreted nor reabsorbed by the kidney. In addition, iohexol is virtually non-toxic and carries a low cost. As iohexol is stable in plasma, administration and sample analysis can be separated in both space and time, allowing access to GFR determination across different settings. An external proficiency programme operated by Equalis AB, Sweden, exists for iohexol, facilitating interlaboratory comparison of results. Plasma clearance measurement is the protocol of choice as it combines a reliable GFR determination with convenience for the patient. Single-sample protocols dominate, but multiple-sample protocols may be more accurate in specific situations. In low GFRs one or more late samples should be included to improve accuracy. In patients with large oedema or ascites, urinary clearance protocols should be employed. In conclusion, plasma clearance of iohexol may well be the best candidate for a common GFR determination method.

  • 144. Delanaye, Pierre
    et al.
    Melsom, Toralf
    Ebert, Natalie
    Bäck, Sten-Erik
    Mariat, Christophe
    Cavalier, Etienne
    Björk, Jonas
    Christensson, Anders
    Nyman, Ulf
    Porrini, Esteban
    Remuzzi, Giuseppe
    Ruggenenti, Piero
    Schaeffner, Elke
    Soveri, Inga
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Sterner, Gunnar
    Eriksen, Bjørn Odvar
    Gaspari, Flavio
    Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 2 Why to measure glomerular filtration rate with iohexol?2016In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 9, no 5, p. 700-704Article in journal (Refereed)
    Abstract [en]

    A reliable assessment of glomerular filtration rate (GFR) is of paramount importance in clinical practice as well as epidemiological and clinical research settings. It is recommended by Kidney Disease: Improving Global Outcomes guidelines in specific populations (anorectic, cirrhotic, obese, renal and non-renal transplant patients) where estimation equations are unreliable. Measured GFR is the only valuable test to confirm or confute the status of chronic kidney disease (CKD), to evaluate the slope of renal function decay over time, to assess the suitability of living kidney donors and for dosing of potentially toxic medication with a narrow therapeutic index. Abnormally elevated GFR or hyperfiltration in patients with diabetes or obesity can be correctly diagnosed only by measuring GFR. GFR measurement contributes to assessing the true CKD prevalence rate, avoiding discrepancies due to GFR estimation with different equations. Using measured GFR, successfully accomplished in large epidemiological studies, is the only way to study the potential link between decreased renal function and cardiovascular or total mortality, being sure that this association is not due to confounders, i.e. non-GFR determinants of biomarkers. In clinical research, it has been shown that measured GFR (or measured GFR slope) as a secondary endpoint as compared with estimated GFR detected subtle treatment effects and obtained these results with a comparatively smaller sample size than trials choosing estimated GFR. Measuring GFR by iohexol has several advantages: simplicity, low cost, stability and low interlaboratory variation. Iohexol plasma clearance represents the best chance for implementing a standardized GFR measurement protocol applicable worldwide both in clinical practice and in research.

  • 145.
    Delbro, Dick
    et al.
    Örebro University, School of Medical Sciences.
    Hallsberg, Lena
    Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Peeker, Ralph
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy. University of Gothenburg, Gothenburg, Sweden.
    Scherbak, Nikolai
    Örebro University, School of Science and Technology.
    Fall, Magnus
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Godtman, Rebecka Arnsrud
    Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    The extracellular matrix-degrading protein ADAMTS5 is expressed in the nuclei of urothelial cells in healthy rats2018In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 52, no 2, p. 139-142Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to investigate whether protein expression of the extracellular matrix-degrading protease ADAMTS5 can be demonstrated in the urinary bladder of healthy rats, and, if so, to determine the localization of this enzyme.

    MATERIALS AND METHODS: The experiments were conducted with eight inbred male Sprague-Dawley rats. Immunohistochemistry was used to investigate the expression of ADAMTS5 in the urinary bladder. Negative controls were established by either excluding the primary antibody or applying the antibody after it had been preabsorbed with its immunogenic peptide. Confocal microscopy was used to visualize the distribution of ADAMTS5 in the urinary bladder tissue.

    RESULTS: Immunoreactivity for ADAMTS5 was demonstrated in the urothelium and in the detrusor. This expression was localized not only in the cytoplasm, but also in the nuclei. Confocal microscopy corroborated these findings.

    CONCLUSION: Expression of ADAMTS5 was demonstrated in the cytoplasm as well as in the nuclei of the urothelium and detrusor cells, suggesting that it may play a role at the transcriptional level.

  • 146. Dellagrammaticas, D
    et al.
    Bryden, A A
    Collins, G N
    Regression of metastatic transitional cell carcinoma in response to tamoxifen.2001In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 165, no 5, article id 1631Article in journal (Refereed)
  • 147.
    Demirel, Isak
    et al.
    Univ Örebro, Dept Clin Med, Sch Hlth & Med Sci, Örebro, Sweden.
    Säve, Susanne
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Kruse, Robert
    Univ Örebro, Dept Clin Med, Sch Hlth & Med Sci, Örebro, Sweden.
    Persson, Katarina
    Univ Örebro, Dept Clin Med, Sch Hlth & Med Sci, Örebro, Sweden.
    Expression of suppressor of cytokine signalling 3 (SOCS3) in human bladder epithelial cells infected with uropathogenic Escherichia coli2013In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 121, no 2, p. 158-167Article in journal (Refereed)
    Abstract [en]

    Suppressor of cytokine signalling (SOCS) proteins inhibit pro-inflammatory signalling mediated by Janus-activated kinase (JAK)-signal transducer and activator of transcription (STAT) pathways. To evade the immune response some pathogens appear to modify the host SOCS proteins. Uropathogenic Escherichia coli (UPEC) are able to subvert the host response evoked by bladder epithelial cells, but the mechanisms are not fully understood. The objective of this study was to investigate whether UPEC can modify the host SOCS and STAT3 response. Real time RT-PCR studies demonstrated an increased SOCS1 and SOCS3 expression in the isolated human bladder epithelial cell lines (RT-4 and 5637) in response to cytokines. UPEC strain IA2 increased SOCS3, but not SOCS1, mRNA levels with a peak at 6h after infection. The increase of SOCS3 was confirmed at the protein level by Western blotting. The UPEC strain IA2 caused a time-dependent decrease in the phosphorylation of STAT3. This study demonstrates that UPEC are able to affect SOCS3 and STAT3 signalling in human uroepithelial cells. The finding that UPEC are able to induce mediators involved in suppression of host cytokine signalling may help to elucidate how UPEC may circumvent the host response during urinary tract infection.

  • 148. Demirel, Isak
    et al.
    Vumma, Ravi
    Mohlin, Camilla
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Svensson, Lovisa
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Säve, Susanne
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Persson, Katarina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Nitric Oxide Activates IL-6 Production and Expression in Human Renal Epithelial Cells2012In: American Journal of Nephrology, ISSN 0250-8095, E-ISSN 1421-9670, Vol. 36, no 6, p. 524-530Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Increased nitric oxide (NO) production or inducible form of NO synthase activity have been documented in patients suffering from urinary tract infection (UTI), but the role of NO in this infection is unclear. We investigated whether NO can affect the host response in human renal epithelial cells by modulating IL-6 production and mRNA expression. Methods: The human renal epithelial cell line A498 was infected with a uropathogenic Escherichia coli (UPEC) strain and/or the NO donor DETA/NO. The IL-6 production and mRNA expression were evaluated by ELISA and real-time RT-PCR. IL-6 mRNA stability was evaluated by analyzing mRNA degradation by real-time RT-PCR. Results: DETA/NO caused a significant (p < 0.05) increase in IL-6 production. Inhibitors of p38 MAPK and ERK1/2 signaling, but not JNK, were shown to significantly suppress DETA/NO-induced IL-6 production. UPEC-induced IL-6 production was further increased (by 73 +/- 23%, p < 0.05) in the presence of DETA/NO. The IL-6 mRNA expression increased 2.1 +/- 0.17-fold in response to DETA/NO, while the UPEC-evoked increase was pronounced (20 +/- 4.5-fold). A synergistic effect of DETA/NO on UPEC-induced IL-6 expression was found (33 +/- 7.2-fold increase). The IL-6 mRNA stability studies showed that DETA/NO partially attenuated UPEC-induced degradation of IL-6 mRNA. Conclusions: NO was found to stimulate IL-6 in renal epithelial cells through p38 MAPK and ERK1/2 signaling pathways and also to increase IL-6 mRNA stability in UPEC-infected cells. This study proposes a new role for NO in the host response during UTI by modulating the transcription and production of the cytokine IL-6. Copyright (C) 2012 S. Karger AG, Basel

  • 149.
    Donker, Dirk W.
    et al.
    Univ Utrecht, Univ Med Ctr Utrecht, Dept Intens Care Med, Utrecht, Netherlands..
    Brodie, Daniel
    Columbia Univ, Coll Phys & Surg, New York Presbyterian Hosp, Div Pulm Allergy & Crit Care Med, New York, NY USA..
    Henriques, Jose P. S.
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, Amsterdam, Netherlands..
    Broomé, Michael
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Univ Hosp, ECMO Dept, SE-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Anaesthesiol & Intens Care, Stockholm, Sweden.
    Left Ventricular Unloading During Veno-Arterial ECMO: A Simulation Study2019In: ASAIO journal (1992), ISSN 1058-2916, E-ISSN 1538-943X, Vol. 65, no 1, p. 11-20Article in journal (Refereed)
    Abstract [en]

    Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is widely used in cardiogenic shock. It provides systemic perfusion, but left ventricular (LV) unloading is suboptimal. Using a closed-loop, real-time computer model of the human cardiovascular system, cardiogenic shock supported by peripheral VA ECMO was simulated, and effects of various adjunct LV unloading interventions were quantified. After VA ECMO initiation (4 L/min) in cardiogenic shock (baseline), hemodynamics improved (increased to 85 mm Hg), while LV overload occurred (10% increase in end-diastolic volume [EDV], and 5 mm Hg increase in pulmonary capillary wedge pressure [PCWP]). Decreasing afterload (65 mm Hg mean arterial pressure) and circulating volume (-800 mL) reduced LV overload (12% decrease in EDV and 37% decrease in PCWP) compared with baseline. Additional intra-aortic balloon pumping only marginally decreased cardiac loading. Instead, adjunct Impella T enhanced LV unloading (23% decrease in EDV and 41% decrease in PCWP). Alternative interventions, for example, left atrial/ventricular venting, yielded substantial unloading. We conclude that real-time simulations may provide quantitative clinical measures of LV overload, depending on the degree of VA ECMO support and adjunct management. Simulations offer insights into individualized LV unloading interventions in cardiogenic shock supported by VA ECMO as a proof of concept for potential future applications in clinical decision support, which may help to improve individualized patient management in complex cardiovascular disease.

  • 150.
    Draaken, Markus
    et al.
    Institute of Human Genetics, University of Bonn, Germany.
    Baudisch, Friederike
    Timmermann, Bernd
    Kuhl, Heiner
    Kerick, Martin
    Proske, Judith
    Wittler, Lars
    Pennimpede, Tracie
    Ebert, Anne-Karoline
    Rösch, Wolfgang
    Stein, Raimund
    Bartels, Enrika
    von Lowtzow, Catharina
    Boemers, Thomas M
    Herms, Stefan
    Gearhart, John P
    Lakshmanan, Yegappan
    Kockum, Christina Clementsson
    Holmdahl, Gundela
    Läckgren, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Nordenskjöld, Agnetha
    Boyadjiev, Simeon A
    Herrmann, Bernhard G
    Nöthen, Markus M
    Ludwig, Michael
    Reutter, Heiko
    Institute of Human Genetics, University of Bonn, Germany.
    Classic bladder exstrophy: Frequent 22q11.21 duplications and definition of a 414 kb phenocritical region2014In: Birth defects research. Clinical and molecular teratology, ISSN 1542-0752, E-ISSN 1542-0760, Vol. 100, no 6, p. 512-517Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Classic bladder exstrophy (CBE) is the most common form of the bladder exstrophy and epispadias complex. Previously, we and others have identified four patients with a duplication of 22q11.21 among a total of 96 unrelated CBE patients.

    METHODS: Here, we investigated whether this chromosomal aberration was commonly associated with CBE/bladder exstrophy and epispadias complex in an extended case-control sample. Multiplex ligation-dependent probe amplification and microarray-based analysis were used to identify 22q11.21 duplications in 244 unrelated bladder exstrophy and epispadias complex patients (including 217 CBE patients) and 665 healthy controls.

    RESULTS: New duplications of variable size were identified in four CBE patients and one control. Pooling of our previous and present data (eight duplications in 313 CBE patients) yielded a combined odds ratio of 31.86 (95% confidence interval, 4.24-1407.97). Array-based sequence capture and high-throughput targeted re-sequencing established that all breakpoints resided within the low-copy repeats 22A to 22D. Comparison of the eight duplications revealed a 414 kb phenocritical region harboring 12 validated RefSeq genes. Characterization of these 12 candidate genes through whole-mount in situ hybridization of mouse embryos at embryonic day 9.5 suggested that CRKL, THAP7, and LZTR1 are CBE candidate genes.

    CONCLUSION: Our data suggest that duplication of 22q11.21 increases CBE risk and implicate a phenocritical region in disease formation.

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