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  • 351.
    van Kessel, Kim E. M.
    et al.
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands..
    Beukers, Willemien
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands..
    Lurkin, Irene
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands..
    Ziel-van der Made, Angelique
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands..
    van der Keur, Kirstin A.
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands..
    Boormans, Joost L.
    Erasmus MC, Dept Urol, Rotterdam, Netherlands..
    Dyrskjot, Lars
    Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark..
    Marquez, Mirari
    Spanish Natl Canc Res Ctr, Genet & Mol Epidemiol Grp, Madrid, Spain..
    Orntoft, Torben F.
    Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark..
    Real, Francisco X.
    Spanish Natl Canc Res Ctr, Epithelial Carcinogenesis Grp, Madrid, Spain.;Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain..
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Malats, Nuria
    Spanish Natl Canc Res Ctr, Genet & Mol Epidemiol Grp, Madrid, Spain..
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Van Criekinge, Wim
    MDxHealth Inc, Irvine, CA USA.;Univ Ghent, Lab Bioinformat & Computat Genom, Ghent, Belgium..
    Zwarthoff, Ellen C.
    Erasmus MC, Dept Pathol, Rotterdam, Netherlands..
    Validation of a DNA Methylation-Mutation Urine Assay to Select Patients with Hematuria for Cystoscopy2017Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 197, nr 3, s. 590-595Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Only 3% to 28% of patients referred to the urology clinic for hematuria are diagnosed with bladder cancer. Cystoscopy leads to high diagnostic costs and a high patient burden. Therefore, to improve the selection of patients for cystoscopy and reduce costs and over testing we aimed to validate a recently developed diagnostic urine assay.

    Materials and Methods: Included in study were 200 patients from a total of 3 European countries who underwent cystoscopy for hematuria, including 97 with bladder cancer and 103 with nonmalignant findings. Voided urine samples were collected prior to cystoscopy. DNA was extracted and analyzed for mutations in FGFR3, TERT and HRAS, and methylation of OTX1, ONECUT2 and TWIST1. Logistic regression was used to analyze the association between predictor variables and bladder cancer.

    Results: Combining the methylation and mutation markers with age led to an AUC of 0.96 (95% CI 0.92e0.99) with 93% sensitivity and 86% specificity, and an optimism corrected AUC of 0.95. The AUC was higher for T1 or greater tumors compared to Ta tumors (0.99 vs 0.93). The AUC was also higher for high grade tumors compared to low grade tumors (1.00 vs 0.93). Overall negative predictive value was 99% based on the 5% to 10% prevalence of bladder cancer in patients with hematuria. This would lead to a 77% reduction in diagnostic cystoscopy.

    Conclusions: Analyzing hematuria patients for the risk of bladder cancer using novel molecular markers may lead to a reduction in diagnostic cystoscopy. Combining methylation analysis (OTX1, ONECUT2 and TWIST1) with mutation analysis (FGFR3, TERT and HRAS) and patient age resulted in a validated accurate prediction model.

  • 352.
    van Kessel, Kim E. M.
    et al.
    Erasmus MC, Erasmus MC Canc Inst, Dept Pathol, Rotterdam, Netherlands.;Erasmus MC, Erasmus MC Canc Inst, Dept Urol, Rotterdam, Netherlands..
    van der Keur, Kirstin A.
    Erasmus MC, Erasmus MC Canc Inst, Dept Pathol, Rotterdam, Netherlands..
    Dyrskjot, Lars
    Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark..
    Algaba, Ferran
    Univ Autonoma Barcelona, Fundacio Puigvert, Sect Pathol, Barcelona, Spain..
    Welvaart, Naeromy Y. C.
    Erasmus MC, Erasmus MC Canc Inst, Dept Pathol, Rotterdam, Netherlands..
    Beukers, Willemien
    Erasmus MC, Erasmus MC Canc Inst, Dept Pathol, Rotterdam, Netherlands..
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Keck, Bastian
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Urol, Erlangen, Germany..
    Maurer, Tobias
    Tech Univ Munich, Klinikum Rechts Isar, Dept Urol, Munich, Germany..
    Simic, Tatjana
    Univ Belgrade, Fac Med, Inst Med & Clin Biochem, Belgrade, Serbia..
    Horstmann, Marcus
    Friedrich Schiller Univ Jena, Dept Urol, Jena, Germany..
    Grimm, Marc-Oliver
    Friedrich Schiller Univ Jena, Dept Urol, Jena, Germany..
    Hermann, Gregers G.
    Univ Copenhagen, Herlev & Gentofte Hosp, Dept Urol, Hellerup, Denmark..
    Mogensen, Karin
    Univ Copenhagen, Herlev & Gentofte Hosp, Dept Urol, Hellerup, Denmark..
    Hartmann, Arndt
    Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, Erlangen, Germany..
    Harving, Niels
    Aalborg Univ Hosp, Dept Urol, Aalborg, Denmark..
    Petersen, Astrid C.
    Aalborg Univ Hosp, Dept Pathol, Aalborg, Denmark..
    Jensen, Jorgen B.
    Aarhus Univ Hosp, Dept Urol, Aarhus, Denmark..
    Junker, Kerstin
    Saarland Univ, Dept Urol, Homburg, Germany..
    Boormans, Joost L.
    Erasmus MC, Erasmus MC Canc Inst, Dept Urol, Rotterdam, Netherlands..
    Real, Francisco X.
    CIBERONC, Spanish Natl Canc Res Ctr CNIO, Epithelial Carcinogenesis Grp, Madrid, Spain.;Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain..
    Malats, Nuria
    CIBERONC, Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain..
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Orntoft, Torben F.
    Aarhus Univ Hosp, Dept Mol Med, Aarhus, Denmark..
    Zwarthoff, Ellen C.
    Erasmus MC, Erasmus MC Canc Inst, Dept Pathol, Rotterdam, Netherlands..
    Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups2018Ingår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 24, nr 7, s. 1586-1593Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: The European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC) recommend risk stratification based on clinicopathologic parameters. Our aim was to investigate the added value of biomarkers to improve risk stratification of NMIBC. Experimental Design: We prospectively included 1,239 patients in follow-up for NMIBC in six European countries. Fresh-frozen tumor samples were analyzed for GATA2, TBX2, TBX3, and ZIC4 methylation and FGFR3, TERT, PIK3CA, and RAS mutation status. Cox regression analyses identified markers that were significantly associated with progression to muscle-invasive disease. The progression incidence rate (PIR = rate of progression per 100 patient-years) was calculated for subgroups. Results: In our cohort, 276 patients had a low, 273 an intermediate, and 555 a high risk of tumor progression based on the EAU NMIBC guideline. Fifty-seven patients (4.6%) progressed to muscle-invasive disease. The limited number of progressors in this large cohort compared with older studies is likely due to improved treatment in the past two decades. Overall, wild-type FGFR3 and methylation of GATA2 and TBX3 were significantly associated with progression (HR = 0.34, 2.53, and 2.64, respectively). The PIR for EAU high-risk patients was 4.25. On the basis of FGFR3 mutation status and methylation of GATA2, this cohort could be reclassified into a good class (PIR = 0.86, 26.2% of patients), a moderate class (PIR = 4.32, 49.7%), and a poor class (PIR = 7.66, 24.0%). Conclusions: We conclude that the addition of selected biomarkers to the EAU risk stratification increases its accuracy and identifies a subset of NMIBC patients with a very high risk of progression. (C) 2018 AACR.

  • 353. Vedder, Moniek M.
    et al.
    Marquez, Mirari
    de Bekker-Grob, Esther W.
    Calle, Malu L.
    Dyrskjot, Lars
    Kogevinas, Manoils
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Algaba, Ferran
    Beukers, Willemien
    Orntoft, Torben F.
    Zwarthoff, Ellen
    Real, Francisco X.
    Malats, Nuria
    Steyerberg, Ewout W.
    Risk Prediction Scores for Recurrence and Progression of Non-Muscle Invasive Bladder Cancer: An International Validation in Primary Tumours2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 6, s. e96849-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: We aimed to determine the validity of two risk scores for patients with non-muscle invasive bladder cancer in different European settings, in patients with primary tumours. Methods: We included 1,892 patients with primary stage Ta or T1 non-muscle invasive bladder cancer who underwent a transurethral resection in Spain (n = 973), the Netherlands (n = 639), or Denmark (n = 280). We evaluated recurrence-free survival and progression-free survival according to the European Organisation for Research and Treatment of Cancer (EORTC) and the Spanish Urological Club for Oncological Treatment (CUETO) risk scores for each patient and used the concordance index (c-index) to indicate discriminative ability. Results: The 3 cohorts were comparable according to age and sex, but patients from Denmark had a larger proportion of patients with the high stage and grade at diagnosis (p < 0.01). At least one recurrence occurred in 839 (44%) patients and 258 (14%) patients had a progression during a median follow-up of 74 months. Patients from Denmark had the highest 10-year recurrence and progression rates (75% and 24%, respectively), whereas patients from Spain had the lowest rates (34% and 10%, respectively). The EORTC and CUETO risk scores both predicted progression better than recurrence with c-indices ranging from 0.72 to 0.82 while for recurrence, those ranged from 0.55 to 0.61. Conclusion: The EORTC and CUETO risk scores can reasonably predict progression, while prediction of recurrence is more difficult. New prognostic markers are needed to better predict recurrence of tumours in primary non-muscle invasive bladder cancer patients.

  • 354. Vellekoop, Annelies
    et al.
    Loeb, Stacy
    Folkvaljon, Yasin
    Uppsala University Hospital, Regional Cancer Centre, Uppsala, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Population Based Study of Predictors of Adverse Pathology among Candidates for Active Surveillance with Gleason 6 Prostate Cancer2014Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 191, nr 2, s. 350-357Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose

    Approximately a third of prostate cancer cases with a Gleason score of 6 are upgraded at radical prostatectomy. We studied trends and predictors of upgrading and up staging among men with Gleason 6 prostate cancer who were potential candidates for active surveillance in a population based cohort.

    Materials and Methods

    From 2007 to 2011, 13,159 men were diagnosed with Gleason 6, clinical stage T1c/T2 prostate cancer in the NPCR (National Prostate Cancer Register of Sweden). Of these men 4,500 underwent radical prostatectomy, including 2,205 with data on the extent of prostate cancer in the biopsy cores. Logistic regression was used to examine variables associated with adverse pathology (defined as upgrading to Gleason 7 or greater, or up staging to pT3 or greater) in the full group and in potential candidates for active surveillance using 6 current published protocols.

    Results

    Among Swedish men with clinically localized Gleason 6 prostate cancer approximately 50% had adverse pathology at radical prostatectomy. Of the men who met the study inclusion criteria of 6 different active surveillance protocols, adverse pathology was present in 33% to 45%. Predictors of adverse pathology were older age, higher prostate specific antigen, prostate specific antigen density greater than 0.15 ng/ml/cm3, palpable disease and extent of cancer greater than 4 mm on biopsy. Larger prostate volume had an inverse relationship with adverse pathology.

    Conclusions

    More than a third of men meeting the most stringent active surveillance criteria had adverse pathology at radical prostatectomy in this population based cohort. Active surveillance programs should consider prostate specific antigen density and extent of cancer on biopsy for patient selection.

  • 355.
    Ventimiglia, Eugenio
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Folkvaljon, Yasin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Carlsson, Stefan
    Karolinska University Hospital, Stockholm, Sweden .
    Bratt, Ola
    Lund University, Lund, Sweden; University Hospitals, Cambridge, UK.
    Montorsi, Francesco
    URI, IRCCS Ospedale San Raffaele, Milan, Italy.
    Volz, Daniela
    Karolinska University Hospital, Stockholm, Sweden .
    Akre, Olof
    Department of Molecular Medicine and Surgery, Karolinska Institutet, and Department of Urology, Karolinska University Hospital, Stockholm, Sweden.
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Nationwide, population-based study of post radical prostatectomy urinary incontinence correction surgery2018Ingår i: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 117, nr 2, s. 321-327Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To assess the use of post radical prostatectomy (RP) urinary incontinence (PPI) surgery and to investigate factors related to its use.

    METHODS: Cohort study in Prostate Cancer database Sweden (PCBaSe) of men who underwent primary RP between 1998 and 2012. PPI correction procedures were identified in the Patient Registry. Hazard ratios (HR) and 95% confidence intervals (CIs) of PPI surgeries were estimated.

    RESULTS: Seven hundred eighty-two out of 26 280 (3%) men underwent PPI surgery at a median time of 3 years after RP. There was an eightfold increase in the absolute number of PPI surgeries during 2000-2014 and a threefold increase in the number per 1000 RPs performed. Factors associated with high use PPI surgery were age >70, HR 1.96 (1.54-2.50), and high hospital RP volume (>100 RPs/year), HR 0.81 (0.66-0.99). There was a 10-fold difference in use of PPI surgery per 1000 RPs between the county with the highest versus lowest use. In a subgroup of men with Patient-Reported Outcome Measures (PROM); severe PPI was reported by 7% of men and 24% of them underwent PPI surgery.

    CONCLUSIONS: Three percent of all men received PPI surgery, with a 10-fold variation among health care providers. Only a quarter of men with severe PPI underwent PPI surgery, suggesting that PPI surgery remains underutilized.

  • 356.
    Ventimiglia, Eugenio
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. IRCCS, Osped San Raffaele, Div Expt Oncol, Unit Urol, Milan, Italy.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res Tour, Guys Hosp, 3rd Floor, London SE1 9RT, England.
    Lindhagen, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res Tour, Guys Hosp, 3rd Floor, London SE1 9RT, England;Uppsala Orebro, Reg Canc Ctr, Uppsala, Sweden.
    How to measure temporal changes in care pathways for chronic diseases using health care registry data2019Ingår i: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 19, artikel-id 103Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Disease trajectories for chronic diseases can span over several decades, with several time-dependent factors affecting treatment decisions. Thus, there is a need for long-term predictions of disease trajectories to inform patients and healthcare professionals on the long-term outcomes and provide information on the need of future health care. Here, we propose a state transition model to describe and predict disease trajectories up to 25 years after diagnosis in men with prostate cancer (PCa), as a proof of principle. Methods: States, state transitions, and transition probabilities were identified and estimated in Prostate Cancer data Base of Sweden (PCBaSeTraject), using nationwide population-based data from 118,743 men diagnosed with PCa. A state transition model in discrete time steps (i.e., 4 weeks) was developed and applied to capture all possible transitions (PCBaSeSim). Transition probabilities were estimated for changes in both treatment and comorbidity. These models combined yielded parameter estimates to run an individual-level simulation based on the state-transition model to obtain prediction estimates. Predicted estimates were then compared to real world data in PCBaSeTraject. Results: PCBaSeSim estimates for the cumulative incidence of first and second transitions, death from PCa and death from other causes were compared to observed transitions in PCBaSeTraject. A good agreement was found between simulated and observed estimates. Conclusions: We developed a reliable and accurate simulation tool, PCBaSeSim that provides information on disease trajectories for subjects with a chronic disease on an individual and population-based level.

  • 357. Vickers, Andrew
    et al.
    Bennette, Caroline
    Steineck, Gunnar
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Palmgren, Juni
    Garmo, Hans
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Individualized Estimation of the Benefit of Radical Prostatectomy from the Scandinavian Prostate Cancer Group Randomized Trial2012Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 62, nr 2, s. 204-209Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Although there is randomized evidence that radical prostatectomy improves survival, there are few data on how benefit varies by baseline risk. Objective: We aimed to create a statistical model to calculate the decrease in risk of death associated with surgery for an individual patient, using stage, grade, prostate-specific antigen, and age as predictors. Design, setting, and participants: A total of 695 men with T1 or T2 prostate cancer participated in the Scandinavian Prostate Cancer Group 4 trial (SPCG-4). Intervention: Patients in SPCG-4 were randomized to radical prostatectomy or conservative management. Outcome measurements and statistical analysis: Competing risk models were created separately for the radical prostatectomy and the watchful waiting group, with the difference between model predictions constituting the estimated benefit for an individual patient. Results and limitations: Individualized predictions of surgery benefit varied widely depending on age and tumor characteristics. At 65 yr of age, the absolute 10-yr risk reduction in prostate cancer mortality attributable to radical prostatectomy ranged from 4.5% to 17.2% for low-versus high-risk patients. Little expected benefit was associated with surgery much beyond age 70. Only about a quarter of men had an individualized benefit within even 50% of the mean. A limitation is that estimates from SPCG-4 have to be applied cautiously to contemporary patients. Conclusions: Our model suggests that it is hard to justify surgery in patients with Gleason 6, T1 disease or in those patients much above 70 yr of age. Conversely, surgery seems unequivocally of benefit for patients who have Gleason 8, or Gleason 7, stage T2. For patients with Gleason 6 T2 and Gleason 7 T1, treatment is more of a judgment call, depending on patient preference and other clinical findings, such as the number of positive biopsy cores and comorbidities. 

  • 358.
    von Below, Catrin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wassberg, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Norberg, Mona
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Tolf, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Ladjevardi, Sam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Additional value of magnetic resonance targeted biopsies to standard transrectal ultrasound guided biopsies for detection of clinical significant prostate cancerManuskript (preprint) (Övrigt vetenskapligt)
  • 359.
    von Below, Catrin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wassberg, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Norberg, Mona
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Tolf, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Ladjevardi, Sam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Additional value of magnetic resonance-targeted biopsies to standard transrectal ultrasound-guided biopsies for detection of clinically significant prostate cancer2017Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, nr 2, s. 107-113Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: The aim of this study was to evaluate the additional value of magnetic resonance imaging-targeted biopsy (MRI-TB) to standard transrectal ultrasound-guided biopsy (SB) for detection of clinically significant prostate cancer (PCa). An additional aim was to compare the biopsy results to MRI evaluation using a Likert scale.

    MATERIALS AND METHODS: Patients with newly diagnosed localized PCa (n = 53) by clinical routine SB were prospectively included. The majority of the patients were scheduled for curative therapy before enrollment. The patients underwent multiparametric MRI (mpMRI) at 3 T using an endorectal coil followed by two MRI-TBs, using ultrasound with cognitive fusion. All included patients underwent MRI-TB, even those who had low to very low suspicion of significant PCa on mpMRI. The detection rate of significant cancer on SB versus SB + MRI-TB was compared in the 53 included patients and with whole-mounted histopathology as reference in 34 cases. Comparison of the biopsy results to MRI evaluation and interreader agreement calculation of five-point Likert score evaluation were performed.

    RESULTS: In total, 32 significant (Gleason ≥7) PCa were detected by SB, while SB + MRI-TB detected an additional five significant PCa. MRI-TB alone detected 20 and missed 17 significant PCa. Ten of the significant PCa cases missed by MRI-TB had a Likert score of 3 or lower. Interreader agreement using the Likert scale was high, with a kappa value of 0.77 (95% confidence interval 0.63-0.92, p < 0.0001).

    CONCLUSION: Detection of significant PCa increased by adding MRI-TB to SB. This may not be of enough clinical value to justify the use of targeted biopsies in this patient group.

  • 360.
    Wadström, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Laparoscopic nephropexy exposes a possible underlying pathogenic mechanism and allows successful treatment with tissue gluing of the kidney and fixation of the colon to the lateral abdominal wall2010Ingår i: International Brazilian journal of urology : official journal of the Brazilian Society of Urology, ISSN 1677-5538, Vol. 36, nr 1, s. 10-17Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Surgical treatment of "Ren Mobilis" has historically been associated with poor results and fairly high morbidity. We have used a transperitoneal laparoscopic approach in order to minimize morbidity. The goal of this study was to evaluate the success rate and to discuss the possible pathogenic mechanism, which has implications for the surgical strategy. MATERIALS AND METHODS: Seven women with a right mobile kidney were examined by intravenous pyelogram and CT scans. Symptoms were judged to emanate from the mobile kidney. Transperitoneal laparoscopic nephropexy was performed. The surgical treatment consisted of fixing the kidney to the dorsal abdominal wall using tissue glue (Tisseel) after diathermy coagulation of the surfaces to induce fibrosis. The right colon was fixed with clips to the lateral abdominal wall, trapping the kidney in place. RESULTS: In 6 of the cases, there was an incomplete rotation of the ascending colon to the right side, allowing the kidney to move freely. In one case, the kidney moved into a retroperitoneal pocket of the mesocolon. The 6 cases with a lateral passage for the kidney were symptom-free at follow-up (30-80 months), but in the 7th case the patient's kidney quickly loosened and she underwent an open reoperation, after which she was symptom-free. CONCLUSION: Our series demonstrates that good results can be achieved with a transperitoneal laparoscopic approach, but also indicates that there is a common pathogenic mechanism with incomplete rotation of the ascending colon that can be corrected during surgery, which might contribute to the good results.

  • 361. Wallerstedt, Anna
    et al.
    Carlsson, Stefan
    Nilsson, Andreas E
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Nyberg, Tommy
    Steineck, Gunnar
    Wiklund, N Peter
    Pad use and patient reported bother from urinary leakage after radical prostatectomy2012Ingår i: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 187, nr 1, s. 196-200Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE:

    To better understand clinically significant definitions of urinary incontinence we investigated the relationship between urinary leakage and patient reported bother from urinary leakage.

    MATERIALS AND METHODS:

    A consecutive series of 1,411 men who underwent radical prostatectomy at Karolinska University Hospital, Stockholm, Sweden, from 2002 to 2006 were invited to complete a study specific questionnaire with questions on pad status, urinary leakage and bother from urinary leakage.

    RESULTS:

    Questionnaires were received from 1,179 men with a followup of greater than 1 year (median 2.2). Results showed that even a small amount of urinary leakage resulted in a high risk of urinary bother. Of 775 survivors 46 (6%) reporting 0 pads indicated moderate or much bother compared to 38 of 123 (31%) who reported using a security pad. When comparing the 2 groups, the risk of bother from urinary leakage was more than 5 times higher in the safety pad vs the 0 pad group (RR 5.2, 95% CI 3.5-7.7). As the number of pads increased, we noted a higher bother risk. Cross-tabulation of pad use and urinary leakage revealed wide variation in pad requirements despite the same answer to urinary leakage questions.

    CONCLUSIONS:

    If the definition of continence is based on pad use, for example safety pads, a certain number of men who report moderate or much bother from urinary leakage will be defined as continent. Our results also show that for each stated rate of urinary leakage men prove to have a major variation in the pad requirement.

  • 362. Wang, Zhaoming
    et al.
    Zhu, Bin
    Zhang, Mingfeng
    Parikh, Hemang
    Jia, Jinping
    Chung, Charles C
    Sampson, Joshua N
    Hoskins, Jason W
    Hutchinson, Amy
    Burdette, Laurie
    Ibrahim, Abdisamad
    Hautman, Christopher
    Raj, Preethi S
    Abnet, Christian C
    Adjei, Andrew A
    Ahlbom, Anders
    Albanes, Demetrius
    Allen, Naomi E
    Ambrosone, Christine B
    Aldrich, Melinda
    Amiano, Pilar
    Amos, Christopher
    Andersson, Ulrika
    Andriole, Gerald
    Andrulis, Irene L
    Arici, Cecilia
    Arslan, Alan A
    Austin, Melissa A
    Baris, Dalsu
    Barkauskas, Donald A
    Bassig, Bryan A
    Beane Freeman, Laura E
    Berg, Christine D
    Berndt, Sonja I
    Bertazzi, Pier Alberto
    Biritwum, Richard B
    Black, Amanda
    Blot, William
    Boeing, Heiner
    Boffetta, Paolo
    Bolton, Kelly
    Boutron-Ruault, Marie-Christine
    Bracci, Paige M
    Brennan, Paul
    Brinton, Louise A
    Brotzman, Michelle
    Bueno-de-Mesquita, H Bas
    Buring, Julie E
    Butler, Mary Ann
    Cai, Qiuyin
    Cancel-Tassin, Geraldine
    Canzian, Federico
    Cao, Guangwen
    Caporaso, Neil E
    Carrato, Alfredo
    Carreon, Tania
    Carta, Angela
    Chang, Gee-Chen
    Chang, I-Shou
    Chang-Claude, Jenny
    Che, Xu
    Chen, Chien-Jen
    Chen, Chih-Yi
    Chen, Chung-Hsing
    Chen, Constance
    Chen, Kuan-Yu
    Chen, Yuh-Min
    Chokkalingam, Anand P
    Chu, Lisa W
    Clavel-Chapelon, Francoise
    Colditz, Graham A
    Colt, Joanne S
    Conti, David
    Cook, Michael B
    Cortessis, Victoria K
    Crawford, E David
    Cussenot, Olivier
    Davis, Faith G
    De Vivo, Immaculata
    Deng, Xiang
    Ding, Ti
    Dinney, Colin P
    Di Stefano, Anna Luisa
    Diver, W Ryan
    Duell, Eric J
    Elena, Joanne W
    Fan, Jin-Hu
    Feigelson, Heather Spencer
    Feychting, Maria
    Figueroa, Jonine D
    Flanagan, Adrienne M
    Fraumeni, Joseph F
    Freedman, Neal D
    Fridley, Brooke L
    Fuchs, Charles S
    Gago-Dominguez, Manuela
    Gallinger, Steven
    Gao, Yu-Tang
    Gapstur, Susan M
    Garcia-Closas, Montserrat
    Garcia-Closas, Reina
    Gastier-Foster, Julie M
    Gaziano, J Michael
    Gerhard, Daniela S
    Giffen, Carol A
    Giles, Graham G
    Gillanders, Elizabeth M
    Giovannucci, Edward L
    Goggins, Michael
    Gokgoz, Nalan
    Goldstein, Alisa M
    Gonzalez, Carlos
    Gorlick, Richard
    Greene, Mark H
    Gross, Myron
    Grossman, H Barton
    Grubb, Robert
    Gu, Jian
    Guan, Peng
    Haiman, Christopher A
    Hallmans, Goran
    Hankinson, Susan E
    Harris, Curtis C
    Hartge, Patricia
    Hattinger, Claudia
    Hayes, Richard B
    He, Qincheng
    Helman, Lee
    Henderson, Brian E
    Henriksson, Roger
    Hoffman-Bolton, Judith
    Hohensee, Chancellor
    Holly, Elizabeth A
    Hong, Yun-Chul
    Hoover, Robert N
    Hosgood, H Dean
    Hsiao, Chin-Fu
    Hsing, Ann W
    Hsiung, Chao Agnes
    Hu, Nan
    Hu, Wei
    Hu, Zhibin
    Huang, Ming-Shyan
    Hunter, David J
    Inskip, Peter D
    Ito, Hidemi
    Jacobs, Eric J
    Jacobs, Kevin B
    Jenab, Mazda
    Ji, Bu-Tian
    Johansen, Christoffer
    Johansson, Mattias
    Johnson, Alison
    Kaaks, Rudolf
    Kamat, Ashish M
    Kamineni, Aruna
    Karagas, Margaret
    Khanna, Chand
    Khaw, Kay-Tee
    Kim, Christopher
    Kim, In-Sam
    Kim, Jin Hee
    Kim, Yeul Hong
    Kim, Young-Chul
    Kim, Young Tae
    Kang, Chang Hyun
    Jung, Yoo Jin
    Kitahara, Cari M
    Klein, Alison P
    Klein, Robert
    Kogevinas, Manolis
    Koh, Woon-Puay
    Kohno, Takashi
    Kolonel, Laurence N
    Kooperberg, Charles
    Kratz, Christian P
    Krogh, Vittorio
    Kunitoh, Hideo
    Kurtz, Robert C
    Kurucu, Nilgun
    Lan, Qing
    Lathrop, Mark
    Lau, Ching C
    Lecanda, Fernando
    Lee, Kyoung-Mu
    Lee, Maxwell P
    Le Marchand, Loic
    Lerner, Seth P
    Li, Donghui
    Liao, Linda M
    Lim, Wei-Yen
    Lin, Dongxin
    Lin, Jie
    Lindstrom, Sara
    Linet, Martha S
    Lissowska, Jolanta
    Liu, Jianjun
    Ljungberg, Börje
    Lloreta, Josep
    Lu, Daru
    Ma, Jing
    Malats, Nuria
    Mannisto, Satu
    Marina, Neyssa
    Mastrangelo, Giuseppe
    Matsuo, Keitaro
    McGlynn, Katherine A
    McKean-Cowdin, Roberta
    McNeill, Lorna H
    McWilliams, Robert R
    Melin, Beatrice S
    Meltzer, Paul S
    Mensah, James E
    Miao, Xiaoping
    Michaud, Dominique S
    Mondul, Alison M
    Moore, Lee E
    Muir, Kenneth
    Niwa, Shelley
    Olson, Sara H
    Orr, Nick
    Panico, Salvatore
    Park, Jae Yong
    Patel, Alpa V
    Patino-Garcia, Ana
    Pavanello, Sofia
    Peeters, Petra H M
    Peplonska, Beata
    Peters, Ulrike
    Petersen, Gloria M
    Picci, Piero
    Pike, Malcolm C
    Porru, Stefano
    Prescott, Jennifer
    Pu, Xia
    Purdue, Mark P
    Qiao, You-Lin
    Rajaraman, Preetha
    Riboli, Elio
    Risch, Harvey A
    Rodabough, Rebecca J
    Rothman, Nathaniel
    Ruder, Avima M
    Ryu, Jeong-Seon
    Sanson, Marc
    Schned, Alan
    Schumacher, Fredrick R
    Schwartz, Ann G
    Schwartz, Kendra L
    Schwenn, Molly
    Scotlandi, Katia
    Seow, Adeline
    Serra, Consol
    Serra, Massimo
    Sesso, Howard D
    Severi, Gianluca
    Shen, Hongbing
    Shen, Min
    Shete, Sanjay
    Shiraishi, Kouya
    Shu, Xiao-Ou
    Siddiq, Afshan
    Sierrasesumaga, Luis
    Sierri, Sabina
    Loon Sihoe, Alan Dart
    Silverman, Debra T
    Simon, Matthias
    Southey, Melissa C
    Spector, Logan
    Spitz, Margaret
    Stampfer, Meir
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stern, Mariana C
    Stevens, Victoria L
    Stolzenberg-Solomon, Rachael Z
    Stram, Daniel O
    Strom, Sara S
    Su, Wu-Chou
    Sund, Malin
    Sung, Sook Whan
    Swerdlow, Anthony
    Tan, Wen
    Tanaka, Hideo
    Tang, Wei
    Tang, Ze-Zhang
    Tardon, Adonina
    Tay, Evelyn
    Taylor, Philip R
    Tettey, Yao
    Thomas, David M
    Tirabosco, Roberto
    Tjonneland, Anne
    Tobias, Geoffrey S
    Toro, Jorge R
    Travis, Ruth C
    Trichopoulos, Dimitrios
    Troisi, Rebecca
    Truelove, Ann
    Tsai, Ying-Huang
    Tucker, Margaret A
    Tumino, Rosario
    Van Den Berg, David
    Van Den Eeden, Stephen K
    Vermeulen, Roel
    Vineis, Paolo
    Visvanathan, Kala
    Vogel, Ulla
    Wang, Chaoyu
    Wang, Chengfeng
    Wang, Junwen
    Wang, Sophia S
    Weiderpass, Elisabete
    Weinstein, Stephanie J
    Wentzensen, Nicolas
    Wheeler, William
    White, Emily
    Wiencke, John K
    Wolk, Alicja
    Wolpin, Brian M
    Wong, Maria Pik
    Wrensch, Margaret
    Wu, Chen
    Wu, Tangchun
    Wu, Xifeng
    Wu, Yi-Long
    Wunder, Jay S
    Xiang, Yong-Bing
    Xu, Jun
    Yang, Hannah P
    Yang, Pan-Chyr
    Yatabe, Yasushi
    Ye, Yuanqing
    Yeboah, Edward D
    Yin, Zhihua
    Ying, Chen
    Yu, Chong-Jen
    Yu, Kai
    Yuan, Jian-Min
    Zanetti, Krista A
    Zeleniuch-Jacquotte, Anne
    Zheng, Wei
    Zhou, Baosen
    Mirabello, Lisa
    Savage, Sharon A
    Kraft, Peter
    Chanock, Stephen J
    Yeager, Meredith
    Landi, Maria Terese
    Shi, Jianxin
    Chatterjee, Nilanjan
    Amundadottir, Laufey T
    Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.332014Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 23, nr 24, s. 6616-6633Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

  • 363. Watts, Eleanor L
    et al.
    Appleby, Paul N
    Albanes, Demetrius
    Black, Amanda
    Chan, June M
    Chen, Chu
    Cirillo, Piera M
    Cohn, Barbara A
    Cook, Michael B
    Donovan, Jenny L
    Ferrucci, Luigi
    Garland, Cedric F
    Giles, Graham G
    Goodman, Phyllis J
    Habel, Laurel A
    Haiman, Christopher A
    Holly, Jeff M P
    Hoover, Robert N
    Kaaks, Rudolf
    Knekt, Paul
    Kolonel, Laurence N
    Kubo, Tatsuhiko
    Le Marchand, Loïc
    Luostarinen, Tapio
    MacInnis, Robert J
    Mäenpää, Hanna O
    Männistö, Satu
    Metter, E Jeffrey
    Milne, Roger L
    Nomura, Abraham M Y
    Oliver, Steven E
    Parsons, J Kellogg
    Peeters, Petra H
    Platz, Elizabeth A
    Riboli, Elio
    Ricceri, Fulvio
    Rinaldi, Sabina
    Rissanen, Harri
    Sawada, Norie
    Schaefer, Catherine A
    Schenk, Jeannette M
    Stanczyk, Frank Z
    Stampfer, Meir
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stenman, Ulf-Håkan
    Tjønneland, Anne
    Trichopoulou, Antonia
    Thompson, Ian M
    Tsugane, Shoichiro
    Vatten, Lars
    Whittemore, Alice S
    Ziegler, Regina G
    Allen, Naomi E
    Key, Timothy J
    Travis, Ruth C
    Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men.2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 12, artikel-id e0187741Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin.

    METHODS: Statistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates.

    RESULTS: Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones.

    CONCLUSION: Circulating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.

  • 364.
    Watts, Eleanor L.
    et al.
    Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford OX3 7LF, England.
    Appleby, Paul N.
    Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford OX3 7LF, England.
    Perez-Cornago, Aurora
    Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford OX3 7LF, England.
    Bueno-de-Mesquita, H. Bas
    Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis, Bilthoven, Netherlands;Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands;Imperial Coll London, Dept Epidemiol & Biostat, London, England;Univ Malaya, Dept Social & Prevent Med, Kuala Lumpur, Malaysia.
    Chan, June M.
    Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA;Univ Calif San Francisco, Dept Urol, San Francisco, CA USA.
    Chen, Chu
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA.
    Cohn, Barbara A.
    Publ Hlth Inst, Child Hlth & Dev Studies, Berkeley, CA USA.
    Cook, Michael B.
    US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
    Flicker, Leon
    Univ Western Australia, Sch Med, Perth, WA, Australia;Univ Western Australia, Med Res Ctr, Western Australian Ctr Hlth & Ageing, Perth, WA, Australia.
    Freedman, Neal D.
    US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
    Giles, Graham G.
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia;Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
    Giovannucci, Edward
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA;Publ Hlth Directorate, Asturias, Spain;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
    Gislefoss, Randi E.
    Inst Epidemiol Canc Res, Canc Registry Norway, Oslo, Norway.
    Hankey, Graeme J.
    Univ Western Australia, Sch Med, Perth, WA, Australia.
    Kaaks, Rudolf
    German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
    Knekt, Paul
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Kolonel, Laurence N.
    Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
    Kubo, Tatsuhiko
    Univ Occupat & Environm Hlth, Dept Prevent Med & Community Hlth, Kitakyushu, Fukuoka, Japan.
    Le Marchand, Loic
    Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
    Luben, Robert N.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge, England.
    Luostarinen, Tapio
    Inst Stat & Epidemiol Canc Res, Finnish Canc Registry, Helsinki, Finland.
    Mannisto, Satu
    Natl Inst Hlth & Welf, Dept Publ Hlth Solut, Helsinki, Finland.
    Metter, E. Jeffrey
    Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA.
    Mikami, Kazuya
    Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Urol, Kyoto, Japan.
    Milne, Roger L.
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia;Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
    Ozasa, Kotaro
    Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima, Japan.
    Platz, Elizabeth A.
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Quiros, J. Ramon
    Publ Hlth Directorate, Asturias, Spain.
    Rissanen, Harri
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Sawada, Norie
    Natl Canc Ctr, Epidemiol & Prevent Grp, Ctr Publ Hlth Sci, Tokyo, Japan.
    Stampfer, Meir
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA;Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Stanczyk, Frank Z.
    Univ Southern Calif, Keck Sch Med, Div Reprod Endocrinol & Infertil, Los Angeles, CA USA.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Tamakoshi, Akiko
    Hokkaido Univ, Grad Sch Med, Dept Publ Hlth, Sapporo, Hokkaido, Japan.
    Tangen, Catherine M.
    Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1124 Columbia St, Seattle, WA 98104 USA;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA.
    Thompson, Ian M.
    Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA.
    Tsilidis, Konstantinos K.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina, Greece.
    Tsugane, Shoichiro
    Natl Canc Ctr, Epidemiol & Prevent Grp, Ctr Publ Hlth Sci, Tokyo, Japan.
    Ursin, Giske
    Inst Epidemiol Canc Res, Canc Registry Norway, Oslo, Norway;Univ Oslo, Inst Basic Med Sci, Dept Nutr, Oslo, Norway;Univ Southern Calif, Dept Prevent Med, Los Angeles, CA USA.
    Vatten, Lars
    Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth, Trondheim, Norway.
    Weiss, Noel S.
    Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
    Yeap, Bu B.
    Univ Western Australia, Sch Med, Perth, WA, Australia;Fiona Stanley Hosp, Dept Endocrinol & Diabet, Perth, WA, Australia.
    Allen, Naomi E.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England.
    Key, Timothy J.
    Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford OX3 7LF, England.
    Travis, Ruth C.
    Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford OX3 7LF, England.
    Low Free Testosterone and Prostate Cancer Risk: A Collaborative Analysis of 20 Prospective Studies2018Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 74, nr 5, s. 585-594Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting. Objective: To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer. Design, setting, and participants: Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group. Outcome measurements and statistical analysis: Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration. Results and limitations: Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR = 0.77, 95% confidence interval [CI] 0.69-0.86; p < 0.001) compared with men with higher concentrations (2nd-10th tenths of the distribution). Heterogeneity was present by tumour grade (p(het) = 0.01), with a lower risk of low-grade disease (OR = 0.76, 95% CI 0.67-0.88) and a nonsignificantly higher risk of high-grade disease (OR = 1.56, 95% CI 0.95-2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation. Conclusions: Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade. Patient summary: In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer. (c) 2018 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology.

  • 365.
    Watts, Eleanor L.
    et al.
    Univ Oxford, Canc Epidemiol Unit, Nuffield Dept Populat Hlth, Oxford OX3 7LF, England.
    Perez-Cornago, Aurora
    Univ Oxford, Canc Epidemiol Unit, Nuffield Dept Populat Hlth, Oxford OX3 7LF, England.
    Appleby, Paul N.
    Univ Oxford, Canc Epidemiol Unit, Nuffield Dept Populat Hlth, Oxford OX3 7LF, England.
    Albanes, Demetrius
    NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA.
    Ardanaz, Eva
    Navarra Publ Hlth Inst, Pamplona, Spain.
    Black, Amanda
    NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA.
    Bueno-de-Mesquita, H. Bas
    Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis, Bilthoven, Netherlands;Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands;Imperial Coll London, Dept Epidemiol & Biostat, London, England;Univ Malaya, Dept Social & Prevent Med, Kuala Lumpur, Malaysia.
    Chan, June M.
    Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA;Univ Calif San Francisco, Dept Urol, San Francisco, CA USA.
    Chen, Chu
    Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA.
    Chubb, S. A. Paul
    Fiona Stanley Hosp, PathWest Lab Med, Perth, WA, Australia;Univ Western Australia, Med Sch, Perth, WA, Australia.
    Cook, Michael B.
    NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA.
    Deschasaux, Melanie
    Paris 13 Univ, Sorbonne Paris Cite Epidemiol & Stat Res Ctr CRES, Nutr Epidemiol Res Team EREN, Inserm,U1153,Inra,U1125,Cnam, Paris, France.
    Donovan, Jenny L.
    Univ Bristol, Dept Populat Hlth Sci, Bristol Med Sch, Bristol, Avon, England.
    English, Dallas R.
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia;Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia.
    Flicker, Leon
    Univ Western Australia, Med Sch, Perth, WA, Australia;Harry Perkins Inst Med Res, WA Ctr Hlth & Ageing, Med Res Ctr, Perth, WA, Australia;Royal Perth Hosp, Dept Geriatr Med, Perth, WA, Australia.
    Freedman, Neal D.
    NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA.
    Galan, Pilar
    Paris 13 Univ, Sorbonne Paris Cite Epidemiol & Stat Res Ctr CRES, Nutr Epidemiol Res Team EREN, Inserm,U1153,Inra,U1125,Cnam, Paris, France.
    Giles, Graham G.
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia;Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia.
    Giovannucci, Edward L.
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
    Gunter, Marc J.
    Int Agcy Res Canc, Sect Nutr & Metab, Lyon, France.
    Habel, Laurel A.
    Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA.
    Häggström, Christel
    Umea Univ, Dept Biobank Res, Umea, Sweden.
    Haiman, Christopher
    Univ Southern Calif, Keck Sch Med, Los Angeles, CA USA.
    Hamdy, Freddie C.
    Univ Oxford, Nuffield Dept Surg, Oxford, England.
    Hercberg, Serge
    Paris 13 Univ, Sorbonne Paris Cite Epidemiol & Stat Res Ctr CRES, Nutr Epidemiol Res Team EREN, Inserm,U1153,Inra,U1125,Cnam, Paris, France.
    Holly, Jeff M.
    Univ Bristol, IGFs & Metab Endocrinol Grp, Translat Hlth Sci, Bristol Med Sch,Fac Hlth Sci, Bristol, Avon, England.
    Huang, Jiaqi
    NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA.
    Huang, Wen-Yi
    NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA.
    Johansson, Mattias
    Int Agcy Res Canc, Genet Epidemiol Grp, Lyon, France.
    Kaaks, Rudolf
    German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
    Kubo, Tatsuhiko
    Univ Occupat & Environm Hlth, Dept Environm Epidemiol, Kitakyushu, Fukuoka, Japan.
    Lane, J. Athene
    Univ Bristol, Dept Populat Hlth Sci, Bristol Med Sch, Bristol, Avon, England;Natl Inst Hlth Res Bristol Biomed Res Unit Nutr, Bristol, Avon, England.
    Layne, Tracy M.
    Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
    Le Marchand, Loic
    Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
    Martin, Richard M.
    Univ Bristol, Dept Populat Hlth Sci, Bristol Med Sch, Bristol, Avon, England;Natl Inst Hlth Res Bristol Biomed Res Unit Nutr, Bristol, Avon, England;Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol, Avon, England.
    Metter, E. Jeffrey
    Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA.
    Mikami, Kazuya
    Japanese Red Cross Kyoto Daiichi Hosp, Kyoto, Japan.
    Milne, Roger L.
    Canc Council Victoria, Canc Epidemiol & Intelligence Div, Melbourne, Vic, Australia;Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia.
    Morris, Howard A.
    SA Pathol, Chem Pathol Directorate, Adelaide, SA, Australia.
    Mucci, Lorelei A.
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA 02115 USA.
    Neal, David E.
    Univ Oxford, Nuffield Dept Surg, Oxford, England.
    Neuhouser, Marian L.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA.
    Oliver, Steven E.
    Univ York, Dept Hlth Sci, York, N Yorkshire, England;Hull York Med Sch, York, N Yorkshire, England.
    Overvad, Kim
    Aarhus Univ, Dept Publ Hlth, Epidemiol Sect, Aarhus, Denmark.
    Ozasa, Kotaro
    Radiat Effects Res Fdn, Hiroshima, Japan.
    Pala, Valeria
    Fdn IRCCS Ist Nazl Tumori Milano, Epidemiol & Prevent Unit, Milan, Italy.
    Pernar, Claire H.
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
    Pollak, Michael
    McGill Univ, Dept Med & Oncol, Montreal, PQ, Canada;Jewish Gen Hosp, Segal Canc Ctr, Montreal, PQ, Canada.
    Rowlands, Mari-Anne
    Univ Bristol, Dept Populat Hlth Sci, Bristol Med Sch, Bristol, Avon, England.
    Schaefer, Catherine A.
    Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA.
    Schenk, Jeannette M.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Tamakoshi, Akiko
    Hokkaido Univ, Fac Med, Sapporo, Hokkaido, Japan.
    Thysell, Elin
    Umea Univ, Dept Med Biosci & Pathol, Umea, Sweden.
    Touvier, Mathilde
    Paris 13 Univ, Sorbonne Paris Cite Epidemiol & Stat Res Ctr CRES, Nutr Epidemiol Res Team EREN, Inserm,U1153,Inra,U1125,Cnam, Paris, France.
    Trichopoulou, Antonia
    Hellen Hlth Fdn, Athens, Greece.
    Tsilidis, Konstantinos K.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina, Greece.
    Van Den Eeden, Stephen K.
    Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA.
    Weinstein, Stephanie J.
    NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA.
    Wilkens, Lynne
    Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
    Yeap, Bu B.
    Univ Western Australia, Med Sch, Perth, WA, Australia;Fiona Stanley Hosp, Dept Endocrinol & Diabet, Perth, WA, Australia.
    Key, Timothy J.
    Univ Oxford, Canc Epidemiol Unit, Nuffield Dept Populat Hlth, Oxford OX3 7LF, England.
    Allen, Naomi E.
    Univ Oxford, Clin Trial Serv Unit, Nuffield Dept Populat Hlth, Oxford, England;Univ Oxford, Epidemiol Studies Unit, Nuffield Dept Populat Hlth, Oxford, England.
    Travis, Ruth C.
    Univ Oxford, Canc Epidemiol Unit, Nuffield Dept Populat Hlth, Oxford OX3 7LF, England.
    The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 in a pooled analysis of 16,024 men from 22 studies2019Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 145, nr 12, s. 3244-3256Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Insulin-like growth factors (IGFs) and insulin-like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22-89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGF-I, IGF-II and IGFBP-3. Higher body mass index was associated with lower concentrations of IGFBP-1 and IGFBP-2. Taller height was associated with higher concentrations of IGF-I and IGFBP-3 and lower concentrations of IGFBP-1. Smokers had higher concentrations of IGFBP-1 and IGFBP-2 and lower concentrations of IGFBP-3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF-II and lower concentrations of IGF-I and IGFBP-2. African Americans had lower concentrations of IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 and Hispanics had lower IGF-I, IGF-II and IGFBP-3 than non-Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.

  • 366.
    Weis, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Hlavcak, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Häggman, Mikael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Ortiz-Nieto, Francisco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Bergman, Antonina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Two-dimensional spectroscopic imaging for pretreatment evaluation of prostate cancer: comparison with the step-section histology after radical prostatectomy2009Ingår i: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 27, nr 1, s. 87-93Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To minimize user and vendor dependence of the spectrum processing of prostate spectra, to measure the ratio of choline (Cho) plus creatine (Cr) to citrate (Cit) in the prostate tissue of normal volunteers and cancer patients, and to compare the results with pathologic findings after radical prostatectomy. MATERIALS AND METHODS: Four healthy volunteers and 13 patients with prostate cancer were measured. Measurements were performed using two-dimensional magnetic resonance spectroscopic imaging (MRSI) and endorectal coil. A standard vendor's spectrum processing approach has been modified. An original feature of this methodology was the combination of vendor-optimized and user-independent spectrum preprocessing in the scanner and user-independent quantitation in the environment of an MRUI software package. (Cho+Cr)/Cit ratio was used for the classification of prostate tissue. Results were compared with histopathology after radical prostatectomy. RESULTS: Eight of 13 cancer patients were classified as suspicious or very suspicious for cancer at spectroscopy, three were ambiguous for cancer and two patients were evaluated as false negative. A considerable overlap of metabolite ratios at various Gleason score was found. CONCLUSION: The proposed spectrum processing has the potential to improve the accuracy and user independency of the (Cho+Cr)/Cit quantitation. This study confirmed the previous results that a considerable overlap of (Cho+Cr)/Cit ratios exists at various Gleason score levels.

  • 367.
    Weis, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Jorulf, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Bergman, Antonina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ortiz-Nieto, Francisco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    MR spectroscopy of the human prostate using surface coil at 3 T: Metabolite ratios, age-dependent effects, and diagnostic possibilities2011Ingår i: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 34, nr 6, s. 1277-1284Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE:

    To measure prostate spectra of healthy volunteers using a surface coil, to demonstrate age-dependent effects, and to investigate diagnostic possibilities for prostate cancer detection.

    MATERIALS AND METHODS:

    Single-voxel and 2D magnetic resonance spectroscopic imaging (MRSI) spectra of 51 healthy volunteers with biopsy-proven prostate carcinoma of 20 patients for comparison were measured and processed using the LCModel. The mean normalized spectra and mean metabolite-to-citrate intensity ratios were computed.

    RESULTS:

    Metabolite-to-citrate ratios of healthy volunteers were lower in the older group (>51 years) than in the younger group (<45 years). The peripheral zone (PZ) revealed a lower metabolite-to-citrate intensity ratio than the central gland (CG). Age-related differences in metabolite-to-citrate ratio were insignificant in the voxels with predominantly CG tissue, whereas significant differences were found in the PZ. Sensitivity in detecting prostate cancer by single-voxel spectroscopy (SVS) and 2D MRSI was 75% and 80%, respectively.

    CONCLUSION:

    SVS and 2D MRSI of the prostate at 3 T, using a surface coil, are useful in situations when insertion of the endorectal coil into the rectum is difficult or impossible. Our findings of age-dependent effects may be of importance for the analysis of patient spectra.

  • 368.
    Weis, Jan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    von Below, Catrin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Tolf, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Ortiz-Nieto, Francisco
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Wassberg, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Haggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Ladjevardi, Sam
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Quantification of metabolite concentrations in benign and malignant prostate tissues using 3D proton MR spectroscopic imaging2017Ingår i: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 45, nr 4, s. 1232-1240Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: To estimate concentrations of choline (Cho), spermine (Spm), and citrate (Cit) in prostate tissue using 3D proton magnetic resonance spectroscopic imaging (MRSI) with water as an internal concentration reference as well as to assess the relationships between the measured metabolites and also between the metabolites and apparent diffusion coefficient (ADC).

    MATERIALS AND METHODS: Forty-six prostate cancer patients were scanned at 3T. Spectra were acquired with the point-resolved spectroscopy (PRESS) localization technique. Single-voxel spectra of four healthy volunteers were used to estimate T1 relaxation time of Spm. Spm, Cho concentrations, and ADC values of benign prostate tissues were correlated with Cit content.

    RESULTS: The T1 value, 708 ± 132 msec, was estimated for Spm. Mean concentrations in the benign peripheral zone (PZ) were Cho, 4.5 ± 1 mM, Spm, 13.0 ± 4.4 mM, Cit, 64.4 ± 16.1 mM. Corresponding values in the benign central gland (CG) were Cho, 3.6 ± 1 mM, Spm, 13.3 ± 4.5 mM, Cit, 34.3 ± 12.9 mM. Concentrations of Cit and Spm were positively correlated in the benign PZ zone (r = 0.730) and CG (r = 0.664). Positive correlation was found between Cit and Cho in the benign CG (r = 0.705). Whereas Cit and ADC were positively correlated in the benign PZ (r = 0.673), only low correlation was found in CG (r = 0.265).

    CONCLUSION: We have shown that it is possible to perform water-referenced quantitative 3D MRSI of the prostate at the cost of a relatively short prolongation of the acquisition time. The individual metabolite concentrations provide additional information compared to the previously used metabolite-to-citrate ratios.

  • 369.
    Wester, Kenneth
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Sjöström, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    de la Torre, Manuel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Carlsson, Jörgen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    HER-2: A possible target for therapy of metastatic urinary bladder carcinoma2002Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 41, nr 3, s. 282-288Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human epidermal growth factor receptor 2, HER-2, is overexpressed in various tumours, e.g. breast- and bladder tumours. The aim of this study was to predict the potential use of HER-2 receptors as targets in systemic treatment of disseminated bladder tumours. HER-2 expression was assessed in bladder carcinoma metastases and the corresponding primary tumours, and subsequently compared with the EGFR expression. HER-2 and EGFR expression was analysed by immunohistochemistry in formalin-fixed, paraffin-embedded tissues from 21 patients with metastatic bladder carcinoma. HER-2 was overexpressed in 81% of the primary tumours and in 67% of the metastases. All HER-2-positive metastases were from HER-2-positive primary tumours. The results for EG FR were 71% of both primary and metastases-positive tumours. In 90% of the primary tumours and 86% of the metastases, at least one of the receptors was overexpressed. These results suggest that HER-2 targeted therapy can be considered as an alternative or a complement to other modalities in the treatment of metastatic urinary bladder carcinoma.

  • 370. Wilson, Kathryn M
    et al.
    Markt, Sarah C
    Fang, Fang
    Nordenvall, Caroline
    Rider, Jennifer R
    Ye, Weimin
    Adami, Hans-Olov
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Nyrén, Olof
    Mucci, Lorelei A
    Snus use, smoking and survival among prostate cancer patients.2016Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 139, nr 12, s. 2753-2759Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Smoking is associated with prostate cancer mortality. The Scandinavian smokeless tobacco product snus is a source of nicotine but not the combustion products of smoke and has not been studied with respect to prostate cancer survival. The study is nested among 9,582 men with incident prostate cancer within a prospective cohort of 336,381 Swedish construction workers. Information on tobacco use was collected at study entry between 1971 and 1992, and categorized into (i) never users of any tobacco, (ii) exclusive snus: ever users of snus only, (iii) exclusive smokers: ever smokers (cigarette, cigar and/or pipe) only and (iv) ever users of both snus and smoking. Hazard ratios for prostate cancer-specific and total mortality for smoking and snus use based on Cox proportional hazards models adjusted for age, calendar period at diagnosis and body mass index at baseline. During 36 years of follow-up, 4,758 patients died-2,489 due to prostate cancer. Compared to never users of tobacco, exclusive smokers were at increased risk of prostate cancer mortality (HR 1.15, 95% CI: 1.05-1.27) and total mortality (HR 1.17, 95% CI: 1.09-1.26). Exclusive snus users also had increased risks for prostate cancer mortality (HR 1.24, 95% CI: 1.03-1.49) and total mortality (HR 1.19, 95% CI: 1.04-1.37). Among men diagnosed with nonmetastatic disease, the HR for prostate cancer death among exclusive snus users was 3.17 (95% CI: 1.66-6.06). The study is limited by a single assessment of tobacco use prior to diagnosis. Snus use was associated with increased risks of prostate cancer and total mortality among prostate cancer patients. This suggests that tobacco-related components such as nicotine or tobacco-specific carcinogens may promote cancer progression independent of tobacco's combustion products.

  • 371.
    Winerdal, Malin E.
    et al.
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Krantz, David
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Hartana, Ciputra A.
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Zirakzadeh, Ali A.
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Linton, Ludvig
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Bergman, Emma A.
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Rosenblatt, Robert
    Umeå Univ, Dept Surg & Perioperat Sci Urol & Androl, Umeå, Sweden; Karolinska Inst, Stockholm South Gen Hosp, Dept Urol, Stockholm, Sweden.
    Vasko, Janos
    Umeå Univ, Dept Med Biosci, Pathol, Umeå, Sweden.
    Alamdari, Farhood
    Vastmanland Hosp, Dept Urol, Vasteras, Sweden.
    Hansson, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Holmström, Benny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Johansson, Markus
    Sundsvall Hosp, Dept Urol, Sundsvall, Sweden.
    Winerdal, Max
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Marits, Per
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Sherif, Amir
    Umeå Univ, Dept Surg & Perioperat Sci Urol & Androl, Umeå, Sweden.
    Winqvist, Ola
    Karolinska Inst, Dept Med, Unit Allergy & Immunol, Stockholm, Sweden.
    Urinary Bladder Cancer Tregs Suppress MMP2 and Potentially Regulate Invasiveness2018Ingår i: CANCER IMMUNOLOGY RESEARCH, ISSN 2326-6066, Vol. 6, nr 5, s. 528-538Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Regulatory T cells (Treg) have long been considered one-sided suppressors of antitumor immune responses and hence associated with poor patient outcome in cancer. However, evidence is mounting of a paradoxical positive prognostic effect of Tregs on certain malignancies, including urinary bladder cancer (UBC). This discrepancy has partly been attributed to the shear misidentification of Tregs, but also to the inflammatory profile of the tumor. Our aim was to determine whether tumor-infiltrating Forkhead box P3+ (FOXP3+) cells confer a stable Treg phenotype and to investigate putative beneficial Treg functions, focusing on tumor-promoting inflammatory pathways in UBC. Patients (n = 52) with suspected UBC were prospectively included. We show, by using a broad range of analytical approaches, that tumor-infiltrating CD4+FOXP3+ T cells in UBC phenotypically, functionally, and epigenetically represent a true Treg population. At the invasive front of UBC tumors, we found an inverse relationship between Treg frequency and expression of matrix metalloproteinase 2 (MMP2), a key proinvasive factor induced by tumor-promoting inflammation. Correspondingly, a significant, dose-dependent Treg-mediated downregulation of MMP2 protein and mRNA expression was observed in both macrophages and UBC cells. Also, we found that Treg frequency specifically at the invasive front positively correlated with survival. Thus, we identify Treg-mediated suppression of MMP2 in the tumor microenvironment as a mechanism explaining the paradoxical positive prognostic impact of tumor-infiltrating Tregs in UBC.

  • 372.
    Wiren, Sara
    et al.
    Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden..
    Drevin, Linda
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Akre, Olof
    Karolinska Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden..
    Robinson, David
    Ryhov Cty Hosp, Dept Urol, Jonkoping, Sweden..
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden..
    Fathering of Dizygotic Twins and Risk of Prostate Cancer: Nationwide, Population-Based Case-Control Study2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 10, artikel-id e110506Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: An association between male fertility and risk of prostate cancer has been suggested, possibly through lower androgen levels in subfertile men. We evaluated male fertility in relation to risk of prostate cancer by assessing the frequency of fathering of dizygotic twins, a marker of high fertility, among cases of prostate cancer and controls. Methods: We performed a case-control study in Prostate Cancer data Base Sweden (PCBaSe), a nationwide, population-based cohort. PCBaSe was linked to the Swedish twin register for information on zygosity for same-sex twins and to other nationwide health care registers and demographic databases for information on socioeconomic factors, comorbidity, and tumor characteristics for 96 301 prostate cancer cases and 378 583 matched controls. To account for the influence of in vitro fertilization on dizygotic twinning, analyses were restricted to men who had fathered children before 1991, when in vitro fertilization was still uncommon in Sweden. Results: 1 112 cases and 4 538 controls had fathered dizygotic twins. Men with dizygotic twins had no increased risk of prostate cancer compared to fathers of singletons; neither for total prostate cancer odds ratio (OR) 0.95(95% CI 0.89-1.02), nor for any risk category, OR 0.97 (95% CI 0.84-1.12) for low-risk disease, and OR 1.04 (95% CI 0.90-1.22) for metastatic disease. Conclusion: The lack of association between fathering of dizygotic twins and prostate cancer risk give no support for an association between male fertility and prostate cancer risk.

  • 373. Wirén, Sara
    et al.
    Häggström, Christel
    Department of Surgery and Perioperative Sciences, Urology and Andrology, Umeå, Sweden.
    Ulmer, Hanno
    Manjer, Jonas
    Bjørge, Tone
    Nagel, Gabriele
    Johansen, Dorthe
    Hallmans, Göran
    Engeland, Anders
    Concin, Hans
    Jonsson, Håkan
    Selmer, Randi
    Tretli, Steinar
    Stocks, Tanja
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Pooled cohort study on height and risk of cancer and cancer death2014Ingår i: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 25, nr 2, s. 151-159Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE:

    To assess the association between height and risk of cancer and cancer death.

    METHODS:

    The metabolic syndrome and cancer project is a prospective pooled cohort study of 585,928 participants from seven cohorts in Austria, Norway, and Sweden. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer incidence and death were estimated in height categories and per 5-cm increment for each cancer site using Cox proportional hazards model.

    RESULTS:

    During a mean follow-up of 12.7 years (SD = 7.2), 38,862 participants were diagnosed with cancer and 13,547 participants died of cancer. Increased height (per 5-cm increment) was associated with an increased overall cancer risk in women, HR 1.07 (95 % CI 1.06-1.09), and in men, HR 1.04 (95 % CI 1.03-1.06). The highest HR was seen for malignant melanoma in women, HR 1.17 (95 % CI 1.11-1.24), and in men HR 1.12 (95 % CI 1.08-1.19). Height was also associated with increased risk of cancer death in women, HR 1.03 (95 % CI 1.01-1.16), and in men, HR 1.03 (95 % CI 1.01-1.05). The highest HR was observed for breast cancer death in postmenopausal women (>60 years), HR 1.10 (95 % CI 1.00-1.21), and death from renal cell carcinoma in men, HR 1.18 (95 % CI 1.07-1.30). All these associations were independent of body mass index.

    CONCLUSION:

    Height was associated with risk of cancer and cancer death indicating that factors related to height such as hormonal and genetic factors stimulate both cancer development and progression.

  • 374. Witjes, J Alfred
    et al.
    Dalbagni, Guido
    Karnes, Robert J
    Shariat, Shahrokh
    Joniau, Steven
    Palou, Joan
    Serretta, Vincenzo
    Larré, Stéphane
    di Stasi, Savino
    Colombo, Renzo
    Babjuk, Marek
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Malats, Nuria
    Irani, Jacques
    Baniel, Jack
    Cai, Tommaso
    Cha, Eugene
    Ardelt, Peter
    Varkarakis, John
    Bartoletti, Riccardo
    Spahn, Martin
    Pisano, Francesca
    Gontero, Paolo
    Sylvester, Richard
    The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer2016Ingår i: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 34, nr 11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Potential differences in efficacy of different bacillus Calmette-Guérin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage.

    OBJECTIVE: To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade non-muscle-invasive bladder cancer patients.

    DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were collected for 2,451 patients with primary T1G3 tumors from 23 centers who were treated with BCG for the first time between 1990 and 2011.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using Cox multivariable regression and adjusting for the most important prognostic factors in this nonrandomized comparison, BCG Connaught and TICE were compared for time to recurrence, progression, and the duration of cancer specific survival and overall survival.

    RESULTS AND LIMITATIONS: Information on the BCG strain was available for 2,099 patients: 957 on Connaught and 1,142 on TICE. Overall, 765 (36%) patients received some form of maintenance BCG, 560 (59%) on Connaught and 205 (18%) on TICE. Without maintenance, Connaught was more effective than TICE only for the time to first recurrence (hazard ratio [HR] = 1.48; 95% CI: 1.20-1.82; P<0.001). With maintenance, TICE was more effective than Connaught for the time to first recurrence (HR = 0.66; 95% CI: 0.47-0.93; P = 0.019) with a trend for cancer specific survival (HR = 0.36; 95% CI: 0.14-0.92; P = 0.033). For time to progression and overall survival, Connaught and TICE had a similar efficacy. Compared to no maintenance therapy, maintenance BCG significantly reduced the risk of recurrence, progression and death, both overall, and disease specific, for TICE, but not for Connaught.

    CONCLUSIONS: We found that BCG Connaught results in a lower recurrence rate as compared with BCG TICE when no maintenance is used. However, the opposite is true when maintenance is given.

    PATIENT SUMMARY: As there is currently a BCG shortage, information on the efficacy of different BCG strains is important. In this nonrandomized retrospective comparison in over 2,000 patients, we found that BCG Connaught reduces the recurrence rate compared to BCG TICE when no maintenance is used, but the opposite is true when maintenance is given.

  • 375. Witjes, J. Alfred
    et al.
    Palou Redorta, Juan
    Jacqmin, Didier
    Sofras, Frank
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Riedl, Claus
    Jocham, Dieter
    Conti, Giario
    Montorsi, Francesco
    Arentsen, Harm C.
    Zaak, Dirk
    Mostafid, A. Hugh
    Babjuk, Marko
    Hexaminolevulinate-Guided Fluorescence Cystoscopy in the Diagnosis and Follow-Up of Patients with Non-Muscle-Invasive Bladder Cancer: Review of the Evidence and Recommendations2010Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 57, nr 4, s. 607-614Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Context: Compared with standard white-light cystoscopy, photodynamic diagnosis with blue light and the photosensitiser hexaminolevulinate has been shown to improve the visualisation of bladder tumours, reduce residual tumour rates by at least 20%, and improve recurrence-free survival. There is currently no overall European consensus outlining specifically where hexaminolevulinate is or is not indicated. Objective: Our aim was to define specific indications for hexaminolevulinate guided fluorescence cystoscopy in the diagnosis and management of non-muscle invasive bladder cancer (NMIBC). Evidence acquisition: A European expert panel was convened to review the evidence for hexaminolevulinate-guided fluorescence cystoscopy in the diagnosis and management of NMIBC (identified through a PubMed MESH search) and available guidelines from across Europe. On the basis of this information and drawing on the extensive clinical experience of the panel, specific indications for the technique were then identified through discussion. Evidence synthesis: The panel recommends that hexaminolevulinate-guided fluorescence cystoscopy be used to aid diagnosis at initial transurethral resection following suspicion of bladder cancer and in patients with positive urine cytology but negative white-light cystoscopy for the assessment of tumour recurrences in patients not previously assessed with hexaminolevulinate, in the initial follow-up of patients with carcinoma in situ (CIS) or multifocal tumours, and as a teaching tool. The panel does not currently recommend the use of hexaminolevulinate-guided fluorescence cystoscopy in patients for whom cystectomy is indicated or for use in the outpatient setting with flexible cystoscopy. Conclusions: Evidence is available to support the use of hexaminolevulinate-guided fluorescence cystoscopy in a range of indications, as endorsed by an expert panel. (c) 2010 European Association of Urology.

  • 376. Yavari, Nazila
    et al.
    Andersson-Engels, Stefan
    Segersten, Ulrika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    An overview on preclinical and clinical experiences with photodynamic therapy for bladder cancer2011Ingår i: Canadian Journal of Urology, ISSN 1195-9479, Vol. 18, nr 4, s. 5778-5786Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Photodynamic therapy (PDT) is one of the most interesting methods of photo treatment. In general, PDT is a modality for the treatment of non-muscle invasive tumors. PDT is very well suited in managing bladder cancer, as the bladder is accessible by endoscopy and the tumors are most often limited to the mucosa or sub-mucosa. PDT is likely more useful for patients with recurrent tumors after conventional therapies, as well as for patients with diffuse non-muscle invasive bladder carcinomas that are refractory to standard treatments before the commitment to radical extirpative surgery, particularly in patients at surgical high risk. The treatment of tumors with PDT includes three major parameters: presence of oxygen in tumor tissue, administration of a photosensitizer, and subsequent exposure to light. The PDT mechanism relies on the in situ generation of cytotoxic agents by the activation of a light-sensitive drug, resulting in cell death. In this review, we present past and current advances in the use of PDT with urinary bladder cancer and discuss the future roles for this type of therapy in the treatment of bladder cancer.

  • 377. Ylitalo, Erik Bovinder
    et al.
    Thysell, Elin
    Jernberg, Emma
    Lundholm, Marie
    Crnalic, Sead
    Egevad, Lars
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Widmark, Anders
    Bergh, Anders
    Wikström, Pernilla
    Subgroups of Castration-resistant Prostate Cancer Bone Metastases Defined Through an Inverse Relationship Between Androgen Receptor Activity and Immune Response.2017Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, nr 5, s. 776-787, artikel-id S0302-2838(16)30438-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Novel therapies for men with castration-resistant prostate cancer (CRPC) are needed, particularly for cancers not driven by androgen receptor (AR) activation.

    OBJECTIVES: To identify molecular subgroups of PC bone metastases of relevance for therapy.

    DESIGN, SETTING, AND PARTICIPANTS: Fresh-frozen bone metastasis samples from men with CRPC (n=40), treatment-naïve PC (n=8), or other malignancies (n=12) were characterized using whole-genome expression profiling, multivariate principal component analysis (PCA), and functional enrichment analysis. Expression profiles were verified by reverse transcription-polymerase chain reaction (RT-PCR) in an extended set of bone metastases (n=77) and compared to levels in malignant and adjacent benign prostate tissue from patients with localized disease (n=12). Selected proteins were evaluated using immunohistochemistry. A cohort of PC patients (n=284) diagnosed at transurethral resection with long follow-up was used for prognostic evaluation.

    RESULTS AND LIMITATIONS: The majority of CRPC bone metastases (80%) was defined as AR-driven based on PCA analysis and high expression of the AR, AR co-regulators (FOXA1, HOXB13), and AR-regulated genes (KLK2, KLK3, NKX3.1, STEAP2, TMPRSS2); 20% were non-AR-driven. Functional enrichment analysis indicated high metabolic activity and low immune responses in AR-driven metastases. Accordingly, infiltration of CD3+ and CD68+ cells was lower in AR-driven than in non-AR-driven metastases, and tumor cell HLA class I ABC immunoreactivity was inversely correlated with nuclear AR immunoreactivity. RT-PCR analysis showed low MHC class I expression (HLA-A, TAP1, and PSMB9 mRNA) in PC bone metastases compared to benign and malignant prostate tissue and bone metastases of other origins. In primary PC, low HLA class I ABC immunoreactivity was associated with high Gleason score, bone metastasis, and short cancer-specific survival. Limitations include the limited number of patients studied and the single metastasis sample studied per patient.

    CONCLUSIONS: Most CRPC bone metastases show high AR and metabolic activities and low immune responses. A subgroup instead shows low AR and metabolic activities, but high immune responses. Targeted therapy for these groups should be explored.

    PATIENT SUMMARY: We studied heterogeneities at a molecular level in bone metastasis samples obtained from men with castration-resistant prostate cancer. We found differences of possible importance for therapy selection in individual patients.

  • 378.
    Zare, Reza
    et al.
    Vestre Viken HF Baerum Hosp, Dept Urol, Oslo, Norway.
    Grabe, Magnus
    Lund Univ, Skane Univ Hosp, Dept Urol, Malmo, Sweden.
    Hermann, Gregers G.
    Univ Copenhagen, Herlev & Gentofte Hosp, Dept Urol, Copenhagen, Denmark.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Can routine outpatient follow-up of patients with bladder cancer be improved?: A multicenter prospective observational assessment of blue light flexible cystoscopy and fulguration2018Ingår i: Research and Reports in Urology, ISSN 2253-2447, E-ISSN 1179-1551, Vol. 10, s. 151-157Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The aim of this prospective cohort study was to determine the feasibility of incorporating blue light flexible cystoscopy (BLFC) and biopsy/fulguration into routine outpatient follow-up of non-muscle invasive bladder cancer patients.

    Methods: The study included patients with non-muscle-invasive bladder cancer (NMIBC) who were scheduled for routine follow-up. Hexaminolevulinate was instilled in the outpatient department, and the bladder was examined under white light and then with BLFC. Biopsies were taken from all suspicious lesions. Small tumors and suspicious lesions were fulgurated on site; patients with larger lesions were referred to the operating room for resection.

    Results: The study included 69 patients, with a mean age of 70 years (range 33 -89 years) and a mean duration since NMIBC diagnosis of 8 years. Most patients had high-grade cancer at initial diagnosis (52/69) and were at high risk of recurrence (48/69). Two patients per hour could be assessed using outpatient BLFC. Preparation and instillation of hexaminolevulinate took less than 10 minutes per patient, and patients had an additional waiting time of 45 60 minutes following instillation, while the hexaminolevulinate solution was retained in the bladder before examination. Eleven patients had histologically confirmed tumors that were identified using both white light flexible cystoscopy and BLFC. An additional three patients had tumors that were identified by BLFC only: two with Ta tumors and one with carcinoma in situ. Of the 14 patients with confirmed tumors, 11 could be managed on site with fulguration, whereas three were referred to the operating room. No adverse events attributable to BLFC were reported.

    Conclusion: Routine outpatient management of patients with NMIBC using BLFC and onsite biopsy/fulguration is feasible, despite the additional time required for hexaminolevulinate instillation, and appears to allow early detection of recurrent lesions, which can be fulgurated without the need for hospitalization.

  • 379.
    Zirakzadeh, A. Ali
    et al.
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Kinn, Johan
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Krantz, David
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Rosenblatt, Robert
    Umeå Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, Umeå, Sweden; Karolinska Inst, Stockholm South Gen Hosp, Dept Urol, Stockholm, Sweden.
    Winerdal, Malin E.
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Hu, Jin
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Hartana, Ciputra Adijaya
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Lundgren, Christian
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Bergman, Emma Ahlén
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Johansson, Markus
    Sundsvall Hosp, Dept Urol, Sundsvall, Sweden.
    Holmström, Benny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Hansson, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Sidikii, Alexander
    Länssjukhuset Ryhov, Dept Urol, Region Jonköping, Sweden.
    Vasko, Janos
    Umeå Univ, Dept Med Biosci, Pathol, Umeå, Sweden.
    Marits, Per
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Sherif, Amir
    Umeå Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, Umeå, Sweden.
    Winqvist, Ola
    Karolinska Inst, Unit Immunol & Allergy, Dept Med, Stockholm, Sweden.
    Doxorubicin enhances the capacity of B cells to activate T cells in urothelial urinary bladder cancer2017Ingår i: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 176, s. 63-70Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cancer is currently treated by a combination of therapies, including chemotherapy which is believed to suppress the immune system. Combination of immunotherapy and chemotherapy correlates with improved survival but needs careful planning in order to achieve a synergistic effect. In this study, we have demonstrated that doxorubicin treatment of B cells resulted in increased expression of CD86 and concordantly increased CD4(+) T cell activation in the presence of superantigen, an effect that was inhibited by the addition of a CD86 blocking antibody. Furthermore, doxorubicin resulted in decreased expression of the anti-inflammatory cytokines IL-10 and TNF-alpha. Finally, B cells from urinary bladder cancer patients, treated with a neoadjuvant regiment containing doxorubicin, displayed increased CD86-expression. We conclude that doxorubicin induces CD86 expression on B cells and hence enhances their antigen-presenting ability in vitro, a finding verified in patients. Development of tailored time and dose schedules may increase the effectiveness of combining chemotherapy and immunotherapy.

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