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  • 1. Abedini, Sadollah
    et al.
    Holme, Ingar
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jardine, Alan
    Cole, Ed
    Maes, Bart
    Holdaas, Hallvard
    Cerebrovascular events in renal transplant recipients2009In: Transplantation, ISSN 0041-1337, Vol. 87, no 1, 112-7 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The incidence of stroke and risk factors for different subtypes of cerebrovascular (CBV) events in renal transplant recipients have not been examined in any large prospective controlled trial. METHODS: The Assessment of Lescol in Renal Transplantation was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40-80 mg) daily on cardiovascular, and renal outcomes in renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5 to 6 year trial was offered open-label fluvastatin in a 2-year extension to the original study. We investigated the incidence of stroke and risk factors for ischemic and hemorrhagic CBV events in 2102 renal graft recipients participating in the Assessment of Lescol in Renal Transplantation core and extension trial with a mean follow-up of 6.7 years. RESULTS: The incidence and type of CBV events did not differ between the lipid lowering arm and the placebo arm. A total of 184 (8.8%, 95% confidence interval 4.6-12.9) of 2102 patients experienced a CBV event during follow-up, corresponding to an incidence of 1.3% CBV event per year. The mortality for patients experiencing a hemorrhagic stroke was 48% (13 of 27), whereas the mortality for ischemic strokes was 6.0% (8 of 133). Diabetes mellitus, previous CBV event, age, and serum creatinine were independent risk factors for cerebral ischemic events. The risk of a hemorrhagic cerebral event was increased by diabetes mellitus, polycystic kidney disease, left ventricular hypertrophy, and systolic blood pressure. INTERPRETATION: Risk factors for CBV events in renal transplant recipients differ according to subtype.

  • 2. Abedini, Sadollah
    et al.
    Holme, Ingar
    März, Winfried
    Weihrauch, Gisela
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jardine, Alan
    Cole, Edward
    Maes, Bart
    Neumayer, Hans-Hellmut
    Grönhagen-Riska, Carola
    Ambühl, Patrice
    Holdaas, Halvard
    Inflammation in renal transplantation2009In: Journal of the American Society of Nephrology, ISSN 1046-6673, Vol. 4, no 7, 1246-1254 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Renal transplant recipients experience premature cardiovascular disease and death. The association of inflammation, all-cause mortality, and cardiovascular events in renal transplant recipients has not been examined in a large prospective controlled trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5- to 6-yr trial were offered open-label fluvastatin in a 2-yr extension to the original study. The association between inflammation markers, high-sensitivity C-reactive protein (hsCRP), and IL-6 on cardiovascular events and all-cause mortality was investigated. RESULTS: The baseline IL-6 value was 2.9 +/- 1.9 pg/ml (n = 1751) and that of hsCRP was 3.8 +/- 6.7 mg/L (n = 1910). After adjustment for baseline values for established risk factors, the hazard ratios for a major cardiac event and all-cause mortality for IL-6 were 1.08 [95% confidence interval (CI), 1.01 to 1.15, P = 0.018] and 1.11 (95% CI, 1.05 to 1.18, P < 0.001), respectively. The adjusted hazard ratio for hsCRP for a cardiovascular event was 1.10 (95% CI, 1.01 to 1.20, P = 0.027) and for all-cause mortality was 1.15 (95% CI, 1.06 to 1.1.25, P = 0.049). CONCLUSIONS: The inflammation markers IL-6 and hsCRP are independently associated with major cardiovascular events and all-cause mortality in renal transplant recipients.

  • 3. Abedini, Sadollah
    et al.
    Meinitzer, Andreas
    Holme, Ingar
    März, Winfried
    Weihrauch, Gisela
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jardine, Alan
    Holdaas, Halvard
    Asymmetrical dimethylarginine is associated with renal and cardiovascular outcomes and all-cause mortality in renal transplant recipients2010In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 77, no 1, 44-50 p.Article in journal (Refereed)
    Abstract [en]

    Increased plasma levels of asymmetric dimethylarginine (ADMA) are associated with endothelial dysfunction and predict the progression to dialysis and death in patients with chronic kidney disease. The effects of these increased ADMA levels in renal transplant recipients, however, are unknown. We used the data from ALERT, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients with stable graft function on enrollment. Patients who were initially randomized to fluvastatin or placebo in the 5- to 6-year trial were offered open-label fluvastatin in a 2-year extension of the original study. After adjustment for baseline values for established factors in this post hoc analysis, ADMA was found to be a significant risk factor for graft failure or doubling of serum creatinine (hazard ratio 2.78), major cardiac events (hazard ratio 2.61), cerebrovascular events (hazard ratio 6.63), and all-cause mortality (hazard ratio 4.87). In this trial extension, the number of end points increased with increasing quartiles of plasma ADMA levels. All end points were significantly increased in the fourth compared to the first quartile. Our study shows that elevated plasma levels of ADMA are associated with increased morbidity, mortality, and the deterioration of graft function in renal transplant recipients.

  • 4. Akre, Olof
    et al.
    Garmo, Hans
    Adolfsson, Jan
    Lambe, Mats
    Bratt, Ola
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Mortality among men with locally advanced prostate cancer managed with noncurative intent: a nationwide study in PCBaSe Sweden2011In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, no 3, 554-563 p.Article in journal (Refereed)
    Abstract [en]

    The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors.

  • 5.
    Akre, Olof
    et al.
    Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Garmo, Hans
    Regional Oncological Center, Uppsala, Sweden.
    Adolfsson, Jan
    Oncological Center, CLINTEC Department, Karolinska Institutet, Stockholm, Sweden.
    Lambe, Mats
    Oncological Center, CLINTEC Department, andDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Bratt, Ola
    Department of Urology, Helsingborg Hospital, Lund University, Sweden.
    Stattin, Pär
    Department of Surgical and Perioperative sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Mortality Among Men with Locally Advanced Prostate Cancer Managed with Noncurative Intent: A Nationwide Study in PCBaSe Sweden2011In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 60, no 3, 554-563 p.Article in journal (Refereed)
    Abstract [en]

    Background

    There are limited prognostic data for locally advanced prostate cancer PCa to guide in the choice of treatment.

    Objective

    To assess mortality in different prognostic categories among men with locally advanced PCa managed with noncurative intent.

    Design, setting, and participants

    We conducted a register-based nationwide cohort study within the Prostate Cancer DataBase Sweden. The entire cohort of locally advanced PCa included 14 908 men. After the exclusion of 2724 (18%) men treated with curative intent, 12 184 men with locally advanced PCa either with local clinical stage T3 or T4 or with T2 with serum levels of prostate-specific antigen (PSA) between 50 and 99 ng/ml and without signs of metastases remained for analysis.

    Measurements

    We followed up the patient cohort in the Cause of Death Register for ≤11 yr and assessed cumulative incidence of PCa -specific death stratified by age and clinical characteristics.

    Results and limitations

    The PCa -specific mortality at 8 yr of follow-up was 28% (95% confidence interval [CI], 25–32%) for Gleason score (GS) 2–6, 41% (95% CI, 38–44%) for GS 7, 52% (95% CI, 47–57%) for GS 8, and 64% (95% CI, 59–69%) for GS 9–10. Even for men aged >85 yr at diagnosis with GS 8–10, PCa was a major cause of death: 42% (95% CI, 37–47%). Men with locally advanced disease and a PSA < 4 ng/ml at diagnosis were at particularly increased risk of dying from PCa. One important limitation is the lack of bone scans in 42% of the patient cohort, but results remained after exclusion of patients with unknown metastasis status.

    Conclusions

    The PCa-specific mortality within 8 yr of diagnosis is high in locally advanced PCa, suggesting undertreatment, particularly among men in older age groups. Our results underscore the need for more studies of treatment with curative intent for locally advanced tumors.

  • 6.
    Al Ahmadi, Ibrahim
    et al.
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Abasi, Amira
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Syed, Raza
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Broering, Dieter-C.
    King Faisal Hosp & Res Ctr, Organ Transplant Ctr, Riyadh, Saudi Arabia..
    Biglarnia, Ali-Reza
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Initial Experience From Implementation of Hand-Assisted Retroperitoneoscopic Live Donor Nephrectomy in Saudi Arabia2013In: Annals of Saudi Medicine, ISSN 0256-4947, E-ISSN 0975-4466, Vol. 33, no 2, S58-S59 p.Article in journal (Refereed)
    Abstract [en]

    Introduction: Donor risks and morbidity are consequences of the invasiveness of donor nephrectomy procedure. The flank incision is currently the default donor nephrectomy procedure at the King Faisal Hospital in Saudi Arabia. In order to minimize the surgical-related trauma, we are implementing the hand-assisted retroperitoneoscopic live donor nephrectomy (HARS), which previously has been shown to promote donor safety. Here, we present our initial experience with this procedure. Material and Methods: The HARS technique was implemented at our center in 2010. We present a survey of our data regarding operative characteristics as well as donor/recipient outcome. Given the small number of cases, data are presented as median with range. Results: Between 2010 and 2013, 18 left -sided HARS nephrectomy procedures were performed. The median donor age and BMI were 26.5 (18-43) and 24.1 (18.7-30.7), respectively. The median hospitalization was 4 days (3-5). One donor presented wound seroma in the pfannenstiell incision with no need for intervention. Another donor presented unspecific thoracoabdominal pain on postoperative day 2. No intra-and postoperative bleeding was observed. The median creatinine at the current follow-up was 90 mu mol/L with 100% graft survival. Conclusion: HARS is a feasible and safe technique. However, for implementation of HARS as the default donor nephrectomy procedure more practice is needed.

  • 7.
    Alderson, Helen V.
    et al.
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK;Salford Royal NHS Foundation Trust, Salford, UK..
    Ritchie, James P
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK;Salford Royal NHS Foundation Trust, Salford, UK..
    Middleton, Rachel
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK;Salford Royal NHS Foundation Trust, Salford, UK..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Larsson, Tobias E
    Department of Clinical Science, Intervention and Technology, Renal Unit, Karolinska Institute, Stockholm, Sweden..
    Kalra, Philip A
    Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK;Salford Royal NHS Foundation Trust, Salford, UK..
    FGF-23 and Osteoprotegerin but not Fetuin-A are associated with death and enhance risk prediction in non-dialysis chronic kidney disease stages 3-52016In: Nephrology (Carlton. Print), ISSN 1320-5358, E-ISSN 1440-1797, Vol. 21, no 7, 566-573 p.Article in journal (Refereed)
    Abstract [en]

    AIM: Numerous biomarkers have been shown to associate with clinical endpoints in chronic kidney disease (CKD). There is limited evidence whether biomarkers improve risk prediction in relation to clinical outcomes. Our study investigates whether a small suite of key chronic kidney disease-mineral and bone disorder biomarkers could be used to enhance risk assessment in CKD.

    METHODS: Fetuin-A, fibroblast growth factor-23 and osteoprotegerin were measured on baseline plasma samples from 463 patients recruited to the Chronic Renal Insufficiency Standards Implementation Study. The biomarkers were analysed in relation to progression to end stage kidney disease, death and major cardiovascular events.

    RESULTS: Over a median follow up of 46 months (interquartile range 21-69), fibroblast growth factor-23 was associated with risk for renal replacement therapy (hazard ratio (HR) 1.35, P = 0.05, 95% confidence interval (CI) 1.001-1.820), cardiovascular events (HR 1.74 P < 0.001, 95% CI 1.303-1.305) and death (HR 1.4 P = 0.005, 95% CI 1.109-1.767). Osteoprotegerin was associated with risk for death (HR 1.06, P = 0.03, 95% CI 1.006-1.117). There was no clear association between Fetuin-A and any of the clinical endpoints. The addition of biomarkers to risk models led to marginal improvement in model discrimination and reclassification.

    CONCLUSION: Biomarkers are often associated with clinical endpoints, and we observed such associations in our study of patients with advanced CKD. However, the markers analysed in our study were of limited benefit in improving the prediction of these outcomes. Any extra information biomarkers may provide to improve risk prediction in clinical practice needs to be carefully balanced against the potential cost of these tools.

  • 8.
    Alexeyev, Oleg
    et al.
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Olsson, Jan
    Department of Medical Biosciences, Umeå University, Umeå, Sweden.
    Elgh, Fredrik
    Örebro University, School of Health and Medical Sciences.
    Is There Evidence for a Role of Propionibacterium acnes in Prostatic Disease?2009In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 73, no 2, 220-224 p.Article, review/survey (Refereed)
  • 9.
    Aljabery, Firas
    et al.
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Lindblom, Gunnar
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Skoog, Susann
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Jahnson, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    PET/CT versus conventional CT for detection of lymph node metastases in patients with locally advanced bladder cancer.2015In: BMC urology, ISSN 1471-2490, Vol. 15, no 1, 87- p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We studied patients treated with radical cystectomy for locally advanced bladder cancer to compare the results of both preoperative positron emission tomography/computed tomography (PET/CT) and conventional CT with the findings of postoperative histopathological evaluation of lymph nodes.

    METHODS: Patients who had bladder cancer and were candidates for cystectomy underwent preoperative PET/CT using 18-fluorodeoxyglucose (FDG) and conventional CT. The results regarding lymph node involvement were independently evaluated by two experienced radiologists and were subsequently compared with histopathology results, the latter of which were reassessed by an experienced uropathologist (HO).

    RESULTS: There were 54 evaluable patients (mean age 68 years, 47 [85 %] males and 7 [15 %] females) with pT and pN status as follows: < pT2-14 (26 %), pT2-10 (18 %), and > pT2-30 (56 %); pN0 37 (69 %) and pN+ 17 (31 %). PET/CT showed positive lymph nodes in 12 patients (22 %), and 7 of those cases were confirmed by histopathology; the corresponding results for conventional CT were 11 (20 %) and 7 patients (13 %), respectively. PET/CT had 41 % sensitivity, 86 % specificity, 58 % PPV, and 76 % NPV, whereas the corresponding figures for conventional CT were 41 %, 89 %, 64 %, and 77 %. Additional analyses of the right and left side of the body or in specified anatomical regions gave similar results.

    CONCLUSIONS: In this study, PET/CT and conventional CT had similar low sensitivity in detecting and localizing regional lymph node metastasis in bladder cancer.

  • 10.
    Al-Mashhadi, Ammar Nadhom Farman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stenberg, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Karanikas, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Persson, A. Erik G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlstrom, Mattias
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Wahlin, Nils
    Department of Pediatric Surgery, Astrid Lindgren Hospital, Karolinska Institutet, Stockholm, Sweden.
    Surgical treatment reduces blood pressure in children with unilateral congenital hydronephrosis2015In: Journal of Pediatric Urology, ISSN 1477-5131, E-ISSN 1873-4898, Vol. 11, no 2, 91.e1-91.e6 p.Article in journal (Refereed)
    Abstract [en]

    Objective Renal disorders can cause hypertension, but less is known about the influence of hydronephrosis on blood pressure. Hydronephrosis due to pelvo-ureteric junction obstruction (PUJO) is a fairly common condition (incidence in newborns of 0.5-1%). Although hypertensive effects of hydronephrosis have been suggested, this has not been substantiated by prospective studies in humans [1-3]. Experimental studies with PUJO have shown that animals with induced hydronephrosis develop salt-sensitive hypertension, which strongly correlate to the degree of obstruction [4-7]. Moreover, relief of the obstruction normalized blood pressure [8]. In this first prospective study our aim was to study the blood pressure pattern in pediatric patients with hydronephrosis before and after surgical correction of the ureteral obstruction. Specifically, we investigated if preoperative blood pressure is reduced after surgery and if split renal function and renographic excretion curves provide any prognostic information. Patients and methods Twelve patients with unilateral congenital hydronephrosis were included in this prospective study. Ambulatory blood pressure (24 h) was measured preoperatively and six months after surgery. Preoperative evaluations of bilateral renal function by Tc99m-MAG3 scintigraphy, and renography curves, classified according to O'Reilly, were also performed. Results As shown in the summary figure, postoperative systolic (103 +/- 2 mmHg) and diastolic (62 +/- 2 mmHg) blood pressure were significantly lower than those obtained preoperatively (110 +/- 4 and 69 +/- 2 mmHg, respectively), whereas no changes in circadian variation or pulse pressure were observed. Renal functional share of the hydronephrotic kidney ranged from 11 to 55%. There was no correlation between the degree of renal function impairment and the preoperative excretory pattern, or between the preoperative excretory pattern and the blood pressure reduction postoperatively. However, preoperative MAG3 function of the affected kidney correlated with the magnitude of blood pressure change after surgery. Discussion Correction of the obstruction lowered blood pressure, and the reduction in blood pressure appeared to correlate with the degree of renal functional impairment, but not with the excretory pattern. Thus, in the setting of hypertension, it appears that the functional share of the hydronephrotic kidney should be considered an indicator of the need for surgery, whereas the renography curve is less reliable. The strength of the present study is the prospective nature and that ambulatory blood pressure monitoring was used. Future longitudinal prolonged follow-up studies are warranted to confirm the present findings, and to understand if a real nephrogenic hypertension with potential necessity of treatment will develop. Conclusion This novel prospective study in patients with congenital hydronephrosis demonstrates a reduction in blood pressure following relief of the obstruction. Based on the present results, we propose that the blood pressure level should also be taken into account when deciding whether to correct hydronephrosis surgically or not.

  • 11.
    Andersson, Gunnel
    et al.
    Örebro University, Department of Clinical Medicine. Department of Urology, Örebro University Hospital, Örebro, Sweden; Centre for Evidence Based Medicine and Assessment of Medical Technology, Örebro, Sweden.
    Johansson, Jan-Erik
    Örebro University, Department of Clinical Medicine. Department of Urology, Örebro University Hospital, Örebro, Sweden; Centre for Evidence Based Medicine and Assessment of Medical Technology, Örebro, Sweden.
    Sahlberg-Blom, Eva
    Örebro University, Department of Nursing and Caring Sciences.
    Pettersson, Nicklas
    Department of Public Health, O¨ rebro County Council, O¨ rebro, Sweden.
    Nilsson, Kerstin
    Örebro University, Department of Clinical Medicine. Centre for Evidence Based Medicine and Assessment of Medical Technology, O¨ rebro, Sweden; Department of Obstetrics and Gynaecology, Örebro University Hospital, Örebro, Sweden.
    Urinary incontinence - why refraining from treatment?: a population based study2005In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 39, no 4, 301-307 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate why persons with urinary incontinence (UI) refrain from seeking care and treatment.

    MATERIAL AND METHODS: A population-based study was undertaken in which a public health survey and a specific UI questionnaire were sent to 15 360 randomly selected residents (age 18-79 years) of Orebro County, Sweden. For all persons reporting UI, the expressed wish for treatment or no treatment was analyzed in relation to relevant variables from both inquiry forms using binary logistic regression analysis.

    RESULTS: The response rate was 64.5%. UI was reported by 2194 persons, 1724 of whom comprised the study population. A statistically significant association was found between the degree of UI and a desire for treatment. Persons who did not experience daily leakage and those who did not perceive the leakage as troublesome or having an affect on their daily life mostly stated that they did not desire treatment. Socioeconomic or other health-related factors were not associated with desiring or not desiring treatment for UI.

    CONCLUSIONS: Our results show that it is the perceived severity of UI that determines whether afflicted persons desire treatment or not. Other factors, relating to seeking healthcare in general, were not found to be of importance. Interventions to identify those in need of treatment for UI should primarily be directed towards those with severe symptoms.

  • 12. Andersson, Gustav
    et al.
    Wennersten, Christoffer
    Gaber, Alexander
    Boman, Karolina
    Nodin, Bjorn
    Uhlen, Mathias
    Segersten, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Jirstrom, Karin
    Reduced expression of ezrin in urothelial bladder cancer signifies more advanced tumours and an impaired survival: validatory study of two independent patient cohorts2014In: BMC Urology, ISSN 1471-2490, Vol. 14, 36- p.Article in journal (Refereed)
    Abstract [en]

    Background: Reduced membranous expression of the cytoskeleton-associated protein ezrin has previously been demonstrated to correlate with tumour progression and poor prognosis in patients with T1G3 urothelial cell carcinoma of the bladder treated with non-maintenance Bacillus Calmette-Guerin (n = 92), and the associations with adverse clinicopathological factors have been validated in another, unselected, cohort (n = 104). In the present study, we examined the prognostic significance of ezrin expression in urothelial bladder cancer in a total number of 442 tumours from two independent patient cohorts. Methods: Immunohistochemical expression of ezrin was evaluated in tissue microarrays with tumours from one retrospective cohort of bladder cancer (n = 110; cohort I) and one population-based cohort (n = 342; cohort II). Classification regression tree analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis, log rank test and Cox regression proportional hazards' modeling were used to evaluate the impact of ezrin on 5-year overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS). Results: Ezrin expression could be evaluated in tumours from 100 and 342 cases, respectively. In both cohorts, reduced membranous ezrin expression was significantly associated with more advanced T-stage (p < 0.001), high grade tumours (p < 0.001), female sex (p = 0.040 and p = 0.013), and membranous expression of podocalyxin-like protein (p < 0.001 and p = 0.009). Moreover, reduced ezrin expression was associated with a significantly reduced 5-year OS in both cohorts (HR = 3.09 95% CI 1.71-5.58 and HR = 2.15(1.51-3.06), and with DSS in cohort II (HR = 2.77, 95% CI 1.78-4.31). This association also remained significant in adjusted analysis in Cohort I (HR1.99, 95% CI 1.05-3.77) but not in Cohort II. In pTa and pT1 tumours in cohort II, there was no significant association between ezrin expression and time to progression. Conclusions: The results from this study validate previous findings of reduced membranous ezrin expression in urothelial bladder cancer being associated with unfavourable clinicopathological characteristics and an impaired survival. The utility of ezrin as a prognostic biomarker in transurethral resection specimens merits further investigation.

  • 13.
    Andersson, Patiyan
    et al.
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Kolaric, Aleksandra
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Windahl, Torgny
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Kirrander, Peter
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Söderkvist, Peter
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Karlsson, Mats G
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    PIK3CA, HRAS and KRAS gene mutations in human penile cancer2008In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, no 5, 2030-2034 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: The knowledge of somatic mutations that arise in penile cancer is limited. We examined the dysregulation of components in the phosphatidylinositol 3-kinase and Ras pathways.

    Materials and Methods: Using single stranded conformational analysis and direct sequencing we performed mutational analysis of the PIK3CA, PTEN, HRAS, KRAS, NRAS and BRAF genes in 28 penile tumors.

    Results: We identified somatic missense mutations in 11 of the 28 penile cancer samples (39%). In the PIK3CA gene 8 mutations (29%) were identified that were E542K or E545K. In the HRAS gene a G12S and a Q61L mutation were found (7%). The KRAS gene contained 1 mutation (3%), that is a G12S change. PIK3CA mutations were found in all grades and stages, whereas HRAS and KRAS mutations were found in larger and more advanced tumors. The mutations were mutually exclusive, suggesting that dysregulation of either pathway is sufficient for the development and progression of penile carcinoma.

    Conclusions: The high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma.

  • 14.
    André, Malin
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Rules of Thumb and Management of Common Infections in General Practice2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis deals with problem solving of general practitioners (GPs), which is explored with different methods and from different perspectives. The general aim was to explore and describe rules of thumb and to analyse the management of respiratory and urinary tract infections (RTI and UTI) in general practice in Sweden. The results are based upon focus group interviews concerning rules of thumb and a prospective diagnosis-prescription study concerning the management of patients allocated a diagnosis of RTI or UTI. In addition unpublished data are given from structured telephone interviews concerning specific rules of thumb in acute sinusitis and prevailing cough.

    GPs were able to verbalize their rules of thumb, which could be called tacit knowledge. A specific set of rules of thumb was used for rapid assessment when emergency and psychosocial problems were identified. Somatic problems seemed to be the expected, normal state. In the further consultation the rules of thumb seemed to be used in an act of balance between the individual and the general perspective. There was considerable variation between the rules of thumb of different GPs for patients with acute sinusitis and prevailing cough. In their rules of thumb the GPs seemed to integrate their medical knowledge and practical experience of the consultation. A high number of near-patient antigen tests to probe Streptococcus pyogenes (Strep A tests) and C-reactive protein (CRP) tests were performed in patients, where testing was not recommended. There was only a slight decrease in antibiotic prescribing in patients allocated a diagnosis of RTI examined with CRP in comparison with patients not tested. In general, the GPs in Sweden adhered to current guidelines for antibiotic prescribing. Phenoxymethylpenicillin (PcV) was the preferred antibiotic for most patients allocated a diagnosis of respiratory tract infection.

    In conclusion, the use of rules of thumb might explain why current practices prevail in spite of educational efforts. One way to change practice could be to identify and evaluate rules of thumb used by GPs and disseminate well adapted rules. The use of diagnostic tests in patients with infectious illnesses in general practice needs critical appraisal before introduction as well as continuing surveillance. The use of rules of thumb by GPs might be one explanation for variation in practice and irrational prescribing of antibiotics in patients with infectious conditions.

  • 15.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences.
    Natural history and prognostic factors in localized prostate cancer2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The natural history of localized prostate cancer is not fully understood. In most patients the tumor will never progress to a lethal disease, while a subset of patients will ultimately die of the disease. Efficient tools to separate indolent from lethal disease is currently lacking which means that many patients will be offered treatment without any benefit, but still be at risk of experiencing treatment related side effects.

    The aims of these studies were to get more insight into the natural history of untreated localized prostate cancer, to assess the prognostic value of established clinical parameters such as Gleason score, nuclear grade and tumor volume and, moreover, some new prognostic markers Ki-67, AMACR and MUC-1. We also aimed to study time trends in the detection of incidental tumors in Sweden.

    Patients with localized disease (n=223) and no initial treatment were followed for 21 years. Most patients had a favorable outcome. However, a subset of patients developed lethal disease even beyond 15 years of follow-up and these patients define the group that may benefit most from treatment with curative intent. Patients with poorly differentiated tumors experienced a 9 time higher risk of dying in prostate cancer.

    The studies on prognostic markers are based on a cohort of patients (n=253) with incidental prostate cancer detected by transurethral resection for presumed benign hyperplasia. All patients were left without initial treatment. Gleason grade, nuclear grade and tumor volume turned all out to be independent prognostic factors. MUC-1, AMACR and Ki-67 also carried prognostic information. However, after adjustment for Gleason grade, nuclear grade and tumor volume only MUC-1 and AMACR remained as statistically significant prognostic factors. When tested for sensitivity and specificity they all failed and, consequently, they seem to be of less value in daily practice for cancelling an individual patient regarding the choice of treatment.

    Time trends in incidental prostate tumors in Sweden were analyzed in a cohort of patients with prostate tumors detected by transurethral resection (TUR-P). Through linkage of the national registration number (NRN) with several registers, e.g. the Swedish Cancer Registry, the National Inpatient registry and the Cause of Death Registry we identified, during the period 1970 through 2003, in total 23288 patients with incidental prostate cancer, who constituted the study group. As comparison group we choose all patients diagnosed with prostate cancer between 1970-2003 excluding those with incidental cancer, in total 112204 patients. Our result confirms earlier findings that there has been a dramatic change over time in incidence of incidental prostate cancers in Sweden, which parallels the introduction of prostate specific antigen. We also found that the cumulative incidence of prostate cancer death is high in the incidental group, opposing earlier findings that incidental tumours are a non-lethal disease.

  • 16.
    Andrén, Ove
    et al.
    Örebro University, Department of Clinical Medicine.
    Fall, Katja
    Franzén, Lennart
    Andersson, Swen-Olof
    Johansson, Jan-Erik
    Rubin, Mark A.
    How well does the Gleason score predict prostate cancer death?: A 20-year followup of a population based cohort in Sweden2006In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 175, no 4, 1337-1340 p.Article in journal (Refereed)
    Abstract [en]

    Purpose

    Adenocarcinoma of the prostate is the most common cancer among men in Western countries. Although the prognostic heterogeneity of prostate cancer is enormous, clinically insignificant aggressive prostate cancers cannot be reliably distinguished. Therefore, identifying prognostic factors is increasingly important, notably among men diagnosed with localized prostate cancer, because many of them may not require aggressive treatment.

    Materials and Methods

    We analyzed a population based cohort of 253 men with early stage (T1a-b, Nx, M0) initially untreated prostate cancer diagnosed between 1977 and 1991, before PSA screening was available. Tissue samples were available for 240 patients diagnosed with transurethral resection. During complete followup through September 2003, standardized criteria were used to classify histopathological characteristics, progression and causes of death.

    Results

    Higher Gleason grade, higher nuclear grade and larger tumor volume were independent predictors of death in prostate cancer with monotonous and statistically significant trends (p <0.05). In contrast, the level of Ki-67 – strongly correlated to Gleason score – was not an independent predictor of prostate cancer death. Given a Gleason score of 7 or greater, the probability of dying of prostate cancer was 29%. The corresponding predictive value for Gleason score 8 or greater was 48%.

    Conclusions

    Although a high Gleason score is a determinant of prostate cancer death, its PPV is relatively low. Thus, further efforts in finding other or complementary indicators of prostate cancer outcome are needed.

  • 17. Angenete, E
    et al.
    Angerås, U
    Börjesson, Mats
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Ekelund, J
    Gellerstedt, M
    Thorsteinsdottir, T
    Steineck, G
    Haglind, E
    Physical activity before radical prostatectomy reduces sick leave after surgery - results from a prospective, non-randomized controlled clinical trial (LAPPRO).2016In: BMC Urology, ISSN 1471-2490, E-ISSN 1471-2490, Vol. 16, no 1, 50Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Studies have reported that early physical rehabilitation after surgical procedures is associated with improved outcome measured as shorter hospital stay and enhanced recovery. The aim of this study was to explore the relationship between the preoperative physical activity level and subsequent postoperative complications, sick-leave and hospital stay after radical prostatectomy for prostate cancer in the setting of the LAPPRO trial (LAParoscopic Prostatectomy Robot Open).

    METHODS: LAPPRO is a prospective controlled trial, comparing robot-assisted laparoscopic and open surgery for localized prostate cancer between 2008 and 2011. 1569 patients aged 64 or less with an occupation were included in this sub-study. The Gleason score was <7 in 52 % of the patients. Demographics and the level of self-assessed preoperative physical activity, length of hospital stay, complications, quality of life, recovery and sick-leave were extracted from clinical record forms and questionnaires. Multivariable logistic regression, with log-link and logit-link functions, was used to adjust for potential confounding variables.

    RESULTS: The patients were divided into four groups based on their level of activity. As the group with lowest engagement of physical activity was found to be significantly different in base line characteristics from the other groups they were excluded from further analysis. Among patients that were physically active preoperativelly (n = 1467) there was no significant difference between the physical activity-groups regarding hospital stay, recovery or complications. However, in the group with the highest self-assessed level of physical activity, 5-7 times per week, 13 % required no sick leave, compared to 6.3 % in the group with a physical activity level of 1-2 times per week only (p < 0.0001).

    CONCLUSIONS: In our study of med operated with radical prostatectomy, a high level of physical activity preoperatively was associated with reduced need for sick leave after radical prostatectomy compared to men with lower physical activity.

    TRIAL REGISTRATION: The trial is registered at the ISCRTN register. ISRCTN06393679 .

  • 18.
    Asklund, Ina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Nyström, Emma
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sjöström, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Umefjord, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Samuelsson, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Mobile app for treatment of stress urinary incontinence: A randomized controlled trial2016In: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777Article in journal (Refereed)
    Abstract [en]

    AIMS: To evaluate the effect of a mobile app treatment for stress urinary incontinence (SUI) in women.

    METHODS: Randomized controlled trial, conducted 2013-2014 in Sweden. Community-dwelling adult women with ≥1 SUI episode/week recruited through our website and randomized to app treatment (n = 62) or control group (postponed treatment, n = 61). One participant from each group was lost to follow-up. Intervention was the mobile app Tät(®) with a treatment program focused on pelvic floor muscle training (PFMT), and information about SUI and lifestyle factors. Primary outcomes, 3 months after randomization: symptom severity (International Consultation on Incontinence Modular Questionnaire Urinary Incontinence Short Form [ICIQ-UI SF]); and condition-specific quality of life (ICIQ Lower Urinary Tract Symptoms Quality of Life [ICIQ-LUTSqol]).

    RESULTS: One hundred and twenty-three women were included (mean age 44.7), with moderate/severe SUI (97.5%, 120/123), mean ICIQ-UI SF score 11.1 (SD 2.8) and mean ICIQ-LUTSqol score 34.4 (SD 6.1) at baseline. At follow-up, the app group reported improvements in symptom severity (mean ICIQ-UI SF score reduction: 3.9, 95% confidence interval 3.0-4.7) and condition-specific quality of life (mean ICIQ-LUTSqol score reduction: 4.8, 3.4-6.2) and the groups were significantly different (mean ICIQ-UI SF score difference: -3.2, -4.3to -2.1; mean ICIQ-LUTSqol score difference: -4.6, -7.8 to -1.4). In the app group, 98.4% (60/61) performed PFMT at follow-up, and 41.0% (25/61) performed it daily.

    CONCLUSIONS: The mobile app treatment was effective for women with SUI and yielded clinically relevant improvements. This app may increase access to first-line treatment and adherence to PFMT.

  • 19. Augsten, Martin
    et al.
    Hägglöf, Christina
    Olsson, Eleonor
    Stolz, Claudia
    Tsagozis, Panagiotis
    Levchenko, Tetyana
    Frederick, Mitchell J.
    Borg, Åke
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Egevad, Lars
    Östman, Arne
    CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 9, 3414-3419 p.Article in journal (Refereed)
    Abstract [en]

    This study explored the role of secreted fibroblast-derived factors in prostate cancer growth. Analyses of matched normal and tumor tissue revealed up-regulation of CXCL14 in cancer-associated fibroblasts of a majority of prostate cancer. Fibroblasts over-expressing CXCL14 promoted the growth of prostate cancer xenografts, and increased tumor angiogenesis and macrophage infiltration. Mechanistic studies demonstrated that autocrine CXCL14-stimulation of fibroblasts stimulate migration and ERK-dependent proliferation of fibroblasts. CXCL14-stimulation of monocyte migration was also demonstrated. Furthermore, CXCL14-producing fibroblasts, but not recombinant CXCL14, enhanced in vitro proliferation and migration of prostate cancer cells and in vivo angiogenesis. These studies thus identify CXCL14 as a novel autocrine stimulator of fibroblast growth and migration, with multi-modal tumor-stimulatory activities. In more general terms, our findings suggest autocrine stimulation of fibroblasts as a previously unrecognized mechanism for chemokine-mediated stimulation of tumor growth, and suggest a novel mechanism whereby cancer-associated fibroblasts achieve their pro-tumorigenic phenotype.

  • 20.
    Austin, Paul F.
    et al.
    Washington Univ, St Louis Childrens Hosp, Div Urol, St Louis, MO 63110 USA..
    Bauer, Stuart B.
    Harvard Univ, Childrens Hosp, Sch Med, Dept Urol, Boston, MA 02115 USA..
    Bower, Wendy
    Skejby Univ Hosp, Pediat Nephrol Sect, Aarhus, Denmark..
    Chase, Janet
    Cabrini Hosp, Childrens Ctr, Melbourne, Vic, Australia..
    Franco, Israel
    New York Med Coll, Valhalla, NY 10595 USA..
    Hoebeke, Piet
    Ghent Univ Hosp, Pediat Urol & Nephrol, Ghent, Belgium..
    Rittig, Soren
    Skejby Univ Hosp, Pediat Nephrol Sect, Aarhus, Denmark..
    Vande Walle, Johan
    Ghent Univ Hosp, Pediat Urol & Nephrol, Ghent, Belgium..
    von Gontard, Alexander
    Saarland Univ Hosp, Dept Child & Adolescent Psychiat, Saarbrucken, Germany..
    Wright, Anne
    St Thomas Hosp, Evelina Childrens Hosp, Pediat, London, England..
    Yang, Stephen S.
    Buddhist Med Fdn, Taipei Tzu Chi Hosp, Div Urol, New Taipei, Taiwan.;Buddhist Tzu Chi Univ, Sch Med, Hualien, Taiwan..
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    The standardization of terminology of lower urinary tract function in children and adolescents: Update report from the standardization committee of the International Children's Continence Society2016In: Neurourology and Urodynamics, ISSN 0733-2467, E-ISSN 1520-6777, Vol. 35, no 4, 471-481 p.Article in journal (Refereed)
    Abstract [en]

    AimThe impact of the original International Children's Continence Society (ICCS) terminology document on lower urinary tract (LUT) function resulted in the global establishment of uniformity and clarity in the characterization of LUT function and dysfunction in children across multiple healthcare disciplines. The present document serves as a stand-alone terminology update reflecting refinement and current advancement of knowledge on pediatric LUT function. MethodsA variety of worldwide experts from multiple disciplines within the ICCS leadership who care for children with LUT dysfunction were assembled as part of the standardization committee. A critical review of the previous ICCS terminology document and the current literature was performed. Additionally, contributions and feedback from the multidisciplinary ICCS membership were solicited. ResultsFollowing a review of the literature over the last 7 years, the ICCS experts assembled a new terminology document reflecting current understanding of bladder function and LUT dysfunction in children using the resources from the literature review, expert opinion and ICCS member feedback. ConclusionsThe present ICCS terminology document provides a current and consensus update to the evolving terminology and understanding of LUT function in children.

  • 21. Baigent, C
    et al.
    Blackwell, L
    Emberson, J
    Holland, LE
    Reith, C
    Bhala, N
    Peto, R
    Barnes , EH
    Keech, A
    Simes, J
    Collins, R
    Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomized trials2010In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 376, no 9753, 1670-1681 p.Article in journal (Refereed)
    Abstract [en]

    Background

    Lowering of LDL cholesterol with standard statin regimens reduces the risk of occlusive vascular events in a wide range of individuals. We aimed to assess the safety and efficacy of more intensive lowering of LDL cholesterol with statin therapy.

    Methods

    We undertook meta-analyses of individual participant data from randomised trials involving at least 1000 participants and at least 2 years' treatment duration of more versus less intensive statin regimens (five trials; 39 612 individuals; median follow-up 5·1 years) and of statin versus control (21 trials; 129 526 individuals; median follow-up 4·8 years). For each type of trial, we calculated not only the average risk reduction, but also the average risk reduction per 1·0 mmol/L LDL cholesterol reduction at 1 year after randomisation.

    Findings

    In the trials of more versus less intensive statin therapy, the weighted mean further reduction in LDL cholesterol at 1 year was 0·51 mmol/L. Compared with less intensive regimens, more intensive regimens produced a highly significant 15% (95% CI 11–18; p<0·0001) further reduction in major vascular events, consisting of separately significant reductions in coronary death or non-fatal myocardial infarction of 13% (95% CI 7–19; p<0·0001), in coronary revascularisation of 19% (95% CI 15–24; p<0·0001), and in ischaemic stroke of 16% (95% CI 5–26; p=0·005). Per 1·0 mmol/L reduction in LDL cholesterol, these further reductions in risk were similar to the proportional reductions in the trials of statin versus control. When both types of trial were combined, similar proportional reductions in major vascular events per 1·0 mmol/L LDL cholesterol reduction were found in all types of patient studied (rate ratio [RR] 0·78, 95% CI 0·76–0·80; p<0·0001), including those with LDL cholesterol lower than 2 mmol/L on the less intensive or control regimen. Across all 26 trials, all-cause mortality was reduced by 10% per 1·0 mmol/L LDL reduction (RR 0·90, 95% CI 0·87–0·93; p<0·0001), largely reflecting significant reductions in deaths due to coronary heart disease (RR 0·80, 99% CI 0·74–0·87; p<0·0001) and other cardiac causes (RR 0·89, 99% CI 0·81–0·98; p=0·002), with no significant effect on deaths due to stroke (RR 0·96, 95% CI 0·84–1·09; p=0·5) or other vascular causes (RR 0·98, 99% CI 0·81–1·18; p=0·8). No significant effects were observed on deaths due to cancer or other non-vascular causes (RR 0·97, 95% CI 0·92–1·03; p=0·3) or on cancer incidence (RR 1·00, 95% CI 0·96–1·04; p=0·9), even at low LDL cholesterol concentrations.

    Interpretation

    Further reductions in LDL cholesterol safely produce definite further reductions in the incidence of heart attack, of revascularisation, and of ischaemic stroke, with each 1·0 mmol/L reduction reducing the annual rate of these major vascular events by just over a fifth. There was no evidence of any threshold within the cholesterol range studied, suggesting that reduction of LDL cholesterol by 2–3 mmol/L would reduce risk by about 40–50%.

    Funding

    UK Medical Research Council, British Heart Foundation, European Community Biomed Programme, Australian National Health and Medical Research Council, and National Heart Foundation.

  • 22. Bekema, Hendrika J.
    et al.
    MacLennan, Steven
    Imamura, Mari
    Lam, Thomas B. L.
    Stewart, Fiona
    Scott, Neil
    MacLennan, Graeme
    McClinton, Sam
    Griffiths, T. R. Leyshon
    Skolarikos, Andreas
    MacLennan, Sara J.
    Sylvester, Richard
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    N'Dow, James
    Systematic Review of Adrenalectomy and Lymph Node Dissection in Locally Advanced Renal Cell Carcinoma2013In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 64, no 5, 799-810 p.Article, review/survey (Refereed)
    Abstract [en]

    Context: Controversy remains over whether adrenalectomy and lymph node dissection (LND) should be performed concomitantly with radical nephrectomy (RN) for locally advanced renal cell carcinoma (RCC) cT3-T4N0M0. Objective: To systematically review all relevant literature comparing oncologic, perioperative, and quality-of-life (QoL) outcomes for locally advanced RCC managed with RN with or without concomitant adrenalectomy or LND.

    Evidence acquisition: Relevant databases were searched up to August 2012. Randomised controlled trials (RCTs) and comparative studies were included. Outcome measures were overall survival, QoL, and perioperative adverse effects. Risks of bias (RoB) were assessed using Cochrane RoB tools. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach.

    Evidence synthesis: A total of 3658 abstracts and 252 full-text articles were screened. Eight studies met the inclusion criteria: six LNDs (one RCT and five nonrandomised studies [NRSs]) and two adrenalectomies (two NRSs). RoB was high across the evidence base, and the quality of evidence from outcomes ranged from moderate to very low. Meta-analyses were not undertaken because of diverse study designs and data heterogeneity. There was no significant difference in survival between the groups, even though 5-yr overall survival appears better for the RN plus LND group compared with the no-LND group in one randomised study. There was no evidence of a difference in adverse events between the RN plus LND and no-LND groups. No studies reported QoL outcomes. There was no evidence of an oncologic difference between the RN with adrenalectomy and RN without adrenalectomy groups. No studies reported adverse events or QoL outcomes.

    Conclusions: There is insufficient evidence to draw any conclusions on oncologic outcomes for patients having concomitant LND or ipsilateral adrenalectomy compared with patients having RN alone for cT3-T4N0M0 RCC. The quality of evidence is generally low and the results potentially biased. Further research in adequately powered trials is needed to answer these questions.

  • 23. Berglund, Anders
    et al.
    Garmo, Hans
    Tishelman, Carol
    Holmberg, Lars
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lambe, Mats
    Comorbidity, treatment and mortality: a population based cohort study of prostate cancer in PCBaSe Sweden2011In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 185, no 3, 833-840 p.Article in journal (Refereed)
    Abstract [en]

    Purpose

    We examined associations among comorbidity, treatment decisions and mortality in patients with prostate cancer.

    Materials and Methods

    A total of 77,536 men diagnosed with prostate cancer between 1997 and 2006 were identified in PCBaSe Sweden from the National Prostate Cancer Register of Sweden. Logistic, Cox and competing risk regression were used to assess associations among Charlson comorbidity index, treatment and mortality. The Charlson comorbidity index was categorized into no (0), mild (1) and severe comorbidity (2+).

    Results

    In men with low risk prostate cancer 5,975 of the 13,245 (45.1%) patients without comorbidity underwent radical prostatectomy compared to 256 of the 1,399 (18.9%) men with severe comorbidity. Following adjustment for age and period of diagnosis, radical prostatectomy was less likely to be offered to men with severe comorbidity (OR 0.48, 95% CI 0.41–0.55). In men with high risk prostate cancer, radiotherapy was more common (range 7.7% to 21.3%) than radical prostatectomy (range 3.0% to 11.2%) regardless of comorbidity burden. All cause and competing cause but not prostate cancer specific mortality were increased in men with severe comorbidity (all cause HR 1.99, 95% CI 1.93–2.05; competing cause sHR 2.66, 95% CI 2.56–2.78; prostate cancer specific sHR 0.98, 95% CI 0.93–1.03). The cumulative probability of prostate cancer death given no death from competing causes was significantly higher in men with severe comorbidity in all risk groups (p <0.01).

    Conclusions

    Comorbidity affects treatment choices, and is associated with all cause, competing cause and conditional prostate cancer specific mortality. An increased conditional prostate cancer specific mortality in men with severe comorbidity may reflect less aggressive treatment, impaired tumor defense, lifestyle factors and poor general health behavior.

  • 24.
    Berglund, Anna-Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Eisemann, Martin
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Lalos, Othon
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Personality characteristics of-A stress incontinent women: a pilot study1994In: Journal of Psychosomatic Obstetrics and Gynaecology, ISSN 0167-482X, E-ISSN 1743-8942, Vol. 15, no 3, 165-170 p.Article in journal (Refereed)
    Abstract [en]

    Personality traits were assessed by means of the Karolinska Scale of Personality (KSP) and the Eysenck Personality Inventory (EPI) in 45 genuine stress incontinent women and compared with a reference group of continent women in order to investigate the possible impact of this chronic condition on the personality. Women with stress incontinence of long duration scored significantly higher than controls on the KSP scales somatic anxiety, psychic anxiety, psychasthenia and suspicion and on the EPI lie-scale. These findings point to the importance of personality factors in chronic conditions such as urinary incontinence.

  • 25.
    Berglund, Anna-Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Fugl-Meyer, Kerstin S.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Some Sexological Characteristics of Stress Incontinent Women1996In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 30, no 3, 207-212 p.Article in journal (Refereed)
    Abstract [en]

    Forty-four women with stress urinary incontinence (SUI) were interviewed in order to investigate sexual activities, sexual function and satisfaction one month before and one year after either one of two possible surgical interventions. The findings were related to sexual response cycle, size of urinary leakage, duration of incontinence and depression. There was no significant difference in sexual activity before and after surgery. One or two sexual dysfunctions within the desire, excitement, orgasmic and resolution phases were reported by the majority both before and after intervention independently of surgical method. Neither the magnitude of the leakage nor the duration of SUI influenced the sexual experiences significantly while continence after surgery promoted sexual desire. The discrepances between the prevalence of sexual dysfunctions and the relatively high level of sexual satisfaction as well as the non-influencing parameters indicate the complexity of human sexuality.

  • 26.
    Berglund, Anna-Lena
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lalos, Othon
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    The pre- and postsurgical nursing of women with stress incontinence1996In: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 23, no 3, 502-511 p.Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate subjective and objective methods used for the investigation of stress urinary incontinence (SUI) and to compare the outcome of two different surgical techniques regarding cure rate, postoperative nursing, bladder drainage and postoperative pain relief. The study included 45 women with SUI, randomized either to retropubic urethrocystopexy (n = 30) or pubococcygeal repair (n = 15). The assessment included medical history, gynaecological examination, urine analysis and culture, residual urine, pad test, frequency-continence charts, water urethrocystoscopy, continence test, and cystometry with micturition analysis. Moreover, Beck's Depression Inventory and the Eysenck Personality Inventory were used before surgery. One year after surgery no significant difference in subjective cure rate was found between the two surgical methods (73% vs. 80%, respectively). According to pad tests, 67% of the women in the urethrocystopexy group and 47% in the pubococcygeal repair group had ceased to leak urine. The bladder volume increased significantly in both groups. Sixty-three per cent of the women in the urethrocystopexy and 33% in the pubococcygeal repair group experienced severe to very severe postoperative pain. In these groups, significantly more dysphoric women were found as compared with the group of women with less postoperative pain. Furthermore, the women with more severe pain scored higher on the neuroticism scale. These findings indicate the importance of personality factors in the treatment and nursing of women with SUI.

  • 27. Berglund, Linnea Hergot
    et al.
    Prytz, Hanne Sandberg
    Perski, Aleksander
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Svartberg, Johan
    Testosterone levels and psychological health status in men from a general population: the Troms circle divide o study2011In: The Aging Male, ISSN 1368-5538, E-ISSN 1473-0790, Vol. 14, no 1, 37-41 p.Article in journal (Refereed)
    Abstract [en]

    Methods. aEuro integral Total testosterone and sex hormone-binding globulin levels were analysed and free testosterone levels was calculated in 3413 men participating in the fifth Troms circle divide o study in 2001. Self-administered questionnaires including information about education, marital status, smoking habits and the Hopkins Symptom Checklist-10 (SCL-10, a 10-item psychological health questionnaire) were completed. The cross-sectional data were analysed with partial association and analysis of variance and covariance. Results. aEuro integral The complete SCL-10 was not associated with total or free testosterone, but symptoms of anxiety were negatively associated with both total and free testosterone (p < 0.05). Men presumed to be testosterone deficient, with testosterone levels in the lowest 10th percentile, had increased SCL-10 score compared to men with higher testosterone levels (p == 0.021), before and after adjusting for age, waist circumference, marital status, education and smoking. There was an even stronger association between men presumed to be testosterone deficient and symptoms of anxiety (p < 0.001). However, men with more pronounced symptoms indicating mental disorder did not have lower testosterone levels. Conclusions. aEuro integral Men presumed being testosterone deficient had a higher symptom score, in particularly regarding anxiety, but they did not have pathological symptoms. Thus, lower testosterone levels was only associated with subthreshold symptoms of anxiety and depression.

  • 28.
    Bergman, Bo
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Studies on patients with ileal conduit diversion with special regard to renal infection1978Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The conditions for retrograde transport of urine and thereby bacteria in the urinary svstem of diverted patients (device and urinary tract) were studied with roentgeno­logical technigue. Back-flow from the urinary collecting device into the conduit occurred in a fifth of those patients who had a flat stoma. A nipple stoma of at least 2 cm height resisted back-flow better than any flat stoma.

    Ureteral reflux occurred to approximately 30 % of the ureters, both in the supine and erect body positions.The intraluminal pressure in the conduit was "low"

    (^12 cm H2O) in approximately 30 % when reflux occurred.

    The autopsy study showed a higher frequency of renal infections in diverted patients than in non-diverted controls. 5 of 11 patients who died more than 2 months after diversion, and without cancer at autopsy, were attributed to death from renal infection.

    There was a relationship between urographical abnormalities, recognized as associated with pyelonephritis, and raised serum antibody titers against E.coli and/or P.mirabilis.

    Most of the ”not normal" renal units deteriorated after the diversion operation.

    The variable "kidney area" was found to be "small" in a higher frequency after a long postoperative period than after a short one.

    Raised -serum antibody titers occurred in 35 % of the patients and were correlated to growth of the corresponding bacteria (E.coli and P.mirabilisrespectively) in the conduit urine. The frequency of raised antibody titers increased with the time after the diversion operation. After treatment with antibiotics of patients with bacteriuria and raised serum antibody titers, the titers were within normal limits («£512), or decreased significantly, in 22 of 25 patients. Serum antibody titer determinations against E.coli and P.mirabilisare suggested as complement to urinary cultures in the follow-up of diverted patients.

    The residual urine volume in the conduit was shown to be of importance for bacteriuria and raised titer against P.mirabilis.

    Some measures, which possibly may reduce bacteriuria and thereby pyelonephritis, are suggested. A nipple stoma of at least 2 cm height ought to be constructed at the operation. To obtain a low residual urine volume the conduit should be short and unobstructed. The urinary collecting device should be emptied often and connected to a uribag during the night.

  • 29.
    Bergman, Cilie
    et al.
    Halmstad University, School of Social and Health Sciences (HOS).
    Lorentsson, Kajsa
    Halmstad University, School of Social and Health Sciences (HOS).
    Gåvan till liv: upplevelser av att donera en njure2010Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Att ge bort en del av sig själv för att förbättra livet för en annan människa, är att ge gåvan till liv. Levande njurdonatorers upplevelser kommer ofta i skymundan eftersom studier ofta fokuserat på mottagarens upple-velse av njurtransplantationen. Donationen beskrivs med både positiva och negativa upplevelser. De negati-va upplevelserna förknippas med fysiska och psykiska komplikationer efter donationen. De positiva upplevel-serna beskrivs som ökad livskvalitet och glädje inför att hjälpa en människa till ett bättre liv. Syftet med denna litteraturstudie var att beskriva levande donatorers upp-levelser av att donera en njure från beslutsfattandet till tiden efter donationen. Studien genomfördes som en lit-teraturstudie, där 13 artiklar granskades och analysera-des. Resultatet visar att det finns flera faktorer, såsom oro inför mottagarens situation och oro inför sin egen framtid som påverkar donatorernas beslutsfattande. Det framkom även att både fysiska och psykiska upplevelser förekommer efter donationen. De fysiska upplevelserna var framförallt smärta, illamående samt ömhet och obe-hag runt operationssåret. Donatorns psykiska upplevel-ser efter donationen var vanligen oro inför mottagarens tillfrisknande, stress, depression samt nedstämdhet. Överlag upplevde donatorerna donationen positivt och var nöjda med sitt beslut. Mer forskning kring levande njurdonatorers upplevelser kan bidra till att sjuksköters-kor lättare kan stödja donatorer i donationsprocessen samt att blivande donatorer kan få en inblick i hur dona-tionen upplevs.

  • 30. Berndt, Sonja I
    et al.
    Sampson, Joshua
    Yeager, Meredith
    Jacobs, Kevin B
    Wang, Zhaoming
    Hutchinson, Amy
    Chung, Charles
    Orr, Nick
    Wacholder, Sholom
    Chatterjee, Nilanjan
    Yu, Kai
    Kraft, Peter
    Feigelson, Heather Spencer
    Thun, Michael J
    Diver, W Ryan
    Albanes, Demetrius
    Virtamo, Jarmo
    Weinstein, Stephanie
    Schumacher, Fredrick R
    Cancel-Tassin, Geraldine
    Cussenot, Olivier
    Valeri, Antoine
    Andriole, Gerald L
    Crawford, E David
    Haiman, Christopher
    Henderson, Brian
    Kolonel, Laurence
    Le Marchand, Loic
    Siddiq, Afshan
    Riboli, Elio
    Travis, Ruth C
    Kaaks, Rudolf
    Isaacs, William
    Isaacs, Sarah
    Wiley, Kathleen E
    Gronberg, Henrik
    Wiklund, Fredrik
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Xu, Jianfeng
    Zheng, S Lilly
    Sun, Jielin
    Vatten, Lars J
    Hveem, Kristian
    Njølstad, Inger
    Gerhard, Daniela S
    Tucker, Margaret
    Hayes, Richard B
    Hoover, Robert N
    Fraumeni, Joseph F
    Hunter, David J
    Thomas, Gilles
    Chanock, Stephen J
    Large-scale fine mapping of the HNF1B locus and prostate cancer risk2011In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 20, no 16, 3322-3329 p.Article in journal (Refereed)
    Abstract [en]

    Previous genome-wide association studies have identified two independent variants in HNF1B as susceptibility loci for prostate cancer risk. To fine-map common genetic variation in this region, we genotyped 79 single nucleotide polymorphisms (SNPs) in the 17q12 region harboring HNF1B in 10 272 prostate cancer cases and 9123 controls of European ancestry from 10 case-control studies as part of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. Ten SNPs were significantly related to prostate cancer risk at a genome-wide significance level of P < 5 × 10(-8) with the most significant association with rs4430796 (P = 1.62 × 10(-24)). However, risk within this first locus was not entirely explained by rs4430796. Although modestly correlated (r(2)= 0.64), rs7405696 was also associated with risk (P = 9.35 × 10(-23)) even after adjustment for rs4430769 (P = 0.007). As expected, rs11649743 was related to prostate cancer risk (P = 3.54 × 10(-8)); however, the association within this second locus was stronger for rs4794758 (P = 4.95 × 10(-10)), which explained all of the risk observed with rs11649743 when both SNPs were included in the same model (P = 0.32 for rs11649743; P = 0.002 for rs4794758). Sequential conditional analyses indicated that five SNPs (rs4430796, rs7405696, rs4794758, rs1016990 and rs3094509) together comprise the best model for risk in this region. This study demonstrates a complex relationship between variants in the HNF1B region and prostate cancer risk. Further studies are needed to investigate the biological basis of the association of variants in 17q12 with prostate cancer.

  • 31. Bex, Axel
    et al.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Comparing Everolimus to Sunitinib in Non-clear-cell Renal Cell Carcinoma2016In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 69, no 5, 875-876 p.Article in journal (Other academic)
  • 32.
    Bill-Axelson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Bratt, Ola
    Re: Screening and Prostate Cancer Mortality: Results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 Years of Follow-up2015In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 67, no 1, 175-175 p.Article in journal (Other academic)
  • 33.
    Bill-Axelson, Anna
    et al.
    University of Uppsala Hospital, Sweden .
    Holmberg, Lars
    University of Uppsala Hospital, Sweden Kings Coll London, England .
    Garmo, Hans
    University of Uppsala Hospital, Sweden Kings Coll London, England .
    Rider, Jennifer R.
    Brigham and Womens Hospital, MA USA Harvard University, MA USA Harvard University, MA 02115 USA .
    Taari, Kimmo
    University of Helsinki, Finland .
    Busch, Christer
    University of Uppsala Hospital, Sweden .
    Nordling, Stig
    University of Helsinki, Finland .
    Haggman, Michael
    University of Uppsala Hospital, Sweden .
    Andersson, Swen-Olof
    University of Örebro, Sweden Örebro University Hospital, Sweden .
    Spångberg, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Urology in Östergötland.
    Andren, Ove
    University of Örebro, Sweden Örebro University Hospital, Sweden .
    Palmgren, Juni
    Karolinska Institute, Sweden .
    Steineck, Gunnar
    Karolinska Institute, Sweden Sahlgrens Acad, Sweden .
    Adami, Hans-Olov
    Karolinska Institute, Sweden Harvard University, MA 02115 USA .
    Johansson, Jan-Erik
    University of Örebro, Sweden Örebro University Hospital, Sweden .
    Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 370, no 10, 932-942 p.Article in journal (Refereed)
    Abstract [en]

    BackgroundRadical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain. MethodsBetween 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy. ResultsDuring 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04). ConclusionsExtended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.) The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up.(1) By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer-specific or overall mortality after 12 years.(2) PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time ...

  • 34. Bjartell, Anders
    et al.
    Bottai, Matteo
    Persson, Josefin
    Bratt, Ola
    Damber, Jan-Erik
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Akre, Olof
    Prediction of clinical progression after radical prostatectomy in a nationwide population-based cohort2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 4, 255-259 p.Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to create a model for predicting progression-free survival after radical prostatectomy for localized prostate cancer. Material and methods: The risk of biochemical recurrence (BCR) was modelled in a cohort of 3452 men aged 70 years or younger who were primarily treated with radical prostatectomy after being diagnosed between 2003 and 2006 with localized prostate cancer [clinical stage T1c-T2, Gleason score 5-10, N0/NX, M0/MX, prostate-specific antigen (PSA)<20 ng/ml]. The cohort was split into two: one cohort for model development (n = 3452) and one for validation (n = 1762). BCR was defined as two increasing PSA values of at least 0.2 ng/ml, initiation of secondary therapy, distant metastases or death from prostate cancer. Multivariable Cox proportional hazard regression was applied, predictive performance was assessed using the bootstrap resampling technique to calculate the c index, and calibration of the model was evaluated by comparing predicted and observed Kaplan-Meier 1 year BCR. Results: The overall 5 year progression-free survival was 83% after a median follow-up time of 6.8 years in the development cohort and 7.3 years in the validation cohort. The final model included T stage, PSA level, primary and secondary Gleason grade, and number of positive and negative biopsies. The c index for discrimination between high and low risk of recurrence was 0.68. The probability of progression-free survival ranged from 22% to 97% over the range of risk scores in the study population. Conclusions: This model is based on nationwide population-based data and can be used with a fair predictive accuracy to guide decisions on clinical follow-up after prostatectomy. An online calculator for convenient clinical use of the model is available at www.npcr.se/nomogram

  • 35.
    Bjartell, Anders
    et al.
    Skane Univ Hosp, Dept Urol, SE-20502 Malmo, Sweden.;Lund Univ, Div Urol Canc, Dept Translat Med, S-22100 Lund, Sweden..
    Bottai, Matteo
    Karolinska Inst, Inst Environm Med, Unit Biostat, Stockholm, Sweden..
    Persson, Josefin
    Sahlgrens Univ Hosp, Dept Cardiothorac Surg, Gothenburg, Sweden..
    Bratt, Ola
    Lund Univ, Div Urol Canc, Dept Translat Med, S-22100 Lund, Sweden.;Cambridge Univ Hosp, Dept Urol, Cambridge, England..
    Damber, Jan-Erik
    Univ Gothenburg, Inst Clin Sci Sahlgrenska Acad, Dept Urol, Gothenburg, Sweden..
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Akre, Olof
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Urol, Stockholm, Sweden..
    Prediction of clinical progression after radical prostatectomy in a nationwide population-based cohort2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 4, 255-259 p.Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this study was to create a model for predicting progression-free survival after radical prostatectomy for localized prostate cancer. Material and methods: The risk of biochemical recurrence (BCR) was modelled in a cohort of 3452 men aged 70 years or younger who were primarily treated with radical prostatectomy after being diagnosed between 2003 and 2006 with localized prostate cancer [clinical stage T1c-T2, Gleason score 5-10, N0/NX, M0/MX, prostate-specific antigen (PSA)<20 ng/ml]. The cohort was split into two: one cohort for model development (n = 3452) and one for validation (n = 1762). BCR was defined as two increasing PSA values of at least 0.2 ng/ml, initiation of secondary therapy, distant metastases or death from prostate cancer. Multivariable Cox proportional hazard regression was applied, predictive performance was assessed using the bootstrap resampling technique to calculate the c index, and calibration of the model was evaluated by comparing predicted and observed Kaplan-Meier 1 year BCR. Results: The overall 5 year progression-free survival was 83% after a median follow-up time of 6.8 years in the development cohort and 7.3 years in the validation cohort. The final model included T stage, PSA level, primary and secondary Gleason grade, and number of positive and negative biopsies. The c index for discrimination between high and low risk of recurrence was 0.68. The probability of progression-free survival ranged from 22% to 97% over the range of risk scores in the study population. Conclusions: This model is based on nationwide population-based data and can be used with a fair predictive accuracy to guide decisions on clinical follow-up after prostatectomy. An online calculator for convenient clinical use of the model is available at www.npcr.se/nomogram

  • 36. Björk, Jonas
    et al.
    Grubb, Anders
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sterner, Gunnar
    Lindström, Veronica
    Nyman, Ulf
    Accuracy of GFR estimating equations combining standardized cystatin C and creatinine assays: a cross-sectional study in Sweden2015In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 53, no 3, 403-414 p.Article in journal (Refereed)
    Abstract [en]

     Background: The recently established international cystatin C calibrator makes it possible to develop non-laboratory specific glomerular filtration rate (GFR) estimating (eGFR) equations. This study compares the performance of the arithmetic mean of the revised Lund-Malmö creatinine and CAPA cystatin C equations (MEANLM-REV+CAPA), the arithmetic mean of the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) creatinine and cystatin C equations (MEANCKD-EPI), and the composite CKD-EPI equation (CKD-EPICREA+CYSC) with the corresponding single marker equations using internationally standardized calibrators for both cystatin C and creatinine.

    Methods: The study included 1200 examinations in 1112 adult Swedish patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of iohexol (median 51 mL/min/1.73 m2). Bias, precision (interquartile range, IQR) and accuracy (percentage of estimates ±30% of mGFR; P30) were compared.

    Results: Combined marker equations were unbiased and had higher precision and accuracy than single marker equations. Overall results of MEANLM-REV+CAPA/MEANCKD-EPI/CKD-EPICREA+CYSC were: median bias -2.2%/-0.5%/-1.6%, IQR 9.2/9.2/8.8 mL/min/1.73 m2, and P30 91.3%/91.0%/91.1%. The P30 figures were about 7-14 percentage points higher than the single marker equations. The combined equations also had a more stable performance across mGFR, age and BMI intervals, generally with P30 ≥90% and never <80%. Combined equations reached P30 of 95% when the difference between eGFRCREA and eGFRCYSC was <10% but decreased to 82% at a difference of ≥40%.

    Conclusions: Combining cystatin C and creatinine assays improves GFR estimations with P30 ≥90% in adults. Reporting estimates of both single and combined marker equations in clinical settings makes it possible to assess the validity of the combined equation based on the agreement between the single marker equations.

  • 37. Björklund, Johan
    et al.
    Folkvaljon, Yasin
    Cole, Alexander
    Carlsson, Stefan
    Robinson, David
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Urology, Ryhov County Hospital, Jönköping, Sweden.
    Loeb, Stacy
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Akre, Olof
    Postoperative mortality 90 days after robot-assisted laparoscopic prostatectomy and retropubic radical prostatectomy: a nationwide population-based study2016In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 118, no 2, 302-306 p.Article in journal (Refereed)
    Abstract [en]

    Objective To assess 90-day postoperative mortality after robot-assisted laparoscopic radical prostatectomy (RARP) and retropubic radical prostatectomy (RRP) using nationwide population-based registry data. Patients and Methods We conducted a cohort study using the National Prostate Cancer Register of Sweden, including 22 344 men with localized prostate cancer of clinical stage T1-T3, whose prostate-specific antigen levels were <50 mu g/mL and who had undergone primary radical prostatectomy in the period 1998-2012. Vital status was ascertained through the Total Population Register. The rates for 90-day postoperative mortality were analysed using logistic regression analysis, and comparisons of 90-day mortality with the background population were made using standardized mortality ratios (SMRs). Results Of the 14 820 men who underwent RRP, 29 (0.20%) died, and of the 7 524 men who underwent RARP, 10 (0.13%) died. Mortality in the cohort during the 90-day postoperative period was lower than in an age-matched background population: SMR 0.57 (95% confidence interval [CI] 0.39-0.75). There was no statistically significant difference in 90-day mortality according to surgical method: RARP vs RRP odds ratio (OR) 1.14; 95% CI 0.46-2.81. Postoperative 90-day mortality decreased over time: 2008-2012 vs 1998-2007 OR 0.44; 95% CI 0.21-0.95, mainly because of lower mortality after RARP. Conclusion The 90-day postoperative mortality rates were low after RARP and RRP and there was no statistically significant difference between the methods. Given the long life expectancy among men with low-and intermediate-risk prostate cancer, very low postoperative mortality is a prerequisite for RP, which was fulfilled by both RRP and RARP. The selection of healthy men for RP is highlighted by the lower 90-day mortality after RP compared with the background population.

  • 38. Bonn, S. E.
    et al.
    Wiklund, F.
    Sjölander, A.
    Szulkin, R.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Holmberg, E.
    Grönberg, H.
    Bälter, K.
    Body Mass Index and Weight Change in Men with Prostate Cancer: Progression and Mortality2015In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 44, 141-142 p.Article in journal (Other academic)
  • 39.
    Bovinder Ylitalo, Erik
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Thysell, Elin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jernberg, Emma
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lundholm, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Crnalic, Sead
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Egevad, Lars
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Subgroups of castration-resistant prostate cancer bone metastases defined through an inverse relationship between androgen receptor activity and immune response2017In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 71, no 5, 776-787 p.Article in journal (Refereed)
    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.

  • 40.
    Braide, Magnus
    et al.
    Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
    Delbro, Dick
    Örebro University, School of Medical Sciences.
    Waniewski, Jacek
    Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland.
    Erythrocytes as volume markers in experimental pd show that albumin transport in the extracellular space depends on pd fluid osmolarity2016In: Peritoneal Dialysis International, ISSN 0896-8608, E-ISSN 1718-4304, Vol. 36, no 3, 247-256 p.Article in journal (Refereed)
    Abstract [en]

    Background: Macromolecules, when used as intraperitoneal volume markers, have the disadvantage of leaking into the surrounding tissue. Therefore, Cr-51-labeled erythrocytes were evaluated as markers of intraperitoneal volume and used in combination with I-125-labeled bovine serum albumin to study albumin transport into peritoneal tissues in a rat model of peritoneal dialysis (PD).

    Methods: Single dwells of 20 mL of lactate-buffered filter-sterilized PD fluid at glucose concentrations of 0.5%, 2.5%, and 3.9% were performed for 1 or 4 hours. Tissue biopsies from abdominal muscle, diaphragm, liver, and intestine, and blood and dialysate samples, were analyzed for radioactivity.

    Results: The dialysate distribution volume of labeled erythrocytes, measured after correction for lymphatic clearance to blood, was strongly correlated with, but constantly 3.3 mL larger than, drained volumes. Erythrocyte activity of rinsed peritoneal tissue biopsies corresponded to only 1 mL of dialysate, supporting our utilization of erythrocytes as markers of intraperitoneal volume. The difference between the distribution volumes of albumin and erythrocytes was analyzed to represent the albumin loss into the peritoneal tissues, which increased rapidly during the first few minutes of the dwell and then leveled out at 2.5 mL. It resumed when osmotic ultrafiltration turned into reabsorption and, at the end of the dwell, it was significantly lower for the highest osmolarity PD fluid (3.9% glucose). Biopsy data showed the lowest albumin accumulation and edema formation in abdominal muscle for the 3.9% fluid.

    Conclusion: Labeled erythrocytes are acceptable markers of intraperitoneal volume and, combined with labeled albumin, provided novel kinetic data on albumin transport in peritoneal tissues.

  • 41.
    Brandstrom, Per
    et al.
    Gothenburg Univ, Sahlgrenska Acad, Queen Silvia Childrens Hosp, Dept Pediat, Gothenburg, Sweden..
    Storby, Kerstin Abelson
    Cent Hosp Vaxjo, Dept Pediat, Vaxjo, Sweden..
    Bekassy, Zivile
    Lund Univ, Dept Pediat, Clin Sci Lund, Lund, Sweden..
    Herthelius, Maria
    Karolinska Inst, Div Paediat, Clintec Dept, Stockholm, Sweden..
    Nevéus, Tryggve
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Rundqvist, Simon
    Cty Hosp Ryhov, Dept Pediat, Jonkoping, Sweden..
    Swerkersson, Svante
    Gothenburg Univ, Sahlgrenska Acad, Queen Silvia Childrens Hosp, Dept Pediat, Gothenburg, Sweden..
    WennerstrOm, Martin
    Gothenburg Univ, Sahlgrenska Acad, Queen Silvia Childrens Hosp, Dept Pediat, Gothenburg, Sweden..
    Hansson, Sverker
    Gothenburg Univ, Sahlgrenska Acad, Queen Silvia Childrens Hosp, Dept Pediat, Gothenburg, Sweden..
    Swedish UTI Guidelines2015In: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 30, no 9, 1574-1575 p.Article in journal (Other academic)
  • 42. Bratt, O.
    et al.
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Ahlgren, G.
    Nordle, O.
    Björk, A.
    Damber, Jan-Erik
    Open-label, clinical phase I studies of tasquinimod in patients with castration-resistant prostate cancer2009In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 101, no 8, 1233-40 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Tasquinimod is a quinoline-3-carboxamide derivative with anti-angiogenic activity. Two open-label phase I clinical trials in patients were conducted to evaluate the safety and tolerability of tasquinimod, with additional pharmacokinetic and efficacy assessments. METHODS: Patients with castration-resistant prostate cancer with no previous chemotherapy were enrolled in this study. The patients received tasquinimod up to 1 year either at fixed doses of 0.5 or 1.0 mg per day or at an initial dose of 0.25 mg per day that escalated to 1.0 mg per day. RESULTS: A total of 32 patients were enrolled; 21 patients were maintained for >or=4 months. The maximum tolerated dose was determined to be 0.5 mg per day; but when using stepwise intra-patient dose escalation, a dose of 1.0 mg per day was well tolerated. The dose-limiting toxicity was sinus tachycardia and asymptomatic elevation in amylase. Common treatment-emergent adverse events included transient laboratory abnormalities, anaemia, nausea, fatigue, myalgia and pain. A serum prostate-specific antigen (PSA) decline of >or=50% was noted in two patients. The median time to PSA progression (>25%) was 19 weeks. Only 3 out of 15 patients (median time on study: 34 weeks) developed new bone lesions. CONCLUSION: Long-term continuous oral administration of tasquinimod seems to be safe, and the overall efficacy results indicate that tasquinimod might delay disease progression.

  • 43. Bratt, Ola
    et al.
    Carlsson, Stefan
    Holmberg, Erik
    Holmberg, Lars
    Johansson, Eva
    Josefsson, Andreas
    Nilsson, Annika
    Nyberg, Maria
    Robinsson, David
    Sandberg, Jonas
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Sandblom, Dag
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    The Study of Active Monitoring in Sweden (SAMS): A randomized study comparing two different follow-up schedules for active surveillance of low-risk prostate cancer2013In: Scandinavian Journal of Urology, ISSN 2168-1805, Vol. 47, no 5, 347-355 p.Article, review/survey (Refereed)
    Abstract [en]

    Objective. Only a minority of patients with low-risk prostate cancer needs treatment, but the methods for optimal selection of patients for treatment are not established. This article describes the Study of Active Monitoring in Sweden (SAMS), which aims to improve those methods. Material and methods. SAMS is a prospective, multicentre study of active surveillance for low-risk prostate cancer. It consists of a randomized part comparing standard rebiopsy and follow-up with an extensive initial rebiopsy coupled with less intensive follow-up and no further scheduled biopsies (SAMS-FU), as well as an observational part (SAMS-ObsQoL). Quality of life is assessed with questionnaires and compared with patients receiving primary curative treatment. SAMS-FU is planned to randomize 500 patients and SAMS-ObsQoL to include at least 500 patients during 5 years. The primary endpoint is conversion to active treatment. The secondary endpoints include symptoms, distant metastases and mortality. All patients will be followed for 10-15 years. Results. Inclusion started in October 2011. In March 2013, 148 patients were included at 13 Swedish urological centres. Conclusions. It is hoped that the results of SAMS will contribute to fewer patients with indolent, low-risk prostate cancer receiving unnecessary treatment and more patients on active surveillance who need treatment receiving it when the disease is still curable. The less intensive investigational follow-up in the SAMS-FU trial would reduce the healthcare resources allocated to this large group of patients if it replaced the present standard schedule.

  • 44.
    Bratt, Ola
    et al.
    Lund Univ, Div Urol Canc, Dept Translat Med Urol, Lund, Sweden.;Cambridge Univ Hosp, CamPARI Clin, Dept Urol, Cambridge, England..
    Drevin, Linda
    Univ Uppsala Hosp, Reg Canc Ctr, Uppsala, Sweden..
    Akre, Olof
    Karolinska Inst, Dept Urol, Stockholm, Sweden..
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Family History and Probability of Prostate Cancer, Differentiated by Risk Category: A Nationwide Population-Based Study2016In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 108, no 10, djw110Article in journal (Refereed)
    Abstract [en]

    Background: Familial prostate cancer risk estimates are inflated by clinically insignificant low-risk cancer, diagnosed after prostate-specific antigen testing. We provide age-specific probabilities of non-low-and high-risk prostate cancer. Methods: Fifty-one thousand, eight hundred ninety-seven brothers of 32 807 men with prostate cancer were identified in Prostate Cancer data Base Sweden (PCBaSe). Nelson-Aalen estimates with 95% confidence intervals (CIs) were calculated for cumulative, family history-stratified probabilities of any, non-low-(any of Gleason score >= 7, prostate-specific antigen [PSA] >= 10 ng/mL, T3-4, N1, and/or M1) and high-risk prostate cancer (Gleason score >= 8 and/or T3-4 and/or PSA >= 20 ng/mL and/or N1 and/or M1). Results: The population probability of any prostate cancer was 4.8% (95% CI = 4.8% to 4.9%) at age 65 years and 12.9% (95% CI = 12.8% to 12.9%) at age 75 years, of non-low-risk prostate cancer 2.8% (95% CI = 2.7% to 2.8%) at age 65 years and 8.9% (95% CI = 8.8% to 8.9%) at age 75 years, and of high-risk prostate cancer 1.4% (95% CI = 1.3% to 1.4%) at age 65 years and 5.2% (95% CI = 5.1% to 5.2%) at age 75 years. For men with one affected brother, probabilities of any prostate cancer were 14.9% (95% CI = 14.1% to 15.8%) at age 65 years and 30.3% (95% CI = 29.3% to 31.3%) at age 75 years, of non-low-risk prostate cancer 7.3% (95% CI = 6.7% to 7.9%) at age 65 years and 18.8% (95% CI = 17.9% to 19.6%) at age 75 years, and of high-risk prostate cancer 3.0% (95% CI = 2.6% to 3.4%) at age 65 years and 8.9% (95% CI = 8.2% to 9.5%) at age 75 years. Probabilities were higher for men with a stronger family history. For example, men with two affected brothers had a 13.6% (95% CI = 9.9% to 17.6 %) probability of high-risk cancer at age 75 years. Conclusions: The age-specific probabilities of non-low-and high-risk cancer presented here are more informative than relative risks of any prostate cancer and more suitable to use for counseling men with a family history of prostate cancer.

  • 45. Bratt, Ola
    et al.
    Folkvaljon, Yasin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Eriksson, Marie Hjalm
    Akre, Olof
    Carlsson, Stefan
    Drevin, Linda
    Lissbrant, Ingela Franck
    Makarov, Danil
    Loeb, Stacy
    Stattin, Par
    Undertreatment of Men in Their Seventies with High-risk Nonmetastatic Prostate Cancer2015In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 68, no 1, 53-58 p.Article in journal (Refereed)
    Abstract [en]

    Background: Many elderly men with high-risk nonmetastatic prostate cancer (HRnMPCa) do not receive radical treatment, despite the high mortality associated with conservative management. Objective: To investigate how age and comorbidity affect treatment of men with HRnMPCa. Design, setting, and participants: This was an observational nationwide register study during 2001-2012. We identified 19 190 men of <80 yr of age diagnosed with HRnMPCa in the National Prostate Cancer Register of Sweden and 95 948 age-matched men without prostate cancer in the register of the total population. Outcome measurements and statistical analysis: The outcome was the proportion of men with HRnMPCa receiving radical treatment (radical prostatectomy or radiotherapy). Vital status and the Charlson comorbidity index (CCI) were obtained from nationwide registers. The 10-yr survival of men without prostate cancer, stratified by age and CCI, was used as a measure of the life expectancy of the men with prostate cancer. Results and limitations: The proportions receiving radical treatment varied with life expectancy among men younger than 70 yr, whereas use of these treatments did not match the long life expectancy of men in their seventies with CCI 0-1. Only 10% of men aged 75-80 yr with CCI 0 received radical treatment despite 52% probability of 10-yr life expectancy, compared with approximately half of the men younger than 70 yr with a similar life expectancy. The use of radical treatment for HRnMPCa increased with time in all Swedish counties, but a threefold difference between counties remained in 2009-2012 for patients aged 70-80 yr with CCI 0-1. Uncertain external validity is a study limitation, and the impact of physician versus patient preferences on treatment selection could not be assessed. Conclusions: Otherwise healthy men in their seventies with HRnMPCa were less likely to receive radical treatment than younger men with a similar life expectancy, although increasing use of radical treatment was observed during the study period. Our findings highlight the need for improved methods for clinical decision-making, including improved assessment of life expectancy. Patient summary: We performed a nationwide register study that showed that many healthy men in their seventies live for at least another 10 yr. Despite this long life expectancy, men in their seventies with high-risk nonmetastatic prostate cancer were often not treated with radical prostatectomy or radiotherapy, possibly because their life expectancy was underestimated. Our study highlights the need for improved clinical decision-making, which should incorporate an assessment of the patient's life expectancy.

  • 46. Bratt, Ola
    et al.
    Folkvaljon, Yasin
    Eriksson, Marie Hjälm
    Akre, Olof
    Carlsson, Stefan
    Drevin, Linda
    Lissbrant, Ingela Franck
    Makarov, Danil
    Loeb, Stacy
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Undertreatment of Men in Their Seventies with High-risk Nonmetastatic Prostate Cancer2015In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 68, no 1, 53-58 p.Article in journal (Refereed)
    Abstract [en]

    Background: Many elderly men with high-risk nonmetastatic prostate cancer (HRnMPCa) do not receive radical treatment, despite the high mortality associated with conservative management. Objective: To investigate how age and comorbidity affect treatment of men with HRnMPCa. Design, setting, and participants: This was an observational nationwide register study during 2001-2012. We identified 19 190 men of <80 yr of age diagnosed with HRnMPCa in the National Prostate Cancer Register of Sweden and 95 948 age-matched men without prostate cancer in the register of the total population. Outcome measurements and statistical analysis: The outcome was the proportion of men with HRnMPCa receiving radical treatment (radical prostatectomy or radiotherapy). Vital status and the Charlson comorbidity index (CCI) were obtained from nationwide registers. The 10-yr survival of men without prostate cancer, stratified by age and CCI, was used as a measure of the life expectancy of the men with prostate cancer. Results and limitations: The proportions receiving radical treatment varied with life expectancy among men younger than 70 yr, whereas use of these treatments did not match the long life expectancy of men in their seventies with CCI 0-1. Only 10% of men aged 75-80 yr with CCI 0 received radical treatment despite 52% probability of 10-yr life expectancy, compared with approximately half of the men younger than 70 yr with a similar life expectancy. The use of radical treatment for HRnMPCa increased with time in all Swedish counties, but a threefold difference between counties remained in 2009-2012 for patients aged 70-80 yr with CCI 0-1. Uncertain external validity is a study limitation, and the impact of physician versus patient preferences on treatment selection could not be assessed. Conclusions: Otherwise healthy men in their seventies with HRnMPCa were less likely to receive radical treatment than younger men with a similar life expectancy, although increasing use of radical treatment was observed during the study period. Our findings highlight the need for improved methods for clinical decision-making, including improved assessment of life expectancy. Patient summary: We performed a nationwide register study that showed that many healthy men in their seventies live for at least another 10 yr. Despite this long life expectancy, men in their seventies with high-risk nonmetastatic prostate cancer were often not treated with radical prostatectomy or radiotherapy, possibly because their life expectancy was underestimated. Our study highlights the need for improved clinical decision-making, which should incorporate an assessment of the patient's life expectancy.

  • 47. Bruck, Katharina
    et al.
    Jager, Kitty J.
    Dounousi, Evangelia
    Kainz, Alexander
    Nitsch, Dorothea
    Ärnlov, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Rothenbacher, Dietrich
    Browne, Gemma
    Capuano, Vincenzo
    Ferraro, Pietro Manuel
    Ferrieres, Jean
    Gambaro, Giovanni
    Guessous, Idris
    Hallan, Stein
    Kastarinen, Mika
    Navis, Gerjan
    Otero Gonzalez, Alfonso
    Palmieri, Luigi
    Romundstad, Solfrid
    Spoto, Belinda
    Stengel, Benedicte
    Tomson, Charles
    Tripepi, Giovanni
    Voelzke, Henry
    Wiecek, Andrzej
    Gansevoort, Ron
    Schoettker, Ben
    Wanner, Christoph
    Vinhas, Jose
    Zoccali, Carmine
    Van Biesen, Wim
    Stel, Vianda S.
    Methodology used in studies reporting chronic kidney disease prevalence: a systematic literature review2015In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 30, no S4, 6-16 p.Article, review/survey (Refereed)
    Abstract [en]

    Background. Many publications report the prevalence of chronic kidney disease (CKD) in the general population. Comparisons across studies are hampered as CKD prevalence estimations are influenced by study population characteristics and laboratory methods. Methods. For this systematic review, two researchers independently searched PubMed, MEDLINE and EMBASE to identify all original research articles that were published between 1 January 2003 and 1 November 2014 reporting the prevalence of CKD in the European adult general population. Data on study methodology and reporting of CKD prevalence results were independently extracted by two researchers. Results. We identified 82 eligible publications and included 48 publications of individual studies for the data extraction. There was considerable variation in population sample selection. The majority of studies did not report the sampling frame used, and the response ranged from 10 to 87%. With regard to the assessment of kidney function, 67% used a Jaffe assay, whereas 13% used the enzymatic assay for creatinine determination. Isotope dilution mass spectrometry calibration was used in 29%. The CKD-EPI (52%) and MDRD (75%) equations were most often used to estimate glomerular filtration rate (GFR). CKD was defined as estimated GFR (eGFR) <60 mL/min/1.73 m(2) in 92% of studies. Urinary markers of CKD were assessed in 60% of the studies. CKD prevalence was reported by sex and age strata in 54 and 50% of the studies, respectively. In publications with a primary objective of reporting CKD prevalence, 39% reported a 95% confidence interval. Conclusions. The findings from this systematic review showed considerable variation in methods for sampling the general population and assessment of kidney function across studies reporting CKD prevalence. These results are utilized to provide recommendations to help optimize both the design and the reporting of future CKD prevalence studies, which will enhance comparability of study results.

  • 48.
    Bruck, Katharina
    et al.
    Amsterdam Med Ctr, European Renal Assoc European Dialysis & Transpla, Dept Med Informat, Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands..
    Stel, Vianda S.
    Amsterdam Med Ctr, European Renal Assoc European Dialysis & Transpla, Dept Med Informat, Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands..
    Gambaro, Giovanni
    Univ Cattolica Sacro Cuore, Columbus Gemelli Univ Hosp, Div Nephrol & Dialysis, I-00168 Rome, Italy..
    Hallan, Stein
    Norwegian Univ Sci & Technol, Fac Med, St Olavs Hosp, Dept Nephrol, N-7034 Trondheim, Norway..
    Volzke, Henry
    Univ Med Greifswald, Dept Clin Epidemiol Res, Greifswald, Germany..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Kastarinen, Mika
    Kuopio Natl Inst Hlth & Welf, Dept Internal Med & Nephrol, Finnish Med Agcy, Helsinki, Finland..
    Guessous, Idris
    Univ Hosp Geneva, Dept Community Med Primary Care & Emergency Med, Geneva, Switzerland..
    Vinhas, Jose
    Setubal Hosp Ctr, Dept Med, Setubal, Portugal..
    Stengel, Benedicte
    INSERM, U1018, Res Ctr Epidemiol & Populat Hlth, Villejuif, France..
    Brenner, Hermann
    Heidelberg Univ, German Canc Res Ctr, Network Aging Res, Div Clin Epidemiol & Aging Res, Heidelberg, Germany..
    Chudek, Jerzy
    Med Univ Silesia, Dept Nephrol Endocrinol & Metab Dis, Med Fac, Dept Pathophysiol, Katowice, Poland..
    Romundstad, Solfrid
    Norwegian Univ Sci & Technol, Levanger Hosp, Hlth Trust Nord Trendelag, Dept Nephrol, N-7034 Trondheim, Norway..
    Tomson, Charles
    Freeman Rd Hosp, Dept Nephrol, Newcastle Upon Tyne, Tyne & Wear, England..
    Otero Gonzalez, Alfonso
    Univ Hosp Orense, Dept Nephrol, Orense, Spain..
    Bello, Aminu K.
    Univ Alberta, Dept Med, Edmonton, AB, Canada..
    Ferrieres, Jean
    Toulouse Univ, Sch Med, Rangueil Hosp, Dept Cardiol, Toulouse, France..
    Palmieri, Luigi
    Ist Super Sanita, Dept Epidemiol Cerebro & Cardiovasc Dis, Viale Regina Elena 299, I-00161 Rome, Italy..
    Browne, Gemma
    Univ Coll Cork, Dept Epidemiol & Publ Hlth, Cork, Ireland.;Mercy Univ Hosp, Cork, Ireland..
    Capuano, Vincenzo
    Mercato S Severino Hosp, Unite Operat Cardiol, Salerno, Italy.;Mercato S Severino Hosp, UTIC, Salerno, Italy..
    Van Biesen, Wim
    Ghent Univ Hosp, Dept Nephrol, Ghent, Belgium..
    Zoccali, Carmine
    CNR, Ist Fisiol Clin, Clin Epidemiol & Pathophysiol Renal Dis & Hyperte, Reggio Di Calabria, Italy..
    Gansevoort, Ron
    Univ Med Ctr Groningen, Grad Sch Med Sci, Dept Nephrol, NL-9713 AV Groningen, Netherlands..
    Navis, Gerjan
    Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, NL-9713 AV Groningen, Netherlands..
    Rothenbacher, Dietrich
    Univ Ulm, Inst Epidemiol & Med Biometry, D-89069 Ulm, Germany..
    Ferraro, Pietro Manuel
    Univ Cattolica Sacro Cuore, Columbus Gemelli Univ Hosp, Div Nephrol & Dialysis, I-00168 Rome, Italy..
    Nitsch, Dorothea
    London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1, England.;UCL, London, England..
    Wanner, Christoph
    Univ Hosp Wurzburg, Dept Nephrol, Wurzburg, Germany..
    Jager, Kitty J.
    Amsterdam Med Ctr, European Renal Assoc European Dialysis & Transpla, Dept Med Informat, Meibergdreef 9, NL-1100 DD Amsterdam, Netherlands..
    Consortium, European C. K. D. Burden
    CKD Prevalence Varies across the European General Population2016In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 27, no 7, 2135-2147 p.Article in journal (Refereed)
    Abstract [en]

    CKD prevalence estimation is central to CKD management and prevention planning at the population level. This study estimated CKD prevalence in the European adult general population and investigated international variation in CKD prevalence by age, sex, and presence of diabetes, hypertension, and obesity. We collected data from 19 general-population studies from 13 European countries. CKD stages 1-5 was defined as eGFR <60 ml/min per 1.73 m(2), as calculated by the CKD-Epidemiology Collaboration equation, or albuminuria >30 mg/g, and CKD stages 3-5 was defined as eGFR<60 ml/min per 1.73 m(2). CKD prevalence was age- and sex-standardized to the population of the 27 Member States of the European Union (EU27). We found considerable differences in both CKD stages 1-5 and CKD stages 3-5 prevalence across European study populations. The adjusted CKD stages 1-5 prevalence varied between 3.31% (95% confidence interval [95% CI], 3.30% to 3.33%) in Norway and 17.3% (95% Cl, 16.5% to 18.1%) in northeast Germany. The adjusted CKD stages 3-5 prevalence varied between 1.0% (95% CI, 0.7% to 1.3%) in central Italy and 5.9% (95% CI, 5.2% to 6.6%) in northeast Germany. The variation in CKD prevalence stratified by diabetes, hypertension, and obesity status followed the same pattern as the overall prevalence. In conclusion, this large-scale attempt to carefully characterize CKD prevalence in Europe identified substantial variation in CKD prevalence that appears to be due to factors other than the prevalence of diabetes, hypertension, and obesity.

  • 49. Bruins, Harman M
    et al.
    Veskimae, Erik
    Hernandez, Virginia
    Imamura, Mari
    Neuberger, Molly M
    Dahm, Philip
    Stewart, Fiona
    Lam, Thomas B
    N'Dow, James
    van der Heijden, Antoine G
    Compérat, Eva
    Cowan, Nigel C
    De Santis, Maria
    Gakis, Georgios
    Lebret, Thierry
    Ribal, Maria J
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Witjes, J Alfred
    The impact of the extent of lymphadenectomy on oncologic outcomes in patients undergoing radical cystectomy for bladder cancer: a systematic review2014In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 66, no 6, 1065-1077 p.Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Controversy exists regarding the therapeutic value of lymphadenectomy (LND) in patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To systematically review the relevant literature assessing the impact of LND on oncologic and perioperative outcomes in patients undergoing RC for MIBC. EVIDENCE ACQUISITION: Medline, Medline In-Process, Embase, the Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Center on Health Sciences Information (LILACS) were searched up to December 2013. Comparative studies reporting on no LND, limited LND (L-LND), standard LND (S-LND), extended LND (E-LND), superextended LND (SE-LND), and oncologic and perioperative outcomes were included. Risk-of-bias and confounding assessments were performed. EVIDENCE SYNTHESIS: Twenty-three studies reporting on 19 793 patients were included. All but one study were retrospective. Planned meta-analyses were not possible because of study heterogeneity; therefore, data were synthesized narratively. There were high risks of bias and confounding across most studies as well as extreme heterogeneity in the definition of the anatomic boundaries of LND templates. All seven studies comparing LND with no LND favored LND in terms of better oncologic outcomes. Seven of 14 studies comparing (super)extended LND with L-LND or S-LND reported a beneficial outcome for (super)extended LND in at least a subset of patients. No difference in outcome was reported in two studies comparing E-LND and S-LND. The comparative harms of different extents of LND remain unclear. CONCLUSIONS: Although the quality of the data was poor, the available evidence indicates that any kind of LND is advantageous over no LND. Similarly, E-LND appears to be superior to lesser degrees of dissection, while SE-LND offered no additional benefits. It is hoped that data from ongoing randomized clinical trials will clarify remaining uncertainties. PATIENT SUMMARY: The current literature suggests that removal of lymph nodes in bladder cancer surgery is beneficial and might result in better outcomes in terms of prolonging survival; however, the quality of the available studies is poor, and high-quality studies are needed.

  • 50. Burlaka, Ievgeniia
    et al.
    Liu, Xiao Li
    Rebetz, Johan
    Arvidsson, Ida
    Yang, Liping
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Karpman, Diana
    Aperia, Anita
    Ouabain Protects against Shiga Toxin-Triggered Apoptosis by Reversing the Imbalance between Bax and Bcl-xL2013In: Journal of the American Society of Nephrology, ISSN 1046-6673, Vol. 24, no 9, 1413-1423 p.Article in journal (Refereed)
    Abstract [en]

    Hemolytic uremic syndrome, a life-threatening disease often accompanied by acute renal failure, usually occurs after gastrointestinal infection with Shiga toxin 2 (Stx2)-producing Escherichia coli. Stx2 binds to the glycosphingolipid globotriaosylceramide receptor, expressed by renal epithelial cells, and triggers apoptosis by activating the apoptotic factor Bax. Signaling via the ouabain/Na,K-ATPase/IP3R/NF-B pathway increases expression of Bcl-xL, an inhibitor of Bax, suggesting that ouabain might protect renal cells from Stx2-triggered apoptosis. Here, exposing rat proximal tubular cells to Stx2 in vitro resulted in massive apoptosis, upregulation of the apoptotic factor Bax, increased cleaved caspase-3, and downregulation of the survival factor Bcl-xL; co-incubation with ouabain prevented all of these effects. Ouabain activated the NF-B antiapoptotic subunit p65, and the inhibition of p65 DNA binding abolished the antiapoptotic effect of ouabain in Stx2-exposed tubular cells. Furthermore, in vivo, administration of ouabain reversed the imbalance between Bax and Bcl-xL in Stx2-treated mice. Taken together, these results suggest that ouabain can protect the kidney from the apoptotic effects of Stx2.

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