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  • 301.
    Sjöström, Malin
    et al.
    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, Epidemiology and Global Health.
    Carlbring, Per
    Andersson, Gerhard
    Samuelsson, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Internet-based treatment of stress urinary incontinence: 1- and 2-year results of a randomized controlled trial with a focus on pelvic floor muscle training.2015In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 116, no 6, p. 955-964Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the long-term effects of two non-face-to-face treatment programmes for stress urinary incontinence (SUI) based on pelvic floor muscle training (PFMT).

    SUBJECTS AND METHODS: The present study was a randomized controlled trial with online recruitment of 250 community-dwelling women aged 18-70 years with SUI ≥ one time/week. Diagnosis was based on validated self-assessed questionnaires, 2-day bladder diary and telephone interview with a urotherapist. Consecutive computer-generated block randomization was carried out with allocation by an independent administrator to 3 months of treatment with either an internet-based treatment programme (n = 124) or a programme sent by post (n = 126). Both interventions focused mainly on PFMT. The internet group received continuous e-mail support from a urotherapist, whereas the postal group trained on their own. Follow-up was performed after 1 and 2 years via self-assessed postal questionnaires. The primary outcomes were symptom severity (International Consultation on Incontinence Questionnaire Short Form [ICIQ-UI SF]) and condition-specific quality of life (ICIQ-Lower Urinary Tract Symptoms Quality of Life [ICIQ-LUTSqol]). Secondary outcomes were the Patient Global Impression of Improvement, health-specific quality of life (EQ-visual analogue scale [EQ-VAS]), use of incontinence aids, and satisfaction with treatment. There was no face-to-face contact with the participants at any time. Analysis was based on intention-to-treat.

    RESULTS: We lost 32.4% (81/250) of participants to follow-up after 1 year and 38.0% (95/250) after 2 years. With both interventions, we observed highly significant (P < 0.001) improvements with large effect sizes (>0.8) for symptoms and condition-specific quality of life (QoL) after 1 and 2 years, respectively. No significant differences were found between the groups. The mean (sd) changes in symptom score were 3.7 (3.3) for the internet group and 3.2 (3.4) for the postal group (P = 0.47) after 1 year, and 3.6 (3.5) for the internet group and 3.4 (3.3) for the postal group (P = 0.79) after 2 years. The mean changes (sd) in condition-specific QoL were 5.5 (6.5) for the internet group and 4.7 the for postal group (6.5) (P = 0.55) after 1 year, and 6.4 (6.0) for the internet group and 4.8 (7.6) for the postal group (P = 0.28) after 2 years. The proportions of participants perceiving they were much or very much improved were similar in both intervention groups after 1 year (internet, 31.9% [28/88]; postal, 33.8% [27/80], P = 0.82), but after 2 years significantly more participants in the internet group reported this degree of improvement (39.2% [29/74] vs 23.8% [19/80], P = 0.03). Health-specific QoL improved significantly in the internet group after 2 years (mean change in EQ-VAS, 3.8 [11.4], P = 0.005). We found no other significant improvements in this measure. At 1 year after treatment, 69.8% (60/86) of participants in the internet group and 60.5% (46/76) of participants in the postal group reported that they were still satisfied with the treatment result. After 2 years, the proportions were 64.9% (48/74) and 58.2% (46/79), respectively.

    CONCLUSION: Non-face-to-face treatment of SUI with PFMT provides significant and clinically relevant improvements in symptoms and condition-specific QoL at 1 and 2 years after treatment.

  • 302.
    Sjöström, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Umefjord, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Carlbring, Per
    Andersson, Gerhard
    Samuelsson, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Internet-based treatment of stress urinary incontinence: a randomised controlled study with focus on pelvic floor muscle training2013In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 112, no 3, p. 362-372Article in journal (Refereed)
    Abstract [en]

    Objective To compare two treatment programmes for stress urinary incontinence (SUI) without face-to-face contact: one Internet-based and one sent by post.

    Patients and Methods Randomised, controlled trial conducted in Sweden 2009-2011. Computer-generated block-randomisation, allocation by independent administrator. No 'blinding'. The study included 250 community-dwelling women aged 18-70 years, with SUI >= 1 time/week. Consecutive online recruitment. The women had 3 months of either; (i) An Internet-based treatment programme (124 women), including e-mail support and cognitive behavioural therapy assignments or (ii) A treatment programme sent by post (126). Both programmes focused mainly on pelvic floor muscle training.

    Primary outcomes symptom-score (International Consultation on Incontinence Questionnaire Short Form, ICIQ-UI SF) and condition-specific quality of life (ICIQ-Lower Urinary Tract Symptoms Quality of Life, ICIQ-LUTSQoL).

    Secondary outcomes (i) Patient Global Impression of Improvement, (ii) Incontinence aids, (iii) Patient satisfaction, (iv) Health-specific QoL (EQ5D-Visual Analogue Scale), and (v) Incontinence episode frequency. Follow-up after 4 months via self-assessed postal questionnaires.

    Results In all, 12% (30 women) were lost to follow-up. Intention-to-treat analysis showed highly significant improvements (P < 0.001) with large effect sizes (>0.8) with both interventions, but there were no significant differences between groups in primary outcomes. The mean (SD) changes in symptom-score were: Internet 3.4 (3.4), Postal 2.9 (3.1) (P = 0.27). The mean (SD) changes in condition-specific QoL were: Internet 4.8 (6.1), Postal 4.6 (6.7) (P = 0.52). Compared with the postal-group, more participants in the Internet-group perceived they were much or very much improved (40.9% (43/105) vs 26.5% (30/113), P = 0.01), reported reduced usage of incontinence aids (59.5% (47/79) vs 41.4% (34/82), P = 0.02) and were satisfied with the treatment programme (84.8% (89/105) vs 62.9% (71/113), P < 0.001). Health-specific QoL improved in the Internet-group (mean change 3.7 (10.9), P = 0.001), but not in the postal-group (1.9 (13.0), P = 0.13). Overall, 69.8% (120/172) of participants reported complete lack of leakage or reduced number of leakage episodes by >50%.

    Conclusions Concerning primary outcomes, treatment effects were similar between groups whereas for secondary outcomes the Internet-based treatment was more effective. Internet-based treatment for SUI is a new, promising treatment alternative.

  • 303.
    Skagerlind, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Nursing.
    How to reduce the exposure to anticoagulants when performing haemodialysis in patients with a bleeding risk: a study of methods used in clinical practise2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    When a patient suffers from kidney failure and also has an enhanced risk of bleeding, the standard haemodialysis (HD) treatment becomes a problem. When human blood comes in contact with artificial material, as in the tubing system and in the dialyser (the extra corporeal circuit, ECC), the coagulation system is activated. If there is no increased risk of bleeding a bolus dose of anticoagulation is given intravenous to the patient before HD to avoid clotting. The most common anticoagulants used during HD are unfractionated heparin (UFH) and low molecule weight heparins (LMWH). Without anticoagulants there will be a total coagulation (clotting) of the blood in the ECC, an interrupted treatment and a blood loss of up to 300 ml for the patient. With an ongoing bleeding or an increased risk of bleeding in a patient that also needs HD, there are various alternatives that can be used to avoid or lower the need of anticoagulation. However, there is no golden standard, neither in Sweden or worldwide.

    The overall aim of this Thesis was to evaluate the safety and the efficacy of various models of anticoagulation that may be used in patients with a bleeding risk.

    The first study examined a low-dose anticoagulation model that was locally developed in Umeå, Sweden in the 1980s. The primary aim was to clarify to what extent this priming model was safe and efficient during intermittent HD for patients with a bleeding risk. Consecutive acute HD treatment protocols (248 procedures in 68 patients) were included. There were 178 patients with an increased bleeding risk who had their ECC (tubes, chambers and dialyser) flushed through (priming) with Heparin-Albumin-priming (HA-priming). There were 70 patients with no increased bleeding risk who received standard intermittent HD (priming with saline); these patients also received a bolus dose of anticoagulation intravenous before dialysis.

    The low-dose method entailed priming of the ECC with HA-priming with the intention to coat the surfaces with the solution and protect from blood to attach to it. Comparisons were made to dialysis in patients with no increased bleeding risk, who had received standard anticoagulation (SHD) with UFH or LMWH. The priming solutions were always discarded before HD was initiated. None or limited doses of UFH were added during the HD. There was no difference in extent of prematurely interrupted HA-primed dialysis compared to SHD (2.2 vs. 4.3%, p = 0.62). No secondary bleeding due to anticoagulation was reported in the protocols.

    Study 2 was performed to further clarify data in an extended group of acute intermittent HD using either HA-priming (885 treatments in 221 patients at risk of bleeding) or SHD (523 treatments in 100 patients with no bleeding risk who had received standard anticoagulation). In this extended study there was no difference in the extent of prematurely interrupted HA-dialysis (0.8%) compared to SHD (1%, p = 0.8). The results also showed less clotting for dialysers with a membrane area ≤ 1.7 m2. No secondary bleeding due to anticoagulation was reported in the protocols.

    Study 3 was an experimental in vitro study. The aim was to compare the anticoagulation effect of priming the ECC with different concentrations of albumin and/or heparin in saline. Priming with saline only was also evaluated. The priming fluids were always discarded after priming. Fresh whole blood from healthy human donors was used to perform in vitro dialyses in a recirculation system. The donated blood was equally divided into two bags, whereas one bag represented the control group and the other the intervention group. Priming with saline only and priming with albumin in saline resulted in rapid clotting of the blood in the ECC. These experiments indicated that HA-priming or priming with heparin in saline enabled fulfilment of all the in vitro dialyses.

    Study 4 was a clinical randomized cross-over study. The aim was to minimize the use of anticoagulant during HD in patients with a bleeding risk. Four different low-dose anticoagulation models were compared to SHD. Stable chronic HD patients participated in the study. The patients were their own controls. Aside from SHD, the four models of low-dose anticoagulation used were Heparin priming (H), HA-priming (HA), HA-priming in combination with a citrate containing dialysate (HAC), and a dialyser manufactured with a heparin-grafted membrane (Evodial®). The H-model was least suitable with 33 % interrupted treatments and the most extra doses of UFH needed. The HAC and Evodial® models were most preferable, both with an activated partial thromboplastin time (APTT) within references and with the least amounts of UFH needed. Evodial® had a lower urea reduction rate compared to the other models. HAC was the only model with no interrupted treatment. One patient suffered from a severe hypersensitivity reaction using Evodial®. No other side-effects were reported during the study.

    In conclusion an acute kidney injury is a life-threating situation that also includes patients with an increased bleeding risk and in need of HD for survival. If intermittent HD is the selected option, a priming of the ECC with a HA-solution in combination with a citrate containing dialysis fluid (HAC) is a safe and sufficient option for anticoagulation. Another option could be the heparin-grafted dialyser (Evodial®), although with a lower clearance coefficient and with a caution for a risk for hypersensitivity reaction or anaphylaxis.

  • 304.
    Skagerlind, Malin
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Heparin albumin priming in a clinical setting for hemodialysis patients at risk for bleeding2017In: Hemodialysis International, ISSN 1492-7535, E-ISSN 1542-4758, Vol. 21, no 2, p. 180-189Article in journal (Refereed)
    Abstract [en]

    Introduction: Intermittent hemodialysis (IHD) is sometimes necessary in patients with a bleeding risk, i.e., before/after surgery or brain hemorrhage. In such case IHD has to be modified to limit the conventional anticoagulation used to avoid clotting of the extracorporeal circuit (ECC). We evaluated if priming using a heparin and albumin (HA) mixture could minimize the exposure to heparin.

    Methods: Retrospective data from 1995 to 2013 were collected from 1408 acute dialysis treatment protocols that included 321 patients. Comparisons were made between IHD patients that had increased risk for bleeding and were treated by standard anticoagulation (Group-S), and patients at increased risk of bleeding (Group-HA). The ECC in Group-HA was primed with a solution of unfractioned heparin (UFH) (5000 Units/L) and albumin (1 g/L) in saline that was discarded after priming. There were 16 different dialyzers in the material.

    Findings: Comparing Group-S (n = 883) with Group-HA (n = 221), the mean age was 61.6 vs. 62.2 years (P = 0.8), dialysis time was 197 vs. 190 minutes (P = 0.002), and total dose of intravenous anticoagulant/IHD was at median 5000 Units vs. 1200 Units (P = 0.001). Twenty-four percent of patients were treated without any additional heparin. Clotting resulting in interrupted dialysis was similar in both groups (0.8% for Group-S vs. 1.0% for Group-HA, P = 0.8). No secondary bleeding was reported in either group.

    Discussion: HA priming minimized the risk of clotting and enabled acute IHD in vulnerable patients without increased bleeding, thus allowing completion of IHD to the same extent as for standard HD.

  • 305. Sooriakumaran, Prasanna
    et al.
    Nyberg, Tommy
    Akre, Olof
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Hamdy, Freddie
    Graefen, Markus
    Carlsson, Stefan
    Steineck, Gunnar
    Wiklund, N. Peter
    Survival Among Men at High Risk of Disseminated Prostate Cancer Receiving Initial Locally Directed Radical Treatment or Initial Androgen Deprivation Therapy2017In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, no 3, p. 345-351Article in journal (Refereed)
    Abstract [en]

    Background: There is increasing low-quality evidence rationalizing the use of radical therapy for men at high risk of disseminated prostate cancer. Objective: To investigate, using high-quality epidemiologic data, whether initial radical therapy in men at high risk of disseminated prostate cancer improves survival. Design, setting, and participants: An observational population-based Swedish study from 1996 to 2010 of men at high risk of disseminated prostate cancer (prostate-specific antigen [PSA] > 50) initially treated by radical therapy (radiation therapy [n = 630] or radical prostatectomy [n = 120]) or androgen deprivation therapy (n = 17 602), and followed for up to 15 yr. Outcome measurements and statistical analysis: Prostate-cancer and other-cause mortality was estimated for the treatment groups. We also matched the two cohorts for grade, T stage, M stage, Charlson score, year of diagnosis, age, and PSA, and found androgen deprivation therapy patient matches for 575 of the radical therapy patients, and then repeated comparative effectiveness analyses. Results and limitation: Prostate-cancer mortality was substantially greater in the androgen deprivation therapy group compared with the radically treated one, in unmatched (9062/17 602 vs 86/750) and matched (177/575 vs 71/575) cohorts. Among matched cohorts, initial androgen deprivation therapy was associated with nearly three-fold higher hazard of prostate-cancer death compared with initial radical therapy (2.87; 95% confidence interval 2.16-3.82). Multiple sensitivity analyses suggested that the findings were robust, although the general limitations of nonrandomized studies remain. Further, the study cohort may have included men with both systemic and nonsystemic disease, as a sole eligibility criterion of PSA > 50 was used. Conclusions: This large and comprehensive population-based study suggests that initial radical therapy in men at high risk of disseminated prostate cancer improves survival. Patient summary: This large Swedish study suggests that men with prostate cancer that has spread beyond the prostate benefit from treating the prostate itself with radiation therapy or surgery rather than treating the disease with hormones alone.

  • 306.
    Stattin, Pär
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgery, Urology Service, Memorial Sloan-Kettering Cancer Centre, New York, NY, USA.
    Loeb, Stacy
    Department of Urology, New York University and Manhattan Veterans Affairs Medical Centre, New York, NY, USA.
    "To Measure Is To Know. If You Cannot Measure It, You Cannot Improve It'': Statistical Modeling Cannot Compensate for Unmeasured Bias2014In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 65, no 4, p. 701-703Article in journal (Other academic)
  • 307.
    Stattin, Pär
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Robinson, David
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lambe, Mats
    Uppsala University Hospital, Regional Cancer Center, Uppsala, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Re: Giorgio Gandaglia, Freddie Bray, Matthew R. Cooperberg, et al.: Prostate Cancer Registries: Current Status and Future Directions. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2015.05.0462015In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 68, no 5, p. E110-E110Article in journal (Refereed)
  • 308.
    Stattin, Pär
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Sandin, Fredrik
    Birkebæk Thomsen, Frederik
    Garmo, Hans
    Robinson, David
    Franck Lissbrant, Ingela
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Bratt, Ola
    Association of Radical Local Treatment with Mortality in Men with Very High-risk Prostate Cancer: A Semiecologic, Nationwide, Population-based Study2017In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, no 1, p. 125-134Article in journal (Refereed)
    Abstract [en]

    Background: Current guidelines recommend androgen deprivation therapy only for men with very high-risk prostate cancer (PCa), but there is little evidence to support this stance.

    Objective: To investigate the association between radical local treatment and mortality in men with very high-risk PCa.

    Design, setting, and participants: Semiecologic study of men aged <80 yr within the Prostate Cancer data Base Sweden, diagnosed in 1998–2012 with very high-risk PCa (local clinical stage T4 and/or prostate-specific antigen [PSA] level 50–200 ng/ml, any N, and M0). Men with locally advanced PCa (local clinical stage T3 and PSA level <50 ng/ml, any N, and M0) were used as positive controls.

    Intervention: Proportion of men who received prostatectomy or full-dose radiotherapy in 640 experimental units defined by county, diagnostic period, and age at diagnosis.

    Outcome measurements and statistical analysis: PCa and all-cause mortality rate ratios (MRRs).

    Results and limitations: Both PCa and all-cause mortality were half as high in units in the highest tertile of exposure to radical local treatment compared with units in the lowest tertile (PCa MRR: 0.51; 95% confidence interval [CI], 0.28–0.95; and all-cause MRR: 0.56; 95% CI, 0.33–0.92). The results observed for locally advanced PCa for highest versus lowest tertile of exposure were in agreement with results from randomized trials (PCa MRR: 0.75; 95% CI, 0.60–0.94; and all-cause MRR: 0.85; 95% CI, 0.72–1.00). Although the semiecologic design minimized selection bias on an individual level, the effect of high therapeutic activity could not be separated from that of high diagnostic activity.

    Conclusions: The substantially lower mortality in units with the highest exposure to radical local treatment suggests that radical treatment decreases mortality even in men with very high-risk PCa for whom such treatment has been considered ineffective.

    Patient summary: Men with very high-risk prostate cancer diagnosed and treated in units with the highest exposure to surgery or radiotherapy had a substantially lower mortality.

  • 309.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Air contamination during hemodialysis should be minimized2017In: Hemodialysis International, ISSN 1492-7535, E-ISSN 1542-4758, Vol. 21, no 2, p. 168-172Article, review/survey (Refereed)
    Abstract [en]

    During preparation of the hemodialysis (HD) extracorporeal circuit (ECC) a priming solution is used to remove air from the tubes and dialyzer. Ultra sound techniques have verified micro embolic signals (MES) in the ECC that may derive from clots or gas embolies. In vitro studies could clarify that embolies of air develop within the ECC and also pass the safety systems such as air traps and enter the venous line that goes into the patient. Clinical studies have confirmed the presence of MES within the ECC that pass into the return-venous-line during conventional HD without inducing an alarm. In addition, studies confirmed that such MES were present within the AV fistula and subclavian vein, but also detected within the carotid artery. Autopsy studies revealed the presence of gas embolies surrounded by clots within the lung but also brain and myocardial tissue. This review will focus on how the MES develop and measures of how the exposure can be limited.

  • 310.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Presidential address: XLI Annual ESAO Congress - 17-20 September 2014, Rome, Italy2014In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 37, no 8, p. 569-Article in journal (Other academic)
  • 311.
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The World Apheresis Association Registry2017In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 56, no 1, p. 69-70Article, review/survey (Refereed)
  • 312.
    Stegmayr, Bernd
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Brännström, M
    Bucht, S
    Crougneau, V
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Dimeny, Emöke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ekspong, A
    Eriksson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Granroth, B
    Gröntoft, KC
    Hadimeri, H
    Holmberg, Benny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ingman, B
    Isaksson, B
    Johansson, G
    Lindberger, K
    Lundberg, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mikaelsson, L
    Olausson, E
    Persson, B
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wikdahl, A-M
    Low-dose atorvastatin in severe chronic kidney disease patients: a randomized, controlled endpoint study2005In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 39, no 6, p. 489-497Article in journal (Refereed)
    Abstract [en]

    Objective. There have been no endpoint studies with statins for patients with severe renal failure. The purpose of this prospective, open, randomized, controlled study was to investigate whether atorvastatin (10 mg/day) would alter cardiovascular endpoints and the overall mortality rate of patients with chronic kidney disease stage 4 or 5 (creatinine clearance < 30 ml/min).

    Material and methods. The study subjects comprised 143 patients who were randomized either to placebo (controls; n=73; mean age 69.5 years) or to treatment with atorvastatin (n=70; mean age 67.9 years). The patients included were either non-dialysis (n=33), haemodialysis (n=97) or peritoneal dialysis (n=13) patients. Analysis focused on the primary endpoints of all-cause mortality, non-lethal acute myocardial infarction, coronary artery bypass graft surgery and percutaneous transluminal coronary angioplasty. Statistical analysis for endpoint data was mainly by intention-to-treat.

    Results. Primary endpoints occurred in 74% of the subjects. There was no difference in outcome between the control and atorvastatin groups. The 5-year endpoint-free survival rate from study entry was 20%. Atorvastatin was withdrawn in 20% of patients due to unacceptable side-effects. In the atorvastatin group, low-density lipoprotein (LDL) cholesterol was reduced by 35% at 1 month and then sustained. The controls showed a progressive reduction in LDL cholesterol until 36 months.

    Conclusions. Although atorvastatin reduced total and LDL cholesterol effectively it was not beneficial regarding the long-term outcomes of cardiovascular endpoints or survival. In contrast to other patient groups, patients with severe chronic kidney disease, especially those on dialysis, seem to derive limited benefit from this lower dose of atorvastatin.

  • 313.
    Stegmayr, Bernd
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Brännström, M
    Bucht, S
    Dimeny, Emöke
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ekspong, A
    Granroth, B
    Gröntoft, KC
    Hadimeri, H
    Holmberg, Benny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ingman, B
    Isaksson, B
    Johansson, G
    Lindberger, K
    Lundberg, Lennart
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundström, Ola
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mikaelsson, L
    Mörtzell, Monica
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olausson, E
    Persson, B
    Svensson, L
    Wikdahl, AM
    Minimized weight gain between hemodialysis contributes to a reduced risk of death2006In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 29, no 7, p. 675-680Article in journal (Refereed)
  • 314.
    Stegmayr, Bernd
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Forsberg, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jonson, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Christofer
    Hultdin, Johan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Microbubbles of air may occur in the organs of hemodialysis patients2012In: ASAIO journal (1992), ISSN 1058-2916, E-ISSN 1538-943X, Vol. 58, no 2, p. 177-179Article in journal (Refereed)
    Abstract [en]

    During hemodialysis (HD), blood that passes the dialysis device gets loaded with microbubbles (MB) of air that are returned to the patient without inducing an alarm. The aim with this study was to clarify if these signals are due to microembolies of air, clots, or artifacts, by histopathology of autopsy material of HD patients. These first results are from a patient on chronic HD. Due to pulmonary edema he was ultrafiltered. Within 30 minutes after the start, he suffered from a cardiac arrest and died. Autopsy verified the clinical findings. Microscopic investigation verified microembolies of air that were surrounded by fibrin in the lungs, brain, and heart. The study verified that MBs can enter the blood during HD and are trapped in the lungs. In addition, MBs pass the pulmonary capillaries and enter the arterial part of the body and are dispersed throughout the body. This can contribute to organ damage and be part of the poor prognoses seen in HD patients. Data support the importance to reduce MBs in the dialysis circuit.

  • 315.
    Stegmayr, Bernd
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Forsberg, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jonsson, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Christofer
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    The sensor in the venous chamber does not prevent passage of air bubbles during hemodialysis2007In: Artificial Organs, ISSN 0160-564X, E-ISSN 1525-1594, Vol. 31, no 2, p. 162-166Article in journal (Refereed)
  • 316.
    Stegmayr, Bernd G
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    New insight in impaired binding capacity for albumin in uraemic patients2015In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 215, no 1, p. 5-8Article in journal (Refereed)
  • 317.
    Stegmayr, Bernd G
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sources of Mortality on Dialysis with an Emphasis on Microemboli2016In: Seminars in dialysis, ISSN 0894-0959, E-ISSN 1525-139X, Vol. 29, no 6, p. 442-446Article in journal (Refereed)
    Abstract [en]

    Patients on chronic hemodialysis have a shortened survival compared to the general population. There are multiple sources of morbidity and mortality unique to the dialysis population that account for this. Reasons include the effects of blood membrane interactions, intradialytic hypotension, myocardial stunning, excessive interdialytic weight gain, high-flow arteriovenous fistulae, and impaired lipid break down by anticoagulation administered during HD. Another risk factor, not well appreciated, is the occurrence of microemboli of air (microbubbles) during HD. Such microemboli are not effectively removed by the venous air trap and the safety system provides no warning when these small microbubbles enter the venous bloodline of the extra corporeal circuit and then the venous circulation of the patient. Data indicate that the gas emboli are not fully adsorbed and become embedded by fibrin resulting in a combined clot that causes microemboli in the lung. In addition, these microbubbles (of the size of blood corpuscles) can pass the pulmonary circulation into the left heart and then into the general arterial circulation explaining their detection not only in the lungs but also in the brain and heart of patients. Risk factors for such microbubble appearance include the high blood pump speed associated with high-efficiency dialyses. This review will discuss these various issues in relation to the better outcome of patients in Japan and also how to reduce some of these risk factors.

  • 318.
    Stegmayr, Bernd G
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ptak, J
    Nilsson, T
    Berlin, G
    Mirea, V
    Axelsson, CG
    Griskevicius, A
    Centoni, P
    Liumbruno, G
    Audzijoniene, J
    Mokvist, K
    Lassen, Ewa
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Immunology.
    Knutson, F
    Norda, R
    Mörtzell, Monica
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Prophet, H
    Ramlow, W
    Blaha, M
    Witt, V
    Efvergren, M
    Tomaz, J
    Newman, E
    Eloot, S
    Dhondt, A
    Lalic, K
    Sikole, A
    Derfler, K
    Hrdlickova, R
    Tomsova, H
    Gasova, Z
    Bhuiyan-Ludvikova, Z
    Ramsauer, Bernd
    Skövde, Sweden.
    Vrielink, H
    Panorama of adverse events during cytapheresis2013In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 48, no 2, p. 155-156Article in journal (Other academic)
  • 319.
    Stegmayr, Bernd G.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sperker, Wolfgang
    Nilsson, Christina H.
    Degerman, Christina
    Persson, Sven-Erik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Stenbaek, Jan
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Arnerlöv, Conny
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Few Outflow Problems With a Self-locating Catheter for Peritoneal Dialysis: A Randomized Trial2015In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 94, no 48, article id e2083Article in journal (Refereed)
    Abstract [en]

    We developed a technique for direct start of peritoneal dialysis. Using a coiled or straight Tenckhoff catheter often results in obstruction of flow. A self-locating Wolfram catheter is on the market. It is not clarified if this results in a benefit.The primary aim of this study was to perform a randomized investigation to clarify if the use of a self-locating peritoneal dialysis (PD) catheter would result in different flow problems than a straight Tenckhoff catheter.A total of 61 insertions were made who were randomized and received either a straight Tenckhoff (n = 32) or a self-locating Wolfram catheter (n = 29). A previously described operation technique allowed immediate postoperative start of dialysis. Seven straight Tenckhoff catheters had to be changed into self-locating catheters, and none vice versa, due to flow problems (P = 0.011). An early leakage resulted in temporarily postponed PD in 4 patients. This study showed that using the present operation technique the self-locating PD-catheter causes fewer obstruction episodes than a straight Tenckhoff catheter. This facilitates immediate postoperative start of PD.

  • 320.
    Stegmayr, Bernd
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jonsson, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mahmood, Dana
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    A significant proportion of patients treated with citrate containing dialysate need additional anticoagulation2013In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 36, no 1, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Background: The blood membrane interaction induced during hemodialysis (HD) activates the coagulation system. To prevent clotting and to maintain dialyzer patency, an anticoagulant such as tinzaparin is used. To increase patency of the dialyzers and to reduce the risk of bleeding related to anticoagulation, citrate-containing dialysate has been introduced in Europe.

    Purpose: The aim of this randomized, cross-over study was to investigate if citrate-containing dialysate was safe and efficient enough as the sole anticoagulation agent in chronic HD patients.

    Material and Methods: In this clinical setting, 23 patients on chronic hemodialysis were randomized in a cross-over design using anticoagulation either by LMWH-tinzaparin or citrate (Cit) as dialysate (22 completed the study). The study included paired analyses of subjective patency, ionized calcium (iCa), urea reduction rate. During Cit-HD, the iCa was significantly more reduced with prolonged time. The lowest iCa measured was 0.96 mmol/l. The median iCa after 210 min of HD was 1.02 for Cit-Hd and 1.16 for standard tinzaparin-HD (p = 0.001). Patency of dialyzers was estimated as clear in 14%, stripes of clotted fibers in 36%, and a red filter in 32% of HD session. The addition of approximately 40% of the patients’ usual dose of tinzaparin was given to 7 of the patients as a bolus. Four Cit-HD sessions had to be interrupted prematurely due to clotting.

    Conclusion: A significant proportion of patients treated with citrate-containing dialysate need additional anticoagulation.

  • 321.
    Stegmayr, Bernd
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Mörtzell Henriksson, Monica
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Newman, E
    Witt, V
    Derfler, K
    Leitner, G
    Eloot, S
    Dhondt, A
    Deeren, D
    Rock, G
    Ptak, J
    Blaha, M
    Lanska, M
    Gasova, Z
    Bhuiyan-Ludvikova, Z
    Hrdlickova, R
    Ramlow, W
    Prophet, H
    Liumbruno, G
    Mori, E
    Griskevicius, A
    Audzijoniene, J
    Vrielink, H
    Rombout-Sestrienkova, E
    Aandahl, A
    Sikole, A
    Tomaz, J
    Lalic, K
    Bojanic, I
    Strineholm, V
    Brink, B
    Berlin, G
    Dykes, J
    Toss, F
    Nilsson, T
    Knutson, F
    Ramsauer, Bernd
    Wahlstrom, A
    Distribution of indications and procedures within the framework of centers participating in the WAA apheresis registry2017In: Transfusion and apheresis science, ISSN 1473-0502, E-ISSN 1878-1683, Vol. 56, no 1, p. 71-74Article in journal (Refereed)
    Abstract [en]

    The WAA apheresis registry was established in 2003 and an increasing number of centers have since then included their experience and data of their procedures. The registry now contains data of more than 74,000 apheresis procedures in more than 10,000 patients. This report shows that the indications for apheresis procedures are changing towards more oncological diagnoses and stem cell collections from patients and donors and less therapeutic apheresis procedures. In centers that continue to register, the total extent of apheresis procedures and patients treated have expanded during the latest years.

  • 322. Steinsvik, E Andreas Svaboe
    et al.
    Fosså, Sophie D
    Axcrona, Karol
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Dahl, Alv A
    Do perceptions of adverse events differ between patients and physicians? Findings from a randomized, controlled trial of radical treatment for prostate cancer2010In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 184, no 2, p. 525-531Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Previous cross-sectional studies show considerable discrepancies between patient and physician ratings of adverse events after prostate cancer treatment. We used data from a randomized, controlled trial to examine such discrepancies.

    MATERIAL AND METHODS: The Scandinavian Prostate Cancer Groups Study 7 randomized men with locally advanced prostate cancer to antiandrogen monotherapy or to the same hormone treatment combined with external beam radiotherapy after 3 months of total androgen blockade. We selected a subsample of 333 men with valid ratings at baseline, and at 12 and 24-month followup for this prospective substudy. We also examined a cross-sectional sample of 305 men at the end of radiotherapy. We compared patient and physician ratings of frequency of daytime and nighttime urination, urinary incontinence, erectile dysfunction, bowel problems, nausea/vomiting, breast tenderness and gynecomastia.

    RESULTS: Perfect agreement between patient and physician ratings was observed in 70% to 100% of cases at baseline, in 73% to 98% at 12 months and in 65% to 97% at 24 months. There were 1% to 20% changes in perfect agreement with time. With patient ratings as the gold standard physicians more often underrated than overrated adverse events, except bowel problems, which were overrated at all posttreatment points.

    CONCLUSIONS: In a randomized, controlled trial of external beam radiotherapy and hormone manipulation physicians recorded pelvis related adverse events in acceptable accordance with their patients with prostate cancer. The oncologist tendency to overestimate bowel problems after radiotherapy needs further investigation. Our positive findings from a formal trial should not be transferred to daily clinical practice without further studies of discrepancies in routine clinical practice.

  • 323. Stenström Bohlin, Katja
    et al.
    Ankardal, Maud
    Pedroletti, Corinne
    Lindkvist, Håkan
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    Milsom, Ian
    The influence of the modifiable life-style factors body mass index and smoking on the outcome of mid-urethral sling procedures for female urinary incontinence2015In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 26, no 3, p. 343-351Article in journal (Refereed)
    Abstract [en]

    Introduction and hypothesis: The aim of this observational study was to investigate the influence of body mass index (BMI) smoking and age on the cure rate, rate of complications and patient satisfaction with mid-urethral sling (MUS) procedures.

    Methods: Pre-, peri- and postoperative (8 weeks and 1 year) data were retrieved from the Swedish National Register for Gynecological Surgery of MUS procedures (retropubic procedures, n = 4,539; transobturator procedures, n =1,769) performed between January 2006 and December 2011. Multiple logistic regression analyses were performed between the outcome variables and BMI and smoking, presented as adjusted odds ratios (adjOR) with 95 % confidence interval (CI).

    Results: Subjective 1-year cure rate was 87.4 % for all MUS procedures (88.3 % with the retropubic technique and 85.2 % with the transobturator technique (p = 0.002). Preoperative daily urinary leakage and urgency were more common with increasing BMI, but surgery reduced symptoms in all BMI groups. Lower cure rate was seen in women with a BMI >30 (0.49; CI 0.33–0.73), in diabetics (0.50; CI 0.35–0.74) and women aged > 80 years (0.18; CI 0.06–0.51). Perioperative complications were more common in the retropubic group (4.7 % vs 2.3 % in the transobturator group, p=0.001) and in women with BMI < 25. Smoking did not influence any of the outcome variables.

    Conclusions: The overall 1-year cure rate for MUS procedures was 87 %, but was negatively influenced by BMI >30, diabetes and age > 80 years. Perioperative complications were more common with the retropubic procedure than with the transobturator technique, and in women with a BMI < 25. Smoking did not impact on any of the studied outcome variables.

  • 324.
    Stocks, Tanja
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Urology and Andrology.
    Metabolic factors and cancer risk: prospective studies on prostate cancer, colorectal cancer, and cancer overall2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: A large number of prospective studies have shown that overweight and diabetes are related to an increased risk of many cancers, including colorectal cancer. In contrast, diabetes has been related to a decreased risk of prostate cancer, and overweight has been related to an increased risk of fatal, but not of incident, prostate cancer. Data from studies on metabolic factors related to overweight and diabetes, and the association with cancer risk, are limited.

     Aim: The aim of this thesis was to study metabolic factors in relation to risk of prostate cancer (paper I and III), colorectal cancer (paper II and V), and cancer overall (paper VI).

     Methods: Study designs were i) case-control studies, nested within the Northern Sweden Health and Disease Cohort (paper I and II), and ii) cohort studies of the Swedish Construction Workers cohort (paper III), and the Metabolic syndrome and Cancer project (Me-Can) comprising seven European cohorts (paper V and VI). Paper IV was a descriptive paper of Me-Can.

     Results, prostate cancer: In paper I, increasing levels of several factors related to insulin resistance (insulin, insulin resistance index, leptin, HbA1c, and glucose) were associated with a decreased risk of overall incident prostate cancer, and the associations were stronger for non-aggressive tumours. In paper III, increasing levels of blood pressure was associated with a significant decreased risk of overall incident prostate cancer and of non-aggressive tumours. Body mass index (BMI) was significantly positively related to fatal prostate cancer. 

     Results, colorectal cancer: In paper II, obesity, hypertension, and hyperglycaemia, were associated with an increased risk of colorectal cancer, and presence of two or three of these factors was associated with a higher risk than the presence of one single factor. In paper V, BMI was associated with a significant linear positive association with risk of colorectal cancer in men and women, and significant positive associations were also found in men for blood pressure and triglycerides. A high metabolic syndrome score, based on levels of BMI, blood pressure, glucose, cholesterol, and triglycerides, was associated with a significant increased risk of colorectal cancer in men and women. The association was stronger than for any of the factors in single, but there was no evidence of a positive interaction between these metabolic factors.

     Results, cancer overall: Blood glucose was significantly positively associated with risk of incident and fatal cancer overall, and at several specific sites. The associations were stronger in women than in men, and for fatal than for incident cancer.

     Conclusions: Results from these studies indicate that elevated blood glucose is related to an increased risk of cancer overall and at several specific sites, and further, that overweight and metabolic aberrations increase the risk of colorectal cancer in an additive way. The association with prostate cancer seems to be more complex; insulin resistance and high blood pressure were in our studies related to a decreased risk of overall incident prostate cancer and of non-aggressive tumours, whereas overweight increased the risk of fatal prostate cancer.

  • 325.
    Stocks, Tanja
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Clinical Sciences in Malmö, Diabetes and Cardiovascular Diseases, Genetic Epidemiology, Lund University, Lund, Sweden.
    Björge, Tone
    Bergen, Norway; Oslo, Norway.
    Ulmer, Hanno
    Innsbruck, Austria.
    Manjer, Jonas
    Lund University, Malmö, Sweden.
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Nagel, Gabriele
    Ulm, Germany; Oslo, Norway.
    Engeland, Anders
    Oslo, Norway; Bergen, Norway.
    Johansen, Dorthe
    Lund University, Malmö, Sweden.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Selmer, Randi
    Oslo, Norway.
    Concin, Hans
    Bregenz, Austria.
    Tretli, Steinar
    Oslo, Norway.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Metabolic risk score and cancer risk: pooled analysis of seven cohorts2015In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 44, no 4, p. 1353-1387Article in journal (Refereed)
    Abstract [en]

    Background: There are few data on the joint influence of metabolic factors on risk of separate cancers. Methods: We analysed data on body mass index, blood pressure and plasma levels of glucose, total cholesterol and triglycerides from seven European cohorts comprising 564 596 men and women with a mean age of 44 years. We weighted those factors equally into a standardized metabolic risk score [MRS, mean = 0, standard deviation (SD) = 1], with an individual's level indicated as SDs from the sex-and cohort-specific means. Cancer hazard ratios were calculated by Cox regression with age as timescale and with relevant adjustments including smoking status. All statistical tests were two-sided. Results: During a mean follow-up of 12 years, 21 593 men and 14 348 women were diagnosed with cancer. MRS was linearly and positively associated with incident cancer in total and at sites (P<0.05). In men, risk per SD MRS was increased by 43% (95% confidence interval: 27-61) for renal cell cancer, 43% (16-76) for liver cancer, 29% (20-38) for colon cancer, 27% (5-54) for oesophageal cancer, 20% (9-31) for rectal cancer, 19% (4-37) for leukaemias, 15% (1-30) for oral cancer and 10% (2-19) for bladder cancer. In women, risk increases per SD MRS were 56% (42-70) for endometrial cancer, 53% (29-81) for pancreatic cancer, 40% (16-67) for renal cell cancer, 27% (9-47) for cervical cancer and 17% (3-32) for rectal cancer. Conclusion: This largest study to date on the joint influence of metabolic factors on risk of separate cancers showed increased risks for several cancers, in particular renal cell and liver cancer in men and endometrial and pancreatic cancer in women.

  • 326.
    Styrke, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Sundsvall Hospital.
    Henriksson, Helene
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Sundsvall Hospital.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Hasan, Mudhar
    Silfverberg, Ingrid
    Einarsson, Roland
    Malmström, Per-Uno
    Sherif, Amir
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Evaluation of the diagnostic accuracy of UBC(®) Rapid in bladder cancer: a Swedish multicentre study2017In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, no 4, p. 293-300Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to determine the diagnostic accuracy of UBC(®) Rapid - a urine-based marker for bladder cancer - in patients with bladder cancer and controls, and to compare the test results across risk groups.

    MATERIALS AND METHODS: This prospective phase II study was conducted at four Swedish hospitals. UBC Rapid was evaluated in four groups: A, newly diagnosed bladder cancer (n = 94); B, follow-up of non-muscle-invasive bladder cancer (n = 75); C, benign urinary tract diseases (n = 51); and D, healthy controls (n = 50). Tumours were divided into high risk (carcinoma in situ, TaG3, T1, T2 and T3) and low risk (low malignant potential, TaG1 and TaG2). Urine samples were quantitatively analysed by UBC Rapid. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated based on optimal cut-off (receiver operator characteristics curve analysis). A linear regression compared the UBC Rapid results in the different risk groups.

    RESULTS: The optimal cut-off was 8.1 μg/l. The median UBC Rapid values were 9.3 μg/l [interquartile range (IQR) 30.9] and 4.3 μg/l (IQR 7.8) in patients with positive and negative cystoscopy, respectively (p < .001). The value for group A was 15.6 μg/l (IQR 37.9), group B 5.6 μg/l (IQR 8.6), group C 5.1 μg/l (IQR 9.0) and group D 3.3 μg/l (IQR 7.1). Sensitivity was 70.8%, specificity 61.4%, PPV 71.3% and NPV 60.8%. The high-risk group had significantly higher UBC Rapid values than the low-risk group: 20.5 μg/l (IQR 42.2), sensitivity 79.2% and specificity 61.4% versus 7.0 μg/l (IQR 9.9), sensitivity 60.0% and specificity 61.4% (p = .039).

    CONCLUSIONS: The UBC Rapid urine-based marker for bladder cancer gave higher values in patients with positive than in those with negative cystoscopy. The diagnostic accuracy was better in patients with high-risk than in those with low-risk tumours, and was better during primary detection than during surveillance.

  • 327.
    Styrke, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Johansson, Markus
    Granåsen, Gabriel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Israelsson, Leif
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Parastomal hernia after Heal conduit with a prophylactic mesh: a 10 year consecutive case series2015In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 49, no 4, p. 308-312Article in journal (Refereed)
    Abstract [en]

    Objective. There are no data on the frequency of parastomal hernia (PSH) after heal conduit with a prophylactic mesh. The primary objective of this study was to determine the prevalence of PSH. Secondary objectives were to elaborate whether age, gender, body mass index (BMI), previous laparotomy or diabetes influenced the outcome; and to find any mesh-related complications. Materials and methods. In a single centre during 2003-2012, a large-pore, lightweight mesh was placed in a sublay position in 114 consecutive patients with ileal conduits. Preoperative and postoperative patient data were retrospectively collected and cross-sectional follow-up was conducted. During the predefined clinical examination a PSH was defined as any protrusion in the vicinity of the ostomy with the patient straining in both an erect and a supine position. Results. Fifty-eight patients (24 women and 34 men, mean age 69 years) had follow-up examinations after a mean of 35 months (median 32 months). Bladder cancer was the most common cause for surgery. Eight patients (14%) had a PSH. Age, gender, BMI, previous laparotomy and diabetes did not affect the outcome. No mesh-related complications occurred among the 114 patients with a prophylactic mesh. Conclusions. The prevalence of PSH after ileal conduit with a prophylactic mesh corresponded to that of colostomies with a prophylactic mesh. A prophylactic mesh did not seem to be associated with complications. The degree to which a prophylactic mesh may reduce the rate of PSH after an ileal conduit should be established in randomized trials.

  • 328. Teleka, Stanley
    et al.
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; .
    Nagel, Gabriele
    Bjorge, Tone
    Manjer, Jonas
    Ulmer, Hanno
    Liedberg, Fredrik
    Ghaderi, Sara
    Lang, Alois
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Jahnson, Staffan
    Orho-Melander, Marju
    Tretli, Steinar
    Stattin, Pär
    Stocks, Tanja
    Risk of bladder cancer by disease severity in relation to metabolic factors and smoking: a prospective pooled cohort study of 800,000 men and women2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 12, p. 3071-3082Article in journal (Refereed)
    Abstract [en]

    Previous studies on metabolic factors and bladder cancer (BC) risk have shown inconsistent results and have commonly not investigated associations separately by sex, smoking, and tumor invasiveness. Among 811,633 participants in six European cohorts, we investigated sex‐specific associations between body mass index (BMI), mid‐blood pressure (BP, [systolic + diastolic]/2), plasma glucose, triglycerides, total cholesterol and risk of BC overall, non‐muscle invasive BC (NMIBC) and muscle invasive BC (MIBC). Among men, we additionally assessed additive interactions between metabolic factors and smoking on BC risk. During follow‐up, 2,983 men and 754 women were diagnosed with BC. Among men, triglycerides and BP were positively associated with BC risk overall (hazard ratio [HR] per standard deviation [SD]: 1.17 [95% confidence interval (CI) 1.06–1.27] and 1.09 [1.02–1.17], respectively), and among women, BMI was inversely associated with risk (HR: 0.90 [0.82–0.99]). The associations for BMI and BP differed between men and women (pinteraction ≤ 0.005). Among men, BMI, cholesterol and triglycerides were positively associated with risk for NMIBC (HRs: 1.09 [95% CI 1.01–1.18], 1.14 [1.02–1.25], and 1.30 [1.12–1.48] respectively), and BP was positively associated with MIBC (HR: 1.23 [1.02–1.49]). Among women, glucose was positively associated with MIBC (HR: 1.99 [1.04–3.81]). Apart from cholesterol, HRs for metabolic factors did not significantly differ between MIBC and NMIBC, and there were no interactions between smoking and metabolic factors on BC. Our study supports an involvement of metabolic aberrations in BC risk. Whilst some associations were significant only in certain sub‐groups, there were generally no significant differences in associations by smoking or tumor invasiveness.

  • 329. Thomsen, Frederik B.
    et al.
    Folkvaljon, Yasin
    Brasso, Klaus
    Loeb, Stacy
    Robinson, David
    Egevad, Lars
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Prognostic Implications of 2005 Gleason Grade Modification. Population-Based Study of Biochemical Recurrence Following Radical Prostatectomy2016In: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 114, no 6, p. 664-670Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the impact of the 2005 modification of the Gleason classification on risk of biochemical recurrence (BCR) after radical prostatectomy (RP).

    Patients and Methods: In the Prostate Cancer data Base Sweden (PCBaSe), 2,574 men assessed with the original Gleason classification and 1,890 men assessed with the modified Gleason classification, diagnosed between 2003 and 2007, underwent primary RP. Histopathology was reported according to the Gleason Grading Groups (GGG): GGG1 = Gleason score (GS) 6, GGG2 = GS 7(3 + 4), GGG3 = GS 7(4 + 3), GGG4 = GS 8 and GGG5 = GS 9–10. Cumulative incidence and multivariable Cox proportional hazards regression models were used to assess difference in BCR.

    Results: The cumulative incidence of BCR was lower using the modified compared to the original classification: GGG2 (16% vs. 23%), GGG3 (21% vs. 35%) and GGG4 (18% vs. 34%), respectively. Risk of BCR was lower for modified versus original classification, GGG2 Hazard ratio (HR) 0.66, (95%CI 0.49–0.88), GGG3 HR 0.57 (95%CI 0.38–0.88) and GGG4 HR 0.53 (95%CI 0.29–0.94).

    Conclusion: Due to grade migration following the 2005 Gleason modification, outcome after RP are more favourable. Consequently, outcomes from historical studies cannot directly be applied to a contemporary setting.

  • 330. Thorstenson, Andreas
    et al.
    Bergman, Martin
    Scherman-Plogell, Ann-Helen
    Hosseinnia, Soheila
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Adolfsson, Jan
    Lundstam, Sven
    Tumour characteristics and surgical treatment of renal cell carcinoma in Sweden 2005-2010: a population-based study from the National Swedish Kidney Cancer Register2014In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 48, no 3, p. 231-238Article in journal (Refereed)
    Abstract [en]

    Objective. Tumour characteristics, preoperative work-up and surgical treatment in patients diagnosed with renal cell carcinoma (RCC) between 2005 and 2010, and changes over time were studied in a national population-based cohort. Material and methods. The National Swedish Kidney Cancer Register (NSKCR) contains information on histopathology, Fuhrman grade and clinical stage at presentation, and on the preoperative work-up and surgical treatment of patients with RCC. Between 2005 and 2010, 5553 RCC patients were registered in the NSKCR, 99% of those registered in the National Cancer Registry. Results. During the study period the mean tumour size decreased from 70 to 64 mm (p = 0.024) and the frequency of metastatic RCC decreased from 22% to 15% (p < 0.001). The use of preoperative chest computed tomography increased from 59% to 84%. In total, 4229 (76%) patients were treated with curative intent, 3453 (82%) underwent radical nephrectomy, 606 (14%) partial nephrectomy (PN) and 170 (4%) cryotherapy or radiofrequency ablation. In tumours up to 4 cm, PN was performed in 33% of the surgically treated patients. PN irrespective of size increased from 8% to 20% and laparoscopic nephrectomy increased from 6% to 17% during the period. In patients with metastatic RCC, 55% underwent cytoreductive nephrectomy. Conclusions. The NSKCR explores population-based data on the clinical handling of patients with RCC. This study, between 2005 and 2010, shows significant decrease in tumour size and metastatic RCC at presentation, a more complete preoperative work-up, and significantly increased use of PN and laparoscopic nephrectomy in Sweden.

  • 331. Thorstenson, Andreas
    et al.
    Bratt, Ola
    Akre, Olof
    Hellborg, Henrik
    Holmberg, Lars
    Lambe, Mats
    Bill-Axelson, Anna
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Adolfsson, Jan
    Incidence of fractures causing hospitalisation in prostate cancer patients: Results from the population-based PCBaSe Sweden2012In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 48, no 11, p. 1672-1681Article in journal (Refereed)
    Abstract [en]

    Background: Prostate cancer patients have an increased risk of fractures as a consequence of skeletal metastases and osteoporosis induced by endocrine treatment. Data on incidence of fractures and risks in subgroups of men with prostate cancer are sparse. Our aim with this study is to report the risk of fractures among men with prostate cancer in a nationwide population-based study. Patients and methods: We identified 76,600 Swedish men diagnosed with prostate cancer 1997-2006 in the Prostate Cancer Data Base (PCBaSe) Sweden and compared the occurrence of fractures requiring hospitalisation with the Swedish male population. Results: Only men treated with gonadotropin releasing-hormone (GnRH) agonists or orchiectomy had increased incidence and increased relative risk of fractures requiring hospitalisation. Men treated with GnRH agonists had 9.8 and 6.3/1000 person-years higher incidence of any fracture and hip fracture requiring hospitalisation than the general population. The corresponding increases in incidence for men treated with orchiectomy were 16 and 12/1000 person-years, respectively. Men treated with orchiectomy, GnRH agonists, and antiandrogen monotherapy, had SIR for hip fracture of 2.0 (95% Confidence Interval 1.8-2.2), 1.6 (95% CI 1.5-1.8) and 0.9 (95% CI 0.7-1.1), respectively. Men treated with a curative intent (radical prostatectomy or radiotherapy) or managed with surveillance had no increased risk of fractures. Older men had the highest incidence of fractures while younger men had the highest relative risk. Conclusion: Prostate cancer patients treated with GnRH agonists or orchiectomy have significantly increased risk of fractures requiring hospitalisation while patients treated with antiandrogen monotherapy had no increase in such fractures. In absolute terms the excess risk in men treated with GnRH agonists corresponded to almost 10 extra fractures leading to hospitalisation per 1000 patient-years. Effects on bone density should be considered for men on long-term endocrine treatment. Unwarranted use of orchiectomy and GnRH agonists should be avoided. (C) 2012 Elsevier Ltd. All rights reserved.

  • 332. Thorstenson, Andreas
    et al.
    Hagberg, Oskar
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Liedberg, Fredrik
    Jancke, Georg
    Holmäng, Sten
    Malmström, Per-Uno
    Hosseini, Abolfazl
    Jahnson, Staffan
    Gender-related differences in urothelial carcinoma of the bladder: a population-based study from the Swedish National Registry of Urinary Bladder Cancer2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 4, p. 292-297Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this investigation was to describe tumour characteristics, treatments and survival in patients with urinary bladder cancer (UBC) in a national population-based cohort, with special reference to gender-related differences. Material and methods: All primary UBC patients with urothelial pathology reported to the Swedish National Registry of Urinary Bladder Cancer (SNRUBC) from 1997 to 2011 were included in the study. Groups were compared regarding tumour, node, metastasis classification, primary treatment and survival. Results: In total, 30,310 patients (74.9% male, 25.1% female) with UBC were analysed. A larger proportion of women than men had stage T2-T4 (p<0.001), and women also had more G1 tumours (p<0.001). However, compared to women, a larger proportion of men with carcinoma in situ or T1G3 received intravesical treatment with bacillus Calmette-Guerin or intravesical chemotherapy, and a larger proportion of men with stage T2-T4 underwent radical cystectomy (38% men vs 33% women, p<0.0001). The cancer-specific survival at 5 years was 77% for men and 72% for women (p<0.001), and the relative survival at 5 years was 72% for men and 69% for women (p<0.001). Conclusions: In this population-based cohort comprising virtually all patients diagnosed with UBC in Sweden between 1997 and 2011, female gender was associated with inferior cancer-specific and relative survival. Although women had a higher rate of aggressive tumours, a smaller proportion of women than men received optimal treatment.

  • 333.
    Thorstenson, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Karolinska Institute, Stockholm, Sweden; University of Oxford, Oxford, UK.
    Harmenberg, Ulrika
    Karolinska University Hospital, Solna, Stockholm, Sweden.
    Lindblad, Per
    Örebro University, Örebro, Sweden.
    Holmström, Benny
    Akademiska University Hospital, Uppsala, Sweden.
    Lundstam, Sven
    Sahlgrenska University Hospital, Göteborg, Sweden.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Cancer Characteristics and Current Treatments of Patients with Renal Cell Carcinoma in Sweden2015In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, article id 456040Article in journal (Refereed)
    Abstract [en]

    Methodology. Since the start in 2005 virtually all patients with newly diagnosed renal cell carcinoma (RCC) in Sweden are reported to the National Swedish Kidney Cancer Register (NSKCR). The register contains information on histopathology, nuclear grade, clinical stage, preoperative work-up, treatment, recurrence, and survival.

    Results. A total of 8556 patients with newly diagnosed RCC were registered in the NSKCR from 2005 to 2013 resulting in a coverage of 99% as compared to the Swedish Cancer Registry. The mean tumor size at detection decreased from 70 mm in 2005 to 64 mm in 2010. The proportion of patients who were incidentally detected increased. The proportion of patients with tumor stage T1a who underwent partial nephrectomy increased from 22% in 2005 to 56% in 2012. Similarly, the proportion of laparoscopically performed radical nephrectomies increased from 6% in 2005 to 17% in 2010. During the five years of follow-up 20% of the patients had a recurrence. Conclusion. Over the last decade there has been a trend of earlier detection and less advanced tumors at detection in patients with RCC. An increasing proportion of the patients undergo laparoscopic and nephron-sparing procedures.

  • 334.
    Thorstenson, Andreas
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology. Department of Molecular Medicine and Surgery, Section of Urology, Karolinska Institute, Stockholm, Sweden; Surgical Intervention Trials Unit, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
    Harmenberg, Ulrika
    Lindblad, Per
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Lundstam, Sven
    Impact of quality indicators on adherence to National and European guidelines for renal cell carcinoma2016In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 50, no 1, p. 2-8Article in journal (Refereed)
    Abstract [en]

    Objective: The aim of this population-based study was to evaluate the impact of quality indicators on the adherence to guidelines for renal cell carcinoma (RCC). Material and methods: Since 2005, virtually all patients with newly diagnosed RCC in Sweden have been registered in the National Swedish Kidney Cancer Register (NSKCR). The register contains information on histopathology, nuclear grade, clinical stage, preoperative work-up, treatment, recurrence and survival. In addition, a number of quality indicators have been measured in the register aiming to increase the quality of care. The quality indicators are: the coverage of the register, histology reports, preoperative chest computed tomography (CT), partial nephrectomy, laparoscopic surgery, centralization to high-volume hospitals and waiting times. Results: A total of 8556 patients with diagnosed RCC were registered from 2005 to 2013 (99% coverage). In 2013, 99% of the histopathology reports were standardized. The number of patients with preoperatively chest CT increased from 59% in 2005 to 89% in 2013. The proportion of patients with RCC T1aN0M0 who underwent partial nephrectomy increased from 22% in 2005 to 56% in 2013. Similarly, laparoscopic radical nephrectomies increased from 6% in 2005 to 24% in 2013. The median tumour size at detection decreased from 60 mm in 2005 to 55 mm in 2013. The proportion of patients who were incidentally detected increased from 43% in 2005 to 55% in 2013. Conclusions: The data show an improved adherence to the guidelines for RCC as measured by quality indicators and a steady process of earlier detection of patients with RCC.

  • 335. Thulin, Helena
    et al.
    Kreicbergs, Ulrika
    Onelöv, Erik
    Ahlstrand, Christer
    Carringer, Malcolm
    Holmäng, Sten
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Malmström, Per-Uno
    Robinsson, David
    Wijkström, Hans
    Wiklund, N Peter
    Steineck, Gunnar
    Henningsohn, Lars
    Defecation disturbances after cystectomy for urinary bladder cancer2011In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 108, no 2, p. 196-203Article in journal (Refereed)
    Abstract [en]

    What’s known on the subject? and What does the study add?Functional gastrointestinal symptoms and problems are common after radical cystectomy with urinary diversion. This study adds new important epidemiological data on this group of symptoms.

    OBJECTIVE: To describe and compare long-term defecation disturbances in patients who had undergone a cystectomy due to urinary bladder cancer with non-continent urostomies, continent reservoirs and orthotopic neobladder urinary diversions.

    PATIENTS AND METHODS: During their follow-up we attempted to contact all men and women aged 30–80 years who had undergone cystectomy and urinary diversion at seven Swedish hospitals. During a qualitative phase we identified defecation disturbances as a distressful symptom and included this item in a study-specific questionnaire together with free-hand comments. The patients completed the questionnaire at home. Outcome variables were dichotomized and the results are presented as relative risks with 95% confidence interval.

    RESULTS: The questionnaire was returned from 452 (92%) of 491 identified patients. Up to 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). A sense of decreased straining capacity was reported by 20% of the men and women with non-continent urostomy and 14% and 8% of those with continent reservoirs and orthotopic neobladders, respectively.

    CONCLUSIONS: Of the cystectomized individuals 30% reported problems with the physiological emptying process of stool (bowel movement, sensory rectal function, awareness of need for defecation, motoric rectal and anal function, straining ability). Those wanting to improve the situation for bladder cancer survivors may consider communicating before surgery the possibility of stool-emptying problems, and asking about them after surgery.

  • 336.
    Thurm, Mascha
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Kröger Dahlin, Britt Inger
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Winsö, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Ljungberg, Börje
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Spinal analgesia improves surgical outcome after open nephrectomy for renal cell carcinoma: a randomized controlled study2017In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, no 4, p. 277-281Article in journal (Refereed)
    Abstract [en]

    Objective: This study evaluated whether more effective perioperative analgesia can be part of a multimodal approach to minimizing morbidity and improving postoperative management after the open surgical approaches frequently used in the treatment of renal cell carcinoma (RCC). The aim of the study was to determine whether spinal anesthesia with clonidine can enhance postoperative analgesia, speed up mobilization and reduce the length of hospital stay (LOS).

    Materials and methods: Between 2012 and 2015, 135 patients with RCC were randomized, in addition to general anesthesia, to receive either spinal analgesia with clonidine or epidural analgesia, stratified to surgical technique. Inclusion criteria were American Society of Anesthesiologists (ASA) score of III or less, age over 18 years and no chronic pain medication or cognitive disorders.

    Results: The median LOS was 4 days for patients in the spinal group and 6 days in the epidural group (p = 0.001). There were no differences regarding duration of surgery, blood loss, RENAL score, tumor size or complications between the given analgesia methods. A limitation was that different anesthesiologists were responsible for administering spinal or epidural anesthesia, as in a real-world clinical situation.

    Conclusions: In this randomized controlled study, spinal analgesia with clonidine was superior to continuous epidural analgesia in patients operated on with open nephrectomy, based on shorter LOS. A shorter LOS in the study group indicates faster mobilization and improved analgesia. Spinal analgesia did not carry more complications than epidural analgesia.

  • 337.
    Thysell, Elin
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ylitalo, Erik B.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Jernberg, Emma
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Reply to Isabel Heidegger, Renate Pichler, and Andreas Pircher's Letter to the Editor re: Erik Bovinder Ylitalo, Elin Thysell, Emma Jernberg, et al. Subgroups of Castration-resistant Prostate Cancer Bone Metastases Defined Through an Inverse Relationship Between Androgen Receptor Activity and Immune Response. Eur Urol 2017;71:776-872017In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 72, no 4, p. E104-E105Article in journal (Refereed)
  • 338.
    Tjon-Kon-Fat, Lee-Ann
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lundholm, Marie
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Schröder, Mona
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wurdinger, Thomas
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wikström, Pernilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nilsson, Rolf Jonas Andreas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Platelets harbor prostate cancer biomarkers and the ability to predict therapeutic response to abiraterone in castration resistant patients2018In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 78, no 1, p. 48-53Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Novel therapies for castration resistant prostate cancer (CRPC) have been introduced in the clinic with possibilities for individualized treatment plans. Best practice of those expensive drugs requires predictive biomarker monitoring. This study used circulating biomarker analysis to follow cancer-derived transcripts implicated in therapy resistance.

    METHOD: The isolated platelet population of blood samples and digital-PCR were used to identify selected biomarker transcripts in patients with CRPC prior chemo- or androgen synthesis inhibiting therapy.

    RESULTS: Fifty patients received either docetaxel (n = 24) or abiraterone (n = 26) therapy, with therapy response rates of 54% and 48%, respectively. Transcripts for the PC-associated biomarkers kallikrein-related peptidase-2 and -3 (KLK2, KLK3), folate hydrolase 1 (FOLH1), and neuropeptide-Y (NPY) were uniquely present within the platelet fraction of cancer patients and not detected in healthy controls (n = 15). In the abiraterone treated cohort, the biomarkers provided information on therapy outcome, demonstrating an association between detectable biomarkers and short progression free survival (PFS) (FOLH1, P < 0.01; KLK3, P < 0.05; and NPY, P < 0.05). Patients with biomarker-negative platelets had the best outcome, while FOLH1 (P < 0.05) and NPY (P = 0.05) biomarkers provided independent predictive information in a multivariate analysis regarding PFS. KLK2 (P < 0.01), KLK3 (P < 0.001), and FOLH1 (P < 0.05) biomarkers were associated with short overall survival (OS). Combining three biomarkers in a panel (KLK3, FOLH1, and NPY) made it possible to separate long-term responders from short-term responders with 87% sensitivity and 82% specificity.

    CONCLUSION: Analyzing tumor-derived biomarkers in platelets of CRPC patients enabled prediction of the outcome after abiraterone therapy with higher accuracy than baseline serum PSA or PSA response.

  • 339.
    Tomic, Katarina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Data quality in the National Prostate Cancer Register (NPCR) of Sweden2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Data in quality registers are increasingly used for quality assurance of health care, benchmarking, and research. If valid conclusions are to be drawn from such studies, it is vital that register data have high quality. The aim of this thesis was to assess data quality in the National Prostate Cancer Register (NPCR) of Sweden, a nationwide register that since 1998 captures 98% of all cases of Prostate cancer (Pca) in Sweden. The proportion and characteristics of Pca cases not registered in NPCR was investigated in paper I. Four dimensions of data quality were evaluated for NPCR in paper II: completeness, timeliness, comparability, and validity. Proportion and characteristics of Pca cases registered in NPCR but with unknown risk category were investigated in paper III. Finally, the association between Socioeconomic Status (SES) and Pca diagnosis, treatment, and mortality was studied in paper IV. 

    Material and methods: Data quality of NPCR was studied by cross-linkages between NPCR and other health care registers and demographical databases by use of the Swedish personal identity number. Validity was further studied by re-abstraction of patient health care records, followed by comparison of re-abstracted and original register data.

    Results: Men not registered in NPCR, who constituted around 2% of all cases in the Swedish Cancer Register, differed only modestly in characteristics from cases in NPCR, indicating that NPCR is generalizable for all men with Pca in Sweden. Data quality in NPCR was high overall, with high completeness compared to the Swedish Cancer Register with registration mandated by law and few Pca cases were detected by use of death certificates. There was timely registration, and good comparability with registration forms and coding routines that were compliant with international guidelines. Data validity was high with high agreement and correlation for key variables. Men with unknown risk category had, compared to men with known risk category, more often concomitant bladder cancer, higher comorbidity, and lower Pca mortality. Men with high SES had, compared to men with low SES, higher probability of Pca detected during health checkup, shorter waiting times for prostatectomy, and higher probability of curative treatment for intermediate and high-risk cancer. Pca mortality was lower in men with high SES than in men with low SES for high-risk cancer.

    Conclusion: These results indicate that data quality in NPCR is high and that NPCR is population-based. There were consistent differences in diagnostic and therapeutic activity according to SES despite an equal access tax-financed healthcare system in Sweden. 

  • 340.
    Tomic, Katarina
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Ventimiglia, Eugenio
    Division of Experimental Oncology/Unit of Urology, URI; IRCCS Ospedale San Raffaele, Milan, Italy.
    Robinson, David
    Department of Urology, Ryhov Hospital, Jönköping, Sweden .
    Häggström, Christel
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Lambe, Mats
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Regional Cancer Centre Uppsala Örebro, Uppsala University Hospital, Uppsala, Sweden.
    Stattin, Pär
    Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Socioeconomic status and diagnosis, treatment, and mortality in men with prostate cancer. Nationwide population-based study2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, no 12, p. 2478-2484Article in journal (Refereed)
    Abstract [en]

    Patients with high socioeconomic status (SES) have better cancer outcomes than patients with low SES. This has also been shown in Sweden, a country with tax-financed health care aiming to provide care on equal terms to all residents. The association between income and educational level and diagnostics and treatment as outlined in national guidelines and prostate cancer (Pca) and all-cause mortality was assessed in 74,643 men by use of data in the National Prostate Cancer Register of Sweden and a number of other health care registers and demographic databases. In multivariable logistic regression analysis, men with high income had higher probability of Pca detected in a health-check-up, top versus bottom income quartile, odds ratio (OR) 1.60 (95% CI 1.45-1.77) and lower probability of waiting more than 3 months for prostatectomy, OR 0.77 (0.69-0.86). Men with the highest incomes also had higher probability of curative treatment for intermediate and high-risk cancer, OR 1.77 (1.61-1.95) and lower risk of positive margins, (incomplete resection) at prostatectomy, OR 0.80 (0.71-0.90). Similar, but weaker associations were observed for educational level. At 6 years of follow-up, Pca mortality was modestly lower for men with high income, which was statistically significant for localized high-risk and metastatic Pca in men with no comorbidities. All-cause mortality was less than half in top versus bottom quartile of income (12% vs. 30%, p < 0.001) among men above age 65. Our findings underscore the importance of adherence to guidelines to ensure optimal and equal care for all patients diagnosed with cancer.

  • 341.
    Tomic, Katarina
    et al.
    Umeå University Hospital.
    Westerberg, Marcus
    Uppsala University Hospital.
    Robinson, David
    Umeå University Hospital; Ryhov Hospital, Jönköping.
    Garmo, Hans
    Uppsala University Hospital.
    Stattin, Pär
    Umeå University Hospital; Uppsala University.
    Proportion and characteristics of men with unknown risk category in the National Prostate Cancer Register of Sweden2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 12, p. 1461-1466Article in journal (Refereed)
    Abstract [en]

    Introduction: Knowledge on missing data in a clinical cancer register is important to assess the validity of research results. For analysis of prostate cancer (Pca), risk category, a composite variable based on serum levels of prostate specific antigen (PSA), stage, and Gleason score, is crucial for treatment decisions and a strong determinant of outcome. The aim of this study was to assess the proportion and characteristics of men in the National Prostate Cancer Register (NPCR) of Sweden with unknown risk category.

    Material and methods: Men diagnosed with prostate cancer between 1998 and 2012 registered in NPCR with known or unknown risk category were compared with respect to age, socioeconomic factors, comorbidity, cancer characteristics, cancer treatment, and mortality from Pca and other causes.

    Results: In total, 3 315 out of 129 391 (3%) men had unknown risk category. Compared to other men in NPCR, these men more often had a concomitant bladder cancer diagnosis, 19% vs. 1%, diagnosis of benign prostatic hyperplasia 31% vs. 5%, received unspecified Pca cancer treatment 16% vs. 3%, had higher comorbidity, Charlson Comorbidity Index 2 or higher, 34% vs. 13%, and had lower Pca mortality 12% vs. 30%, but similar mortality from other causes.

    Conclusion: Men with unknown risk category were rare in NPCR but distinctly different from other men in many aspects in particular regarding comorbidity and Pca mortality.

  • 342.
    Toppe, Cecilia
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Internal Medicine, Ryhov County Hospital, Jönköping, Sweden.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Waernbaum, Ingeborg
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Schön, Staffan
    Swedish Renal Registry, Jönköping, Sweden.
    Gudbjörnsdottir, Soffia
    Swedish National Diabetes Register, Gothenburg, Sweden.
    Landin-Olsson, Mona
    Diabetes Incidence Study in Sweden Department of Clinical Sciences, Lund University, Lund, Sweden.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Decreasing Cumulative Incidence of End-Stage Renal Disease in Young Patients With Type 1 Diabetes in Sweden: a 38-Year Prospective Nationwide Study2019In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 42, no 1, p. 27-31Article in journal (Refereed)
    Abstract [en]

    Objective: Diabetic nephropathy is a serious complication of type 1 diabetes. Recent studies indicate that end-stage renal disease (ESRD) incidence has decreased or that the onset of ESRD has been postponed; therefore, we wanted to analyze the incidence and time trends of ESRD in Sweden.

    Research design and methods: In this study, patients with duration of type 1 diabetes >14 years and age at onset of diabetes 0–34 years were included. Three national diabetes registers were used: the Swedish Childhood Diabetes Register, the Diabetes Incidence Study in Sweden, and the National Diabetes Register. The Swedish Renal Registry, a national register on renal replacement therapy, was used to identify patients who developed ESRD.

    Results: We found that the cumulative incidence of ESRD in Sweden was low after up to 38 years of diabetes duration (5.6%). The incidence of ESRD was lower in patients with type 1 diabetes onset in 1991–2001 compared to onset in 1977–1984 and 1985–1990, independently of diabetes duration.

    Conclusion: The risk of developing ESRD in Sweden in this population is still low and also seems to decrease with time.

  • 343.
    Tuhkanen, Joel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    A multicenter evaluation of S-albumin, S-LD, S-LPK and S-TPK as possible predictors of response to neoadjuvant chemotherapy in muscle invasive urinary bladder cancer2018Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 344.
    Ulf, Forsberg
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Presence of microemboli during haemodialysis and methods to reduce the exposure to microbubbles2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Despite chronic dialysis treatment, patients with end stage renal disease undergoing maintenance haemodialysis (HD) remain at a substantially increased risk of morbidity. Previous reports using Doppler ultrasound (DU) during HD have revealed microembolic signals (ME) in the venous circulation.

    In vitro studies confirm the emergence of microbubbles of air that may pass the security system of the HD circuit without triggering the alarm. The aim of this thesis was to elucidate the presence of ME during HD and examine methods that might reduce exposure to ME in vivo.

    The first study utilized DU to verify the presence of ME in 40 patients during standard HD. Investigation within 30 minutes after the start of HD and just before the end of session revealed the presence of ME in the venous blood line during both phases. The air trap did not alert for the presence of ME. This indicated that ME may pass into the patient during the entire HD run.

    Study 2 analyzed the presence of ME prior to start and during HD when measured at the AV-access and also carotid artery. A total of 54 patients were examined using DU as the investigative technique. ME increased significantly after start of HD in the AV-access, but also at the carotid artery site. These data indicated that ME can enter the body and even pass the lung barrier. The question arose if microbubbles of air are resorbed or may cause ischemic lesions in organs such as the brain.

    Study 3 examined whether the amount of ME detected in the AV-access would change by using either a high or a low blood level in the venous air trap/chamber. This was a prospective, randomized and double-blind study of 20 HD patients who were their own controls. After 30 min of standard HD, measurement of ME with DU was performed for two minutes. The chamber setting was changed and after another 30 minutes a new recording was carried out for two minutes. Data showed that setting a high blood level significantly reduced the extent of ME that entered the patient. The results also indicated that ME consisted mainly of microbubbles.

    In study 4, twenty patients were randomized in a cross-over setting of HD. Three options were used: a wet-stored dialyzer with high blood level (WH) and a dry-stored dialyzer using either a high (DH) or a low (DL) blood level in the venous chamber. The exposure of ME, detected by DU, was least when using mode WF, more with mode DH, and most with mode DL. There was a correlation between higher blood flow and more extensive exposure to ME.

    Study 5 was an autopsy study of a chronic HD patient with the aim of searching for microbubbles deposited in organs. Microbubbles of gas were verified in the vessels of the lungs, brain and heart. By using a fluorescent stain of anti-fibrinogen it was verified that the microbubbles were covered by clots that had to be preformed before death occurred. This indicated that air microbubbles are not completely absorbed and could result in embolic deposition in the organs of HD patients.

    In conclusion, these in vivo studies showed that ME pass the air trap without inducing an alarm and enter the venous blood line of the patient. The data confirmed the presence of ME in the AV-access and also in the carotid artery. Autopsy data of a deceased HD patient demonstrated the presence of microbubbles in the capillaries of the lungs, but also in the systemic circulation such as in the brain and the heart. A high blood level in the venous chamber and wet-stored dialyzer can reduce, but not eliminate the exposure to microbubbles for patients undergoing HD.

  • 345.
    Ulf, Forsberg
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jonsson, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Stegmayr, Christofer
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jonsson, Fredrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nilsson, Bo
    Nilsson Ekdahl, Kristina
    Stegmayr, Bernd
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    A high blood level in the venous chamber and a wet-stored dialyzer help to reduce exposure for microemboli during hemodialysis2013In: Hemodialysis International, ISSN 1492-7535, E-ISSN 1542-4758, Vol. 17, no 4, p. 612-617Article in journal (Refereed)
    Abstract [en]

    During hemodialysis (HD), microemboli develop in the blood circuit of the apparatus. These microemboli can pass through the venous chamber and enter into the patient's circulation. The aim of this study was to investigate whether it is possible to reduce the risk for exposure of microemboli by altering of the treatment mode. Twenty patients on chronic HD were randomized to a prospective cross-over study of three modes of HD: (a) a dry-stored dialyzer (F8HPS, Fresenius, steam sterilized) with a low blood level in the venous chamber (DL), (b) the same dialyzer as above, but with a high level in the venous chamber (DH), and (c) a wet-stored dialyzer (Rexeed, Asahi Kasei Medical, gamma sterilized) with a high blood level (WH). Microemboli measurements were obtained in a continuous fashion during 180 minutes of HD for all settings. A greater number of microemboli were detected during dialysis with the setting DL vs. WH (odds ratio [OR] 4.07, 95% confidence interval [CI] 4.03–4.11, P < 0.0001) and DH vs. WH (OR 1.18, 95% CI 1.17–1.19, P < 0.0001) and less for DH vs. DL (OR 0.290, 95% CI 0.288–0.293, P < 0.0001). These data indicate that emboli exposure was least when using WH, greater with DH, and most with DL. This study shows that using a high blood level in the venous chamber and wet-stored dialyzers may reduce the number of microemboli.

  • 346.
    Vallin, Simon
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    "The recurrence rate of urinary bladder cancer (T1-tumors) in relation to lead times from first documented symptom to first TURb"2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 347. Van Hemelrijck, M.
    et al.
    Garmo, H.
    Holmberg, L.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Adolfsson, J.
    Thromboembolic events following surgical procedures for prostate cancer2012In: European urology. Supplement, ISSN 1569-9056, E-ISSN 1878-1500, Vol. 11, no 1, p. E456-U996Article in journal (Other academic)
  • 348. Van Hemelrijck, Mieke
    et al.
    Garmo, Hans
    Holmberg, Lars
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Adolfsson, Jan
    Multiple events of fractures and cardiovascular and thromboembolic disease following prostate cancer diagnosis: results from the population-based PCBaSe Sweden2012In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 61, no 4, p. 690-700Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To date, adverse events of prostate cancer (PCa) treatment have only been studied as a single event, and little is known about the risk of subsequent adverse events.

    OBJECTIVE: We assessed the frequency of multiple events (fractures, stroke, heart disease [HD], and thromboembolic disease [TED]) following PCa diagnosis.

    DESIGN, SETTING, AND PARTICIPANTS: PCBaSe Sweden is based on the National Prostate Cancer Register (NPCR) that covers >96% of incident PCa cases in Sweden.

    MEASUREMENTS: We evaluated the number of events (fractures, stroke, HD, and TED) leading to hospitalisation recorded in the National Hospital Discharge Registry after PCa diagnosis and conducted multivariate age-adjusted Cox proportional hazards regression to estimate the risk of developing multiple events.

    RESULTS AND LIMITATIONS: Between 1997 and 2007, 30 642 men received primary endocrine treatment, 26 432 curative treatment, and 19 526 surveillance: 75% had no event during follow-up, 17% had one event, and 9% had more than one event. The incidence of any event was 102 in 1000 person-years. Men who already had experienced an event, particularly HD, before or after the date of PCa diagnosis were more likely to have multiple events afterwards. For example, the hazard ratio of developing a third event for those with two or more events of HD before PCa diagnosis was 1.40 (95% confidence interval, 1.28-1.52) compared with those with no events of HD before PCa diagnosis. Events treated without hospitalisation were not included, so the number of adverse events is possibly underestimated.

    CONCLUSIONS: A third of PCa patients with an adverse event after treatment subsequently experienced another adverse event, but apart from history of HD or stroke before PCa diagnosis, no specific characteristics were found for these men. Thus PCa management needs to take into account the risk of adverse events in all PCa patients, especially those with a history of adverse events before PCa diagnosis.

  • 349. Van Hemelrijck, Mieke
    et al.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Adolfsson, Jan
    Reply from authors re: Matthew R. Cooperberg. Adverse effects of androgen deprivation and the limits of national tumor registries. Eur Urol. 2012;61:701–3, DOI 10.1016/j.eururo.2011.09.0102012In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 61, no 4, p. 703-704Article in journal (Other academic)
  • 350. Van Hemelrijck, Mieke
    et al.
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Adolfsson, Jan
    Reply to Tommaso Cai, Carolina D'Elia, and Beatrice Detti's letter to the editor re: Mieke Van Hemelrijck, Hans Garmo, Lars Holmberg, et al. Multiple events of fractures and cardiovascular and thromboembolic disease following prostate cancer diagnosis: results from the population-based PCBaSe Sweden. Eur Urol 2012;61:690–7002012In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 61, no 4, p. e28-Article in journal (Other academic)
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