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  • 1. Adolfsson, Jan
    et al.
    Garmo, Hans
    Varenhorst, Eberhard
    Ahlgren, Göran
    Ahlstrand, Christer
    Andren, Ove
    Örebro University, School of Health and Medical Sciences.
    Bill-Axelson, Anna
    Bratt, Ola
    Damber, Jan-Erik
    Hellström, Karin
    Hellström, Magnus
    Holmberg, Erik
    Holmberg, Lars
    Hugosson, Jonas
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Petterson, Bill
    Törnblom, Magnus
    Widmark, Anders
    Stattin, Pär
    Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005: Data from the national prostate cancer register in Sweden2007In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 41, no 6, p. 456-477Article in journal (Refereed)
    Abstract [en]

    Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer

  • 2. Amundadottir, Laufey T.
    et al.
    Sulem, Patrick
    Gudmundsson, Julius
    Helgason, Agnar
    Baker, Adam
    Agnarsson, Bjarni A.
    Sigurdsson, Asgeir
    Benediktsdottir, Kristrun R.
    Cazier, Jean-Baptiste
    Sainz, Jesus
    Jakobsdottir, Margret
    Kostic, Jelena
    Magnusdottir, Droplaug N.
    Ghosh, Shyamali
    Agnarsson, Kari
    Birgisdottir, Birgitta
    Le Roux, Louise
    Olafsdottir, Adalheidur
    Blondal, Thorarinn
    Andresdottir, Margret
    Gretarsdottir, Olafia Svandis
    Bergthorsson, Jon T.
    Gudbjartsson, Daniel
    Gylfason, Arnaldur
    Thorleifsson, Gudmar
    Manolescu, Andrei
    Kristjansson, Kristleifur
    Geirsson, Gudmundur
    Isaksson, Helgi
    Douglas, Julie
    Johansson, Jan-Erik
    Örebro University, Department of Clinical Medicine.
    Bälter, Katarina
    Wiklund, Fredrik
    Montie, James E.
    Yu, Xiaoying
    Suarez, Brian K.
    Ober, Carole
    Cooney, Kathleen A.
    Gronberg, Henrik
    Catalona, William J.
    Einarsson, Gudmundur V.
    Barkardottir, Rosa B.
    Gulcher, Jeffrey R.
    Kong, Augustine
    Thorsteinsdottir, Unnur
    Stefansson, Kari
    A common variant associated with prostate cancer in European and African populations2006In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 38, no 6, p. 652-658Article in journal (Refereed)
    Abstract [en]

    With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.

  • 3.
    Andersson, Gunnel
    et al.
    Örebro University, School of Health and Medical Sciences. Department of Clinical Medicine and Section of Urology Örebro University Hospital, Örebro University, Örebro, Sweden; Centre for Evidence Based Medicine, Assessment of Medical Technology, Örebro County Council, Örebro, Sweden.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences. Department of Clinical Medicine and Section of Urology Örebro University Hospital, Örebro University, Örebro, Sweden; Centre for Evidence Based Medicine, Assessment of Medical Technology, Örebro County Council, Örebro, Sweden.
    Garpenholt, Örjan
    Örebro University, Department of Nursing and Caring Sciences. Department of Clinical Medicine and Section of Urology Örebro University Hospital, Örebro University, Örebro, Sweden; Centre for Evidence Based Medicine, Assessment of Medical Technology, Örebro County Council, Örebro, Sweden.
    Nilsson, Kerstin
    Centre for Evidence Based Medicine, Assessment of Medical Technology, Örebro County Council, Örebro, Sweden; Department of Obstetrics and Gynaecology, Örebro University Hospital, Örebro, Sweden.
    Urinary incontinence: prevalence, impact on daily living and desire for treatment : a population-based study2004In: Scandinavian journal of urology and nephrology, ISSN 0036-5599, Vol. 38, no 2, p. 125-130Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate the prevalence of urinary incontinence in a representative population in Sweden, and to assess to what extent the condition affects daily life and to what degree those afflicted desire treatment.

    MATERIAL AND METHODS:

    In a population-based study, a postal questionnaire comprising 12 questions on urinary incontinence was sent to a representative sample of 15 360 randomly selected residents (aged 18-79 years) of Orebro County, Sweden. This was a supplement to a comprehensive survey of public health and general living conditions.

    RESULTS:

    The response rate was 64.5%. The prevalence of urinary incontinence was 19% when defined as "any leakage" and 7% when defined as "at least once a week". Women were more afflicted than men, and the proportion of people with urinary incontinence increased markedly with increasing age. Most considered their problems to be minor, having little impact on daily life, which was reflected by the fact that only 18% of those with urinary incontinence desired treatment. About 17% of those with urinary incontinence reported severe problems that interfered with daily life. Of respondents with severe problems, 42% did not want treatment.

    CONCLUSION:

    According to this population-based study, urinary incontinence is not a major problem for most people in the community. Although a considerable proportion of the population report urinary incontinence, the majority experience minor problems and only 18% desire treatment. For a limited group of people, urinary incontinence is a severe problem. It is important that healthcare resources are optimized to identify and meet the needs of those who are most afflicted.

  • 4.
    Andersson, Gunnel
    et al.
    Department of Urology. Department oí Clinical Medioine. Örebro University Hospital, Örebro, Sweden, Centre for Evidence-Based Medicine and Assessment of Medical Technology, Örebro, Sweden.
    Johansson, Jan-Erik
    Department of Urology. Department oí Clinical Medioine. Örebro University Hospital, Örebro, Sweden, Centre for Evidence-Based Medicine and Assessment of Medical Technology, Örebro, Sweden.
    Nilsson, Kerstin
    Department of Obstretics andGynaecology, Örebro University Hospital, Örebro, Sweden; Department of Clinical Medicine, Örebro, Sweden; Centre for Evidence-Based Medicine and Assessment of Medical Technology, Örebro, Sweden.
    Sahlberg-Blom, Eva
    Örebro University, School of Health and Medical Sciences.
    Accepting and adjusting: Older women´s experiences of living with urinary incontinence2008In: Urologic Nursing, ISSN 1053-816X, Vol. 28, no 2, p. 115-121Article in journal (Refereed)
    Abstract [en]

    In-depth interviews were performed with 11 Swedish women who contacted a district nurse to obtain sanitary protection. Three key constituents (themes) emerged: "learning to live with it despite difficulties," "other illnesses are more important," and "reluctance to seek care." The essence of the phenomenon of living with urinary incontinence (Ul) was expressed as "a situation to accept and adjust to."

  • 5.
    Andersson, Gunnel
    et al.
    Örebro University Hospital, Sweden.
    Johansson, Jan-Erik
    Örebro University Hospital, Sweden.
    Nilsson, Kerstin
    Örebro University Hospital, Sweden.
    Sahlberg-Blom, Eva
    Örebro University Hospital, Sweden.
    Perceptions of urinary incontinence among syrian Christian women living in Sweden2009In: Journal of Transcultural Nursing, ISSN 1043-6596, E-ISSN 1552-7832, Vol. 20, no 3, p. 296-303Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to describe the perception of urinary incontinence (UI) among Syrian women living in Sweden. DESIGN: A qualitative, descriptive design with focus group discussions (FGDs) was used and analyzed with content analysis. Fourteen Syrian women were interviewed in three FGDs. FINDINGS: Three categories emerged, "Thoughts on UI," "Managing UI," and "Communication With the Health Care System." Among the interviewees, UI was a common, and expected, problem, which could be managed. However, some expressed shame and embarrassment. Some talked about communication problems with health care. DISCUSSION: and Implications for Practice: The health care system should be adjusted to the women's needs, with awareness of the communication difficulties, which could result in misunderstanding and neglected treatments.

  • 6.
    Andersson, Gunnel
    et al.
    Örebro University, Department of Clinical Medicine. Department of Urology, Örebro University Hospital, Örebro, Sweden; Centre for Evidence Based Medicine and Assessment of Medical Technology, Örebro, Sweden.
    Johansson, Jan-Erik
    Örebro University, Department of Clinical Medicine. Department of Urology, Örebro University Hospital, Örebro, Sweden; Centre for Evidence Based Medicine and Assessment of Medical Technology, Örebro, Sweden.
    Sahlberg-Blom, Eva
    Örebro University, Department of Nursing and Caring Sciences.
    Pettersson, Nicklas
    Department of Public Health, O¨ rebro County Council, O¨ rebro, Sweden.
    Nilsson, Kerstin
    Örebro University, Department of Clinical Medicine. Centre for Evidence Based Medicine and Assessment of Medical Technology, O¨ rebro, Sweden; Department of Obstetrics and Gynaecology, Örebro University Hospital, Örebro, Sweden.
    Urinary incontinence - why refraining from treatment?: a population based study2005In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 39, no 4, p. 301-307Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 7.
    Andersson, Swen-Olof
    et al.
    Örebro University, School of Health and Medical Sciences.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences.
    Lyth, J.
    Stark, JR
    Henriksson, M.
    Adami, HO
    Carlsson, P.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Managing localized prostate cancer by radical prostatectomy or watchful waiting: cost analysis of a randomized trial (SPCG-4)2011In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 45, no 3, p. 177-183Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The cost of radical prostatectomy (RP) compared to watchful waiting (WW) has never been estimated in a randomized trial. The goal of this study was to estimate long-term total costs per patient associated with RP and WW arising from inpatient and outpatient hospital care.

    MATERIAL AND METHODS: This investigation used the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) trial, comparing RP to WW, and included data from 212 participants living in two counties in Sweden from 1989 to 1999 (105 randomized to WW and 107 to RP). All costs were included from randomization date until death or end of follow-up in July 2007. Resource use arising from inpatient and outpatient hospital costs was measured in physical units and multiplied by a unit cost to come up with a total cost per patient.

    RESULTS: During a median follow-up of 12 years, the overall cost in the RP group was 34% higher (p < 0.01) than in the WW group, corresponding to €6123 in Sweden. The difference was driven almost exclusively by the cost of the surgical procedure. The cost difference between RP and WW was two times higher among men with low (2-6) than among those with high (7-10) Gleason score.

    CONCLUSION: In this economic evaluation of RP versus WW of localized prostate cancer in a randomized study, RP was associated with 34% higher costs. This difference, attributed exclusively to the cost of the RP procedure, was not overcome during extended follow-up.

  • 8.
    Andrén, Ove
    et al.
    Örebro University, School of Health and Medical Sciences.
    Fall, Katja
    Andersson, Swen-Olof
    Rubin, Mark A.
    Bismar, Tarek A.
    Karlsson, M.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Mucci, Lorelei A.
    MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden2007In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 97, no 6, p. 730-734Article in journal (Refereed)
    Abstract [en]

    Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score >=7 and MUC-1 deviating from the normal had a 17 (RR=17.1 95% confidence interval=2.3–128) times higher risk to die in prostate cancer compared with men with Gleason score <7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death.

  • 9. Andrén, Ove
    et al.
    Garmo, H.
    Mucci, L.
    Andersson, Swen-Olof
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Fall, Katja
    Incidence and mortality of incidental prostate cancer: a Swedish register-based study2009In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 100, no 1, p. 170-173Article in journal (Refereed)
    Abstract [en]

    In a national register-based study of incidence trends and mortality of incidental prostate cancer in Sweden, we found that a significant proportion (26.6%) of affected men diagnosed died of their disease, which challenges earlier descriptions of incidental prostate cancer as a non-lethal disease.

  • 10. Bill-Axelson, Anna
    et al.
    Holmberg, Lars
    Filén, Frej
    Ruutu, Mirja
    Garmo, Hans
    Busch, Christer
    Nordling, Stig
    Häggman, Michael
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences.
    Bratell, Stefan
    Spångberg, Anders
    Palmgren, Juni
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial2008In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 100, no 16, p. 1144-1154Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.

    METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.

    RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).

    CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery. 

  • 11.
    Bill-Axelson, Anna
    et al.
    Univ Uppsala Hosp, Dept Surg Sci, Uppsala, Sweden.
    Holmberg, Lars
    Univ Uppsala Hosp, Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden; Kings Coll London, Sch Med, Div Canc Studies, London WC2R 2LS, England.
    Garmo, Hans
    Univ Uppsala Hosp, Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden; Kings Coll London, Sch Med, Div Canc Studies, London WC2R 2LS, England.
    Rider, Jennifer R.
    Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA; Harvard Univ, Sch Med, Boston, MA USA; Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
    Taari, Kimmo
    Univ Helsinki, Cent Hosp, Dept Urol, Helsinki, Finland.
    Busch, Christer
    Univ Uppsala Hosp, Dept Immunol Genet & Pathol, Uppsala, Sweden.
    Nordling, Stig
    Univ Helsinki, Dept Pathol, Helsinki, Finland.
    Häggman, Michael
    Univ Uppsala Hosp, Dept Surg Sci, Uppsala, Sweden.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept Urol.
    Spångberg, Anders
    Linköping Univ Hosp, Dept Urol, Linköping, Sweden.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept Urol.
    Palmgren, Juni
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Steineck, Gunnar
    Karolinska Inst, Dept Pathol & Oncol, Div Clin Canc Epidemiol, Stockholm, Sweden; Sahlgrens Acad, Div Clin Canc Epidemiol, Gothenburg, Sweden.
    Adami, Hans-Olov
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden; Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept Urol.
    Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 370, no 10, p. 932-942Article in journal (Refereed)
    Abstract [en]

    Background: Radical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain.

    Methods: Between 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy.

    Results: During 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04).

    Conclusions: Extended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.)

    The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up.(1) By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer-specific or overall mortality after 12 years.(2) PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time ...

  • 12. Bill-Axelson, Anna
    et al.
    Holmberg, Lars
    Ruutu, Mirja
    Garmo, Hans
    Stark, Jennifer R
    Busch, Christer
    Nordling, Stig
    Häggman, Michael
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences. Department of Urology.
    Bratell, Stefan
    Spångberg, Anders
    Palmgren, Juni
    Steineck, Gunnar
    Adami, Hans-Olov
    Johansson, J-E
    Örebro University, School of Health and Medical Sciences.
    Radical prostatectomy versus watchful waiting in early prostate cancer2011In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 364, no 18, p. 1708-1717Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results.

    METHODS: From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model.

    RESULTS: During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4).

    CONCLUSIONS: Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment.

  • 13.
    Burman, Joachim
    et al.
    Department of Neuroscience, Uppsala University, Uppsala, Sweden; Department of Neurology, Uppsala University Hospital, Uppsala, Sweden .
    Iacobaeus, Ellen
    Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institute Solna, Center for Molecular Medicine, Stockholm, Sweden.
    Svenningsson, Anders
    Department of Pharmacology and Clinical Neuroscience, Umeå University and University Hospital of Northern Sweden, Umeå, Sweden .
    Lycke, Jan
    Department of Neurology, Institute of Neuroscience and Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Gunnarsson, Martin
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Neurology, Örebro University Hospital, Örebro, Sweden .
    Nilsson, Petra
    Department of Neurology, Skåne University Hospital Lund, Lund, Sweden.
    Vrethem, Magnus
    Neurology and Clinical Neurophysiology, Faculty of Health Sciences, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Neurology and Neurophysiology, County Council of Östergötland, Linköping, Sweden .
    Fredrikson, Sten
    Department of Clinical Neuroscience, Karolinska Institute Huddinge, Stockholm, Sweden .
    Martin, Claes
    Neurology Unit, Division of Internal Medicine, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden .
    Sandstedt, Anna
    Department of Hematology, Linköping University Hospital, Linköping, Sweden .
    Uggla, Bertil
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Division of Hematology, Department of Medicine.
    Lenhoff, Stig
    Department of Hematology and Coagulation, Skåne University Hospital, Lund, Sweden .
    Johansson, Jan-Erik
    Department of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Isaksson, Cecilia
    Department of Radiosciences, Umeå University, Umeå, Sweden .
    Hägglund, Hans
    Division of Hematology, Department of Medical Science, Uppsala University Hospital, Uppsala, Sweden.
    Carlson, Kristina
    Division of Hematology, Department of Medical Science, Uppsala University Hospital, Uppsala, Sweden.
    Fagius, Jan
    Department of Neuroscience, Uppsala University, Uppsala, Sweden; Department of Neurology, Uppsala University Hospital, Uppsala, Sweden .
    Autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: the Swedish experience2014In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, no 10, p. 1116-1121Article in journal (Refereed)
    Abstract [en]

    Background: Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS.

    Methods: Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months.

    Results: At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%).

    Conclusions: HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.

  • 14. Carlsson, Sigrid
    et al.
    Adolfsson, Jan
    Bratt, Ola
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Ahlstrand, Christer
    Holmberg, Erik
    Stattin, Pär
    Hugosson, Jonas
    Nationwide population-based study on 30-day mortality after radical prostatectomy in Sweden2009In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 43, no 5, p. 350-356Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The incidence of prostate cancer in Sweden is increasing rapidly, as is treatment with curative intent. Radical prostatectomy (RP) is currently commonly performed, either within or outside large high-volume centres. The aim of this study was to assess the 30-day mortality rate after RP in Sweden. MATERIAL AND METHODS: In this nationwide population-based study, all men diagnosed with localized prostate cancer (< or =70 years, clinical stadium T1-2, prostate-specific antigen < 20 ng/ml) who underwent RP in Sweden between 1997 and 2002 were identified through the National Prostate Cancer Register (NPCR). Mortality within 30 days of RP was analysed through linkage between the follow-up study of the NPCR and the Regional Population Registers. The cause of death in the death certificates were compared with data from the hospitals concerned. To validate the results, a record linkage between the Inpatient Register and the National Population Register was also performed. RESULTS: The number of RPs performed increased over time. Among 3700 RPs performed, four deaths occurred during the first 30 days, yielding a 0.11% 30-day mortality rate. These deaths occurred at three different types of hospital and were all probably related to the RP. CONCLUSION: This study provides further evidence that RP is a procedure with very low perioperative mortality even when performed outside high-volume centres.

  • 15. Demichelis, F.
    et al.
    Fall, K.
    Perner, S.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences.
    Schmidt, F.
    Setlur, S.R.
    Hoshida, Y.
    Mosquera, J-M.
    Pawitan, Y.
    Lee, C.
    Adami, H-O.
    Mucci, L.A.
    Kantoff, P.W.
    Andersson, S-O.
    Chinnaiyan, A.M.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Rubin, M.A.
    TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort2007In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 26, no 31, p. 4596-4599Article in journal (Refereed)
    Abstract [en]

    The identification of the TMPRSS2:ERG fusion in prostate cancer suggests that distinct molecular subtypes may define risk for disease progression. In surgical series, TMPRSS2:ERG fusion was identified in 50% of the tumors. Here, we report on a population-based cohort of men with localized prostate cancers followed by expectant (watchful waiting) therapy with 15% (17/111) TMPRSS2:ERG fusion. We identified a statistically significant association between TMPRSS2:ERG fusion and prostate cancer specific death (cumulative incidence ratio=2.7, P<0.01, 95% confidence interval=1.3–5.8). Quantitative reverse-transcription–polymerase chain reaction demonstrated high estrogen-regulated gene (ERG) expression to be associated with TMPRSS2:ERG fusion (P<0.005). These data suggest that TMPRSS2:ERG fusion prostate cancers may have a more aggressive phenotype, possibly mediated through increased ERG expression.

  • 16. Discacciati, A.
    et al.
    Orsini, N.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept Urol.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept Urol.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept Urol.
    Mantzoros, C. S.
    Wolk, A.
    Coffee consumption and risk of localized, advanced and fatal prostate cancer: a population-based prospective study2013In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no 7, p. 1912-1918Article in journal (Refereed)
    Abstract [en]

    Background: The epidemiological evidence on possible relationships between coffee consumption and prostate cancer (PCa) risk by subtype of the disease (localized, advanced) and fatal PCa risk is limited.

    Materials and methods: A population-based cohort of 44 613 Swedish men aged 45-79 years was followed up from January 1998 through December 2010 for incidence of localized (n = 2368), advanced (n = 918) and fatal (n = 515) PCa. We assessed the associations between coffee consumption and localized, advanced and fatal PCa risk using competing-risk regressions. We examined possible effect modification by body mass index (BMI).

    Results: For localized PCa, each one cup increase in daily coffee consumption was associated with a 3% reduced risk [sub-hazard ratio (SHR) = 0.97, 95% confidence interval (CI) = 0.95-0.99]. For advanced and fatal PCa, we found a non-significant inverse association; each one cup increase was associated with a 2% reduced risk of advanced [SHR (95% CI) = 0.98 (0.95-1.02)] and fatal PCa [SHR (95% CI) = 0.98 (0.93-1.03)]. We observed evidence of effect modification by BMI for localized PCa (P-interaction = 0.03); the inverse association was stronger among overweight and obese men (BMI >= 25 kg/m(2)) compared with normal-weight men (BMI < 25 kg/m(2)).

    Conclusions: We observed a clear inverse association between coffee consumption and risk of localized PCa, especially among overweight and obese men.

  • 17.
    Epstein, Mara M.
    et al.
    [1,2].
    Kasperzyk, Julie L.
    [1,2].
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Giovannucci, Edward L.
    [1,2,3].
    Wolk, Alicja
    [5].
    Håkansson, Niclas
    [5].
    Andersson, Swen-Olof
    [4].
    Johansson, Jan-Erik
    [4].
    Fall, Katja
    [2,6,7].
    Mucci, Lorelei A.
    [1,2,7].
    Dietary zinc and prostate cancer survival in a Swedish cohort2011In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 93, no 3, p. 586-593Article in journal (Refereed)
    Abstract [en]

    Background: Zinc is involved in many essential cellular functions, including DNA repair and immune system maintenance. Although experimental evidence supports a role for zinc in prostate carcinogenesis, epidemiologic data are inconsistent; no data on cancer-specific survival have been reported.

    Objective: Our objective was to determine whether dietary zinc assessed near the time of prostate cancer diagnosis is associated with improved disease-specific survival.

    Design: This population-based cohort consists of 525 men aged < 80 y from Orebro County, Sweden, with a diagnosis of prostate cancer made between 1989 and 1994. Study participants completed self-administered food-frequency questionnaires, and zinc intake was derived from nutrient databases. Cox proportional hazards regression was used to estimate multivariate hazard ratios (HRs) and 95% CIs for time to death from prostate cancer as well as death from all causes through February 2009 by quartile (Q) of dietary zinc intake. Models were also stratified by disease stage at diagnosis (localized or advanced).

    Results: With a median follow-up of 6.4 y, 218 (42%) men died of prostate cancer and 257 (49%) died of other causes. High dietary zinc intake was associated with a reduced risk of prostate cancer-specific mortality (HR(Q4 vs Q1): 0.64; 95% CI: 0.44, 0.94; P for trend = 0.05) in the study population. The association was stronger in men with localized tumors (HR: 0.24; 95% CI: 0.09, 0.66; P for trend = 0.005). Zinc intake was not associated with mortality from other causes.

    Conclusion: These results suggest that high dietary intake of zinc is associated with lower prostate cancer-specific mortality after diagnosis, particularly in men with localized disease. Am J Clin Nutr 2011;93:586-93.

  • 18.
    Etzioni, Ruth
    et al.
    Program in Biostatistics, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
    Mucci, Lorelei
    Department of Epidemiology, Harvard School of Public Health, Harvard Medical School, Boston, MA, United States; Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
    Chen, Shu
    Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Fall, Katja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Adami, Hans-Olov
    Department of Epidemiology, Harvard School of Public Health, Harvard Medical School, Boston, MA, United States; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Increasing use of radical prostatectomy for nonlethal prostate cancer in Sweden2012In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 18, no 24, p. 6742-6747Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The number of patients in Sweden treated with radical prostatectomy for localized prostate cancer has increased exponentially. The extent to which this increase reflects treatment of nonlethal disease detected through prostate-specific antigen (PSA) screening is unknown.

    EXPERIMENTAL DESIGN: We undertook a nationwide study of all 18,837 patients with prostate cancer treated with radical prostatectomy in Sweden from 1988 to 2008 with complete follow-up through 2009. We compared cumulative incidence curves, fit Cox regression and cure models, and conducted a simulation study to determine changes in treatment of nonlethal cancer, in cancer-specific survival over time, and effect of lead-time due to PSA screening.

    RESULTS: The annual number of radical prostatectomies increased 25-fold during the study period. The 5-year cancer-specific mortality rate decreased from 3.9% [95% confidence interval (CI), 2.5-5.3] among patients diagnosed between 1988 and 1992 to 0.7% (95% CI, 0.4-1.1) among those diagnosed between 1998 and 2002 (P(trend) < 0.001). According to the cure model, the risk of not being cured declined by 13% (95% CI, 12%-14%) with each calendar year. The simulation study indicated that only about half of the improvement in disease-specific survival could be accounted for by lead-time.

    CONCLUSION: Patients overdiagnosed with nonlethal prostate cancer appear to account for a substantial and growing part of the dramatic increase in radical prostatectomies in Sweden, but increasing survival rates are likely also due to true reductions in the risk of disease-specific death over time. Because the magnitude of harm and costs due to overtreatment can be considerable, identification of men who likely benefit from radical prostatectomy is urgently needed.

  • 19.
    Fall, Katja
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
    Fang, Fang
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Mucci, Lorelei A.
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America; Channing Laboratory, Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
    Ye, Weimin
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Andrén, Ove
    Örebro University Hospital, Örebro, Sweden.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden.
    Andersson, Swen-Olof
    Örebro University Hospital, Örebro, Sweden.
    Sparén, Pär
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Klein, Georg
    The Microbiology Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
    Stampfer, Meir
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America; Channing Laboratory, Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.
    Adami, Hans-Olov
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America.
    Valdimarsdóttir, Unnur
    Centre of Public Health Sciences, University of Iceland, Reykjavík, Iceland.
    Immediate risk for cardiovascular events and suicide following a prostate cancer diagnosis: prospective cohort study2009In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 6, no 12, p. e1000197-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Stressful life events have been shown to be associated with altered risk of various health consequences. The aim of the present study was to investigate whether the emotional stress evoked by a prostate cancer diagnosis increases the immediate risks of cardiovascular events and suicide.

    METHODS AND FINDINGS: We conducted a prospective cohort study by following all men in Sweden who were 30 y or older (n = 4,305,358) for a diagnosis of prostate cancer (n = 168,584) and their subsequent occurrence of cardiovascular events and suicide between January 1, 1961 and December 31, 2004. We used Poisson regression models to calculate relative risks (RRs) and 95% confidence intervals (CIs) of cardiovascular events and suicide among men who had prostate cancer diagnosed within 1 y to men without any cancer diagnosis. The risks of cardiovascular events and suicide were elevated during the first year after prostate cancer diagnosis, particularly during the first week. Before 1987, the RR of fatal cardiovascular events was 11.2 (95% CI 10.4-12.1) during the first week and 1.9 (95% CI 1.9-2.0) during the first year after diagnosis. From 1987, the RR for cardiovascular events, nonfatal and fatal combined, was 2.8 (95% CI 2.5-3.2) during the first week and 1.3 (95% CI 1.3-1.3) during the first year after diagnosis. While the RR of cardiovascular events declined, the RR of suicide was stable over the entire study period: 8.4 (95% CI 1.9-22.7) during the first week and 2.6 (95% CI 2.1-3.0) during the first year after diagnosis. Men 54 y or younger at cancer diagnosis demonstrated the highest RRs of both cardiovascular events and suicide. A limitation of the present study is the lack of tumor stage data, which precluded possibilities of investigating the potential impact of the disease severity on the relationship between a recent diagnosis of prostate cancer and the risks of cardiovascular events and suicide. In addition, we cannot exclude residual confounding as a possible explanation.

    CONCLUSIONS: Men newly diagnosed with prostate cancer are at increased risks for cardiovascular events and suicide. Future studies with detailed disease characteristic data are warranted.

  • 20. Fall, Katja
    et al.
    Garmo, Hans
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences.
    Bill-Axelson, Anna
    Adolfsson, Jan
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Holmberg, Lars
    Prostate-specific antigen levels as a predictor of lethal prostate cancer2007In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 99, no 7, p. 526-532Article in journal (Refereed)
    Abstract [en]

    Background: Rates of long-term survival among patients with untreated localized prostate cancer are high. To avoid unnecessary treatment, tools are needed to identify the small proportion of patients who are destined to develop lethal prostate cancer.

    Methods: To evaluate the accuracy of early changes in prostate-specific antigen (PSA) levels as predictors of prostate cancer outcome, we assessed serial measurements of PSA level among 267 men with localized prostate cancer in a Scandinavian cohort of men who were diagnosed between 1989 and 1999 and who were managed by watchful waiting. We then 1) fitted individual regression lines to the PSA values assessed for each patient during the first 2 years of follow-up by using three different models, 2) evaluated early PSA curve characteristics as determinants of the cumulative incidence of lethal prostate cancer and calculated hazard ratios for baseline PSA value and rate of change in PSA level to prostate cancer outcome, and 3) plotted time-dependent receiver operating characteristic (ROC) curves. All P values are two-sided.

    Results: During complete follow-up for a mean of 8.5 years, 34 patients (13%) died from prostate cancer, and 18 (7%) developed metastases but were still alive at end of follow-up. In a log-linear model, both PSA value at baseline (P = .05) and the rate of PSA change (P<.001) were associated with the development of lethal prostate cancer. In the ROC analysis, however, the accuracy of classifying the disease as either indolent or destined to progress was low, regardless of the cut point chosen for initial PSA level or rate of change in PSA level.

    Conclusions: Although baseline PSA value and rate of PSA change are prognostic factors for lethal prostate cancer, they are poor predictors of lethal prostate cancer among patients with localized prostate cancer who are managed by watchful waiting.

  • 21.
    Flaberg, E.
    et al.
    Department of Microbiology, Tumor and Cell Biology (MTC), Center for Integrative Recognition in the Immune System (IRIS), Karolinska Institutet, Stockholm, Sweden; Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institute, Stockholm, Sweden.
    Markasz, L.
    Department of Microbiology, Tumor and Cell Biology (MTC), Center for Integrative Recognition in the Immune System (IRIS), Karolinska Institutet, Stockholm, Sweden.
    Petranyi, Gabor
    Department of Microbiology, Tumor and Cell Biology (MTC), Center for Integrative Recognition in the Immune System (IRIS), Karolinska Institutet, Stockholm, Sweden.
    Stuber, G.
    Department of Microbiology, Tumor and Cell Biology (MTC), Center for Integrative Recognition in the Immune System (IRIS), Karolinska Institutet, Stockholm, Sweden.
    Dicsö, F.
    Division of Pediatrics, Jósa András County Hospital, Nyíregyháza, Hungary.
    Alchihabi, N.
    Division of Pediatrics, Jósa András County Hospital, Nyíregyháza, Hungary.
    Oláh, E.
    Department of Pediatrics, Medical and Health Science Center, Debrecen University, Debrecen, Hungary.
    Csízy, I.
    Department of Pediatrics, Medical and Health Science Center, Debrecen University, Debrecen, Hungary.
    Józsa, T.
    Department of Pediatrics, Medical and Health Science Center, Debrecen University, Debrecen, Hungary.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences. Clinic of Urology.
    Johansson, J-E
    Örebro University, School of Health and Medical Sciences. Clinic of Urology.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences. Clinic of Urology.
    Klein, G.
    Department of Microbiology, Tumor and Cell Biology (MTC), Center for Integrative Recognition in the Immune System (IRIS), Karolinska Institutet, Stockholm, Sweden.
    Szekely, L.
    Department of Microbiology, Tumor and Cell Biology (MTC), Center for Integrative Recognition in the Immune System (IRIS), Karolinska Institutet, Stockholm, Sweden.
    High-throughput live cell imaging reveals differential inhibition of tumor cell proliferation by human fibroblasts2011In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 128, no 12, p. 2793-2802Article in journal (Refereed)
    Abstract [en]

    Increasing evidence indicates that cancer development requires changes both in the precancerous cells and in their microenvironment. To study one aspect of the microenvironmental control, we departed from Michael Stoker's observation (Stroker et al, J Cell Sci 1966;1:297-310) that normal fibroblasts can inhibit the growth of admixed cancer cells (neighbour suppression). We have developed a high-throughput microscopy and image analysis system permitting the examination of live mixed cell cultures growing on 384-well plates, at the single cell level and over time. We have tested the effect of 107 samples of low passage number (<5) primary human fibroblasts from pediatric and adult donors, on the growth of six human tumor cell lines. Three of the lines were derived from prostate carcinomas, two from lung carcinomas and one was an EBV transformed lymphoblastoid line. Labeled tumor cells were grown in the presence of unlabeled fibroblasts. The majority of the tested fibroblasts inhibited the proliferation of the tumor cells, compared to the control cultures where labeled tumor cells were co-cultured with unlabeled tumor cells. The proliferation inhibiting effect of the fibroblasts differed depending on their site of origin and the age of the donor. Inhibition required direct cell contact. Mouse 3T3 fibroblasts inhibited the growth of SV40-transformed 3T3 cells and human tumor cells, showing that the inhibitory effect could prevail across the species barrier. Our high-throughput system allows the quantitative analysis of the inhibitory effect of fibroblasts on the population level and the exploration of differences depending on the source of the normal cells.

  • 22.
    Franzén, Karin
    et al.
    Örebro University, School of Health and Medical Sciences.
    Johansson, Jan Erik
    Örebro University, School of Health and Medical Sciences.
    Karlsson, Jan
    Örebro University, School of Health and Medical Sciences.
    Nilsson, Kerstin
    Örebro University, School of Health and Medical Sciences.
    Validation of the Swedish version of the Incontinence Impact Questionnaire, IIQ-7 and the Urogenital Distress Inventory, UDI-6.Manuscript (preprint) (Other academic)
    Abstract [en]

    Introduction and hypothesis:

    The purpose was to validate the Swedish versions of the Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6). Methods: We analyzed reliability, validity, and responsiveness in a clinical sample of 96 women with UI. Result:Test-retest reliability ranged from moderate to almost perfect. Cronbach’s alpha was 0.39 (UDI-6) and 0.83 (IIQ-7). Effect size calculation of change after treatment demonstrated good responsiveness. The effect size at 6 months was moderate in the SUI group and small in the UUI+MUI group. There was a moderate to strong correlation between UDI-6 and IIQ-7 and treatment satisfaction at 6, 12, and 24 months for both groups. ConclusionThe Swedish UDI-6 and IIQ-7 show good responsiveness and are easy to administer and fill out. UDI-6 did not produce the same solid psychometrical results as IIQ-7, but both scales can be of clinical importance and are recommended for clinical use.

  • 23.
    Franzén, Karin
    et al.
    Department of Clinical Medicine and Section of Obstetrics and Gynaecology, Örebro University Hospital, Örebro, Sweden.
    Johansson, Jan-Erik
    Department of Clinical Medicine and Section of Urology, Örebro University Hospital, Örebro, Sweden; Centre for Assessment of Medical Technology, Örebro County Council, Örebro, Sweden.
    Andersson, Gunnel
    Department of Clinical Medicine and Section of Urology, Örebro University Hospital, Örebro, Sweden; Centre for Assessment of Medical Technology, Örebro County Council, Örebro, Sweden.
    Nilsson, Kerstin
    Department of Clinical Medicine and Section of Obstetrics and Gynaecology, Örebro University Hospital, Örebro, Sweden.
    Urinary incontinence: evaluation of an information campaign directed towards the general public2008In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 42, no 6, p. 534-538Article in journal (Refereed)
    Abstract [en]

    Objective. To study and evaluate the effect of an information campaign in the form of a brochure on urinary incontinence (UI) directed towards the general public, concerning knowledge, individual health behaviour, self-reported healthcare utilization and how the information was perceived.

    Material and methods. Within a community in central Sweden a random sample of the population, in age groups from 18 years upwards, was selected from the population registry, resulting in a total sample of 3658 people. The study group was sent the brochure "Treatment of urinary incontinence", produced by SBU (Swedish Council on Technology Assessment in Health Care) in March 2003 and a questionnaire 1–2 months after the brochure was received.

    Results. The overall response rate was 47.5%. Eighty per cent of the responders stated UI as an important health problem in society and 66% that they had gained new knowledge on UI. Twenty-eight per cent of the responders reported a current or previous history of UI, of whom 49% felt that they had received useful information for self-treatment and 21% had begun self-treatment.

    Conclusion. This population-based study found that the distribution of a brochure on UI to the general public was well received and can be an efficient method to spread knowledge and encourage self-management. 

  • 24.
    Franzén, Karin
    et al.
    Örebro University, School of Health and Medical Sciences. 2 Obstetrics and Gynaecology, Örebro County Council, Örebro, Sweden.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences. Urology, Örebro University Hospital, Örebro, Sweden; Centre for Assessment of Medical Technology, Örebro County Council, Örebro, Sweden.
    Andersson, Gunnel
    Örebro University, School of Health and Medical Sciences. Urology, Örebro University Hospital, Örebro, Sweden.
    Pettersson, Nicklas
    Department of Statistics, Stockholm University, Stockholm, Sweden.
    Nilsson, Kerstin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Obstetrics and Gynaecology,Örebro County Council, Örebro, Sweden; Centre for Assessment of Medical Technology, Örebro County Council, Örebro, Sweden.
    Urinary incontinence in women is not exclusively a medical problem: a population-based study on urinary incontinence and general living conditions2009In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 43, no 3, p. 226-232Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of the study was to analyse differences in general health and general living conditions between women with and without urinary incontinence (UI).

    MATERIAL AND METHODS: This cross-sectional population-based study was conducted in Orebro County, Sweden. A public health questionnaire, "Life and Health", was sent to a randomly selected sample of the population. The questionnaire consisted of 87 questions on broad aspects of general and psychiatric health. An additional questionnaire was enclosed for those respondents who reported experiencing UI. The data were analysed using binary logistic regression. The final study population constituted 4609 women, 1332 of whom had completed both questionnaires. The remaining 3277 had completed only the Life and Health questionnaire. Effect measures were odds ratios (ORs) with corresponding 95% confidence intervals (CIs).

    RESULTS: Statistically significant associations were found between UI and the occurrence of musculoskeletal pain (OR 1.45, 95% CI 1.20-1.76), fatigue and sleeping disorders (OR 1.59, 95% CI 1.30-1.95), feelings of humiliation (OR 1.29, 95% CI 1.12-1.50), financial problems (OR 1.36, 95% CI 1.11-1.66), and reluctance to seek medical care (OR 1.43, 95% CI 1.21-1.68).

    CONCLUSION: UI among women is commonly associated with a number of different psychosocial problems as well as an expressed feeling of vulnerability.

  • 25.
    Franzén, Karin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Karlsson, Jan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Nilsson, Kerstin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Validation of the Swedish version of the incontinence impact questionnaire and the urogenital distress inventory2013In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 92, no 5, p. 555-561Article in journal (Refereed)
    Abstract [en]

    Objective. To validate the Swedish versions of the Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6). Design and setting. Prospective study, university hospital. Population and method. We analyzed reliability, validity, and responsiveness in a clinical sample of 96 women with urinary incontinence. Main outcome measures. Construct and criterion validity, reliability via test-retest and internal consistency. Responsiveness via calculation of effect size. Result. Test-retest reliability ranged from moderate to almost perfect. Cronbach's alpha was 0.39 (UDI-6) and 0.83 (IIQ-7). Effect size calculation of change after treatment demonstrated good responsiveness. The effect size at six months was moderate in the Stress Urinary Incontinence group and small in the Urge Urinary Incontinence + Mixed Urinary Incontinence group. There was a moderate to strong correlation between UDI-6 and IIQ-7 and treatment satisfaction at six, 12, and 24 months for both groups. Conclusion. The UDI-6 scale did not produce the same solid result in the psychometric analysis as the IIQ-7 scale, but these newly translated Swedish forms of UDI-6 and IIQ-7 show good responsiveness and are easy to administer and to fill out.

  • 26.
    Franzén, Karin
    et al.
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden; Ctr Assessment Med Technol, Örebro Cty Council, Örebro, Sweden.
    Lauridsen, Inger
    Dept Urol, Torsby Hosp, Torsby, Sweden.
    Canelid, Jill
    Dept Obstet & Gynaecol, Karlstad Hosp, Karlstad, Sweden.
    Heiwall, Bengt
    Dept Obstet & Gynaecol, Karlstad Hosp, Karlstad, Sweden.
    Nilsson, Kerstin
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden; Ctr Assessment Med Technol, Örebro Cty Council, Örebro, Sweden.
    Electrical stimulation compared with tolterodine for treatment of urge/urge incontinence amongst women: a randomized controlled trial2010In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 21, no 12, p. 1517-1524Article in journal (Refereed)
    Abstract [en]

    Introduction and hypothesis: Few randomized controlled trials have compared electrical stimulation treatment with drug therapy. Our hypothesis was that electrical stimulation treatment in women with urgency/urge incontinence would be more efficient compared to drug treatment.

    Methods: Women ≥18 years of age with urgency/urge incontinence were randomized to receive either ten electrical stimulation treatments vaginally and transanally over a period of 5-7 weeks or tolterodine 4 mg orally once daily.

    Results: Sixty-one women completed the study. There was no significant difference between the two treatment groups in micturition rate from baseline to 6 months, mean difference, -0.40 (95% confidence interval (CI), -1.61 to 0.82), but a clearly significant difference within each group for electrical stimulation, -2.8 (95% CI, -3.7 to -1.9), and for tolterodine, -3.2 (95% CI, -4.1 to -2.4).

    Conclusions: Both treatments reduced the number of micturitions, but electrical stimulation was not found to be superior to tolterodine.

  • 27.
    Gupta, Anil
    et al.
    Örebro University, School of Health and Medical Sciences.
    Fant, Federica
    Örebro University, School of Health and Medical Sciences.
    Axelsson, Kjell
    Örebro University, School of Health and Medical Sciences.
    Sandblom, Dag
    Rykowski, Jan
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences.
    Postoperative analgesia after radical retropubic prostatectomy: a double-blind comparison between low thoracic epidural and patient-controlled intravenous analgesia2006In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 105, no 4, p. 784-793Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Postoperative pain after radical retropubic prostatectomy can be severe unless adequately treated. Low thoracic epidural analgesia and patient-controlled intravenous analgesia were compared in this double-blind, randomized study.

    METHODS: Sixty patients were randomly assigned to receive either low thoracic epidural analgesia (group E) or patient-controlled intravenous analgesia (group P) for postoperative pain relief. All patients had general anesthesia combined with thoracic epidural analgesia during the operation. Postoperatively, patients in group E received an infusion of 1 mg/ml ropivacaine, 2 microg/ml fentanyl, and 2 microg/ml adrenaline, 10 ml/h during 48 h epidurally, and a placebo patient-controlled intravenous analgesia pump intravenously. Patients in group P received a patient-controlled intravenous analgesia pump with morphine intravenously and 10 ml/h placebo epidurally. Pain, the primary outcome variable, was measured using the numeric rating scale at rest (incision pain and "deep" visceral pain) and on coughing. Secondary outcome variables included gastrointestinal function, respiratory function, mobilization, and full recovery. Health-related quality of life was measured using the Short Form-36 questionnaire, and plasma concentration of fentanyl was measured in five patients to exclude a systemic effect of fentanyl.

    RESULTS: Incisional pain and pain on coughing were lower in group E compared with group P at 2-24 h, as was deep pain between 3 and 24 h postoperatively (P < 0.05). Maximum expiratory pressure was greater in group E at 4 and 24 h (P < 0.05) compared with group P. No difference in time to home discharge was found between the groups. The mean plasma fentanyl concentration varied from 0.2 to 0.3 ng/ml during 0-48 h postoperatively. At 1 month, the scores on emotional role, physical functioning, and general health of the Short Form-36 were higher in group E compared with group P. However, no group x time interaction was found in the Short Form-36.

    CONCLUSIONS: The authors found evidence for better pain relief and improved expiratory muscle function in patients receiving low thoracic epidural analgesia compared with patient-controlled analgesia for radical retropubic prostatectomy. Low thoracic epidural analgesia can be recommended as a good method for postoperative analgesia after abdominal surgery.

  • 28. Hagel, Eva
    et al.
    Garmo, Hans
    Bill-Axelson, Anna
    Bratt, Ola
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Adolfsson, Jan
    Lambe, Mats
    Stattin, Pär
    PCBaSe Sweden: a register-based resource for prostate cancer research2009In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 43, no 5, p. 342-9Article in journal (Refereed)
    Abstract [en]

    Objective. To construct a database for clinical epidemiological prostate cancer research based on linkages between the National Prostate Cancer Register (NPCR) of Sweden, a population-based, nationwide quality database, and other nationwide registries. Material and methods. By use of the individually unique Swedish Personal Identity Number, the NPCR was linked to the Swedish Cancer Registry, the Cause of Death Register, the Prescribed Drug Register, the National Patient Register and the Acute Myocardial Infarction Register, all held at the Centre for Epidemiology at the National Board of Health and Welfare, and the Register of the Total Population, the Longitudinal Integration Database for Health Insurance and Labor Market Studies and the Multi-Generation Register, held at Statistics Sweden, and to the Swedish Hernia Register. Results. Record linkages between the NPCR and the Swedish Cancer Registry, the Cause of Death Register and the Register of the Total Population generated a database, named PCBaSe Sweden, including 80 079 prostate cancer cases, diagnosed between 1 January 1996 and 31 December 2006. Record linkage between PCBaSe Sweden and the Prescribed Drug Register generated 59 721 unique matches and linkage to the Acute Myocardial Infarction Register resulted in 11 459 matches. Conclusion. PCBaSe Sweden is a newly created and unique database with over 80 000 cases of prostate cancer with comprehensive data on inpatient and outpatient care, patterns of use of prescribed drugs and socioeconomic and familial factors. Many topics in clinical prostate cancer epidemiology can be investigated. using PCBaSe Sweden.

  • 29. Hedelin, Maria
    et al.
    Bälter, Katarina Augustsson
    Chang, Ellen T.
    Bellocco, Rino
    Klint, Åsa
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Wiklund, Fredrik
    Thellenberg-Karlsson, Camilla
    Adami, Hans-Olov
    Grönberg, Henrik
    Dietary intake of phytoestrogens, estrogen receptor-beta polymorphisms and the risk of prostate cancer2006In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 66, no 14, p. 1512-1520Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The causes of prostate cancer are poorly understood, but genetic factors may be more important than for many other malignancies, and dietary phytoestrogens may be protective. Because phytoestrogens bind tightly to the estrogen receptor-beta, we conducted an epidemiologic investigation of synergistic effects between phytoestrogen intake and estrogen receptor-beta gene polymorphisms. METHODS: We performed a population-based case-control study in Sweden. All participants reported their phytoestrogen intake and donated a blood sample. We identified four haplotype-tagging single nucleotide polymorphisms (htSNPs) and genotyped these htSNPs in 1314 prostate cancer patients and 782 controls. Odds ratios were estimated by multivariate logistic regression. Interactions between phytoestrogen intake and estrogen receptor-beta SNPs on prostate cancer risk were evaluated considering both multiplicative and additive effect scales. RESULTS: We found a significant multiplicative interaction (P = 0.04) between dietary intake of phytoestrogens and a promoter SNP in the estrogen receptor-beta gene (rs 2987983-13950), but not with any of the three other htSNPs (P = 0.11, 0.69, 0.85). Among carriers of the variant promoter alleles, we found strong inverse associations with increasing intake of total phytoestrogens (odds ratio for highest vs. lowest quartile = 0.43; P for trend <0.001), isoflavonoids (odds ratio = 0.63; P for trend = 0.05), and coumestrol (odds ratio = 0.57; P for trend = 0.003). We found no association between phytoestrogens and prostate cancer among carriers homozygous for the wild-type allele (TT). CONCLUSIONS: Our study provides strong evidence that high intake of phytoestrogens substantially reduce prostate cancer risk among men with specific polymorphic variation in the promoter region of the estrogen receptor-beta gene.

  • 30. Hedelin, Maria
    et al.
    Klint, Åsa
    Chang, Ellen T.
    Bellocco, Rino
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences.
    Heinonen, Satu-Maarit
    Adlercreutz, Herman
    Adami, Hans-Olov
    Grönberg, Henrik
    Bälter, Katarina Augustsson
    Dietary phytoestrogen, serum enterolactone and risk of prostate cancer: the cancer prostate Sweden study (Sweden)2006In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 17, no 2, p. 169-180Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Based on evidence that phytoestrogens may protect against prostate cancer, we evaluated the associations between serum enterolactone concentration or dietary phytoestrogen intake and risk of prostate cancer. METHODS: In our Swedish population-based case-control study, questionnaire-data were available for 1,499 prostate cancer cases and 1,130 controls, with serum enterolactone levels in a sub-group of 209 cases and 214 controls. Unconditional logistic regression was performed to estimate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with risk of prostate cancer. RESULTS: High intake of food items rich in phytoestrogens was associated with a decreased risk of prostate cancer. The OR comparing the highest to the lowest quartile of intake was 0.74 (95% CI: 0.57-0.95; p-value for trend: 0.01). In contrast, we found no association between dietary intake of total or individual lignans or isoflavonoids and risk of prostate cancer. Intermediate serum levels of enterolactone were associated with a decreased risk of prostate cancer. The ORs comparing increasing quartiles of serum enterolactone concentration to the lowest quartile were, respectively, 0.28 (95% CI: 0.15-0.55), 0.63 (95% CI: 0.35-1.14) and 0.74 (95% CI: 0.41-1.32). CONCLUSIONS: Our results support the hypothesis that certain foods high in phytoestrogens are associated with a lower risk of prostate cancer.

  • 31. Holmberg, Lars
    et al.
    Bill-Axelson, Anna
    Garmo, Hans
    Palmgren, Juni
    Norlén, Bo Johan
    Adami, Hans Olov
    Johansson, Jan Erik
    Örebro University, School of Health and Medical Sciences.
    Prognostic markers under watchful waiting and radical prostatectomy2006In: Hematology/Oncology Clinics of North America, ISSN 0889-8588, E-ISSN 1558-1977, Vol. 20, no 4, p. 845-855Article in journal (Refereed)
    Abstract [en]

    A suitable setting to analyze factors that determine prognosis or treatment response in prostate cancer is an unbiased comparison of radical prostatectomy and watchful waiting as in the Scandinavian Prostate Cancer Group Trial number 4. In our previous presentation of 10-year results, we studied Gleason score, serum prostate-specific antigen (PSA) at diagnosis, and age at diagnosis as modifiers of the effect of radical prostatectomy on survival. Because overall prognostic information obtained by these parameters or by tumor stage was not provided in our publication, we now present these data in the two study arms separately.

  • 32.
    Holmberg, Lars
    et al.
    Regional Cancer Center Uppsala Örebro, Uppsala, Sweden; Division of Cancer Studies, Medical School, King’s College London, London, UK; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden .
    Bill-Axelsson, Anna
    Division of Clinical Cancer Epidemiology, Department of Oncology and Pathology Karolinska Institute, Stockholm, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden .
    Steineck, Gunnar
    Division of Clinical Cancer Epidemiology, Department of Oncology and Pathology Karolinska Institute, Stockholm, Sweden; Division of Clinical Cancer Epidemiology, Sahlgrenska Academy, Gothenburg, Sweden .
    Garmo, Hans
    Regional Cancer Center Uppsala Örebro, Uppsala, Sweden; Division of Cancer Studies, Medical School, King’s College London, London, UK .
    Palmgren, Juni
    Department of Medical Epidemiology and Biostatistics Karolinska Institute, Stockholm, Sweden.
    Johansson, Eva
    Division of Clinical Cancer Epidemiology, Department of Oncology and Pathology Karolinska Institute, Stockholm, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden .
    Adami, Hans-Olov
    Department of Medical Epidemiology and Biostatistics Karolinska Institute, Stockholm, Sweden; Department of Epidemiology, Harvard School of Public Health, Boston, USA.
    Johansson, Jan-Erik
    Center for Assessment of Medical Technology, Örebro, Sweden .
    Results from the scandinavian prostate cancer group trial number 4: a randomized controlled trial of radical prostatectomy versus watchful waiting2012In: Journal of the National Cancer Institute. Monographs, ISSN 1052-6773, E-ISSN 1745-6614, Vol. 2012, no 45, p. 230-233Article in journal (Refereed)
    Abstract [en]

    In the Scandinavian Prostate Cancer Group Trial Number 4 (SPCG-4), 347 men were randomly assigned to radical prostatectomy and 348 to watchful waiting. In the most recent analysis (median follow-up time = 12.8 years), the cumulative mortality curves had been stable over the follow-up. At 15 years, the absolute risk reduction of dying from prostate cancer was 6.1% following randomization to radical prostatectomy, compared with watchful waiting. Hence, 17 need to be randomized to operation to avert one death. Data on self-reported symptoms, stress from symptoms, and quality of life were collected at 4 and 12.2 years of median follow-up. These questionnaire studies show an intricate pattern of symptoms evolving after surgery, hormonal treatments, signs of tumor progression, and also from natural aging. This article discusses some of the main findings of the SPCG-4 study. The Scandinavian Prostate Cancer Group Trial Number 4 (SPCG-4) started in 1989 when radical prostatectomy was newly introduced in Scandinavia and when there was essentially no prostate-specific antigen (PSA) testing in asymptomatic men; such testing only became common at the end of the inclusion of the trial a decade later. However, the trial data continue to be important for several reasons. In many parts of the world, the clinical panorama of prostate cancer still resembles that in Sweden in the early 1990s. The trial results point to many of the issues that modern diagnosis and treatment have to solve. SPCG-4 is to date the only trial to inform about both forces of mortality and self-reported symptoms and quality of life in men after radical prostatectomy or watchful waiting two decades and more out after a primary diagnosis of prostate cancer. According to the protocol (http://www.roc.se/prostata/SPCG-4.pdf), the main trial data have been updated every 3 years since 2002 (1–6). In this presentation, we highlight some of the main findings with bearing on the topic of this conference and discuss some issues that have been raised when the trial results have been presented.

  • 33.
    Hälleberg-Nyman, Maria
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Orthopaedics, Örebro University Hospital, Örebro, Sweden.
    Gustafsson, Margareta
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Langius-Eklöf, Ann
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Urology.
    Norlin, Rolf
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Orthopaedics, Örebro University Hospital, Örebro, Sweden.
    Hagberg, Lars
    Centre for Health Care Science, Örebro County Council, O¨ rebro, Sweden.
    Intermittent versus indwelling urinary catheterisation in hip surgery patients: a randomised controlled trial with cost-effectiveness analysis2013In: International Journal of Nursing Studies, ISSN 0020-7489, E-ISSN 1873-491X, Vol. 50, no 12, p. 1589-1598Article in journal (Refereed)
    Abstract [en]

    Background Hip surgery is associated with the risk of postoperative urinary retention. To avoid urinary retention hip surgery patients undergo urinary catheterisation. Urinary catheterisation, however, is associated with increased risk for urinary tract infection (UTI). At present, there is limited evidence for whether intermittent or indwelling urinary catheterisation is the preferred choice for short-term bladder drainage in patients undergoing hip surgery.

    Objectives The aim of the study was to investigate differences between intermittent and indwelling urinary catheterisation in hip surgery patients in relation to nosocomial UTI and cost-effectiveness.

    Design Randomised controlled trial with cost-effectiveness analysis.

    Setting The study was carried out at an orthopaedic department at a Swedish University Hospital.

    Methods One hundred and seventy hip surgery patients (patients with fractures or with osteoarthritis) were randomly allocated to either intermittent or indwelling urinary catheterisation. Data collection took place at four time points: during stay in hospital, at discharge and at 4 weeks and 4 months after discharge.

    Results Eighteen patients contracted nosocomial UTIs, 8 in the intermittent catheterisation group and 10 in the indwelling catheterisation group (absolute difference 2.4%, 95% CI −6.9–11.6%) The patients in the intermittent catheterisation group were more often catheterised (p < 0.001) and required more bladder scans (p < 0.001) but regained normal bladder function sooner than the patients in the indwelling catheterisation group (p < 0.001). Fourteen percent of the patients in the intermittent group did not need any catheterisation. Cost-effectiveness was similar between the indwelling and intermittent urinary catheterisation methods.

    Conclusions Both indwelling and intermittent methods could be appropriate in clinical practice. Both methods have advantages and disadvantages but by not using routine indwelling catheterisation, unnecessary catheterisations might be avoided in this patient group.

  • 34.
    Hälleberg-Nyman, Maria
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Gustafsson, Margareta
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Langius-Eklöf, Ann
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, sweden.
    Johansson, Jan-Erik
    Norlin, Rolf
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hagberg, Lars
    Vårdvetenskapligt forskningscentrum, Universitetssjukhuset, Örebro, sweden.
    Intermittent versus indwelling urinary catheterisation in hip surgery patients: a randomised controlled trial with cost-effectiveness analysisManuscript (preprint) (Other academic)
    Abstract [en]

    Background:  Hip surgery is associated with a risk for postoperative urinary retention. To avoid urinary retention hip surgery patients undergo urinary catheterisation. Urinary catheterisation, however, is associated with increased risk for urinary tract infection (UTI). Presently, there is limited knowledge whether intermittent or indwelling urinary catheterisation is the preferred choice for short-term bladder drainage in patients undergoing hip surgery.

    Objectives: The aim of the study was to investigate differences between intermittent and indwelling urinary catheterisation in hip surgery patients in relation to nosocomial UTI and cost-effectiveness.

    Design: Randomised controlled trial with cost-effectiveness analysis.

    Setting: The study was carried out at an orthopaedic department at a Swedish university hospital.

    Method: One hundred seventy hip surgery patients (patients with fractures or with osteoarthritis) were randomly allocated to either intermittent or indwelling urinary catheterisation. Data collection took place at four time points: during stay in hospital, at discharge and at 4 weeks and 4 months after discharge.

    Results: Eighteen patients contracted nosocomial UTIs, 8 in the intermittent catheterisation group and 10 in the indwelling catheterisation group (p = 0.618).  The patients in the intermittent catheterisation group were more often catheterised (p <0.001) and required more bladder scans (p <0.001) but regained normal bladder function sooner than the patients in the indwelling catheterisation group (p <0.001). Fourteen percent of the patients in the intermittent group did not need any catheterisation. Cost-effectiveness was similar between the indwelling and intermittent urinary catheterisation methods.

    Conclusions: In the perspective of cost-effectiveness both indwelling and intermittent methods could be appropriate in clinical praxis. Both methods have advantages and disadvantages but by not using indwelling catheterisation routinely in this patient group unnecessary catheterisations might be avoided.

  • 35.
    Hälleberg-Nyman, Maria
    et al.
    Department of Orthopaedics, Örebro University Hospital, Örebro, Sweden.
    Johansson, Jan-Erik
    Department of Urology, Örebro University Hospital,Örebro, Sweden; Centre for Assessment of Medical Technology, Örebro County Council, Örebro, Sweden.
    Gustafsson, Margareta
    Örebro University, School of Health and Medical Sciences. Centre for Assessment of Medical Technology, Örebro County Council, Örebro, Sweden.
    A randomised controlled trial on the effect of clamping the indwelling urinary catheter in patients with hip fracture2010In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 19, no 3-4, p. 405-413Article in journal (Refereed)
    Abstract [en]

    Aim. To investigate the effect of clamping the urinary catheter before its removal in patients with hip fracture. Background. Difficulties to return to normal bladder function after removal of the urinary catheter are frequent in patients with hip fracture. Clamping the urinary catheter before removal is proposed to shorten the amount of time required to return to normal bladder function. Design. A randomised controlled trial was conducted at the orthopaedic clinic at a Swedish university hospital. Methods. Patients with hip fracture aged >= 50 without a urinary catheter, without cognitive impairment or additional severe physical problems at the time of admission (n = 113) were included. They were randomly assigned either to have their urinary catheter clamped before removal or to have their catheter removed with free drainage. Blinding was not possible because of the nature of the study. The primary outcome was the amount of time required to return to normal bladder function. Secondary outcomes were need for re-catheterisation and length of hospital stay. All patients were analysed in accordance with the intention-to-treat principle. Results. The median time required to return to normal bladder function was six (Q(1) 4-Q(3) 8) hours in the clamped catheter group and four (Q(1) 3-Q(3) 7.25) hours in the free drainage group. There were no significant differences between the groups regarding the time required to regain normal bladder function (p = 0.156), the number of patients requiring re-catheterisation (p = 0.904) and the mean time in hospital (p = 0.777). Conclusion. This randomised trial did not show any advantage or disadvantage with clamping the urinary catheter before removal. Relevance to clinica practice. Clamping is an additional task for the nursing staff in the removal of the indwelling urinary catheter. Therefore, when considering the present results, it seems that clamping the indwelling urinary catheters in patients with hip fracture is not indicated.

  • 36.
    Hälleberg-Nyman, Maria
    et al.
    Department of Orthopaedics, Örebro University Hospital, Örebro, Sweden.
    Johansson, Jan-Erik
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Persson, Katarina
    Örebro University, School of Health and Medical Sciences.
    Gustafsson, Margareta
    Örebro University, School of Health and Medical Sciences.
    A prospective study of nosocomial urinary tract infection in hip fracture patients2011In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 20, no 17-18, p. 2531-2539Article in journal (Refereed)
    Abstract [en]

    Aim.  To investigate risk factors and consequences of nosocomial urinary tract infection in hip fracture patients. Background.  Nosocomial urinary tract infection is a well-known problem in hip fracture patients. There are several risk factors for nosocomial urinary tract infection described in the literature.

    Design.  Prospective observational study with a descriptive and comparative design.

    Methods.  Hip fracture patients were included consecutively between April 2006-March 2007. Excluded were those under 50, having an indwelling urinary catheter, signs of cognitive impairment or additional severe physical problems at the time of admission. To verify nosocomial urinary tract infection, a urine specimen was taken at admission and discharge. Patients with and without nosocomial urinary tract infection were compared.

    Results.  The study included 86 hip fracture patients, of whom 45 (52·3%) contracted nosocomial urinary tract infection in hospital. Earlier reported risk factors for nosocomial urinary tract infection were not confirmed in this study, with one exception: diabetes. All diabetic patients in the study contracted urinary tract infections. Patients receiving cloxacillin as antibiotic prophylaxis for wound infection contracted UTI less often than other patients. There were no statistical differences between groups with regard to urinary tract infection frequency four months after fracture or with regard to mortality after one year.

    Conclusion.  Diabetes was the only previously known risk factor for nosocomial urinary tract infection confirmed among hip fracture patients in this study. Cloxacillin as antibiotic prophylaxis for surgery seemed to offer a certain protection against nosocomial urinary tract infection. Relevance to clinical practice.  Nurses in clinical practice should be aware of the risk of urinary tract infections in hip fracture patients and especially in hip fracture patients with diabetes. Patients given cloxacillin as antibiotic prophylaxis seem less likely to contract nosocomial urinary tract infection.

  • 37. Iversen, Peter
    et al.
    Johansson, Jan-Erik
    Örebro University, Department of Clinical Medicine.
    Lodding, Pär
    Kylmälä, Timo
    Lundmo, Per
    Klarskov, Peter
    Tammela, Teuvo L. J.
    Tasdemir, Ilker
    Morris, Thomas
    Armstrong, Jon
    Bicalutamide 150 mg in addition to standard care for patients with early non-metastatic prostate cancer: updated results from the Scandinavian Prostate Cancer Period Group-6 Study after a median follow-up period of 7.1 years2006In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 40, no 6, p. 441-452Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The Early Prostate Cancer (EPC) programme is evaluating the efficacy and tolerability of bicalutamide following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with localized (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N + ) non-metastatic prostate cancer. Herein we report the latest findings after a median follow-up period of 7.1 years from the Scandinavian Prostate Cancer Group (SPCG)-6 study, one of three trials in the EPC programme. MATERIAL AND METHODS: A total of 1218 patients were randomized on a 1:1 basis to either bicalutamide 150 mg/day (n=607) or placebo (n=611) following standard care; 81.4% were followed conservatively (watchful waiting). The primary endpoints were objective progression-free survival (PFS) and overall survival (OS). RESULTS: In patients with localized disease there was no significant difference in PFS [hazard ratio (HR) 0.85; 95% CI 0.69-1.06; p=0.15] and a trend towards decreased OS with bicalutamide plus standard care compared with standard care alone (HR 1.23; 95% CI 0.96-1.58; p=0.11). In patients with locally advanced disease, bicalutamide significantly improved PFS, reducing the risk of progression by 53% compared with standard care alone (HR 0.47; 95% CI 0.37-0.59; p<0.001). The median time to progression was 8.8 years for bicalutamide plus standard care and 7.1 years for standard care alone. There was a significant improvement in OS with bicalutamide plus standard care, with a reduction in the risk of death of 35% versus standard care alone (HR 0.65; 95% CI 0.50-0.85; p=0.001). CONCLUSION: This analysis of the SPCG-6 study showed that bicalutamide plus standard care offers significant PFS and OS benefits for patients with locally advanced disease, but not for those with localized disease.

  • 38.
    Johansson, E.
    et al.
    Department of Surgical Sciences, University Hospital of Uppsala, Uppsala, Sweden.
    Steineck, G.
    Division of Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden; Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Holmberg, L.
    King's College London, Medical School, Division of Cancer Studies, London, United Kingdom.
    Johansson, J-E
    Örebro University, School of Health and Medical Sciences. Department of Urology and the Center of Assessment of Medical Technology.
    Nyberg, T.
    Division of Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Ruutu, M.
    Department of Urology, Helsinki University Hospital, Helsinki, Finland.
    Bill-Axelsson, A.
    Department of Surgical Sciences, University Hospital of Uppsala, Uppsala, Sweden; Division of Clinical Cancer Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial2011In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 12, no 9, p. 891-899Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: For men with localised prostate cancer, surgery provides a survival benefit compared with watchful waiting. Treatments are associated with morbidity. Results for functional outcome and quality of life are rarely reported beyond 10 years and are lacking from randomised settings. We report results for quality of life for men in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) after a median follow-up of more than 12 years.

    METHODS: All living Swedish and Finnish men (400 of 695) randomly assigned to radical prostatectomy or watchful waiting in SPCG-4 from 1989 to 1999 were included in our analysis. An additional 281 men were included in a population-based control group matched for region and age. Physical symptoms, symptom-induced stress, and self-assessed quality of life were evaluated with a study-specific questionnaire. Longitudinal data were available for 166 Swedish men who had answered quality-of-life questionnaires at an earlier timepoint.

    FINDINGS: 182 (88%) of 208 men in the radical prostatectomy group, 167 (87%) of 192 men in the watchful-waiting group, and 214 (76%) of 281 men in the population-based control group answered the questionnaire. Men in SPCG-4 had a median follow-up of 12·2 years (range 7-17) and a median age of 77·0 years (range 61-88). High self-assessed quality of life was reported by 62 (35%) of 179 men allocated radical prostatectomy, 55 (34%) of 160 men assigned to watchful waiting, and 93 (45%) of 208 men in the control group. Anxiety was higher in the SPCG-4 groups (77 [43%] of 178 and 69 [43%] of 161 men) than in the control group (68 [33%] of 208 men; relative risk 1·42, 95% CI 1·07-1·88). Prevalence of erectile dysfunction was 84% (146 of 173 men) in the radical prostatectomy group, 80% (122 of 153) in the watchful-waiting group, and 46% (95 of 208) in the control group and prevalence of urinary leakage was 41% (71 of 173), 11% (18 of 164), and 3% (six of 209), respectively. Distress caused by these symptoms was reported significantly more often by men allocated radical prostatectomy than by men assigned to watchful waiting. In a longitudinal analysis of men in SPCG-4 who provided information at two follow-up points 9 years apart, 38 (45%) of 85 men allocated radical prostatectomy and 48 (60%) of 80 men allocated watchful waiting reported an increase in number of physical symptoms; 50 (61%) of 82 and 47 (64%) of 74 men, respectively, reported a reduction in quality of life.

    INTERPRETATION: For men in SPCG-4, negative side-effects were common and added more stress than was reported in the control population. In the radical prostatectomy group, erectile dysfunction and urinary leakage were often consequences of surgery. In the watchful-waiting group, side-effects can be caused by tumour progression. The number and severity of side-effects changes over time at a higher rate than is caused by normal ageing and a loss of sexual ability is a persistent psychological problem for both interventions. An understanding of the patterns of side-effects and time dimension of their occurrence for each treatment is important for full patient information.

  • 39. Johansson, Eva
    et al.
    Bill-Axelson, Anna
    Holmberg, Lars
    Onelöv, Erik
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Steineck, Gunnar
    Time, Symptom Burden, Androgen Deprivation, and Self-Assessed Quality of Life after Radical Prostatectomy or Watchful Waiting: The Randomized Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) Clinical Trial2008In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 55, no 2, p. 422-432Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Quality-of-life outcomes are important in the choice of treatment strategy for men with localized prostate cancer.

    OBJECTIVE: To evaluate how follow-up time, number of physical symptoms, and presence of androgen deprivation affected quality of life among men randomized to radical prostatectomy or watchful waiting.

    DESIGN, SETTING, AND PARTICIPANTS: The study group was composed of all 376 living men included in the Swedish part of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) between January 1, 1989, and February 29, 1996. Quality-of-life data were collected after a mean follow-up time of 4.1 yr.

    INTERVENTION: All patients were randomly assigned to radical prostatectomy or watchful waiting. Forty-five men were androgen deprived.

    MEASUREMENTS: Data of specific symptoms, symptom-induced stress, sense of well-being, and self-assessed quality of life were obtained by means of a questionnaire. Psychological symptoms were assessed using seven-point visual digital scales.

    RESULTS AND LIMITATIONS: In analyses stratified on the basis of the numbers of physical symptoms, anxiety and depressed mood were less common, and sense of well-being and self-assessed quality of life were better throughout in the radical prostatectomy group than in the watchful waiting group. As the number of physical symptoms increased, all psychological variables became worse and more prominent in the watchful waiting group. After a follow-up time of 6-8 yr, a significant decrease in quality of life (p=0.03) was seen in the watchful waiting group. Twenty-four percent of androgen-deprived patients assigned to watchful waiting reported high self-assessed quality of life compared with 60% in the radical prostatectomy group. Eighty-eight percent of patients had clinically detected tumors.

    CONCLUSIONS: Androgen deprivation negatively affected self-assessed quality of life in men assigned to watchful waiting. The number of physical symptoms was associated with the level of quality of life. Quality of life was lower with longer follow-up time in both groups and was statistically significant in the watchful waiting group (p=0.03).

  • 40.
    Julin, B.
    et al.
    Unit of Nutritional Epidemiology, The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wolk, A.
    Unit of Nutritional Epidemiology, The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Åkesson, A.
    Unit of Nutritional Epidemiology, The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Dietary cadmium exposure and prostate cancer incidence: a population-based prospective cohort study2012In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 21, no 5, p. 895-900Article in journal (Refereed)
    Abstract [en]

    Background: Experimental data convincingly propose the toxic metal cadmium as a prostate carcinogen. Cadmium is widely dispersed into the environment and, consequently, food is contaminated.

    Methods: A population-based cohort of 41 089 Swedish men aged 45-79 years was followed prospectively from 1998 through 2009 to assess the association between food frequency questionnaire-based estimates of dietary cadmium exposure (at baseline, 1998) and incidence of prostate cancer (3085 cases, of which 894 were localised and 794 advanced) and through 2008 for prostate cancer mortality (326 fatal cases).

    Results: Mean dietary cadmium exposure was 19 μg per day±s.d. 3.7. Multivariable-adjusted dietary cadmium exposure was positively associated with overall prostate cancer, comparing extreme tertiles; rate ratio (RR) 1.13 (95% confidence interval (CI): 1.03-1.24). For subtypes of prostate cancer, the RR was 1.29 (95% CI: 1.08-1.53) for localised, 1.05 (95% CI: 0.87-1.25) for advanced, and 1.14 (95% CI: 0.86-1.51) for fatal cases. No statistically significant difference was observed in the multivariable-adjusted risk estimates between tumour subtypes (P(heterogeneity)=0.27). For localised prostate cancer, RR was 1.55 (1.16-2.08) among men with a small waist circumference and RR 1.45 (1.15, 1.83) among ever smokers.

    Conclusion: Our findings provide support that dietary cadmium exposure may have a role in prostate cancer development.

  • 41. Kang, D
    et al.
    Chokkalingam, A P
    Gridley, G
    Nyren, O
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Adami, H O
    Silverman, D
    Hsing, A W
    Benign prostatic hyperplasia and subsequent risk of bladder cancer2007In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 96, no 9, p. 1475-1479Article in journal (Refereed)
    Abstract [en]

    We evaluated the risk of bladder cancer in a cohort of 79,280 Swedish men hospitalised for benign prostatic hyperplasia (BPH), identified in the Swedish Inpatient Register between 1964 and 1983 and followed until 1989 via multiple record linkages with nationwide data on cancer registry, death and emigration. Standardised incidence ratios (SIRs), the ratios of the observed to the expected numbers of incident bladder cancers, were used to calculate the risk associated with BPH. The expected number was calculated by multiplying the number of person-years by the age-specific cancer incidence rates in Sweden for each 5-year age group and calendar year of observation. Analyses were stratified by BPH treatment, latency, calendar year and presence of genitourinary (GU) comorbid conditions. After excluding the first 3 years of follow-up after the index hospitalisation, we observed 506 incident bladder cancer cases during follow-up in the cohort. No overall increased risk of bladder cancer was apparent in our main analysis involving the entire BPH cohort. However, among BPH patients with transurethral resection of the prostate (TURP), there was an increased risk in all follow-up periods; SIRs of bladder cancer during years 4-6 of follow-up was 1.22 (95% confidence interval=1.02-1.46), 1.32 for 7-9 years of follow-up, and 1.47 for 10-26 years of follow-up. SIRs of bladder cancer among TURP-treated BPH patients were particularly elevated among those with comorbid conditions of the GU tract (e.g., stone, infection, etc.); 1.72, 1.74 and 2.01 for 4-6, 7-9, 10-26 years of follow-up, respectively, and also for those whose diagnoses occurred before 1975, when TURP was more likely to be performed by a urologist than a general practitioner: 1.87, 1.90 and 1.74, respectively. These findings suggest that BPH overall is not associated with bladder cancer risk. However, among men treated with TURP, particularly those with other comorbid GU tract conditions, risk of bladder cancer was elevated.

  • 42. Kasperzyk, Julie L.
    et al.
    Fall, Katja
    Mucci, Lorelei A.
    Håkansson, Niclas
    Wolk, Alicja
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Andersson, Swen-Olof
    Andrén, Ove
    One-carbon metabolism-related nutrients and prostate cancer survival2009In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 90, no 3, p. 561-569Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Folate and other one-carbon metabolism nutrients may influence prostate cancer pathogenesis. Prior studies of these nutrients in relation to prostate cancer incidence have been inconclusive, and none have explored prostate cancer survival. OBJECTIVE: The objective was to assess whether dietary intakes of folate, riboflavin, vitamin B-6, vitamin B-12, and methionine measured around the time of prostate cancer diagnosis are associated with prostate cancer survival. DESIGN: This population-based prospective study comprised 525 men from Orebro, Sweden, who received a diagnosis of incident prostate cancer between 1989 and 1994 and completed a self-administered food-frequency questionnaire. Record linkages to the Swedish Death Registry enabled all cases to be followed for up to 20 y after diagnosis, and the cause of death was assigned via medical record review. Cox proportional hazards regression was used to calculate multivariable hazard ratios (HRs) and 95% CIs. During a median of 6.4 y of follow-up, 218 men (42%) died of prostate cancer and 257 (49%) of other causes. RESULTS: A comparison of the highest with the lowest quartile showed that vitamin B-6 intake was inversely associated with prostate cancer-specific death (HR: 0.71; 95% CI: 0.46, 1.10; P for trend = 0.08), especially in men with a diagnosis of localized-stage disease (HR; 0.05; 95% CI: 0.01, 0.26; P for trend = 0.0003). However, vitamin B-6 intake was not associated with improved prostate cancer survival among advanced-stage cases (HR: 1.04; 95% CI: 0.64, 1.72; P for trend = 0.87). Folate, riboflavin, vitamin B-12, and methionine intakes were not associated with prostate cancer survival. CONCLUSION: A high vitamin B-6 intake may improve prostate cancer survival among men with a diagnosis of localized-stage disease.

  • 43. Landberg, Rikard
    et al.
    Kamal-Eldin, Afaf
    Andersson, Swen-Olof
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Zhang, Jie-Xian
    Hallmans, Göran
    Åman, Per
    Reproducibility of plasma alkylresorcinols during a 6-week rye intervention study in men with prostate cancer2009In: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 139, no 5, p. 975-980Article in journal (Refereed)
    Abstract [en]

    Alkylresorcinols (AR), phenolic lipids exclusively present in the outer parts of wheat and rye grains, have been proposed as concentration biomarkers of whole-grain wheat and rye intake. A key feature of a good biomarker is high reproducibility, which indicates how accurately a single sample reflects the true mean biomarker concentration caused by a certain intake. In this study, the short- to medium-term reproducibility of plasma AR was determined using samples from a crossover intervention study, where men with prostate cancer (n = 17) were fed rye whole-grain/bran or refined wheat products for 6-wk periods. AR homologs C17:0 and C21:0 differed between the treatments (P < 0.001). The reproducibility determined by the intraclass correlation coefficient (ICC) was high (intervention period 1: ICC = 0.90 [95% CI = 0.82-0.98], intervention period 2: ICC = 0.88 [95% CI = 0.78-0.98]). The results show that a single fasting plasma sample could be used to estimate the mean plasma AR concentration during a 6-wk intervention period with constant intake at a precision of +/- 20% (80% CI). This suggests that the plasma AR concentration can be used as a reliable short- to medium-term biomarker for whole-grain wheat and rye under intervention conditions where intake is kept constant.

  • 44. Larsson, Susanna C.
    et al.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Wolk, Alicja
    Cultured milk, yogurt, and dairy intake in relation to bladder cancer risk in a prospective study of Swedish women and men2008In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 88, no 4, p. 1083-1087Article in journal (Refereed)
    Abstract [en]

    Background:Findings from epidemiologic studies of the effect of dairy foods (mainly milk) on the risk of bladder cancer have been inconsistent.

    Objective:We aimed to examine the association between the intake of cultured milk and other dairy foods and the incidence of bladder cancer in a prospective, population-based cohort.

    Design:We prospectively followed 82 002 Swedish women and men who were cancer-free and who completed a 96-item food-frequency questionnaire in 1997. Incident cases of bladder cancer were identified in the Swedish cancer registries.

    Results:During a mean follow-up of 9.4 y, 485 participants (76 women and 409 men) were diagnosed with bladder cancer. Total dairy intake was not significantly associated with risk of bladder cancer [7.0 servings/d compared with < 3.5 servings/d: multivariate rate ratio (RR) = 0.87; 95% CI: 0.66, 1.15; P for trend = 0.33]. However, a statistically significant inverse association was observed for the intake of cultured milk (sour milk and yogurt). The multivariate RRs for the highest category of cultured milk intake (2 servings/d) compared with the lowest category (0 serving/d) were 0.62 (95% CI: 0.46, 0.85; P for trend = 0.006) in women and men combined, 0.55 (95% CI: 0.25, 1.22; P for trend = 0.06) in women, and 0.64 (95% CI: 0.46, 0.89; P for trend = 0.03) in men. The intake of milk or cheese was not associated with bladder cancer risk.

  • 45. Larsson, Susanna C.
    et al.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Wolk, Alicja
    Diabetes mellitus, body size and bladder cancer risk in a prospective study of Swedish men2008In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 44, no 17, p. 2655-2660Article in journal (Refereed)
    Abstract [en]

    Epidemiologic studies on diabetes and body size in relation to risk of bladder cancer have yielded inconsistent results. We examined prospectively the associations between a history of diabetes, height, weight, body mass index and waist circumference, and the incidence of bladder cancer in the Cohort of Swedish Men, a prospective study of 45,906 men aged 45–79 years at baseline. During follow-up from 1998 through December 2007, 414 incident cases of bladder cancer were ascertained. A history of diabetes was not associated with risk of bladder cancer (multivariate rate ratio=1.16; 95% confidence interval=0.81–1.64). Similarly, no associations were observed for height, weight, body mass index or waist circumference. These findings in men do not support a role for diabetes, height or excess body mass in the aetiology of bladder cancer. 

  • 46. Larsson, Susanna C.
    et al.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Wolk, Alicja
    Fruit and vegetable consumption and risk of bladder cancer: a prospective cohort study2008In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 17, no 9, p. 2519-2522Article in journal (Refereed)
    Abstract [en]

    Fruit and vegetable consumption has been inconsistently associated with risk of bladder cancer. We used data from a prospective population-based cohort study of 82,002 Swedish women and men to examine the association between fruit and vegetable consumption and bladder cancer incidence. Diet was assessed with a validated food frequency questionnaire. During a mean follow-up of 9.4 years, 485 incident cases of bladder cancer were identified in the Swedish cancer registries. We found no statistically significant association between intakes of total fruits and vegetables, total fruits, or total vegetables and bladder cancer risk after adjustment for age, sex, education, and cigarette smoking. The multivariate rate ratios (95% confidence intervals) comparing the highest with the lowest quartile of intake were 0.80 (0.60-1.05) for total fruits and vegetables, 0.93 (0.69-1.25) for fruits, and 0.89 (0.67-1.19) for vegetables. Likewise, no associations were observed for citrus fruits, cruciferous vegetables, or green leafy vegetables. The associations did not differ by sex or smoking status. In conclusion, findings from this prospective study suggest that fruit and vegetable intakes are not likely to be appreciably associated with the risk of bladder cancer.

  • 47. Larsson, Susanna C.
    et al.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences.
    Wolk, Alicja
    Meat intake and bladder cancer risk in a Swedish prospective cohort2009In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 20, no 1, p. 35-40Article in journal (Refereed)
    Abstract [en]

    Background  High meat consumption could potentially increase the risk of bladder cancer, but findings from epidemiologic studies are inconsistent. We prospectively examined the association between meat intake and bladder cancer risk in a population-based cohort study. Methods  We prospectively followed 82,002 Swedish women and men who were free from cancer and completed a food-frequency questionnaire in 1997. Incident cases of bladder cancer were identified in the Swedish cancer registries. Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, smoking status, pack-years of smoking, and total energy intake. Results  During a mean follow-up of 9.4 years, 485 incident cases of bladder cancer (76 women and 409 men) were ascertained in the cohort. We observed no association between the intake of total or any specific type of meat and the risk of bladder cancer. The multivariate HRs (95% CIs) comparing the highest and the lowest category of intake were 1.05 (0.71–1.55) for total meat, 1.00 (0.71–1.41) for red meat, 1.01 (0.80–1.28) for processed meats, 0.96 (0.70–1.30) for chicken/poultry, and 0.92 (0.65–1.30) for fried meats/fish. The associations did not vary by sex or smoking status. Conclusions  These results do not support the hypothesis that intake of red meat, processed meat, poultry, or fried meats/fish is associated with the risk of developing bladder cancer.

  • 48. Laven, Brett A.
    et al.
    Orsini, Nicola
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Gerber, Glenn S.
    Wolk, Alicja
    Birth weight, abdominal obesity and the risk of lower urinary tract symptoms in a population based study of Swedish men2008In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, no 5, p. 1891-1896Article in journal (Refereed)
    Abstract [en]

    Purpose

    Lower urinary tract symptoms and obesity are prominent health problems. Low birth weight increases the adult risk of adiposity and insulin resistance, which may increase sympathetic activity and potentially lower urinary tract symptoms. Results of obesity and lower urinary tract symptoms studies are conflicting, and low birth weight and lower urinary tract symptoms relationships have not been investigated.

    Materials and Methods

    This cross-sectional study examines lower urinary tract symptoms, body measures, activity, birth weight and lifestyle data collected by questionnaire from 1997 to 1998. Overall 27,858 men were analyzed and odds ratios calculated after excluding those with cancer, cerebrovascular accident, diabetes and incomplete information.

    Results

    After adjustment for age, activity level, smoking, alcohol, coffee intake and body mass index, a significant positive association was seen between abdominal obesity (waist-to-hip ratio) and moderate to severe lower urinary tract symptoms. The risks of moderate to severe and severe lower urinary tract symptoms were 22% (95% CI 1.09–1.37) and 28% (95% CI 1.01–1.63) higher, respectively, for the top vs the lowest abdominal obesity quartile. The risk of nocturia (twice or more per night) was 1.16 (95% CI 1.02–1.33) in men in the top compared to the bottom waist-to-hip ratio quartile. Men with low birth weight (less than 2,500 gm) had a 61% (95% CI 1.12–2.30) higher risk of severe lower urinary tract symptoms compared to men with normal birth weight (2,500 to 3,999 gm). Men in the top waist-to-hip ratio quartile who had low birth weight had twice the risk of severe lower urinary tract symptoms (95% CI 1.29–3.02) compared to men with normal birth weight and in the lowest waist-to-hip ratio quartile.

    Conclusions

    Low birth weight and abdominal adiposity are associated with increased risk of moderate to severe lower urinary tract symptoms in adults. Further investigations are needed to determine if decreases in obesity can ameliorate lower urinary tract symptoms.

  • 49.
    Lyth, J.
    et al.
    Department of Biomedical Engineering, Division of Medical Informatics, Linköping University, Linköping, Sweden; Regional Cancer Center Southeast, Linköping University, Linköping, Sweden.
    Andersson, Swen-Olof
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Andrén, Ove
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Carlsson, P.
    Center for Medical Technology Assessment, Linköping University, Linköping, Sweden.
    Shahsavar, N.
    Department of Biomedical Engineering, Division of Medical Informatics, Linköping University, Linköping, Sweden; Regional Cancer Center Southeast, Linköping University, Linköping, Sweden.
    A decision support model for cost-effectiveness of radical prostatectomy in localized prostate cancer2012In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, no 1, p. 19-25Article in journal (Refereed)
    Abstract [en]

    Objective: This study aimed to develop a probabilistic decision support model to calculate the lifetime incremental cost-effectiveness ratio (ICER) between radical prostatectomy and watchful waiting for different patient groups.

    Material and methods: A randomized trial (SPCG-4) provided most data for this study. Data on survival, costs and quality of life were inputs in a decision analysis, and a decision support model was developed. The model can generate cost-effectiveness information on subgroups of patients with different characteristics.

    Results: Age was the most important independent factor explaining cost-effectiveness. The cost-effectiveness value varied from 21,026 Swedish kronor (SEK) to 858,703 SEK for those aged 65 to 75 years, depending on Gleason scores and prostate-specific antigen (PSA) values. Information from the decision support model can support decision makers in judging whether or not radical prostatectomy (RP) should be used to treat a specific patient group.

    Conclusions: The cost-effectiveness ratio for RP varies with age, Gleason scores, and PSA values. Assuming a threshold value of 200,000 SEK per quality-adjusted life-year (QALY) gained, for patients aged ≤70 years the treatment was always cost-effective, except at age 70, Gleason 0-4 and PSA ≤10. Using the same threshold value at age 75, Gleason 7-9 (regardless of PSA) and Gleason 5-6 (with PSA >20) were cost-effective. Hence, RP was not perceived to be cost-effective in men aged 75 years with low Gleason and low PSA. Higher threshold values for patients with clinically localized prostate cancer could be discussed

  • 50.
    Martin, Neil E.
    et al.
    Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
    Gerke, Travis
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
    Sinnott, Jennifer A.
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
    Stack, Edward C.
    Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Urology.
    Johansson, Jan-Erik
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Fiorentino, Michelangelo
    Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Pathology Unit, Addarii Institute, S Orsola-Malpighi Hospital, Bologna, Italy.
    Finn, Stephen
    Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Department of Pathology, Trinity College, Dublin, Ireland.
    Fedele, Giuseppe
    Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
    Stampfer, Meir
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
    Kantoff, Philip W.
    Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
    Mucci, Lorelei A.
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
    Loda, Massimo
    Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA; Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA; Division of Cancer Studies, King's College London, London, United Kingdom.
    Measuring PI3K Activation: Clinicopathologic, Immunohistochemical, and RNA Expression Analysis in Prostate Cancer2015In: Molecular Cancer Research, ISSN 1541-7786, E-ISSN 1557-3125, Vol. 13, no 10, p. 1431-1440Article in journal (Refereed)
    Abstract [en]

    Assessing the extent of PI3K pathway activity in cancer is vital to predicting sensitivity to PI3K-targeting drugs, but the best biomarker of PI3K pathway activity in archival tumor specimens is unclear. Here, PI3K pathway activation was assessed, in clinical tissue from 1,021 men with prostate cancers, using multiple pathway nodes that include PTEN, phosphorylated AKT (pAKT), phosphorylated ribosomal protein S6 (pS6), and stathmin. Based on these markers, a 9-point score of PI3K activation was created using the combined intensity of the 4-markers and analyzed its association with proliferation (Ki67), apoptosis (TUNEL), and androgen receptor (AR) status, as well as pathologic features and cancer-specific outcomes. In addition, the PI3K activation score was compared with mRNA expression profiling data for a large subset of men. Interestingly, those tumors with higher PI3K activation scores also had higher Gleason grade (P = 0.006), increased AR (r = 0.37; P < 0.001) and Ki67 (r = 0.24; P < 0.001), and decreased TUNEL (r = -0.12; P = 0.003). Although the PI3K activation score was not associated with an increased risk of lethal outcome, a significant interaction between lethal outcome, Gleason and high PI3K score (P = 0.03) was observed. Finally, enrichment of PI3K-specific pathways was found in the mRNA expression patterns differentiating the low and high PI3K activation scores; thus, the 4-marker IHC score of PI3K pathway activity correlates with features of PI3K activation.

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