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  • 251.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Obesity, Nutrition, and Prostate Cancer: Insights and Issues2013Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 63, nr 5, s. 821-822Artikel i tidskrift (Övrigt vetenskapligt)
  • 252.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Prostate cancer screening: the need for problem-solving that puts men's interests first2009Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 56, nr 1, s. 34-37Artikel i tidskrift (Refereegranskat)
  • 253.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Reduction in breast cancer mortality from organized service screening with mammography: 1. Further confirmation with extended data2006Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, nr 1, s. 45-51Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: In an earlier publication, our evaluation of data from breast cancer screening programs in seven Swedish counties suggested a 40% reduction in incidence-based breast cancer mortality among women actually screened. In the current study, we expand the previous analysis from seven counties to 13 large areas within nine counties, including six of the original counties and seven additional areas, examine a longer period of follow-up (20-44 years), apply new analytic methods for the evaluation of incidence-based breast cancer mortality, and estimate the number needed to screen to save one life.METHODS: Data from six of the original counties (one being excluded as it does not yet have 10 years of follow-up after the initiation of screening), with increased follow-up, and seven additional large areas, within three counties, representing approximately 45% of Swedish women, provide information about age at diagnosis, age at death, and screening history for 542,187 women in the prescreening and 566,423 women in the screening epochs. Regardless of year of diagnosis, there were a total of 6,231 deaths due to breast cancer in the period of study as a whole. Of these, 4,778 were incidence-based deaths in the two epochs, i.e., death among cases diagnosed within either the prescreening or screening period. Data were analyzed using Poisson regression and adjusted, when necessary, for self-selection bias, contemporaneous changes in incidence, and changes in mortality independent of screening.RESULTS: Attendance was uniformly high, averaging 75% in the screening epochs. Recall rates for assessment varied from 4% to 5% at the first round of screening and approximately 3% at later rounds. Detection rates averaged five breast cancers per 1,000 women screened in the first round, and four breast cancers per 1,000 women screened in subsequent rounds. There was a significant 45% reduction in incidence-based breast cancer mortality among screened women in the screening epoch relative to incidence-based breast cancer mortality in the prescreening epoch (relative risk, 0.55; 95% confidence intervals, 0.51-0.59). After adjusting for self-selection bias, there still was a significant 43% reduction in incidence-based breast cancer mortality associated with screening (relative risk, 0.57; 95% confidence intervals, 0.53-0.62).CONCLUSIONS: These results indicate a reduction in breast cancer mortality of between 40% and 45% in association with screening, after adjustment for self-selection bias. These results were obtained with modest human costs: the number needed to screen to save one life was estimated as 472.

  • 254.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Reduction in breast cancer mortality from the organised service screening with mammography: 2. Validation with alternative analytic methods2006Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, nr 1, s. 52-6Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: In our companion article, incidence-based mortality analysis of data from breast cancer screening programs in 13 areas in Sweden indicated a 40% to 45% reduction in incidence-based breast cancer mortality among women actually screened. In this article, we apply new analytic methods for the evaluation of breast cancer mortality, using all breast cancer deaths in the period under study.METHODS: Data were available from 13 areas on breast cancer mortality by year of diagnosis, year of death, and screening exposure. The period of study varied by area, the overall range of year of diagnosis being 1968 to 2001. We had data on 6,231 deaths and an average population of 555,676 women ages 40 to 69 years. Analysis of the effect of being screened was conducted using an alternative statistical analysis applied to all breast cancer deaths in the period of study, in addition to the incidence-based mortality analysis in our companion article. Data were analyzed using Poisson regression and adjusted for self-selection bias, contemporaneous changes in incidence, and changes in mortality independent of screening.RESULTS: Using all deaths in the period of observation, a significant 42% reduction in breast cancer mortality was observed, adjusting for contemporaneous changes independent of screening [relative risk (RR), 0.58; 95% confidence interval (95% CI), 0.53-0.62]. After further adjustment for self-selection bias, the mortality reduction was 39% (RR, 0.61; 95% CI, 0.55-0.68), also highly significant.CONCLUSIONS: These results indicate a reduction in breast cancer mortality of 39% in association with screening, after adjustment for contemporaneous changes and self-selection bias. These results confirm previous conclusions arrived at using incidence-based mortality analyses.

  • 255.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Skillnader i cancerbehandling2009Ingår i: Tidsskrift for Den norske lægeforening, ISSN 0029-2001, E-ISSN 0807-7096, Vol. 129, nr 24, s. 2583-Artikel i tidskrift (Refereegranskat)
  • 256.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    The role of the primary-care physician in oncology care. Primary healthcare and specialist cancer services.2005Ingår i: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 6, nr 2, s. 121-2Artikel i tidskrift (Refereegranskat)
  • 257.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Adolfsson, Jan
    Mucci, Lorelei
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Adami, Hans-Olov
    Möller, Henrik
    Johansson, Jan-Erik
    Stampfer, Meir
    Season of diagnosis and prognosis in breast and prostate cancer2009Ingår i: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 20, nr 5, s. 633-670Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Patients with breast or prostate cancer diagnosed during the summer season have been observed to have better survival. The extent to which this is due to biological and/or health care system related factors is unclear. METHODS: Using the Swedish Cancer Register and clinical databases, we analyzed overall survival by month of diagnosis among the incident cases of breast (n = 89,630) cancer and prostate (n = 72,375) cancer diagnosed from 1960 to 2004. We retrieved data on tumor stage from 1976 for breast cancer and 1997 for prostate cancer. Cox proportional hazards models were used to calculate relative risk of survival by the season of diagnosis. RESULTS: There was a higher hazard ratio of death in men and women diagnosed with cancer in the summer with a relative hazard of 1.20 (95% confidence interval 1.15-1.25) for July for prostate cancer and 1.14 (95% confidence interval 1.09-1.19) for August for breast cancer when compared to being diagnosed in January. This difference coincided with a lower mean number of cases diagnosed per day, and a higher proportion of advanced cases diagnosed in the summer. This pattern of presentation was stronger in the later years. CONCLUSION: The difference in stage distribution explains the seasonal variation in prognosis seen in this study. The variation may be because of structure of the health care system and a strong tradition of vacationing from mid June to mid August. Thus, the health care infrastructure and the late presentation of symptomatic disease may influence cancer survival studied by season of diagnosis substantially.

  • 258.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Akre, Olof
    Screening for prostate cancer: defining critical issues2011Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, nr S1, s. 2-3Artikel i tidskrift (Refereegranskat)
  • 259.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Garmo, Hans
    Palmgren, Juni
    Norlén, Bo Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Prognostic markers under watchful waiting and radical prostatectomy2006Ingår i: Hematology/Oncology Clinics of North America, ISSN 0889-8588, E-ISSN 1558-1977, Vol. 20, nr 4, s. 845-855Artikel i tidskrift (Refereegranskat)
    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.

  • 260.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Helgesen, Fred
    Salo, Jaakko O.
    Folmerz, Per
    Häggman, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Andersson, Swen-Olof
    Spångberg, Anders
    Busch, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Nordling, Steg
    Palmgren, Juni
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Norlén, Bo Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer2002Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 347, nr 11, s. 781-789Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Radical prostatectomy is widely used in the treatment of early prostate cancer. The possible survival benefit of this treatment, however, is unclear. We conducted a randomized trial to address this question. METHODS: From October 1989 through February 1999, 695 men with newly diagnosed prostate cancer in International Union against Cancer clinical stage T1b, T1c, or T2 were randomly assigned to watchful waiting or radical prostatectomy. We achieved complete follow-up through the year 2000 with blinded evaluation of causes of death. The primary end point was death due to prostate cancer, and the secondary end points were overall mortality, metastasis-free survival, and local progression. RESULTS: During a median of 6.2 years of follow-up, 62 men in the watchful-waiting group and 53 in the radical-prostatectomy group died (P=0.31). Death due to prostate cancer occurred in 31 of 348 of those assigned to watchful waiting (8.9 percent) and in 16 of 347 of those assigned to radical prostatectomy (4.6 percent) (relative hazard, 0.50; 95 percent confidence interval, 0.27 to 0.91; P=0.02). Death due to other causes occurred in 31 of 348 men in the watchful-waiting group (8.9 percent) and in 37 of 347 men in the radical-prostatectomy group (10.6 percent). The men assigned to surgery had a lower relative risk of distant metastases than the men assigned to watchful waiting (relative hazard, 0.63; 95 percent confidence interval, 0.41 to 0.96). CONCLUSIONS: In this randomized trial, radical prostatectomy significantly reduced disease-specific mortality, but there was no significant difference between surgery and watchful waiting in terms of overall survival.

  • 261.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Steineck, Gunnar
    Garmo, Hans
    Palmgren, Juni
    Johansson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Results from the scandinavian prostate cancer group trial number 4: a randomized controlled trial of radical prostatectomy versus watchful waiting2012Ingår i: Journal of the National Cancer Institute. Monographs, ISSN 1052-6773, E-ISSN 1745-6614, Vol. 2012, nr 45, s. 230-233Artikel i tidskrift (Refereegranskat)
    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.

  • 262.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Duffy, S. W.
    Yen, A. M.
    Tabár, L.
    Vitak, B.
    Nyström, L.
    Frisell, J.
    Differences in endpoints between the Swedish W-E (two county) trial of mammographic screening and the Swedish overview: methodological consequences2009Ingår i: Journal of Medical Screening, ISSN 0969-1413, E-ISSN 1475-5793, Vol. 16, nr 2, s. 73-80Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To characterize and quantify the differences in the number of cases and breast cancer deaths in the Swedish W-E Trial compared with the Swedish Overview Committee (OVC) summaries and to study methodological issues related to trials in secondary prevention. SETTING: The study population of the W-E Trial of mammography screening was included in the first (W and E county) and the second (E-county) OVC summary of all Swedish randomized mammography screening trials. The OVC and the W-E Trial used different criteria for case definition and causes of death determination. METHOD: A Review Committee compared the original data files from W and E county and the first and second OVC. The reason for a discrepancy was determined individually for all non-concordant cases or breast cancer deaths. RESULTS: Of the 2615 cases included by the W-E Trial or the OVC, there were 478 (18%) disagreements. Of the disagreements 82% were due to inclusion/exclusion criteria, and 18% to disagreement with respect to cause of death or vital status at ascertainment. For E-County, the OVC inclusion rules and register based determination of cause of death (second OVC) rather than individual case review (W-E Trial and 1st OVC) resulted in a reduction of the estimate of the effect of screening, but for W-County the difference between the original trial and the OVC was modest. CONCLUSIONS: The conclusion that invitation to mammography screening reduces breast cancer mortality remains robust. Disagreements were mainly due to study design issues, while disagreements about cause of death were a minority. When secondary research does not adhere to the protocols of the primary research projects, the consequences of such design differences should be investigated and reported. Register linkage of trials can add follow-up information. The precision of trials with modest size is enhanced by individual monitoring of case status and outcome status such as determination of cause of death.

  • 263.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Garmo, Hans
    Granstrand, Bengt
    Ringberg, Anita
    Arnesson, Lars-Gunnar
    Sandelin, Kerstin
    Karlsson, Per
    Anderson, Harald
    Emdin, Stefan
    Absolute risk reductions for local recurrence after postoperative radiotherapy after sector resection for ductal carcinoma in situ of the breast2008Ingår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 26, nr 8, s. 1247-52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: Evaluate the effects of radiotherapy after sector resection for ductal carcinoma in situ of the breast (DCIS) in patient groups as defined by age, size of the lesion, focality, completeness of excision and mode of detection. PATIENTS AND METHODS: A total of 1,067 women in Sweden were randomly assigned to either postoperative radiotherapy (RT) or control from 1987 to 1999, and 1,046 were followed for a mean of 8 years. The main outcome was new ipsilateral breast cancer events and distant metastasis-free survival analyzed according to intention to treat. RESULTS: There were 64 ipsilateral events in the RT arm and 141 in the control group corresponding to a risk reduction of 16.0 percentage points at 10 years (95% CI, 10.3% to 21.6%) and a relative risk of 0.40 (95% CI, 0.30 to 0.54). There was no statistically significant difference in distant metastasis-free survival. There was an effect modification by age, yielding a low effect of RT in women younger than 50, but substantial protection in women older than 60 years. The age effect was not confounded by focality, lesion size, completeness of excision, or detection mode. There was no group as defined by our stratification variables that had a low risk without radiotherapy. CONCLUSION: Our results indicate that younger women have a low protective effect of conventional RT after sector resection. Older women benefit substantially. We caution that the age effect was seen in a subgroup analysis. Further search with conventional clinical variables for a low risk group that does not need RT does not seem fruitful.

  • 264.
    Holmberg, Lars H.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Regional Cancer Centre, Uppsala, Sweden.
    Can national cancer registration support clinical databases and clinical cancer research?2012Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, nr 6, s. 691-693Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Can national cancer registration support clinical databases and clinical cancer research? The short answer is: Yes, it can. A longer version is: Yes, it can and if it cannot substantially help now, we will have to make sure that it can in the future. In many countries and regions for decades there has been a mandatory registration of new and incident cancers. In many of these countries and regions there is also a rapidly growing interest in keeping clinical databases for clinical audit and research. The discussion about how to marry these two systems is growing, not least because both are time and resource demanding and it is important to get priorities right.

  • 265.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Iversen, Ole-Erik
    Rudenstam, Carl Magnus
    Hammar, Mats
    Kumpulainen, Eero
    Jaskiewicz, Janusz
    Jassem, Jacek
    Dobaczewska, Daria
    Fjosne, Hans E.
    Peralta, Octavio
    Arriagada, Rodrigo
    Holmqvist, Marit
    Maenpa, Johanna
    Increased risk of recurrence after hormone replacement therapy in breast cancer survivors2008Ingår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 100, nr 7, s. 475-482Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Hormone replacement therapy (HT) is known to increase the risk of breast cancer in healthy women, but its effect on breast cancer risk in breast cancer survivors is less clear. The randomized HABITS study, which compared HT for menopausal symptoms with best management without hormones among women with previously treated breast cancer, was stopped early due to suspicions of an increased risk of new breast cancer events following HT. We present results after extended follow-up. METHODS: HABITS was a randomized, non-placebo-controlled noninferiority trial that aimed to be at a power of 80% to detect a 36% increase in the hazard ratio (HR) for a new breast cancer event following HT. Cox models were used to estimate relative risks of a breast cancer event, the maximum likelihood method was used to calculate 95% confidence intervals (CIs), and chi(2) tests were used to assess statistical significance, with all P values based on two-sided tests. The absolute risk of a new breast cancer event was estimated with the cumulative incidence function. Most patients who received HT were prescribed continuous combined or sequential estradiol hemihydrate and norethisterone. RESULTS: Of the 447 women randomly assigned, 442 could be followed for a median of 4 years. Thirty-nine of the 221 women in the HT arm and 17 of the 221 women in the control arm experienced a new breast cancer event (HR = 2.4, 95% CI = 1.3 to 4.2). Cumulative incidences at 5 years were 22.2% in the HT arm and 8.0% in the control arm. By the end of follow-up, six women in the HT arm had died of breast cancer and six were alive with distant metastases. In the control arm, five women had died of breast cancer and four had metastatic breast cancer (P = .51, log-rank test). CONCLUSION: After extended follow-up, there was a clinically and statistically significant increased risk of a new breast cancer event in survivors who took HT.

  • 266.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Olausson, Petra Otterblad
    Tegnell, Anders
    Tiden är mogen för målnivåer inom cancervården: [It's time for target levels in cancer care]2011Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, nr 13, s. 708-709Artikel i tidskrift (Refereegranskat)
  • 267.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Robinson, D
    Sandin, F
    Bray, F
    Linklater, K M
    Klint, A
    Lambert, P C
    Adolfsson, J
    Hamdy, F C
    Catto, J
    Møller, H
    A comparison of prostate cancer survival in England, Norway and Sweden: A population-based study2012Ingår i: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 36, nr 1, s. e7-e12Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose

    The objective of the study was to compare patterns of survival 2001-2004 in prostate cancer patients from England, Norway and Sweden in relation to age and period of follow-up.

    Subjects and methods

    Excess mortality in men with prostate cancer was estimated using nation-wide cancer register data using a period approach for relative survival. 179,112 men in England, 23,192 in Norway and 59,697 in Sweden were included.

    Results

    In all age groups, England had the lowest survival, particularly so among men aged 80+. Overall age-standardised five-year survival was 76.4%, 80.3% and 83.0% for England, Norway and Sweden, respectively. The majority of the excess deaths in England were confined to the first year of follow-up.

    Conclusion

    The results indicate that a small but important group of older patients present at a late stage and succumb early to their cancers, possibly in combination with severe comorbidity, and this situation is more common in England than in Norway or Sweden.

  • 268.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Sandin, Fredrik
    Bray, Freddie
    Richards, Mike
    Spicer, James
    Lambe, Mats
    Klint, Åsa
    Peake, Mick
    Strand, Trond-Eirik
    Linklater, Karen
    Robinson, David
    Møller, Henrik
    National comparisons of lung cancer survival in England, Norway and Sweden 2001-2004: differences occur early in follow-up2010Ingår i: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 65, nr 5, s. 436-441Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND

    Countries with a similar expenditure on healthcare within Europe exhibit differences in lung cancer survival. Survival in lung cancer was studied in 2001-2004 in England, Norway and Sweden.

    METHODS

    Nationwide cancer registries in England, Norway and Sweden were used to identify 250 828 patients with lung cancer from England, 18 386 from Norway and 24 886 from Sweden diagnosed between 1996 and 2004, after exclusion of patients registered through death certificate only or with missing, zero or negative survival times. 5-Year relative survival was calculated by application of the period approach. The excess mortality between the countries was compared using a Poisson regression model.

    RESULTS

    In all subcategories of age, sex and follow-up period, the 5-year survival was lower in England than in Norway and Sweden. The age-standardised survival estimates were 6.5%, 9.3% and 11.3% for men and 8.4%, 13.5% and 15.9% for women in the respective countries in 2001-2004. The difference in excess risk of dying between the countries was predominantly confined to the first year of follow-up. The relative excess risk ratio during the first 3 months of follow-up comparing England with Norway 2001-2004 varied between 1.23 and 1.46, depending on sex and age, and between 1.56 and 1.91 comparing England with Sweden.

    CONCLUSION

    Access to healthcare and population awareness are likely to be major reasons for the differences, but it cannot be excluded that diagnostic and therapeutic activity play a role. Future improvements in lung cancer management may be seen early in follow-up.

  • 269.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Tamini, Rulla
    Reducing cancer drug doses in obese patients: dogma disputed2005Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 366, nr 9491, s. 1056-7Artikel i tidskrift (Refereegranskat)
  • 270.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Vickers, Andrew
    Evaluation of Prediction Models for Decision-Making: Beyond Calibration and Discrimination2013Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 10, nr 7, s. e1001491-Artikel i tidskrift (Övrigt vetenskapligt)
  • 271.
    Holmberg, Lars
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Wong, Y. N. S.
    Tabar, Laszlo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ringberg, A.
    Karlsson, P.
    Arnesson, L-G
    Sandelin, K.
    Anderson, H.
    Garmo, H.
    Emdin, S.
    Mammography casting-type calcification and risk of local recurrence in DCIS: analyses from a randomised study2013Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 108, nr 4, s. 812-819Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: We studied the association between mammographic calcifications and local recurrence in the ipsilateral breast. Methods: Case-cohort study within a randomised trial of radiotherapy in breast conservation for ductal cancer in situ of the breast (SweDCIS). We studied mammograms from cases with an ipsilateral breast event (IBE) and from a subcohort randomly sampled at baseline. Lesions were classified as a density without calcifications, architectural distortion, powdery, crushed stone-like or casting-type calcifications. Results: Calcifications representing necrosis were found predominantly in younger women. Women with crushed stone or casting-type microcalcifications had higher histopathological grade and more extensive disease. The relative risk (RR) of a new IBE comparing those with casting-type calcifications to those without calcifications was 2.10 (95% confidence interval (Cl) 0.92-4.80). This risk was confined to in situ recurrences; the RR of an IBE associated with casting-type calcifications on the mammogram adjusted for age and disease extent was 16.4 (95% Cl 2.20-140). Conclusion: Mammographic appearance of ductal carcinoma in situ of the breast is prognostic for the risk of an in situ IBE and may also be an indicator of responsiveness to RT in younger women.

  • 272.
    Hultin, Hella
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Calciumhomeostasis and Vitamin D in Obesity and Preeclampsia2011Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Normal physiological functioning is highly dependent of calcium and the concentration range is very narrow. Normal calcium levels are so crucial to survival that the body will de-mineralize bone if the levels are insufficient. A prerequisite for normal calcium uptake is a normal Vitamin D level. Insufficient levels of Vitamin D are associated to several diseases.

    The aims of this thesis were to study the relationship between pregnancies and hyperparathyroidism (pHPT) (I), between pHPT and pregnancy with preeclampsia (II) and also to determine if disturbances in calcium homeostasis with vitamin D deficiency are apparent in preeclamptic women (III).  The aim was also to study calciumhomeostasis in obese patients before and after bariatric surgery (IV and V) with emphasis on vitamin D status, parathyroid secretion and bone mineral density (BMD).

    A correlation was found between a history of pHPT and pregnancy with preeclampsia, with an odds ratio of 6,89 ( 95% CI 2.30, 20.58).  Parathyroid hormone was significantly raised in preeclamptic pregnancies but vitamin D deficiency was present both in preeclamptic and healthy pregnancies. A certain polymorphism of the Vitamin D receptor (baT haplotype), overrepresented in pHPT, was not over expressed in preeclampsia. Hypovitaminosis D was present in more than 70% of bariatric patients preoperatively, which did not change after surgery, despite great weight loss and start of Vitamin D supplementation. BMD was significantly lower in bariatric patients with a negative correlation to the time elapsed since surgery. A small increase in BMD could be noted 10-13 years after bariatric surgery, possibly due to gradual weight gain. CiCa-clamping in obese patients demonstrated a disturbed calcium homeostasis with a left-shifted calcium-PTH relationship and a lower set-point of calcium. This disturbance persisted one year postoperatively.

    In conclusion, derangements in calcium homeostasis with decreased levels of Vitamin D are present in preeclampsia and obesity. A history of pHPT should be viewed as a risk factor for preeclampsia. Life long follow-up is necessary after bariatric surgery, and an individually adjusted high dose Vitamin D substitute is probably needed to avoid a development of osteoporosis.

    Delarbeten
    1. Childbearing and the risk of parathyroid adenoma - a dominant cause for primary hyperparathyroidism
    Öppna denna publikation i ny flik eller fönster >>Childbearing and the risk of parathyroid adenoma - a dominant cause for primary hyperparathyroidism
    Visa övriga...
    2001 (Engelska)Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 250, s. 43-49Artikel i tidskrift (Refereegranskat) Published
    Identifikatorer
    urn:nbn:se:uu:diva-145193 (URN)
    Tillgänglig från: 2011-02-07 Skapad: 2011-02-07 Senast uppdaterad: 2017-12-11
    2. Association of parathyroid adenoma and pregnancy with preeclampsia
    Öppna denna publikation i ny flik eller fönster >>Association of parathyroid adenoma and pregnancy with preeclampsia
    Visa övriga...
    2009 (Engelska)Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 94, nr 9, s. 3394-3399Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    OBJECTIVE: Case reports have described associations between calcium metabolism disturbances and primary hyperparathyroidism with preeclampsia, suggesting parathyroid involvement in preeclampsia etiology. This study examines whether parathyroid adenoma, the main cause of hyperparathyroidism, diagnosed and treated before pregnancy is associated with preeclampsia. DESIGN: We conducted a register-based study to assess the association between parathyroid adenoma and subsequent preeclampsia. SETTING: Births among Sweden's general population were studied. POPULATION: The study population included 52 women with a diagnosis of parathyroid adenoma and 519 without, all of whom had a subsequent singleton pregnancy between 1973 and 1997. METHODS: We performed a conditional logistic regression investigating the association of parathyroid adenoma with subsequent preeclampsia in the first singleton pregnancy with adjustment for potential confounding factors. MAIN OUTCOME MEASURE: The main outcome was a diagnosis of preeclampsia that does not include women with prior chronic hypertension. To ensure that treatment of parathyroid adenoma was completed before pregnancy, those with a diagnosis of parathyroid adenoma made less than 2 yr before delivery (and the matched comparison women) were excluded. RESULTS: Statistically, parathyroid adenoma prior to delivery is significantly (P < 0.001) associated with preeclampsia, producing an adjusted odds ratio of 6.89 (95% confidence interval, 2.30, 20.58). CONCLUSION: A history of parathyroid adenoma should be viewed as a risk for preeclampsia.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-121064 (URN)10.1210/jc.2009-0012 (DOI)000269584600035 ()19531594 (PubMedID)
    Tillgänglig från: 2010-03-18 Skapad: 2010-03-18 Senast uppdaterad: 2017-12-12Bibliografiskt granskad
    3. Calcium homeostasis derangements in women with preeclampsia 
    Öppna denna publikation i ny flik eller fönster >>Calcium homeostasis derangements in women with preeclampsia 
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nyckelord
    preeclampsia, calciumhomeostasis, vitamin D
    Nationell ämneskategori
    Kirurgi Reproduktionsmedicin och gynekologi
    Forskningsämne
    Kirurgi; Obstetrik och gynekologi
    Identifikatorer
    urn:nbn:se:uu:diva-145207 (URN)
    Tillgänglig från: 2011-02-07 Skapad: 2011-02-07 Senast uppdaterad: 2011-05-04
    4. Left-Shifted Relation between Calcium and Parathyroid Hormone in Obesity
    Öppna denna publikation i ny flik eller fönster >>Left-Shifted Relation between Calcium and Parathyroid Hormone in Obesity
    2010 (Engelska)Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, nr 8, s. 3973-3981Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: A condition resembling secondary hyperparathyroidism (HPT), including raised levels of PTH and normal levels of serum calcium, has been reported in obesity. A plausible reason may be vitamin D deficiency, but conflicting data have been reported. Objective: Our objective was to investigate calcium homeostasis in obese individuals with emphasis on the function of the parathyroid glands. Design and Intervention: Morbidly obese patients (mean body mass index = 46.6 +/- 6) were examined for their status of calcium homeostasis. A subset was thoroughly investigated with calcium-citrate (CiCa) clamping. Patients: Of 108 morbidly obese patients, 11 underwent CiCa clamping as well as 21 healthy volunteers of normal weight and 15 with primary HPT (pHPT). Large patient cohorts of normal individuals and pHPT patients were also used as comparisons. Outcome Measures and Results: All obese individuals had normal serum calcium and creatinine levels. Mean levels of 25-OH-vitamin D-3 in serum were low, 53 nmol/liter (reference range 75-250 nmol/liter). Mean intact plasma PTH was 5.1 pmol/liter (reference range 1.1-6.9 pmol/liter). There was a significant positive correlation between PTH and duration of obesity. CiCa clamping in obese subjects revealed a remarkably high sensitivity for calcium and a left-shifted relation between plasma calcium and PTH (set point) compared with the normal population. CiCa clamping in pHPT patients demonstrated a right-shifted PTH-Ca curve. Conclusion: Although vitamin D levels in the obese individuals were low, few displayed overt signs of secondary HPT. The CiCa clamping implied a disturbance in the calcium homeostasis comparable to early renal insufficiency, with a left-shifted Ca-PTH curve and a lower set point compared with the normal population.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-135604 (URN)10.1210/jc.2009-2822 (DOI)000280652400057 ()20519351 (PubMedID)
    Tillgänglig från: 2010-12-07 Skapad: 2010-12-07 Senast uppdaterad: 2017-12-11Bibliografiskt granskad
    5. Persisting disturbances in calcium homeostasis after gastric bypass surgery
    Öppna denna publikation i ny flik eller fönster >>Persisting disturbances in calcium homeostasis after gastric bypass surgery
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nyckelord
    calciumhomeostasis, vitamin D, BMD, bariatric surgery
    Nationell ämneskategori
    Kirurgi
    Forskningsämne
    Kirurgi
    Identifikatorer
    urn:nbn:se:uu:diva-145208 (URN)
    Tillgänglig från: 2011-02-07 Skapad: 2011-02-07 Senast uppdaterad: 2018-11-30
  • 273.
    Hultin, Hella
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Edfeldt, Katarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Left-Shifted Relation between Calcium and Parathyroid Hormone in Obesity2010Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, nr 8, s. 3973-3981Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: A condition resembling secondary hyperparathyroidism (HPT), including raised levels of PTH and normal levels of serum calcium, has been reported in obesity. A plausible reason may be vitamin D deficiency, but conflicting data have been reported. Objective: Our objective was to investigate calcium homeostasis in obese individuals with emphasis on the function of the parathyroid glands. Design and Intervention: Morbidly obese patients (mean body mass index = 46.6 +/- 6) were examined for their status of calcium homeostasis. A subset was thoroughly investigated with calcium-citrate (CiCa) clamping. Patients: Of 108 morbidly obese patients, 11 underwent CiCa clamping as well as 21 healthy volunteers of normal weight and 15 with primary HPT (pHPT). Large patient cohorts of normal individuals and pHPT patients were also used as comparisons. Outcome Measures and Results: All obese individuals had normal serum calcium and creatinine levels. Mean levels of 25-OH-vitamin D-3 in serum were low, 53 nmol/liter (reference range 75-250 nmol/liter). Mean intact plasma PTH was 5.1 pmol/liter (reference range 1.1-6.9 pmol/liter). There was a significant positive correlation between PTH and duration of obesity. CiCa clamping in obese subjects revealed a remarkably high sensitivity for calcium and a left-shifted relation between plasma calcium and PTH (set point) compared with the normal population. CiCa clamping in pHPT patients demonstrated a right-shifted PTH-Ca curve. Conclusion: Although vitamin D levels in the obese individuals were low, few displayed overt signs of secondary HPT. The CiCa clamping implied a disturbance in the calcium homeostasis comparable to early renal insufficiency, with a left-shifted Ca-PTH curve and a lower set point compared with the normal population.

  • 274.
    Hultin, Hella
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Lundgren, Ewa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Ekbom, Anders
    Rastad, Jonas
    Montgomery, Scott M.
    Association of parathyroid adenoma and pregnancy with preeclampsia2009Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 94, nr 9, s. 3394-3399Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Case reports have described associations between calcium metabolism disturbances and primary hyperparathyroidism with preeclampsia, suggesting parathyroid involvement in preeclampsia etiology. This study examines whether parathyroid adenoma, the main cause of hyperparathyroidism, diagnosed and treated before pregnancy is associated with preeclampsia. DESIGN: We conducted a register-based study to assess the association between parathyroid adenoma and subsequent preeclampsia. SETTING: Births among Sweden's general population were studied. POPULATION: The study population included 52 women with a diagnosis of parathyroid adenoma and 519 without, all of whom had a subsequent singleton pregnancy between 1973 and 1997. METHODS: We performed a conditional logistic regression investigating the association of parathyroid adenoma with subsequent preeclampsia in the first singleton pregnancy with adjustment for potential confounding factors. MAIN OUTCOME MEASURE: The main outcome was a diagnosis of preeclampsia that does not include women with prior chronic hypertension. To ensure that treatment of parathyroid adenoma was completed before pregnancy, those with a diagnosis of parathyroid adenoma made less than 2 yr before delivery (and the matched comparison women) were excluded. RESULTS: Statistically, parathyroid adenoma prior to delivery is significantly (P < 0.001) associated with preeclampsia, producing an adjusted odds ratio of 6.89 (95% confidence interval, 2.30, 20.58). CONCLUSION: A history of parathyroid adenoma should be viewed as a risk for preeclampsia.

  • 275.
    Hultin, Hella
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Lillhager, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Hematologi och immunologi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Calcium homeostasis derangements in women with preeclampsia Manuskript (preprint) (Övrigt vetenskapligt)
  • 276.
    Hultin, Hella
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Ribom, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Michaelsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Mallmin, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Persisting disturbances in calcium homeostasis after gastric bypass surgeryManuskript (preprint) (Övrigt vetenskapligt)
  • 277.
    Hultin, Hella
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Stevens, Katharina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Cholecalciferol Injections Are Effective in Hypovitaminosis D After Duodenal Switch: a Randomized Controlled Study2018Ingår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 28, nr 10, s. 3007-3011Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: By treating obesity, one of the major epidemics of this past century, through bariatric surgery, we may cause complications due to malnourishment in a growing population. At present, vitamin D deficiency is of interest, especially in patients with inferior absorption of fat-soluble nutrients after biliopancreatic diversion with duodenal switch (BPD/DS).

    Methods: Twenty BPD/DS patients, approximately 4 years postoperatively, were randomized to either intramuscular supplementation of vitamin D with a single dose of 600,000 IU cholecalciferol, or a control group. Patients were instructed to limit their supplementation to 1400 IU of vitamin D and to avoid the influence of UV-B radiation; the study was conducted when sunlight is limited (December to May).

    Results: Despite oral supplementation, a pronounced deficiency in vitamin D was seen (injection 19.3; control 23.2 nmol/l) in both groups. The cholecalciferol injection resulted in elevated 25[OH]D levels at 1 month (65.4 nmol/l), which was maintained at 6 months (67.4 nmol/l). This resulted in normalization of intact parathyroid hormone (PTH) levels. No changes in vitamin D or PTH occurred in the control group.

    Conclusions: In BPD/DS patients, having hypovitaminosis D despite full oral supplementation, a single injection of 600,000 IU of cholecalciferol was effective in elevating vitamin D levels and normalizing levels of intact PTH. The treatment is simple and highly effective and thus recommended, especially in cases of reduced UV-B radiation.

  • 278.
    Häggström, Christel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Biobank Res, Umea, Sweden.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England;Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden.
    de Luna, Xavier
    Umea Univ, Dept Stat, USBE, Umea, Sweden.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England;Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Söderkvist, Karin
    Umea Univ, Dept Radiat Sci, Oncol, Umea, Sweden.
    Aljabery, Firas
    Linkoping Univ, Div Urol, Dept Clin & Expt Med, Linkoping, Sweden.
    Ströck, Viveka
    Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Dept Urol, Stockholm, Sweden.
    Gårdmark, Truls
    Danderyd Hosp, Dept Clin Sci, Karolinska Inst, Stockholm, Sweden.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Jahnson, Staffan
    Linkoping Univ, Div Urol, Dept Clin & Expt Med, Linkoping, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Dept Urol, Malmo, Sweden;Lund Univ, Dept Translat Med, Malmo, Sweden.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Survival after radiotherapy versus radical cystectomy for primary muscle-invasive bladder cancer: A Swedish nationwide population-based cohort study2019Ingår i: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 8, nr 5, s. 2196-2204Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Studies of survival comparing radical cystectomy (RC) and radiotherapy for muscle-invasive bladder cancer have provided inconsistent results and have methodological limitations. The aim of the study was to investigate risk of death after radiotherapy as compared to RC.

    Methods: We selected patients with muscle-invasive urothelial carcinoma without distant metastases, treated with radiotherapy or RC from 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe) and estimated absolute and relative risk of bladder cancer death and all-cause death. In a group of patients, theoretically eligible for a trial comparing radiotherapy and RC, we calculated risk difference in an instrumental variable analysis. We have not investigated chemoradiotherapy as this treatment was not used in the study time period.

    Results: The study included 3 309 patients, of those 17% were treated with radiotherapy and 83% with RC. Patients treated with radiotherapy were older, had more advanced comorbidity, and had a higher risk of death as compared to patients treated with RC (relative risks of 1.5-1.6). In the "trial population," all-cause death risk difference was 6 per 100 patients lower after radiotherapy at 5 years of follow-up, 95% confidence interval -41 to 29.

    Conclusion(s): Patient selection between the treatments make it difficult to evaluate results from conventionally adjusted and propensity-score matched survival analysis. When taking into account unmeasured confounding by instrumental variable analysis, no differences in survival was found between the treatments for a selected group of patients. Further clinical studies are needed to characterize this group of patients, which can serve as a basis for future comparison studies for treatment recommendations.

  • 279.
    Häggström, Christel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Biobank Res, S-90185 Umea, Sweden;Umea Univ, Dept Publ Hlth & Clin Med, Nutr Res, Umea, Sweden.
    Jonsson, Håkan
    Umea Univ, Dept Radiat Sci, Umea, Sweden.
    Björge, Tone
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway;Canc Registry Norway, Oslo, Norway.
    Nagel, Gabriele
    Ulm Univ, Inst Epidemiol & Med Biometry, Ulm, Germany;Agcy Prevent & Social Med, Vorarlberg Canc Registry, Bregenz, Aks, Austria.
    Manjer, Jonas
    Lund Univ, Skane Univ Hosp, Dept Surg, Malmo, Sweden.
    Ulmer, Hanno
    Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Innsbruck, Austria.
    Drake, Isabel
    Lund Univ, Dept Clin Sci Malmo, Lund, Sweden.
    Ghaderi, Sara
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
    Lang, Alois
    Agcy Prevent & Social Med, Vorarlberg Canc Registry, Bregenz, Aks, Austria.
    Engeland, Anders
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway;Norwegian Inst Publ Hlth, Bergen, Norway.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Stocks, Tanja
    Lund Univ, Dept Clin Sci Lund, Lund, Sweden.
    Linear age-course effects on the associations between body mass index, triglycerides, and female breast and male liver cancer risk: An internal replication study of 800,000 individuals2020Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, nr 1, s. 58-67Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Apart from the consistently observed differential association between obesity and breast cancer risk by menopausal status, the associations between obesity and other metabolic imbalances with risks of cancers have not been systematically investigated across the age-course. We created two random 50-50% cohorts from six European cohorts comprising 813,927 individuals. In the "discovery cohort", we used Cox regression with attained age as time-scale and tested interactions between body mass index (BMI), blood pressure, plasma glucose, triglycerides and cholesterol, and attained age in relation to cancer risk. Results with a p-value below 0.05 were additionally tested in the "replication cohort" where a replicated result was considered evidence of a linear interaction with attained age. These findings were investigated by flexible parametric survival models for any age-plateaus in their shape of associations with cancer risk across age. Consistent with other studies, BMI was negatively related to breast cancer risk (n cases = 11,723) among younger (premenopausal) women. However, the association remained negative for several years after menopause and, although gradually weakening over age, the association became positive only at 62 years of age. This linear and positive age-interaction was also found for triglycerides and breast cancer, and for BMI and triglycerides in relation to liver cancer among men (n cases = 444). These findings are unlikely to be due to chance owing to the replication. The linear age-interactions in breast cancer may suggest an influence by other age-related factors than menopause; however, further investigation of age-related effect modifiers in both breast and liver cancer is needed.

  • 280.
    Häggström, Christel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umeå University, Department of Biobank Research.
    Liedberg, Fredrik
    Skåne University Hospital, Department of Urology; Lund University, Department of Translational Medicine.
    Hagberg, Oskar
    Regional Cancer Centre South, Lund.
    Aljabery, Firas
    Linköping University, Division of Urology, Department of Clinical and Experimental Medicine.
    Ströck, Viveka
    Sahlgrenska University Hospital, Department of Urology.
    Hosseini, Abolfazl
    Karolinska University Hospital, Department of Urology.
    Gårdmark, Truls
    Karolinska Institute, Danderyd Hospital, Department of Clinical Sciences.
    Sherif, Amir
    Umeå University, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Garmo, Hans
    King’s College London, Faculty of Life Sciences and Medicine, Division of Cancer Studies; Regional Cancer Centre Uppsala/Örebro.
    Jahnson, Staffan
    Linköping University, Division of Urology, Department of Clinical and Experimental Medicine.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. King’s College London, Faculty of Life Sciences and Medicine, Division of Cancer Studies.
    Cohort profile: The Swedish National Register of Urinary Bladder Cancer (SNRUBC) and the Bladder Cancer Data Base Sweden (BladderBaSe)2017Ingår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, nr 9, artikel-id e016606Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To monitor the quality of bladder cancer care, the Swedish National Register of Urinary Bladder Cancer (SNRUBC) was initiated in 1997. During 2015, in order to study trends in incidence, effects of treatment and survival of men and women with bladder cancer, we linked the SNRUBC to other national healthcare and demographic registers and constructed the Bladder Cancer Data Base Sweden (BladderBaSe).

    Participants: The SNRUBC is a nationwide register with detailed information on 97% of bladder cancer cases in Sweden as compared with the Swedish Cancer Register. Participants in the SNRUBC have registered data on tumour characteristics at diagnosis, and for 98% of these treatment data have been captured. From 2009, the SNRUBC holds data on 88% of eligible participants for follow-up 5 years after diagnosis of non-muscle invasive bladder cancer, and from 2011, data on surgery details and complications for 85% of participants treated with radical cystectomy. The BladderBaSe includes all data in the SNRUBC from 1997 to 2014, and additional covariates and follow-up data from linked national register sources on comorbidity, socioeconomic factors, detailed information on readmissions and treatment side effects, and causes of death.

    Findings to date: Studies based on data in the SNRUBC have shown inequalities in survival and treatment indication by gender, regions and hospital volume. The BladderBaSe includes 38 658 participants registered in SNRUBC with bladder cancer diagnosed from 1 January 1997 to 31 December 2014. The BladderBaSe initiators are currently in collaboration with researchers from the SNRUBC investigating different aspects of bladder cancer survival.

    Future plans: The SNRUBC and the BladderBaSe project are open for collaborations with national and international research teams. Collaborators can submit proposals for studies and study files can be uploaded to servers for remote access and analysis. For more information, please contact the corresponding author.

  • 281.
    Häggström, Christel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Biobank Res, S-90185 Umea, Sweden;Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England;Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR). Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Rowley, Mark
    Kings Coll London, Inst Math & Mol Biomed, London, England;Saddle Point Sci, London, England.
    Coolen, Anthony C. C.
    Kings Coll London, Inst Math & Mol Biomed, London, England.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Heterogeneity in risk of prostate cancer: A Swedish population-based cohort study of competing risks and Type 2 diabetes mellitus2018Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, nr 8, s. 1868-1875Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Most previous studies of prostate cancer have not taken into account that men in the studied populations are also at risk of competing event, and that these men may have different susceptibility to prostate cancer risk. The aim of our study was to investigate heterogeneity in risk of prostate cancer, using a recently developed latent class regression method for competing risks. We further aimed to elucidate the association between Type 2 diabetes mellitus (T2DM) and prostate cancer risk, and to compare the results with conventional methods for survival analysis. We analysed the risk of prostate cancer in 126,482 men from the comparison cohort of the Prostate Cancer Data base Sweden (PCBaSe) 3.0. During a mean follow-up of 6years 6,036 men were diagnosed with prostate cancer and 22,393 men died. We detected heterogeneity in risk of prostate cancer with two distinct latent classes in the study population. The smaller class included 9% of the study population in which men had a higher risk of prostate cancer and the risk was stronger associated with class membership than any of the covariates included in the study. Moreover, we found no association between T2DM and risk of prostate cancer after removal of the effect of informative censoring due to competing risks. The recently developed latent class for competing risks method could be used to provide new insights in precision medicine with the target to classify individuals regarding different susceptibility to a particular disease, reaction to a risk factor or response to treatment.

  • 282.
    Häggström, Christel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.; Umea Univ, Dept Biobank Res, S-90185 Umea, Sweden..
    Van Hemelrijck, Mieke
    Kings Coll London, Div Canc Studies, Fac Life Sci & Med, London, England.;Karolinska Inst, Inst Environm Med, Stockholm, Sweden..
    Zethelius, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik. Med Prod Agcy, Dept Sci Support, Uppsala, Sweden..
    Robinson, David
    Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Grundmark, Birgitta
    Med Prod Agcy, Dept Sci Support, Uppsala, Sweden.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Div Canc Studies, Fac Life Sci & Med, London, England.
    Gudbjörnsdottir, Soffia
    Gothenburg Univ, Sahlgrenska Univ Hosp, Dept Med, Gothenburg, Sweden..
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. Kings Coll London, Div Canc Studies, Fac Life Sci & Med, London, England.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
    Prospective study of Type 2 diabetes mellitus, anti-diabetic drugs and risk of prostate cancer2017Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, nr 3, s. 611-617Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Type 2 diabetes mellitus (T2DM) has consistently been associated with decreased risk of prostate cancer; however, if this decrease is related to the use of anti-diabetic drugs is unknown. We prospectively studied men in the comparison cohort in the Prostate Cancer data Base Sweden 3.0, with data on T2DM, use of metformin, sulfonylurea and insulin retrieved from national health care registers and demographic databases. Cox proportional hazards regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) of prostate cancer, adjusted for confounders. The study consisted of 612,846 men, mean age 72 years (standard deviation; SD=9 years), out of whom 25,882 men were diagnosed with prostate cancer during follow up, mean time of 5 years (SD=3 years). Men with more than 1 year's duration of T2DM had a decreased risk of prostate cancer compared to men without T2DM (HR=0.85, 95% CI=0.82-0.88) but among men with T2DM, those on metformin had no decrease (HR=0.96, 95% CI=0.77-1.19), whereas men on insulin (89%) or sulfonylurea (11%) had a decreased risk (HR=0.73, 95% CI=0.55-0.98), compared to men with T2DM not on anti-diabetic drugs. Men with less than 1 year's duration of T2DM had no decrease in prostate cancer risk (HR=1.11, 95% CI=0.95-1.31). Our results gave no support to the hypothesis that metformin protects against prostate cancer as recently proposed. However, our data gave some support to an inverse association between T2DM severity and prostate cancer risk.

    What's new? Although Type 2 diabetes mellitus (T2DM) increases the risk of several cancers, multiple studies point toward a significantly inverse relationship between T2DM and prostate cancer risk in men. Use of the anti-diabetic drug metformin is suspected of underlying the association. In this prospective study in Sweden, however, metformin failed to decrease the risk of prostate cancer. By comparison, risk was decreased in association with the use of insulin or sulfonylurea. These findings add some support to an inverse association between T2DM severity and prostate cancer risk.

  • 283. Härmark, Linda
    et al.
    van Hunsel, Florence
    Grundmark, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    ADR Reporting by the General Public: Lessons Learnt from the Dutch and Swedish Systems2015Ingår i: Drug Safety, ISSN 0114-5916, E-ISSN 1179-1942, Vol. 38, nr 4, s. 337-347Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Consumer reporting of adverse drug reactions (ADRs) has existed in several countries for decades, but throughout Europe the role of consumers as a source of information on ADRs has not been fully accepted until recently. In Europe, The Netherlands and Sweden were among the first countries to implement consumer reporting well before it was mandated by law throughout the EU. Consumer reporting is an integral part of the spontaneous reporting systems in both The Netherlands and Sweden, with yearly numbers of reports constantly increasing. Consumer reporting forms and handling procedures are essentially the same as for healthcare professional reporting; the message in the reports, not the type of messenger, is what is of importance. Studies have established the significant contribution of consumer reporting to ADR signal detection. Combining all reports regardless of reporter type is recommended since it yields the largest critical mass of reports for signal detection. Examples of signals where consumer reports have been of crucial importance for signal detection are electric shock-like sensations associated with the use of duloxetine, and persistent sexual dysfunction after discontinuation of selective serotonin reuptake inhibitors. An example of consumer reporting significantly strengthening a detected signal is Pandemrix(®) (influenza H1N1 vaccine)-induced narcolepsy. Raising public awareness of ADR reporting is important, but time- and resource-consuming. The minimum effort taken should be to passively inform consumers, e.g. via stakeholders' homepages and via drug product information leaflets. Another possibility of reaching out to this target group could be through co-operation with other (non-government) organizations. Information from consumer reports may give a new perspective on ADRs via the consumers' unfiltered experiences. Consumers' views may change the way the benefit-harm balance of drugs is perceived and assessed today, and, being the ultimate users of drugs, consumers could have a relevant influence in the regulatory decision-making processes for drugs. All stakeholders in pharmacovigilance should embrace this new valuable source of information.

  • 284.
    Hållmarker, Ulf
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    James, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Michaëlsson, Karl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Ärnlöv, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiovaskulär epidemiologi.
    Sandin, Fredrik
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Cancer incidence in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population.2015Ingår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 51, nr 4, s. 558-568Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: We studied the association between taking part in a long distance ski race and cancer incidence to address the hypothesis that a lifestyle involving a high degree of physical activity (PA) lowers cancer incidence with a pattern that is different by cancer site.

    METHODS: Cancer incidence was estimated in a large cohort of skiers (n=185,412) participating in the Vasaloppet long distance ski race in Sweden 1989-2010 and non-participants in the ski race, randomly selected from the Swedish general population (n=184,617). Data include race finishing times as a measurement of physical fitness. Hazard ratios (HRs) and net probability of cancer over twenty years of follow-up were estimated for all invasive cancer, and separately for prostate, breast, colo-rectal and lung cancer, and groups of cancers with presumed relation to lifestyle.

    FINDINGS: Participating in Vasaloppet was associated with a relative risk reduction for all invasive cancer of 6% (95% confidence interval 2-9%) and a relative risk reduction of 32% (95% confidence interval 28-37%) of cancer sites where there is epidemiological evidence that smoking, bodyweight, regular PA and consumption of fruit and vegetables are aetiological factors. For skin cancer the risk was increased, as for prostate cancer. Skiers with shorter finishing times had lower incidence of cancer.

    INTERPRETATION: This study indicates that it is unrealistic to reduce overall population cancer incidence drastically with life style. However, cancers that are epidemiologically associated with life style factors were significantly reduced by what presumably is a blend of non-smoking, normal body weight, sound dietary habits and PA. Our data thus provide additional support for present days' recommendations about life style prevention. Higher health awareness is associated with attendance to screening, which may explain our results for prostate cancer.

    FUNDING: University fund, independent funds from an insurance company and a private foundation.

  • 285.
    Jabs, Verena
    et al.
    TU Dortmund Univ, Fac Stat, Dortmund, Germany..
    Edlund, Karolina
    Dortmund Univ, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany..
    Koenig, Helena
    TU Dortmund Univ, Fac Stat, Dortmund, Germany..
    Grinberg, Marianna
    TU Dortmund Univ, Fac Stat, Dortmund, Germany..
    Madjar, Katrin
    TU Dortmund Univ, Fac Stat, Dortmund, Germany..
    Rahnenfuehrer, Joerg
    TU Dortmund Univ, Fac Stat, Dortmund, Germany..
    Ekman, Simon
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Bergkvist, Michael
    Gavle Cent Hosp, Dept Oncol, Gavle, Sweden..
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Reg Canc Ctr Uppsala Orebro, Uppsala, Sweden.;Kings Coll London, Fac Life Sci & Med, Div Canc Studies, London, England..
    Ickstadt, Katja
    TU Dortmund Univ, Fac Stat, Dortmund, Germany..
    Botling, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Hengstler, Jan G.
    Dortmund Univ, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany..
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk och experimentell patologi.
    Integrative analysis of genome-wide gene copy number changes and gene expression in non-small cell lung cancer2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 11, artikel-id e0187246Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Non-small cell lung cancer (NSCLC) represents a genomically unstable cancer type with extensive copy number aberrations. The relationship of gene copy number alterations and subsequent mRNA levels has only fragmentarily been described. The aim of this study was to conduct a genome-wide analysis of gene copy number gains and corresponding gene expression levels in a clinically well annotated NSCLC patient cohort (n = 190) and their association with survival. While more than half of all analyzed gene copy number-gene expression pairs showed statistically significant correlations (10,296 of 18,756 genes), high correlations, with a correlation coefficient >0.7, were obtained only in a subset of 301 genes (1.6%), including KRAS, EGFR and MDM2. Higher correlation coefficients were associated with higher copy number and expression levels. Strong correlations were frequently based on few tumors with high copy number gains and correspondingly increased mRNA expression. Among the highly correlating genes, GO groups associated with posttranslational protein modifications were particularly frequent, including ubiquitination and neddylation. In a meta-analysis including 1,779 patients we found that survival associated genes were overrepresented among highly correlating genes (61 of the 301 highly correlating genes, FDR adjusted p<0.05). Among them are the chaperone CCT2, the core complex protein NUP107 and the ubiquitination and neddylation associated protein CAND1. In conclusion, in a comprehensive analysis we described a distinct set of highly correlating genes. These genes were found to be overrepresented among survival-associated genes based on gene expression in a large collection of publicly available datasets.

  • 286.
    Jack, Ruth H
    et al.
    King’s College London, Thames Cancer Registry, London.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. King’s College London, Division of Cancer Studies, Research Oncology, Guy’s Hospital, London .
    Waiting times for radiotherapy after breast cancer2010Ingår i: BMJ. British Medical Journal (International Ed.), ISSN 0959-8146, E-ISSN 0959-535X, Vol. 340, s. c1007-Artikel i tidskrift (Refereegranskat)
  • 287.
    Jahnson, Staffan
    et al.
    Linkoping Univ, Dept Clin & Expt Med, Div Urol, Linkoping, Sweden.
    Gårdmark, Truls
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Hosseini, Abolfazl
    Karolinska Univ Hosp, Dept Urol, Stockholm, Sweden.
    Jedström, Tomas
    Orebro Univ Hosp, Dept Urol, Orebro, Sweden.
    Liedberg, Fredrik
    Skane Univ Hosp, Dept Urol, Malmo, Sweden;Lund Univ, Inst Translat Med, Malmo, Sweden.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Rosell, Johan
    Linkoping Univ, Reg Canc Ctr Southeast Sweden, Linkoping, Sweden;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Sherif, Amir
    Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
    Ströck, Viveka
    Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden.
    Häggström, Christel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umea Univ, Dept Biobank Res, Umea, Sweden.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Kings Coll London, Sch Med, London, England.
    Aljabery, Firas
    Linkoping Univ, Dept Clin & Expt Med, Div Urol, Linkoping, Sweden.
    Management and outcome of TaG3 tumours of the urinary bladder in the nationwide, population-based bladder cancer database Sweden (BladderBaSe)2019Ingår i: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 53, nr 4, s. 200-205Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To investigate the management of TaG3 tumours of the urinary bladder using nationwide population-based data in relation to the prevailing guidelines, patients' characteristics, and outcome. Materials and methods: The Bladder Cancer Data Base Sweden (BladderBaSe), including data from the Swedish National Register for Urinary Bladder Cancer (SNRUBC), was used to study all patients with TaG3 bladder cancer diagnosed from 2008 to 2014. Patients were divided into the following management groups: (1) transurethral resection (TUR) only, (2) TUR and intravesical instillation therapy (IVIT), (3) TUR and second-look resection (SLR), and (4) TUR with both SLR and IVIT. Patient and tumour characteristics and outcome were studied. Results: There were 831 patients (83% males) with a median age of 74 years. SLR was performed more often on younger patients, on men, and less often in the Western and Uppsala/orebro Healthcare regions. IVIT was performed more often with younger patients, with men, in the Western Healthcare region, and less often in the Uppsala/orebro Healthcare region. Death from bladder cancer occurred in 6% of cases within a median of 29 months (0-84 months) and was lower in the TUR/IVIT and TUR/SLR/IVIT groups compared to the other two groups. Conclusion: In the present study, there was, according to the prevailing treatment guidelines, an under-treatment with SLR for older patients, women, and in some healthcare regions and, similarly, there was an under-treatment with IVIT for older patients. Cancer-specific survival and relative survival were lower in the TUR only group compared to the TUR/IVIT and TUR/SLR/IVIT groups.

  • 288.
    Jangland, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Sjuksköterskeutbildningar.
    Becker, Deborah
    Börjeson, Susanne
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Doherty, Caroline
    Gimm, Oliver
    Griffith, Patricia
    Johansson, AnnaKarin
    Juhlin, Claes
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Pawlow, Patricia
    Sicoutris, Corinna
    Yngman-Uhlin, Pia
    The development of a Swedish Nurse Practitioner Program: a request from clinicians and a process supported by US experience2014Ingår i: Journal of Nursing Education and Practice, ISSN 1925-4040, E-ISSN 1925-4059, Vol. 4, nr 2, s. 38-48Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High nursing turnover and a shortage of nurses in acute hospital settings in Sweden challenge health care systems to deliver and ensure safe care. Advanced nursing roles implemented in other countries have offered nurses new career opportunities and had positive effects on patient safety, effectiveness of care, and patient satisfaction. The advanced nursing position of Nurse Practitioner has existed for many years in the United States, while similar extended nursing roles and changes in the scope of nursing practice are being developed in many other countries. In line with this international trend, the role of Nurse Practitioner in surgical care has been proposed for Sweden, and a master’s programme for Acute Nurse Practitioners has been in development for many years. To optimize and facilitate the introduction of this new nursing role and its supporting programme, we elicited the experiences and support of the group who developed a Nurse Practitioner programme for a university in the US. This paper describes this collaboration and sharing of experiences during the process of developing a Swedish Nurse Practitioner programme. We also discuss the challenges of implement- ting any new nursing role in any national health care system. We would like to share our collaborative experiences and thoughts for the future and to open further national and international dialogue about how best to expand the scope of practice for nurses in acute hospital care, and thereby to improve patient care in Sweden and elsewhere.

  • 289.
    Jangland, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Sjuksköterskeutbildningar.
    Carlsson, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    Lundgren, Ewa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Gunningberg, Lena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Vårdvetenskap.
    The impact of an intervention to improve patient participation in a surgical care unit: a quasi-experimental study2012Ingår i: International Journal of Nursing Studies, ISSN 0020-7489, E-ISSN 1873-491X, Vol. 49, nr 5, s. 528-538Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Organizational changes in surgical care are requiring patients to become more responsible for their own care, both before and after surgery, and also during recovery. Involving patients in their care is vital to improving quality of care and patient safety.

    Objective: The aim of this study was to investigate the impact of the ‘Tell-us’ card on patients’ perceptions of quality of care, with a specific focus on patient participation. Another aim was to evaluate the use of the Tell-us card from the patients’ perspective.

    Design: A quasi-experimental design with an intervention group and control groups was used. The patient's self-written Tell-us card was introduced as the intervention.

    Setting: The study was conducted in two surgical care units at a Swedish university hospital.

    Participants: A consecutive sample of patients admitted from the waiting list and from the emergency department was included (n = 310). The inclusion criteria were surgical patients with a hospital stay of at least one day. Patients who were younger than 18 years, not able to speak or write in Swedish, or unable or unwilling to give informed consent to participate were excluded.

    Methods: Quality of care was assessed using the questionnaire ‘Quality from the Patient's Perspective’. The patients included in the intervention group were asked to write what was most important for them during the day or just before discharge on patient-written Tell-us cards.

    Results: The use of the Tell-us card resulted in significant improvements (5 out of 17 items) in patients’ abilities to participate in decisions about their nursing and medical care. The patients found the Tell-us card more useful in their interaction with registered nurses and assistant nurses than with physicians.

    Conclusions: The use of the Tell-us card improved patients’ participation in some areas of nursing and medical care in the surgical care units. The Tell-us card is an uncomplicated and inexpensive tool that could be an important step towards improved patient participation in the surgical care unit. More research is needed to evaluate the use of the Tell-us card in different hospital units and over a longer period of time.

  • 290.
    Janson, Eva Tiensuu
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Sorbye, Halfdan
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Onkologisk endokrinologi.
    Federspiel, Birgitte
    Grønbæk, Henning
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Ladekarl, Morten
    Langer, Seppo W
    Mortensen, Jann
    Schalin-Jäntti, Camilla
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Sundlöv, Anna
    Thiis-Evensen, Espen
    Knigge, Ulrich
    Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms2014Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, nr 10, s. 1284-1297Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background

    The diagnostic work-up and treatment of patients with neuroendocrine neoplasms (NENs) has undergone major recent advances and new methods are currently introduced into the clinic. An update of the WHO classification has resulted in a new nomenclature dividing NENs into neuroendocrine tumours (NETs) including G1 (Ki67 index ≤ 2%) and G2 (Ki67 index 3-20%) tumours and neuroendocrine carcinomas (NECs) with Ki67 index > 20%, G3. Aim. These Nordic guidelines summarise the Nordic Neuroendocrine Tumour Group's current view on how to diagnose and treat NEN-patients and are meant to be useful in the daily practice for clinicians handling these patients.

  • 291.
    Janson, Eva Tiensuu
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Sørbye, Halfdan
    Welin, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Federspiel, Birgitte
    Grønbaek, Henning
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Mathisen, Oystein
    Mortensen, Jann
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Thiis-Evensen, Espen
    Välimäki, Matti J
    Öberg, Kjell
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Medicin.
    Knigge, Ulrich
    Nordic Guidelines 2010 for diagnosis and treatment of gastroenteropancreatic neuroendocrine tumours2010Ingår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 49, nr 6, s. 740-756Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The diagnostic work-up and treatment of patients with neuroendocrine tumours has undergone a major change during the last decade. New diagnostic possibilities and treatment options have been developed. These Nordic guidelines, written by a group with a major interest in the subject, summarises our current view on how to diagnose and treat these patients. The guidelines are meant to be useful in the daily practice for clinicians handling patients with neuroendocrine tumours.

  • 292.
    Jarbo, Caroline
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Buckley, Patrick G
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Piotrowski, Arkadiusz
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Mantripragada, Kiran K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Benetkiewicz, Magdalena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Diaz de Ståhl, Teresita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Langford, Cordelia F
    Gregory, Simon G
    Dralle, Henning
    Gimm, Oliver
    Bäckdahl, Martin
    Geli, Janos
    Larsson, Catharina
    Westin, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Åkerström, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Dumanski, Jan P
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Detailed assessment of chromosome 22 aberrations in sporadic pheochromocytoma using array-CGH.2006Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 118, nr 5, s. 1159-64Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pheochromocytoma is a predominantly sporadic neuroendocrine tumor derived from the adrenal medulla. Previous low resolution LOH and metaphase-CGH studies reported the loss of chromosomes 1p, 3q, 17p and 22q at various frequencies. However, the molecular mechanism(s) behind development of sporadic pheochromocytoma remains largely unknown. We have applied high-resolution tiling-path microarray-CGH with the primary aim to characterize copy number imbalances affecting chromosome 22 in 66 sporadic pheochromocytomas. We detected copy number alterations on 22q at a frequency of 44%. The predominant finding was monosomy 22 (30%), followed by terminal deletions in 8 samples (12%) and a single interstitial deletion. We further applied a chromosome 1 tiling-path array in 7 tumors with terminal deletions of 22q and found deletions of 1p in all cases. Our overall results suggest that at least 2 distinct regions on both 22q and 1p are important in the tumorigenesis of sporadic pheochromocytoma. A large proportion of pheochromocytomas also displayed indications of cellular heterogeneity. Our study is to our knowledge the first array-CGH study of sporadic pheochromocytoma. Future analysis of this tumor type should preferably be performed in the context of the entire human genome using genome-wide array-CGH, which is a superior methodological approach. Supplemental material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.htm

  • 293.
    Jiao, Xiang
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Hooper, Sean D.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Djureinovic, Tatjana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Larsson, Chatarina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Wärnberg, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Tellgren-Roth, Christian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Botling, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Sjöblom, Tobias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik.
    Gene rearrangements in hormone receptor negative breast cancers revealed by mate pair sequencing2013Ingår i: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 14, artikel-id 165Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Chromosomal rearrangements in the form of deletions, insertions, inversions and translocations are frequently observed in breast cancer genomes, and a subset of these rearrangements may play a crucial role in tumorigenesis. To identify novel somatic chromosomal rearrangements, we determined the genome structures of 15 hormone-receptor negative breast tumors by long-insert mate pair massively parallel sequencing. Results: We identified and validated 40 somatic structural alterations, including the recurring fusion between genes DDX10 and SKA3 and translocations involving the EPHA5 gene. Other rearrangements were found to affect genes in pathways involved in epigenetic regulation, mitosis and signal transduction, underscoring their potential role in breast tumorigenesis. RNA interference-mediated suppression of five candidate genes (DDX10, SKA3, EPHA5, CLTC and TNIK) led to inhibition of breast cancer cell growth. Moreover, downregulation of DDX10 in breast cancer cells lead to an increased frequency of apoptotic nuclear morphology. Conclusions: Using whole genome mate pair sequencing and RNA interference assays, we have discovered a number of novel gene rearrangements in breast cancer genomes and identified DDX10, SKA3, EPHA5, CLTC and TNIK as potential cancer genes with impact on the growth and proliferation of breast cancer cells.

  • 294.
    Johansson, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Onelöv, Erik
    Johansson, Jan-Erik
    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 trial2009Ingår i: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 55, nr 2, s. 422-430Artikel i tidskrift (Refereegranskat)
    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).

  • 295.
    Johansson, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Steineck, Gunnar
    Klinisk cancer epidemiologi, Stockholm, Göteborg.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Division of Cancer Studies, Medical School, King's College London, London, UK..
    Johansson, Jan-Erik
    Urologiska Kliniken, Örebro.
    Nyberg, Tommy
    Klinisk cancer epidemiologi, Stockholm.
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Quality of life after radical prostatectomy or watchful waiting with or without androgen deprivation therapy: The SPCG-4 Randomized Trial2018Ingår i: European Urology Oncology, Vol. 1, nr 2, s. 134-142Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Men with prostate cancer experience adjuvant androgen deprivation therapy (ADT) differently.

    Objective: To evaluate the effect of ADT on quality of life (QoL), patients' experience of clinical check-ups, and differences in cancer information as explanatory factors.

    Design, setting, and participants: A study-specific questionnaire was sent to all men randomized in the SPCG-4 trial to radical prostatectomy (RP) or watchful waiting (WW) still alive (400/695) and a control group of 281 men.

    Intervention: ADT.

    Outcome measurements and statistical analysis: Self-assessed QoL, worry at clinical check-ups, and amount of information received. Estimated relative risks with associated 95% confidence intervals (CI) for risk comparisons between groups using a log-binomial regression.

    Results and limitations: The SPCG-4 men had median follow-up of 12.2 yr and median age of 77.0 yr; 26% in the RP group and 40% in the WW group received ADT treatment. High QoL for men without ADT was 36% for the RP group, 44% for the WW group, and 45% for the control group. High QoL for men with ADT was 30% for the RP group and 20% for the WW group. Among men with ADT, those in the WW group received significantly less information about the disease than men in the RP group. Receiving no or little information about prostate cancer was reported by 17% of patients in the RP group and 39% in the WW group among men receiving ADT (relative risk 0.44, 95% CI 022-0.89). At clinical check-ups, men treated with ADT had significantly higher levels of worry, regardless of study group, than men without ADT. Limitations include the lack of longitudinal data and a low number of men receiving ADT in the RP group.

    Conclusions: Men on WW without ADT reported high QoL comparable to that for men without prostate cancer. ADT treatment in the WW group was associated with the lowest scores for all psychological parameters, and these men reported that they were least informed about prostate cancer and its consequences.

    Patient summary: Good communication and information from caregivers are associated with less negative psychological effects at prostate cancer progression.

  • 296.
    Johansson, Eva
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Steineck, Gunnar
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Johansson, Jan-Erik
    Nyberg, Tommy
    Ruutu, Mirja
    Bill-Axelson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial.2011Ingår i: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 12, nr 9, s. 891-899Artikel i tidskrift (Refereegranskat)
    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. FUNDING: US National Institutes of Health; Swedish Cancer Society; Foundation in Memory of Johanna Hagstrand and Sigfrid Linnér.

  • 297.
    Johansson, Henry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    The Uppsala anatomist Ivar Sandstrom and the parathyroid gland2015Ingår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, nr 2, s. 72-77Artikel i tidskrift (Refereegranskat)
  • 298.
    Johansson, Mattias
    et al.
    IARC, Lyon, France.
    Carreras-Torres, Robert
    IARC, Lyon, France.
    Scelo, Ghislaine
    IARC, Lyon, France.
    Purdue, Mark P.
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD USA.
    Mariosa, Daniela
    IARC, Lyon, France.
    Muller, David C.
    Imperial Coll, London, England.
    Timpson, Nicolas J.
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
    Haycock, Philip C.
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
    Brown, Kevin M.
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD USA.
    Wang, Zhaoming
    St Jude Childrens Res Hosp, Memphis, TN USA.
    Ye, Yuanqing
    Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX USA.
    Hofmann, Jonathan N.
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD USA.
    Foll, Matthieu
    IARC, Lyon, France.
    Gaborieau, Valerie
    IARC, Lyon, France.
    Machiela, Mitchell J.
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD USA.
    Colli, Leandro M.
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD USA.
    Li, Peng
    IARC, Lyon, France;Max Planck Inst Demog Res, Rostock, Germany.
    Garnier, Jean-Guillaume
    Ctr Energie Atom & Energies Alternat, Inst Genom, Ctr Natl Genotypage, Evry, France; Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, Paris, France.
    Blanche, Helene
    Ctr Energie Atom & Energies Alternat, Inst Genom, Ctr Natl Genotypage, Evry, France.
    Boland, Anne
    Ctr Energie Atom & Energies Alternat, Inst Genom, Ctr Natl Genotypage, Evry, France.
    Burdette, Laurie
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD USA.
    Prokhortchouk, Egor
    Russian Acad Sci, Fed Res Ctr Fundamentals Biotechnol, Moscow, Russia.
    Skryabin, Konstantin G.
    Russian Acad Sci, Fed Res Ctr Fundamentals Biotechnol, Moscow, Russia; Kurchatov Sci Ctr, Moscow, Russia.
    Yeager, Meredith
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD USA.
    Radojevic-Skodric, Sanja
    Univ Belgrade Sch Med, Inst Pathol, Belgrade, Serbia; Clin Ctr Serbia, Clin Urol, Belgrade, Serbia.
    Ognjanovic, Simona
    Mayo Clin, Grad Sch Biomed Sci, Rochester, MN USA; IOCPR, Belgrade, Serbia.
    Foretova, Lenka
    Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
    Holcatova, Ivana
    Charles Univ Prague, Fac Med 2, Inst Publ Hlth & Prevent Med, Prague, Czech Republic.
    Janout, Vladimir
    Palacky Univ, Fac Med, Dept Prevent Med, Olomouc, Czech Republic.
    Mates, Dana
    Natl Inst Publ Hlth, Bucharest, Romania.
    Mukeriya, Anush
    Russian NN Blokhin Canc Res Ctr, Moscow, Russia.
    Rascu, Stefan
    Carol Davila Univ Med & Pharm, Th Burghele Hosp, Bucharest, Romania.
    Zaridze, David
    Russian NN Blokhin Canc Res Ctr, Moscow, Russia.
    Bencko, Vladimir
    Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic.
    Cybulski, Cezary
    Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
    Fabianova, Eleonora
    Reg Author Publ Hlth Banska Bystr, Banska Bystrica, Slovakia.
    Jinga, Viorel
    Carol Davila Univ Med & Pharm, Th Burghele Hosp, Bucharest, Romania.
    Lissowska, Jolanta
    M Sklodowska Curie Canc Ctr, Warsaw, Poland; Inst Oncol, Warsaw, Poland.
    Lubinski, Jan
    Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
    Navratilova, Marie
    Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
    Rudnai, Peter
    Natl Publ Hlth Ctr, Natl Directorate Environm Hlth, Budapest, Hungary.
    Benhamou, Simone
    INSERM, U946, Paris, France; CNRS, Inst Gustave Roussy, UMR 8200, Villejuif, France.
    Cancel-Tassin, Geraldine
    CeRePP, Paris, France; UPMC Univ Paris 06, Inst Univ Cancerol, GRC 5, Paris, France.
    Cussenot, Olivier
    CeRePP, Paris, France; UPMC Univ Paris 06, Inst Univ Cancerol, GRC 5, Paris, France; Hopitaux Univ Est Parisien Tenon, AP HP, Dept Urol, Paris, France.
    Weiderpass, Elisabete
    Canc Registry Norway, Inst Population Based Canc Res, Dept Res, Oslo, Norway; Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden; Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland; Arctic Univ Norway, Univ Tromso, Dept Community Med, Tromso, Norway.
    Ljungberg, Borje
    Umeå Univ, Dept Surg & Perioperat Sci Urol & Androl, Umeå, Sweden.
    Sitaram, Raviprakash Tumkur
    Umeå Univ, Dept Surg & Perioperat Sci Urol & Androl, Umeå, Sweden.
    Häggström, Christel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi. Umeå Univ, Dept Biobank Res, Umeå, Sweden.
    Bruinsma, Fiona
    Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
    Jordan, Susan J.
    QIMR Berghofer Med Res Inst, Herston, Qld, Australia; Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia.
    Severi, Gianluca
    Univ Paris Saclay, Univ Paris Sud, Hlth Generat Team, CESP,INSERM,Fac Med,UVSQ,Gustave Roussy, Villejuif, France; Human Genet Fdn HuGeF, Turin, Italy.
    Winship, Ingrid
    Univ Melbourne, Royal Melbourne Hosp, Dept Med, Melbourne, Vic, Australia.
    Hveem, Kristian
    Norwegian Univ Sci & Technol, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, Trondheim, Norway.
    Vatten, Lars J.
    Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth & Gen Practice, Trondheim, Norway.
    Fletcher, Tony
    Univ London, London Sch Hyg & Trop Med, London, England.
    Larsson, Susanna C.
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Wolk, Alicja
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.
    Banks, Rosamonde E.
    Univ Leeds, St Jamess Univ Hosp, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England.
    Selby, Peter J.
    Imperial Coll London, St Marys Hosp, Div Surg, Natl Inst Hlth Res Diagnost Evidence Cooperat, London, England.
    Easton, Douglas F.
    Univ Cambridge, Dept Oncol, Cambridge, England; Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
    Andreotti, Gabriella
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD USA.
    Freeman, Laura E. Beane
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
    Koutros, Stella
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
    Mannisto, Satu
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Weinstein, Stephanie
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
    Clark, Peter E.
    Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
    Edwards, Todd L.
    Vanderbilt Genet Inst, Vanderbilt Ingram Canc Ctr, Div Epidemiol, Dept Med, Nashville, TN USA.
    Lipworth, Loren
    Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
    Gapstur, Susan M.
    Amer Canc Soc, Atlanta, GA 30329 USA.
    Stevens, Victoria L.
    Amer Canc Soc, Atlanta, GA 30329 USA.
    Carol, Hallie
    Dana Farber Canc Inst, Boston, MA 02115 USA.
    Freedman, Matthew L.
    Dana Farber Canc Inst, Boston, MA 02115 USA.
    Pomerantz, Mark M.
    Dana Farber Canc Inst, Boston, MA 02115 USA.
    Cho, Eunyoung
    Brown Univ, Providence, RI 02912 USA.
    Wilson, Kathryn M.
    Harvard TH Chan Sch Publ Hlth, Boston, MA USA.
    Gaziano, J. Michael
    Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA.
    Sesso, Howard D.
    Harvard TH Chan Sch Publ Hlth, Boston, MA USA; Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
    Freedman, Neal D.
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
    Parker, Alexander S.
    Mayo Clin, Dept Hlth Sci Res, Jacksonville, FL 32224 USA.
    Eckel-Passow, Jeanette E.
    Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA.
    Huang, Wen-Yi
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
    Kahnoski, Richard J.
    Spectrum Hlth, Div Urol, Grand Rapids, MI USA.
    Lane, Brian R.
    Spectrum Hlth, Div Urol, Grand Rapids, MI USA; Michigan State Univ, Coll Human Med, Grand Rapids, MI USA.
    Noyes, Sabrina L.
    Van Andel Res Inst, Ctr Canc Genom & Quantitat Biol, Grand Rapids, MI USA; Spectrum Hlth, Grand Rapids, MI USA.
    Petillo, David
    Van Andel Res Inst, Ctr Canc Genom & Quantitat Biol, Grand Rapids, MI USA; Ferris State Univ, Diagnost Program, Grand Rapids, MI USA.
    Teh, Bin Tean
    Van Andel Res Inst, Ctr Canc Genom & Quantitat Biol, Grand Rapids, MI USA; Natl Univ Singapore, Med Sch, Program Canc & Stem Cell Biol, Duke Natl, Singapore, Singapore; ASTAR, Inst Mol & Cell Biol, Singapore, Singapore; Natl Canc Ctr Singapore, Div Med Sci, Lab Canc Epigenome, Singapore, Singapore; Natl Univ Singapore, Canc Sci Inst Singapore, Singapore, Singapore.
    Peters, Ulrike
    Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA.
    White, Emily
    Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA.
    Anderson, Garnet L.
    Fred Hutchinson Canc Res Ctr, WHI Clin Coordinating Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
    Johnson, Lisa
    Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
    Luo, Juhua
    Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN USA.
    Buring, Julie
    Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA; Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
    Lee, I-Min
    Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA; Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
    Chow, Wong-Ho
    Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA.
    Moore, Lee E.
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
    Eisen, Timothy
    Univ Cambridge, Cambridge, England.
    Henrion, Marc
    Inst Canc Res, London, England; Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Larkin, James
    Royal Marsden NHS Fdn Trust, London, England.
    Barman, Poulami
    Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA.
    Leibovich, Bradley C.
    Mayo Clin, Dept Urol, Rochester, MN USA.
    Choueiri, Toni K.
    Dana Farber Canc Inst, Boston, MA 02115 USA.
    Lathrop, G. Mark
    McGill Univ, Montreal, PQ, Canada;Genome Quebec Innovat Ctr, Montreal, PQ, Canada.
    Deleuze, Jean-Francois
    Ctr Energie Atom & Energies Alternat, Inst Genom, Ctr Natl Genotypage, Evry, France; Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, Paris, France.
    Gunter, Marc
    IARC, Lyon, France.
    McKay, James D.
    IARC, Lyon, France.
    Wu, Xifeng
    Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Div Canc Prevent & Populat Sci, Houston, TX 77030 USA.
    Houlston, Richard S.
    Inst Canc Res, London, England.
    Chanock, Stephen J.
    NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
    Relton, Caroline
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England; Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
    Richards, J. Brent
    McGill Univ, Jewish Gen Hosp, Dept Med, Montreal, PQ, Canada;McGill Univ, Jewish Gen Hosp, Dept Human Genet, Montreal, PQ, Canada;McGill Univ, Jewish Gen Hosp, Dept Epidemiol & Biostat, Montreal, PQ, Canada.
    Martin, Richard M.
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England; Univ Bristol, Sch Social & Community Med, Bristol, Avon, England; Univ Bristol, Univ Hosp Bristol NHS Fdn Trust, Natl Inst Hlth Res, Bristol Nutr Biomed Res Unit, Bristol, Avon, England.
    Smith, George Davey
    Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England; Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
    Brennan, Paul
    IARC, Lyon, France.
    The influence of obesity-related factors in the etiology of renal cell carcinoma—A mendelian randomization study2019Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 16, nr 1, artikel-id e1002724Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.

    Methods and findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.

    Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.

  • 299.
    Johansson, T
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lejonklou, Margareta Halin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ekeblad, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Stålberg, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lack of Nuclear Expression of Hairy and Enhancer of Split-1 (HES1) in Pancreatic Endocrine Tumors2008Ingår i: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 40, nr 5, s. 354-359Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Notch signaling cascade plays a vital role in the proliferation and differentiation of cells during pancreatic development. Cell line experiments have suggested the involvement of Notch signaling in pancreatic endocrine tumorigenesis. We investigated the expression of NOTCH1, HES1, HEY1 and ASCL1 in pancreatic endocrine tumors and compared the data to tumor phenotype including hormone production, heredity, and WHO classification. Real-time quantitative PCR and immunohistochemistry were performed on samples of 26 pancreatic endocrine tumors. For comparison, 10 specimens of macroscopically normal pancreas were analyzed using immunohistochemistry. The subcellular localization of proteins was determined. Neither hormone production, nor heredity, or WHO classification was found to be associated with the expression of these proteins. There were discrepancies between mRNA and protein expression levels. All tumors displayed ASCL1 immunoreactivity. HES1 immunoreactivity was lacking altogether in 46% of the tumors, and in the remaining lesions its expression was weak and confined to the cytoplasm. In the nontumorous pancreatic endocrine cells, weak nuclear expression of HES1 as well as of HEY1 and NOTCH1 was observed. There was a significant positive correlation between NOTCH1 and HES1 mRNA levels, but no indication that HES1 was inhibiting ASCL1 transcription was found. No nuclear expression of HES1 was found in the tumors. This lack of nuclear expression of HES1 may contribute to the abundance of ASCL1 and to tumorigenesis in the endocrine pancreas.

  • 300.
    Johansson, Térèse A.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Westin, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Skogseid, Britt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Identification of Achaete-scute complex-like 1 (ASCL1) target genes and evaluation of DKK1 and TPH1 expression in pancreatic endocrine tumours2009Ingår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 9, s. 321-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    ASCL1 role in pancreatic endocrine tumourigenesis has not been established. Recently it was suggested that ASCL1 negatively controls expression of the Wnt signalling antagonist DKK1. Notch signalling regulates expression of TPH1, the rate limiting enzyme in the biosynthesis of serotonin. Understanding the development and proliferation of pancreatic endocrine tumours (PETs) is essential for the development of new therapies.

    METHODS:

    ASCL1 target genes in the pancreatic endocrine tumour cell line BON1 were identified by RNA interference and microarray expression analysis. Protein expressions of selected target genes in PETs were evaluated by immunohistochemistry.

    RESULTS:

    158 annotated ASCL1 target genes were identified in BON1 cells, among them DKK1 and TPH1 that were negatively regulated by ASCL1. An inverse relation of ASCL1 to DKK1 protein expression was observed for 15 out of 22 tumours (68%). Nine tumours displayed low ASCL1/high DKK1 and six tumours high ASCL1/low DKK1 expression. Remaining PETs showed high ASCL1/high DKK1 (n = 4) or low ASCL1/low DKK1 (n = 3) expression. Nine of twelve analysed PETs (75%) showed TPH1 expression with no relation to ASCL1.

    CONCLUSION:

    A number of genes with potential importance for PET tumourigenesis have been identified. ASCL1 negatively regulated the Wnt signalling antagonist DKK1, and TPH1 expression in BON1 cells. In concordance with these findings DKK1 showed an inverse relation to ASCL1 expression in a subset of PETs, which may affect growth control by the Wnt signalling pathway.

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