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  • 251.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    The role of the primary-care physician in oncology care. Primary healthcare and specialist cancer services.2005In: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 6, no 2, p. 121-2Article in journal (Refereed)
  • 252.
    Holmberg, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Adolfsson, Jan
    Mucci, Lorelei
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Adami, Hans-Olov
    Möller, Henrik
    Johansson, Jan-Erik
    Stampfer, Meir
    Season of diagnosis and prognosis in breast and prostate cancer2009In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 20, no 5, p. 633-670Article in journal (Refereed)
    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.

  • 253.
    Holmberg, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Akre, Olof
    Screening for prostate cancer: defining critical issues2011In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, no S1, p. 2-3Article in journal (Refereed)
  • 254.
    Holmberg, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Garmo, Hans
    Palmgren, Juni
    Norlén, Bo Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Prognostic markers under watchful waiting and radical prostatectomy2006In: Hematology/Oncology Clinics of North America, ISSN 0889-8588, E-ISSN 1558-1977, Vol. 20, no 4, p. 845-855Article in journal (Refereed)
    Abstract [en]

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

  • 255.
    Holmberg, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Helgesen, Fred
    Salo, Jaakko O.
    Folmerz, Per
    Häggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Andersson, Swen-Olof
    Spångberg, Anders
    Busch, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Nordling, Steg
    Palmgren, Juni
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Norlén, Bo Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer2002In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 347, no 11, p. 781-789Article in journal (Refereed)
    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.

  • 256.
    Holmberg, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bill-Axelson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Steineck, Gunnar
    Garmo, Hans
    Palmgren, Juni
    Johansson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    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 waiting2012In: Journal of the National Cancer Institute. Monographs, ISSN 1052-6773, E-ISSN 1745-6614, Vol. 2012, no 45, p. 230-233Article in journal (Refereed)
    Abstract [en]

    In the Scandinavian Prostate Cancer Group Trial Number 4 (SPCG-4), 347 men were randomly assigned to radical prostatectomy and 348 to watchful waiting. In the most recent analysis (median follow-up time = 12.8 years), the cumulative mortality curves had been stable over the follow-up. At 15 years, the absolute risk reduction of dying from prostate cancer was 6.1% following randomization to radical prostatectomy, compared with watchful waiting. Hence, 17 need to be randomized to operation to avert one death. Data on self-reported symptoms, stress from symptoms, and quality of life were collected at 4 and 12.2 years of median follow-up. These questionnaire studies show an intricate pattern of symptoms evolving after surgery, hormonal treatments, signs of tumor progression, and also from natural aging. This article discusses some of the main findings of the SPCG-4 study.

  • 257.
    Holmberg, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    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 consequences2009In: Journal of Medical Screening, ISSN 0969-1413, E-ISSN 1475-5793, Vol. 16, no 2, p. 73-80Article in journal (Refereed)
    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.

  • 258.
    Holmberg, Lars
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    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 breast2008In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 26, no 8, p. 1247-52Article in journal (Refereed)
    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.

  • 259.
    Holmberg, Lars H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Regional Cancer Centre, Uppsala, Sweden.
    Can national cancer registration support clinical databases and clinical cancer research?2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 6, p. 691-693Article in journal (Refereed)
    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.

  • 260.
    Holmberg, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    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 survivors2008In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 100, no 7, p. 475-482Article in journal (Refereed)
    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.

  • 261.
    Holmberg, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Olausson, Petra Otterblad
    Tegnell, Anders
    Tiden är mogen för målnivåer inom cancervården: [It's time for target levels in cancer care]2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 13, p. 708-709Article in journal (Refereed)
  • 262.
    Holmberg, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    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 study2012In: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 36, no 1, p. e7-e12Article in journal (Refereed)
    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.

  • 263.
    Holmberg, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    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-up2010In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 65, no 5, p. 436-441Article in journal (Refereed)
    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.

  • 264.
    Holmberg, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Tamini, Rulla
    Reducing cancer drug doses in obese patients: dogma disputed2005In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 366, no 9491, p. 1056-7Article in journal (Refereed)
  • 265.
    Holmberg, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Vickers, Andrew
    Evaluation of Prediction Models for Decision-Making: Beyond Calibration and Discrimination2013In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 10, no 7, p. e1001491-Article in journal (Other academic)
  • 266.
    Holmberg, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Wong, Y. N. S.
    Tabar, Laszlo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    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 study2013In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 108, no 4, p. 812-819Article in journal (Refereed)
    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.

  • 267.
    Hultin, Hella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Calciumhomeostasis and Vitamin D in Obesity and Preeclampsia2011Doctoral thesis, comprehensive summary (Other academic)
    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.

    List of papers
    1. Childbearing and the risk of parathyroid adenoma - a dominant cause for primary hyperparathyroidism
    Open this publication in new window or tab >>Childbearing and the risk of parathyroid adenoma - a dominant cause for primary hyperparathyroidism
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    2001 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 250, p. 43-49Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-145193 (URN)
    Available from: 2011-02-07 Created: 2011-02-07 Last updated: 2017-12-11
    2. Association of parathyroid adenoma and pregnancy with preeclampsia
    Open this publication in new window or tab >>Association of parathyroid adenoma and pregnancy with preeclampsia
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    2009 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 94, no 9, p. 3394-3399Article in journal (Refereed) 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.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-121064 (URN)10.1210/jc.2009-0012 (DOI)000269584600035 ()19531594 (PubMedID)
    Available from: 2010-03-18 Created: 2010-03-18 Last updated: 2017-12-12Bibliographically approved
    3. Calcium homeostasis derangements in women with preeclampsia 
    Open this publication in new window or tab >>Calcium homeostasis derangements in women with preeclampsia 
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    (English)Manuscript (preprint) (Other academic)
    Keywords
    preeclampsia, calciumhomeostasis, vitamin D
    National Category
    Surgery Obstetrics, Gynecology and Reproductive Medicine
    Research subject
    Surgery; Obstetrics and Gynaecology
    Identifiers
    urn:nbn:se:uu:diva-145207 (URN)
    Available from: 2011-02-07 Created: 2011-02-07 Last updated: 2011-05-04
    4. Left-Shifted Relation between Calcium and Parathyroid Hormone in Obesity
    Open this publication in new window or tab >>Left-Shifted Relation between Calcium and Parathyroid Hormone in Obesity
    2010 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, no 8, p. 3973-3981Article in journal (Refereed) 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.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-135604 (URN)10.1210/jc.2009-2822 (DOI)000280652400057 ()20519351 (PubMedID)
    Available from: 2010-12-07 Created: 2010-12-07 Last updated: 2017-12-11Bibliographically approved
    5. Persisting disturbances in calcium homeostasis after gastric bypass surgery
    Open this publication in new window or tab >>Persisting disturbances in calcium homeostasis after gastric bypass surgery
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Keywords
    calciumhomeostasis, vitamin D, BMD, bariatric surgery
    National Category
    Surgery
    Research subject
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-145208 (URN)
    Available from: 2011-02-07 Created: 2011-02-07 Last updated: 2018-11-30
  • 268.
    Hultin, Hella
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Edfeldt, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Left-Shifted Relation between Calcium and Parathyroid Hormone in Obesity2010In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 95, no 8, p. 3973-3981Article in journal (Refereed)
    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.

  • 269.
    Hultin, Hella
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lundgren, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ekbom, Anders
    Rastad, Jonas
    Montgomery, Scott M.
    Association of parathyroid adenoma and pregnancy with preeclampsia2009In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 94, no 9, p. 3394-3399Article in journal (Refereed)
    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.

  • 270.
    Hultin, Hella
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lillhager, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Calcium homeostasis derangements in women with preeclampsia Manuscript (preprint) (Other academic)
  • 271.
    Hultin, Hella
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ribom, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Persisting disturbances in calcium homeostasis after gastric bypass surgeryManuscript (preprint) (Other academic)
  • 272.
    Hultin, Hella
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stevens, Katharina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Cholecalciferol Injections Are Effective in Hypovitaminosis D After Duodenal Switch: a Randomized Controlled Study2018In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 28, no 10, p. 3007-3011Article in journal (Refereed)
    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.

  • 273.
    Häggström, Christel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. 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 study2019In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 8, no 5, p. 2196-2204Article in journal (Refereed)
    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.

  • 274.
    Häggström, Christel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. 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)2017In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 9, article id e016606Article in journal (Refereed)
    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.

  • 275.
    Häggström, Christel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. 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 University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Kings Coll London, Sch Canc & Pharmaceut Sci, TOUR, London, England.
    Robinson, David
    Ryhov Hosp, Dept Urol, Jonkoping, Sweden.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. 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 mellitus2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 8, p. 1868-1875Article in journal (Refereed)
    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.

  • 276.
    Häggström, Christel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Kings Coll London, Div Canc Studies, Fac Life Sci & Med, London, England.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
    Prospective study of Type 2 diabetes mellitus, anti-diabetic drugs and risk of prostate cancer2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 140, no 3, p. 611-617Article in journal (Refereed)
    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.

  • 277. Härmark, Linda
    et al.
    van Hunsel, Florence
    Grundmark, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    ADR Reporting by the General Public: Lessons Learnt from the Dutch and Swedish Systems2015In: Drug Safety, ISSN 0114-5916, E-ISSN 1179-1942, Vol. 38, no 4, p. 337-347Article, review/survey (Refereed)
    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.

  • 278.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sandin, Fredrik
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Cancer incidence in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population.2015In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 51, no 4, p. 558-568Article in journal (Refereed)
    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.

  • 279.
    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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. 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 University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Hengstler, Jan G.
    Dortmund Univ, Leibniz Res Ctr Working Environm & Human Factors, Dortmund, Germany..
    Micke, Patrick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Integrative analysis of genome-wide gene copy number changes and gene expression in non-small cell lung cancer2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 11, article id e0187246Article in journal (Refereed)
    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.

  • 280.
    Jack, Ruth H
    et al.
    King’s College London, Thames Cancer Registry, London.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. King’s College London, Division of Cancer Studies, Research Oncology, Guy’s Hospital, London .
    Waiting times for radiotherapy after breast cancer2010In: BMJ. British Medical Journal (International Ed.), ISSN 0959-8146, E-ISSN 0959-535X, Vol. 340, p. c1007-Article in journal (Refereed)
  • 281.
    Jangland, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Becker, Deborah
    Börjeson, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Doherty, Caroline
    Gimm, Oliver
    Griffith, Patricia
    Johansson, AnnaKarin
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    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 experience2014In: Journal of Nursing Education and Practice, ISSN 1925-4040, E-ISSN 1925-4059, Vol. 4, no 2, p. 38-48Article in journal (Refereed)
    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.

  • 282.
    Jangland, Eva
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Education in Nursing.
    Carlsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Lundgren, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Gunningberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    The impact of an intervention to improve patient participation in a surgical care unit: a quasi-experimental study2012In: International Journal of Nursing Studies, ISSN 0020-7489, E-ISSN 1873-491X, Vol. 49, no 5, p. 528-538Article in journal (Refereed)
    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.

  • 283.
    Janson, Eva Tiensuu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Sorbye, Halfdan
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Federspiel, Birgitte
    Grønbæk, Henning
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ladekarl, Morten
    Langer, Seppo W
    Mortensen, Jann
    Schalin-Jäntti, Camilla
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sundlöv, Anna
    Thiis-Evensen, Espen
    Knigge, Ulrich
    Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 10, p. 1284-1297Article, review/survey (Refereed)
    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.

  • 284.
    Janson, Eva Tiensuu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Sørbye, Halfdan
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Federspiel, Birgitte
    Grønbaek, Henning
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Mathisen, Oystein
    Mortensen, Jann
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Thiis-Evensen, Espen
    Välimäki, Matti J
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Knigge, Ulrich
    Nordic Guidelines 2010 for diagnosis and treatment of gastroenteropancreatic neuroendocrine tumours2010In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 49, no 6, p. 740-756Article in journal (Refereed)
    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.

  • 285.
    Jarbo, Caroline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Buckley, Patrick G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Piotrowski, Arkadiusz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Mantripragada, Kiran K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Benetkiewicz, Magdalena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Diaz de Ståhl, Teresita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Langford, Cordelia F
    Gregory, Simon G
    Dralle, Henning
    Gimm, Oliver
    Bäckdahl, Martin
    Geli, Janos
    Larsson, Catharina
    Westin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Dumanski, Jan P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Detailed assessment of chromosome 22 aberrations in sporadic pheochromocytoma using array-CGH.2006In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 118, no 5, p. 1159-64Article in journal (Refereed)
    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

  • 286.
    Jiao, Xiang
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Hooper, Sean D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Djureinovic, Tatjana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Larsson, Chatarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, De