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  • 201.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. 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.
    Larsson, Tobias E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    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 Public Health and Caring Sciences, Geriatrics.
    Plasma parathyroid hormone and the risk of cardiovascular mortality in the community2009In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 119, no 21, p. 2765-2771Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Diseases with elevated levels of parathyroid hormone (PTH) such as primary and secondary hyperparathyroidism are associated with increased incidence of cardiovascular disease and death. However, data on the prospective association between circulating PTH levels and cardiovascular mortality in the community are lacking. METHODS AND RESULTS: The Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (mean age, 71 years; n=958), was used to investigate the association between plasma PTH and cardiovascular mortality. During follow-up (median, 9.7 years), 117 participants died of cardiovascular causes. In Cox proportional-hazards models adjusted for established cardiovascular risk factors (age, systolic blood pressure, diabetes, smoking, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease), higher plasma PTH was associated with higher risk for cardiovascular mortality (hazard ratio for 1-SD increase in PTH, 1.38; 95% confidence interval, 1.18 to 1.60; P<0.001). This association remained essentially unaltered in participants without previous cardiovascular disease and in participants with normal PTH (<6.8 pmol/L) with no other signs of a disturbed mineral metabolism (normal serum calcium, 2.2 to 2.6 mmol/L; normal glomerular filtration rate, >50 mL . min(-1) . 1.73 m(-2) and without vitamin D deficiency, plasma 25-OH vitamin D >37.5 nmol/L). Interestingly, elevated plasma PTH (>5.27 pmol/L) accounted for 20% (95% confidence interval, 10 to 26) of the population-attributable risk proportion for cardiovascular mortality. CONCLUSIONS: Plasma PTH levels predict cardiovascular mortality in the community, even in individuals with PTH within the normal range. Further studies are warranted to evaluate the clinical implications of measuring PTH in cardiovascular risk prediction and to elucidate whether PTH is a modifiable risk factor.

  • 202.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. 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.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Serum calcium is independently associated with insulin sensitivity measured with euglycaemic-hyperinsulinaemic clamp in a community-based cohort2007In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 50, no 2, p. 317-324Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: Diabetes mellitus type 2 is associated with altered calcium metabolism. Moreover, in diseases with supranormal serum calcium levels, such as primary hyperparathyroidism, the prevalence of diabetes is increased. Relatively little is known about the relationship between serum calcium concentration and the underlying causes of diabetes-insulin resistance and defective insulin secretion-in the normocalcaemic general population. MATERIALS AND METHODS: We investigated associations between serum calcium concentration and insulin sensitivity and secretion in a population-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men, n = 961). Insulin sensitivity index (M/I; glucose disposal rate [M] divided by mean insulin concentration [I]) was assessed using euglycaemic-hyperinsulinaemic clamp, and insulin secretion was estimated from the early insulin response (EIR) during an OGTT. RESULTS: In a multivariable linear regression model adjusting for BMI, physical activity, smoking, consumption of tea, alcohol, coffee and dietary calcium, serum phosphate and serum creatinine, 1 SD increase in serum calcium was associated with 0.17 mg kg(-1) min(-1) (mU/l)(-1) x 100 (0.024 mg kg(-1) min(-1) [pmol/l](-1) x 100) decrease in M/I (p = 0.01). The results remained robust in individuals with normal fasting glucose, normal glucose tolerance and serum calcium within the normal range (n = 413, regression coefficient for 1 SD increase -0.45, p = 0.001). Serum calcium was not associated with EIR. Dietary intake of calcium was not independently associated with insulin sensitivity or EIR. CONCLUSION/INTERPRETATION: Our data support the notion that endogenous calcium may be involved early in the development of diabetes and that this effect is mediated mainly through effects on insulin sensitivity rather than defective insulin secretion. Dietary intake of calcium does not seem to influence insulin sensitivity.

  • 203.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Larsson, Tobias E.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Plasma parathyroid hormone and risk of congestive heart failure in the community2010In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 12, no 11, p. 1186-1192Article in journal (Refereed)
    Abstract [en]

    In experimental studies parathyroid hormone (PTH) has been associated with underlying causes of heart failure (HF) such as atherosclerosis, left ventricular hypertrophy, and myocardial fibrosis. Individuals with increased levels of PTH, such as primary or secondary hyperparathyroidism patients, have increased risk of ischaemic heart disease and HF. Moreover, increasing PTH is associated with worse prognosis in patients with overt HF. However, the association between PTH and the development HF in the community has not been reported. In a prospective, community-based study of 864 elderly men without HF or valvular disease at baseline (mean age 71 years, the ULSAM study) the association between plasma (P)-PTH and HF hospitalization was investigated adjusted for established HF risk factors (myocardial infarction, hypertension, diabetes, electrocardiographic left ventricular hypertrophy, smoking, and hypercholesterolaemia) and variables reflecting mineral metabolism (S-calcium, S-phosphate, P-vitamin D, S-albumin, dietary calcium and vitamin D intake, physical activity, glomerular filtration rate, and blood draw season). During follow-up (median 8 years), 75 individuals were hospitalized due to HF. In multivariable Cox-regression analyses, higher P-PTH was associated with increased HF hospitalization (hazard ratio for 1-SD increase of PTH, 1.41, 95% CI 1.12-1.77, P = 0.003). Parathyroid hormone also predicted hospitalization in participants without apparent ischaemic HF and in participants with normal P-PTH. In a large community-based sample of elderly men, PTH predicted HF hospitalizations, also after accounting for established risk factors and mineral metabolism variables. Our data suggest a role for PTH in the development of HF even in the absence of overt hyperparathyroidism.

  • 204.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lundgren, Ewa
    Lithell, Hans
    Berglund, Lars
    Ljunghall, Sverker
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Rastad, Jonas
    Normalized dyslipidaemia after parathyroidectomy in mild primary hyperparathyroidism: population-based study over five years2002In: Clinical Endocrinology (Oxf), ISSN 0300-0664, Vol. 56, no 2, p. 253-260Article in journal (Refereed)
  • 205.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. 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.
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Rastad, Jonas
    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.
    Positive effect of parathyroidectomy on bone mineral density in mild asymptomatic primary hyperparathyroidism2006In: Journal of Internal Medicine, ISSN 0954-6820, Vol. 259, no 2, p. 191-198Article in journal (Refereed)
  • 206.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. 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.
    Rastad, Jonas
    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.
    Metabolic abnormalities in patients with normocalcemic hyperparathyroidism detected at a population-based screening2006In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 155, no 1, p. 33-39Article in journal (Refereed)
    Abstract [en]

    Objective: Dyslipidemia, hypertension, diabetes mellitus and also primary hyperparathyroidism (pHPT)are associated with an increased risk of cardiovascular diseases. Metabolic abnormalities in mild pHPThave been reported, but never in cases with normal calcium and high parathyroid hormone (PTH)levels, i.e. suffering from ‘normocalcemic pHPT’. Our aim was to explore the occurrence of thesemetabolic abnormalities in individuals with normocalcemic pHPT identified in a population-basedscreening, and the effects of parathyroidectomy vs conservative treatment on metabolic variables.Design and methods: A population-based screening of 5202 post-menopausal women identified 30patients with normal calcium, inappropriately high PTH and normal creatinine. A 5-year follow-upincluded 15 parathyroidectomized (PTx) and nine conservatively followed cases, in a non-randomizedsetting, together with age-matched controls. Biochemical variables and body mass index (BMI) wereinvestigated.Results: At study entry, cases had higher calcium, PTH, glucose, low-density lipoprotein (LDL)/highdensitylipoprotein (HDL)-cholesterol, very low-density lipoprotein (VLDL)-cholesterol, total triglycerides,and BMI compared to controls (PZ!0.0001–0.035). The cases had a lower HDL-cholesterolvalue (PZ0.013) and one third of the cases had hypertriglyceridemia. During follow-up, the PTx casesdecreased in calcium, PTH, LDL/HDL-cholesterol, total and LDL-cholesterol (PZ0.0076–0.022).Investigated biochemical variables remained adverse in conservatively followed cases during follow-upexcept a decreased LDL-cholesterol value. All surgically treated patients had parathyroid adenoma.Conclusions: Cases with normocalcemic pHPT have increased proatherogenic lipoprotein levels, BMIand glucose levels compared to age-matched controls. Parathyroidectomy has positive effects on someof these variables and reverses them to the same level as the controls, while conservative treatmentfails to normalize the investigated metabolic variables.

  • 207.
    Hagström, Emil
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Norlund, Fredrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare. Uppsala Univ, Dept Publ Hlth, Uppsala, Sweden.;Uppsala Univ, Caring Sci, Clin Psychol Healthcare, Uppsala, Sweden..
    Harrington, R. A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Lopez-Sendon, J.
    Hosp Univ La Paz, Dept Cardiol, IdiPaz, Madrid, Spain..
    Soffer, J.
    GlaxoSmithKline, Metabol Pathways & Cardiovasc Therapeut Area, King Of Prussia, PA USA..
    Stebbins, A.
    Duke Univ, Duke Clin Res Inst, Durham, NC 27706 USA..
    Stewart, R. A. H.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland 1, New Zealand..
    Wallentin, Lars
    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.
    White, H. D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland 1, New Zealand..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Living alone and depressive symptoms are associated with major cardiovascular events in patients with chronic coronary heart disease2015Conference paper (Refereed)
  • 208. Hajiebrahimi, M.
    et al.
    Bahmanyar, S.
    Lambe, M.
    Adolfsson, J.
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Cnattingius, S.
    Placental weight and mortality in premenopausal breast cancer by tumour characteristics2012In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 21, no S1, p. S14-S14Article in journal (Other academic)
  • 209. Harries, M
    et al.
    Taylor, A
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Agbaje, O
    Garmo, Hans
    Kabilan, S
    Purushotham, A
    Incidence of bone metastases and survival after a diagnosis of bone metastases in breast cancer patients2014In: Cancer Epidemiology, ISSN 1877-7821, Vol. 38, no 4, p. 427-434Article in journal (Refereed)
    Abstract [en]

    Background: Bone is the most common metastatic site associated with breast cancer. Using a database of women with breast cancer treated at Guy's Hospital, London 1976–2006 and followed until end 2010, we determined incidence of and survival after bone metastases. Methods: We calculated cumulative incidence of bone metastases considering death without prior bone metastases as a competing risk. Risk of bone metastases was modelled through Cox-regression. Survival after bone metastases diagnosis was calculated using Kaplan–Meier methodology. Results: Of the 7064 women, 589 (22%) developed bone metastases during 8.4 years (mean). Incidence of bone metastases was significantly higher in younger women, tumour size >5 cm, higher tumour grade, lobular carcinoma and ≥four positive nodes, but was not affected by hormone receptor status. Median survival after bone metastases diagnosis was 2.3 years in women with bone-only metastases compared with <1 year in women with visceral and bone metastases. There was a trend for decreased survival for patients who developed visceral metastases early, and proportionately fewer patients in this group. Interpretation: Incidence of bone metastases has decreased but bone metastases remain a highly relevant clinical problem due to the large number of patients being diagnosed with breast cancer.

  • 210. Harris, H R
    et al.
    Bergkvist, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wolk, A
    Coffee and black tea consumption and breast cancer mortality in a cohort of Swedish women2012In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 107, no 5, p. 874-878Article in journal (Refereed)
    Abstract [en]

    Background:

    Coffee and black tea contain a mixture of compounds that have the potential to influence breast cancer risk and survival. However, epidemiologic data on the relation between coffee and black tea consumption and breast cancer survival are sparse.

    Methods:

    We investigated the association between coffee and black tea consumption and survival among 3243 women with invasive breast cancer in the Swedish Mammography Cohort. Intake was estimated using a food frequency questionnaire. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs).

    Results:

    From 1987 to 2010 there were 394 breast cancer-specific deaths and 973 total deaths. Coffee and black tea were not associated with breast cancer-specific or overall mortality. Women consuming 4+ cups of coffee per day had a covariate and clinical characteristics-adjusted HR (95% CI) of death from breast cancer of 1.14 (0.71-1.83; ptrend=0.81) compared with those consuming <1 cup per day. Women consuming 2+ cups of black tea per day had a covariate and clinical characteristics-adjusted HR (95% CI) of death from breast cancer of 1.02 (0.67-1.55; ptrend=0.94) compared with non-tea drinkers. Caffeine was also not associated with breast cancer-specific (HR for top to bottom quartile=1.06; 95% CI=0.79-1.44; ptrend=0.71) or overall mortality.

    Conclusion:

    Our findings suggest that coffee, black tea, and caffeine consumption before breast cancer diagnosis do not influence breast cancer-specific and overall survival.

  • 211.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Culture of parathyroid cells2005In: Human Cell Culture: Second edition / [ed] Joanna Picot, Humana Press, 2005, p. 291-301Chapter in book (Refereed)
  • 212.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Endokrina tumörer - ett folkhälsoproblem?2009In: Svensk kirurgi, ISSN 0346-847X, Vol. 67, no 2, p. 69-71Article in journal (Other academic)
    Abstract [sv]

    Kan endokrina tumörer vara en av de större bakomliggande orsakerna till hjärtkärlsjukdom i Sverige och skall endokrinkirugin drastiskt öka för att motverka detta? En fråga som Per Hellman, professor i kirurgi vid Akademiska sjukhuset i Uppsala och tillika kirurgföreningens vetenskaplige sekreterare, väcker.

  • 213.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Primary aldosteronism: Molecular Genetics, Endocrinology, and Translational Medicine2014Book (Refereed)
    Abstract [sv]

    Primary Aldosteronism (PA) is a disease caused by the overproduction of aldosterone hormone from the adrenal glands. PA causes hypertension and the majority with this disease are undiagnosed for PA. There are new insights into this matter by using biochemistry as well as advanced radiology. In 2011, a breakthrough in the genetic derangements came, identifying a mutated potassium channel gene – KCNJ5 – in about 40% of PA with adenoma. Chapters in this book include a history of the disorder, epidemiology, genetics derangements, the KCNJ5 mutations and phenotype and more.

  • 214.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bergström, M
    Sundín, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Westerberg, G
    Juhlin, C
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Rastad, J
    Positron emission tomography with 11C-methionine in hyperparathyroidism1994In: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 116, no 6, p. 974-981Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Positron emission tomography (PET) has not been evaluated for preoperative localization and functional characterization of the parathyroid tissue in hyperparathyroidism.

    METHODS:

    Images of the neck and upper mediastinum of 23 patients with hyperparathyroidism were obtained by PET after intravenous administration of 400 to 800 MBq L-[methyl-11C]-methionine. The investigation was repeated in six patients after Na2-ethylenediamine tetraacetic acid infusion, whereby stable 65% to 157% rise in intact serum parathyroid hormone values was attained.

    RESULTS:

    Parathyroid surgical procedure revealed single (21 patients) or two enlarged parathyroid glands (two patients) that were characterized as chief cell adenoma (n = 13), hyperplasia (n = 10), or carcinoma (n = 2) and weighed 80 to 6000 mg. Twenty (80%) of these glands were localized by PET. The remaining examinations (20%) were false negative and mainly encompassed small parathyroids in juxtathyroid position. Among 15 patients undergoing parathyroid reoperation true-positive localizations were obtained for 87% of the glands. The images displayed lower tracer uptake in residual thyroid lobes (n = 40), esophagus, and cervical vertebrae. Na2-ethylenediamine tetraacetic acid infusion failed to enhance parathyroid uptake values. Ultrasonography, computed tomography, technetium-thallium scintigraphy, and venous sampling revealed 25% to 53% of the pathologic parathyroid tissues of the patients undergoing reoperation and was largely complementary to PET.

    CONCLUSIONS:

    The results suggest that PET may provide novel possibilities for the imaging of pathologic parathyroid glands in hyperparathyroidism.

  • 215.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Andersson, Linda
    Eriksson, Håkan
    Ligand surface density is important for efficient capture of immunoglobulin and phosphatidylcholine coated particles by human peripheral dendritic cells2009In: Cellular Immunology, ISSN 0008-8749, E-ISSN 1090-2163, Vol. 258, no 2, p. 123-30Article in journal (Refereed)
    Abstract [en]

    A unique property of dealuminated zeolite particles is the exceptional ability to bind both hydrophilic and hydrophobic biomolecules without any covalent linkages. By adsorbing phospholipids onto the particle surface, capture of particles by human peripheral myeloid dendritic cells (mDCs) was observed. Capture of zeolite particles was only seen when a low density of phosphatidylcholine was present on the particles, indicating a specific recognition of the structural features realised by phosphatidylcholine after adsorption on the particle. Adsorbing IgG on the particles revealed capture by mDCs that was dependent upon the density of the IgG molecules. To obtain a smaller particle exposing a high density of IgG molecules, immune complexes (ICs) were formed and both mDCs and pDCs (peripheral plasmacytoid DCs) captured immune complexes, although the mDCs showed a more efficient capture of ICs. As expected, mDCs captured and internalized ICs, whereas pDCs captured ICs but showed no internalization of ICs.

  • 216.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Andersson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Karacagil, Sadettin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Surgical strategy for large or malignant endocrine pancreatic tumors2000In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 24, no 11, p. 1353-1360Article in journal (Refereed)
    Abstract [en]

    Endocrine pancreatic tumors (EPTs) are rare but have a remarkably better prognosis than adenocarcinoma of the pancreas. Patients with EPTs benefit from surgical and medical therapy, which may alleviate symptoms due to hormonal excess and increase survival. Patients with large or malignant EPTs with infiltrative disease may suffer from local complications, including gastrointestinal bleeding and obstruction and involvement of the superior mesenteric (SMV) and portal (PV) veins. Among 31 patients with operable and large or malignant EPTs, 7 had hormone-producing syndromes (insulin, glucagon), and 24 had clinically nonfunctioning EPTs. Surgery in these patients included vascular reconstruction of the SMV/PV (n = 4), resection of infiltrated adjacent organs (n = 5; stomach, transverse colon), or resection of concomitant liver metastases (n = 3). Four patients with conspicuously large insulinomas, and three with glucagonoma were successfully operated on with alleviation of hormonal symptoms. Among the 24 nonfunctioning EPTs, 5 patients had been explored earlier and their tumors judged inoperable due to locally invasive disease or misdiagnosis as pancreatic adenocarcinoma. The operations were performed with no mortality and low morbidity. We conclude that large and malignant EPTs with limited spread of disease may benefit from a combination of medical and surgical therapy.

  • 217.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Arvidsson, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Hand-port assisted laparoscopic splenectomy in massive splenomegaly2000In: Surg Endosc, Vol. 14, p. 1177-Article in journal (Refereed)
  • 218.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Carling, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Rask, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Pathophysiology of primary hyperparathyroidism2000In: Histol Histopathol, Vol. 15, p. 619-Article in journal (Refereed)
  • 219.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Goretzki, P
    Simon, D
    Dotzenrath, C
    Roher, HD
    Therapeutic expereince of 65 cases with organic hyperinsulinism2000In: Langenbeck's Arch SurgArticle in journal (Refereed)
  • 220.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Goretzki, P
    Witte, J
    Röher, HD
    Follicular thyroid carcinoma2000In: Surgical Endocrinology, Lippincott W & W , 2000, p. 75-Chapter in book (Other academic)
  • 221.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Goretzki, Peter
    Simon, D
    Dotzenrath, Cornelia
    Röher, HD
    Therapeutic experience of 65 cases with organic hyperinsulinism.2000In: Langenbeck's Arch Surg, Vol. 385, p. 329-Article in journal (Refereed)
  • 222.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Low-renin hypertension2014In: Primary aldosteronism: Molocular Genetics, Endocrinology and Translational Medicine / [ed] Hellman, Per, New York: Springer , 2014, p. 39-44Chapter in book (Refereed)
  • 223.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hessman, Ola
    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.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hennings, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Eriksson, Lars-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Stenting of the superior mesenteric vein in midgut carcinoid disease with large mesenteric masses2010In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 34, no 6, p. 1373-1379Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Midgut carcinoid (MGC) tumors generally develop in the small intestine and in >50% of cases also present with lymph node metastases in the mesentery. The majority of these tumors are surgically resectable, but a fraction are inoperable and may cause obstruction of the superior mesenteric vein (SMV), often associated with stasis of the intestinal wall and severe symptoms. These symptoms include severe abdominal pain, attacks of diarrhea, and malnutrition. METHODS: Seven patients with severe MGC including a large fibrotic inoperable mesenteric mass and severe symptoms were studied. After an obstructed SMV and signs of venous stasis in the small intestine were demonstrated, an expandable stent was inserted after puncturing an intrahepatic portal venous branch. The associated venography, patient symptoms, and radiological signs on computed tomography (CT) scans were evaluated. RESULTS: Four patients demonstrated resolution of their symptoms. In one patient who had intra-abdominal lymph leakage/chyloperitoneum, a complete normalization of the circulation followed and the intra-abdominal lymph leakage stalled. The venographies demonstrated normalization of the venous blood flow through the SMV, and CT scans demonstrated reduction in the thickness of the intestinal wall. In two cases there were no changes in the symptoms, and in one case a slight worsening of the symptoms ensued. In general, reductions of symptoms were associated with the degree of normalization of venous blood flow. CONCLUSIONS: We conclude that in selected patients with MGC stenting of the SMV may improve symptoms.

  • 224.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ladjevardi, Sam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Elvin, A
    Radiofrequency tissue ablation using colled tip for liver metastases of endocrine tumors2002In: World J Surg, Vol. 26, p. 1052-Article in journal (Refereed)
  • 225.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lundström, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Öhrvall, Ulf
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Tiensuu Janson, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Effect of surgery on the outcome of midgut carcinoid disease with lymph node and liver metastases2002In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 26, no 8, p. 991-997Article in journal (Refereed)
    Abstract [en]

    We have evaluated survival and tumor-related symptoms in the presence of mesenteric lymph node and liver metastases in relation to surgical procedures in 314 patients (148 women, mean age at diagnosis 61 years; 249 with liver metastases) treated for midgut carcinoid tumors. Of the operated patients, 46% presented with severe abdominal pain and intestinal obstruction and were operated on before the diagnosis. Medical treatment (somatostatin analogs, interferon-a) was initiated in 67% and 86%, respectively. Surgical attempts included small intestine or ileocecal/right-sided colon resection with excision of mesenteric lymph node metastases. Most of the patients (n = 286) had mesenteric lymph node metastases; 33% of them had unresectable mesenteric lymph node metastases and underwent surgery without mesenteric dissection. Patients who underwent resection for the primary tumor had a longer survival than those with no resection (median survival 7.4 vs. 4.0 years; p <0.01). Patients who underwent successful excision of mesenteric metastases had a significantly longer survival than those with remaining lymph node metastases. Patients operated on for a primary tumor but with remaining lymph nodes but no liver metastases and who subsequently received interferon and somatostatin analog treatment had a median survival of 7.4 years. Resection of the primary tumor and the mesenteric lymph node metastases led to a significant reduction in tumor-related symptoms. Surgery to remove the primary intestinal tumor including mesenteric lymph node metastases is supported by the present results, even in the presence of liver metastases. Liver metastases and significant preoperative weight loss are identified as major negative prognostic factors for survival.

  • 226.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Juhlin, Claes
    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.
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Postoperative recurrence and hypoparathyroidism in hyperparathyroidism of multiple endocrine neoplasia type 11998In: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 124, no 6, p. 993-999Article in journal (Refereed)
    Abstract [en]

    Background.

    Operation and reoperation for hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN 1) is controversial regarding surgical strategy, preoperative localization, and biochemical indexes of recurrence.

    Methods.

    Fifty patients with MEN 1 with hyperparathyroidism were followed up 2 to 27 years after subtotal (SPX; n = 35) or total parathyroidectomy with forearm autografiing (TPX; n = 15), including 24 who underwent 28 reoperations because of persistent or recurrent hyperparathyroidism.

    Results.

    Persistent or recurrent hyperparathyroidism was seen in 66% and 20% of patients after SPX involving extirpation of at least 3 glands and TPX, respectively, and 100% after single-gland excision as a primary procedure. After reoperation, hypercalcemia was reversed in 33% of patients by SPX and 61% by intended TPX procedures. All patients received vitamin D substitution after TPX, but restricted thyroid function allowed withdrawal in all but 10 patients (36%). Intact serum parathyroid hormone levels in nongrafted and grafted arms rose with time, but only exceptional ratios localized graft recurrence. Localization of recurrent hyperparathyroidism was achieved with 11 C-labeled methionine positron emission tomography.

    Conclusion.

    MEN 1 hyperparathyroidism has a high risk of recurrence, and operation may include primarily SPX of at least 3 glands or TPX, although the latter includes a higher risk of long-term hypoparathyroidism. Reoperation should involve TPX with recognition of the enhanced recurrence rate in individuals with postoperative hyperparathyroidism.

  • 227.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Juhlin, Claes
    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.
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Primary and reoperative parathyroid operations in hyperparathyroidism of multiple endocrine neoplasia type 11998In: Surgery, ISSN 0039-6060, E-ISSN 1532-7361, Vol. 124, no 6, p. 993-999Article in journal (Refereed)
    Abstract [en]

    Background.

    Operation and reoperation for hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN 1) is controversial regarding surgical strategy, preoperative localization, and biochemical indexes of recurrence.

    Methods.

    Fifty patients with MEN 1 with hyperparathyroidism were followed up 2 to 27 years after subtotal (SPX; n = 35) or total parathyroidectomy with forearm autografiing (TPX; n = 15), including 24 who underwent 28 reoperations because of persistent or recurrent hyperparathyroidism.

    Results.

    Persistent or recurrent hyperparathyroidism was seen in 66% and 20% of patients after SPX involving extirpation of at least 3 glands and TPX, respectively, and 100% after single-gland excision as a primary procedure. After reoperation, hypercalcemia was reversed in 33% of patients by SPX and 61% by intended TPX procedures. All patients received vitamin D substitution after TPX, but restricted thyroid function allowed withdrawal in all but 10 patients (36%). Intact serum parathyroid hormone levels in nongrafted and grafted arms rose with time, but only exceptional ratios localized graft recurrence. Localization of recurrent hyperparathyroidism was achieved with 11 C-labeled methionine positron emission tomography.

    Conclusion.

    MEN 1 hyperparathyroidism has a high risk of recurrence, and operation may include primarily SPX of at least 3 glands or TPX, although the latter includes a higher risk of long-term hypoparathyroidism. Reoperation should involve TPX with recognition of the enhanced recurrence rate in individuals with postoperative hyperparathyroidism.

  • 228.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Gastrointestinal Neuroendocrine Tumor (NET) Surgery2014In: Tips and tricks in Endocrine Surgery / [ed] Watkinson JC and Scott-Coombs DM, London: Springer London, 2014, p. 91-103Chapter in book (Refereed)
    Abstract [en]

    GI NETs arise from stomach, duodenum, small intestine, appendix, large bowel, and appendix.

  • 229.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Neuroendokrina tumörer i gastrointestinalkanalen2013In: Mag-tarmkanalens cancersjukdomar / [ed] Hafström LO, Naredi P, Glimelius B, Lund: Studentlitteratur AB, 2013, p. 341-354Chapter in book (Refereed)
  • 230.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Wallin, Göran
    Endokrina sjukdomar2016In: Kirurgi / [ed] Bengt Jeppsson, Olle Ljungqvist, Peter Naredi, Malin Sund, Lund: Studentlitteratur AB, 2016, 4, p. 521-564Chapter in book (Refereed)
  • 231.
    Hellman, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Åkerström, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Björklund, Peyman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Molecular derangements in primary aldosteronism2014In: Primary Aldosteronism: Molecular Genetics, Endocrinology, and Translational Medicine, New York: Springer, 2014, p. 45-52Chapter in book (Refereed)
  • 232.
    Hellström, Vivan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Enström, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Dermatology and Venereology.
    von Zur-Mühlen, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Nyberg, Filippa
    Karolinska Institutet.
    Bäckman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Opelz, Gerhard
    Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
    Döhler, Bernd
    department of Transplant Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Regional Cancer Centre Uppsala Örebro, Uppsala University, Uppsala.
    Tufveson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lorant, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Malignancies in transplanted patients: Multidisciplinary evaluation and switch to mTOR inhibitors after kidney transplantation - experiences from a prospective, clinical, observational study2016In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 55, no 6, p. 774-781Article in journal (Refereed)
    Abstract [en]

    Background Solid organ transplant recipients are at increased risk of developing malignancies. The objective of this prospective, observational, one-armed study was to study the feasibility to add a mammalian target of rapamycin (mTOR) inhibitor to the immunosuppressive regimen in transplanted patients with post-transplant malignancies. During the trial the need to improve identification of post-transplant malignancies and to reassure adequate oncological treatment of these patients became evident. Multidisciplinary team (MDT) evaluation of oncological and immunosuppressive treatments was implemented for all patients with malignancies after renal or combined renal and pancreas transplantation because of the trial.Material and methods At Uppsala University Hospital, Sweden, a MDT consisting of transplant surgeons, nephrologists, oncologists and dermatologists evaluated 120 renal or combined renal and pancreas-transplanted recipients diagnosed with malignancies from September 2006 to July 2012. To identify all malignancies, the population was linked to the Regional Tumor Registry (RTR). We recorded to which extent a switch to mTOR inhibitors was possible and how often the originally planned oncological managements were adjusted. All patients were followed for three years. (ClinicalTrials.gov: NCT02241564).Results In 76 of 120 patients (63%) a switch to mTOR inhibitors was possible. Immunosuppression was interrupted in seven patients (6%), reduced in three patients (2%) and remained unchanged in 34 of 120 patients (28%). Identification of post-transplant malignancies increased significantly after linkage to RTR (p=0.015). The initially recommended oncological treatment was adjusted in 23 of 44 patients (52%) with solid or hematological malignancies; 36 of these patients (82%) were treated according to national guidelines.Conclusion In two thirds of the patients the immunosuppressive treatment could be changed to an mTOR inhibitor with anti-tumor effects in transplanted patients with post-transplant malignancies. The use of regional tumor registers considerably improved the identification of patients with post-transplant malignancies indicating that post-transplant malignancies might be timely underreported in transplant registers.

  • 233.
    Hennings, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Andreasson, S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Botling, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Hägg, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Long-term effects of surgical correction of adrenal hyperplasia and adenoma causing primary aldosteronism2010In: Langenbeck's archives of surgery (Print), ISSN 1435-2443, E-ISSN 1435-2451, Vol. 395, no 2, p. 133-137Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purpose of this is to study long-time results of surgery for primary aldosteronism. MATERIALS AND METHODS: Thirty patients operated on for primary aldosteronism were followed for an average of 7 years. All but five required potassium substitution. Systolic as well as diastolic hypertension (mean 157/93 mmHg) was present necessitating one to five antihypertensive drugs daily (mean 2.33). Preoperative indications for surgery included presumed adenoma (aldosterone-producing adenoma (APA)) or in one case unilateral dominance of hyperplasia. RESULTS: Histopathology was classified into adenoma (n = 9), dominant nodule (n = 16), and general hyperplasia without dominating nodules (n = 5), demonstrating a higher frequency of hyperplasia than anticipated. Long-term results revealed well-controlled blood pressure (BP; mean 134/80 mmHg). Antihypertensive medication was reduced (average of 1.78 per day), but only 36% of the patients were taken off these drugs completely. S-Aldosterone was normalized. All but one (a recurrence) were normokalemic without potassium substitution at follow-up. The APA group needed less medication (median 0.5 vs. 1.5 and 2 per day) and more patients in this group were totally medication free (50%). Two recurrences occurred in the group with general hyperplasia without dominating nodules. CONCLUSION: Nodular hyperplasia is more common than anticipated. Hypersecretion of aldosterone may be released from a large nodule identified as an adenoma, as well as from a generally hyperplastic gland that has not been identified as such. Nevertheless, surgery for lateralized disease results in good long-term control of BP with less antihypertensive medication. However, patients with dominant nodule or general hyperplasia without dominating nodules need more postoperative treatment than patients with APA. The majority of patients do not achieve normotension without medications, but they do become normokalemic.

  • 234.
    Hennings, Joakim
    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.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Computed tomography, magnetic resonance imaging and 11C-metomidate positron emission tomography for evaluation of adrenal incidentalomas2009In: European Journal of Radiology, ISSN 0720-048X, E-ISSN 1872-7727, Vol. 69, no 2, p. 314-23Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Given the higher sensitivity of modern computed tomography (CT) scanners, adrenal incidentalomas are being discovered increasingly often. This implies a growing quantitative diagnostic and clinical problem. CT and/or magnetic resonance imaging (MRI) and usually thorough hormonal testing are routinely used to determine the origin of these lesions. Recently, positron emission tomography (PET) using the tracer (11)C-metomidate (MTO) has been established as an alternative diagnostic method with high sensitivity for identifying adrenocortical lesions. The aim of this study was to evaluate the clinical use and value of MTO-PET compared to CT and MRI in the characterisation and work-up of adrenal incidentalomas. METHODS: Initially, we retrospectively evaluated 20 adrenal incidentalomas in patients who had undergone CT, MRI and MTO-PET and from whom we had either histopathological diagnosis or clinical follow-up data. After this analysis we conducted a prospective study in order to compare the imaging modalities. In the latter study, 24 incidentalomas were imaged by CT, MRI and MTO-PET and the results were correlated to those from histopathology (n=8) and clinical diagnosis after follow-up (n=16). RESULTS: In the retrospective analysis, MRI and especially MTO-PET, correlated well to histopathology and clinical diagnosis after follow-up, whereas specificity with CT was low. This was possibly due to the presence of several haematomas/fibrosis which were misdiagnosed as adrenocortical adenomas. In the prospective cohort, sensitivity and specificity with CT were 0.71 and 1.0, respectively, and further characterisation by MRI increased these values to 0.86 and 1.0, whereas maximum sensitivity and specificity were reached when MTO-PET was added. CONCLUSION: The diagnosis of an adrenocortical adenoma may be established by CT in most patients and by MRI in an additional number. For the few remaining patients needing further characterisation, MTO-PET is advantageous as an additional imaging modality.

  • 235.
    Hennings, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lindhe, Örjan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Endokrin tumörbiologi.
    Bergström, Mats
    Långström, Bengt
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    [11C]metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings2006In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 91, no 4, p. 1410-4Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Adrenal incidentalomas are common findings necessitating extensive laboratory work-up and repetitive radiological examinations. Positron emission tomography (PET) using (11)C-labeled metomidate (MTO) has previously been described as a tool for specific adrenocortical imaging. OBJECTIVE: We evaluated 212 MTO-PET examinations in 173 patients to identify its role in the management of adrenal tumors. DESIGN: Seventy-five histopathological examinations from 73 patients were retrospectively analyzed. SETTING: All examinations were performed at a referral center. PATIENTS: Patients who were operated or biopsied due to adrenal tumors had histopathological diagnoses of adrenocortical adenoma (n = 26), adrenocortical cancer (ACC; n = 13), adrenocortical hyperplasia (n = 8), pheochromocytoma (n = 6), metastasis (n = 3), and tumors of nonadrenal origin (n = 19). MAIN OUTCOME MEASURES: The main outcome measures were statistical analyses and findings while scrutinizing images. The hypothesis that MTO-PET is of value in the management of adrenal tumors, especially incidentaloma, was stated before data collection. RESULTS: Sensitivity was 0.89 and specificity was 0.96 for MTO-PET in proving adrenocortical origin of the lesions. Pheochromocytomas, metastases to the adrenal gland, and nonadrenal masses were all MTO negative. PET measurements using standardized uptake values (SUV) in pathological adrenocortical tissue could differentiate lesions larger than 1-1.5 cm from normal adrenocortical tissue. SUV was higher in aldosterone-hypersecreting adenomas, and the SUV ratio between the tumor and the contralateral gland was significantly higher in all hormonally hypersecreting adenomas as well as in ACC. CONCLUSION: MTO-PET is a specific and sensitive method for diagnosing adrenocortical tumors. MTO-PET is useful in the imaging work-up of adrenal incidentalomas and may be beneficial for the examination of patients with primary aldosteronism or ACC.

  • 236.
    Hennings, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Hägg, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    11C-metomidate positron emission tomography after dexamethasone suppression for detection of small adrenocortical adenomas in primary aldosteronism2010In: Langenbeck's archives of surgery (Print), ISSN 1435-2443, E-ISSN 1435-2451, Vol. 395, no 7, p. 963-967Article in journal (Refereed)
    Abstract [en]

    Purpose: To evaluate whether dexamethasone suppression treatment can improve 11 C-metomidate positron emission tomography (MTO-PET) detection of small adrenocortical adenomas in primary aldosteronism (PA).

    Materials and Methods: Eleven patients with proven PA and two patients with non-hyperfunctioning adrenocortical incidentalomas and small adrenocortical tumours observed on CT underwent MTO-PET before and 3 days after administration of oral dexamethasone suppression treatment. Small “hot-spot” regions of interest (ROIs) comprising 4-pixels (SUVhs) and 1-pixel  (SUVmax) were placed in the tumour area with the highest radioactivity concentration and their respective standardised uptake values (SUV) were recorded.

    Results: All tumours were detected and categorised as adrenocortical by MTO-PET. SUVhs as well as SUVmax were higher in PA compared to non-functional adenomas. Normal adrenal cortex was suppressed after dexamethasone (p<0.05) but tumour SUV was not significantly decreased after suppression in either PA or non-functional tumours (p>0.05).  However, these changes caused no significant increase in the tumour-to-normal adrenal ratio (p>0.05).

    Conclusion: MTO-PET is a highly sensitive method for detecting and categorising even small adrenocortical tumours in PA. In this series dexamethasone-suppressed MTO-PET was ubable to increase the tumour-to-normal-adrenal ratio to further facilitate detection of small adenomas in PA as an alternative to adrenal venous sampling.

  • 237. Herrera, Miguel F.
    et al.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Angelos, Peter
    Grant, Clive S.
    Hoff, Ana O.
    Pantoja, Juan Pablo
    Perez-Johnston, Rocio
    Sahani, Dushyant V.
    Wong, Richard J.
    Randolph, Gregory
    AACE/ACE DISEASE STATE CLINICAL REVIEW: PANCREATIC NEUROENDOCRINE INCIDENTALOMAS2015In: Endocrine Practice, ISSN 1530-891X, E-ISSN 1934-2403, Vol. 21, no 5, p. 546-553Article, review/survey (Refereed)
    Abstract [en]

    Incidental detection of pancreatic neuroendocrine tumors (PNETs) has substantially increased over the last decade due to widespread use of advanced imaging studies. Reliable initial imaging-based characterization is crucial for the differential diagnosis from other exocrine neoplasms and to determine the appropriate management plan. Measurements of chromogranin A, pancreatic polypeptide, and calcitonin are recommended for the biochemical evaluation. A thorough medical history needs to be performed to rule out multiple endocrine neoplasia (MEN) type 1. The European Neuroendocrine Tumor Society (ENETS)/Tumor Node Metastasis (TNM) staging system together with a grading based on the Ki-67 proliferation index and mitotic counts has proven to give more appropriate prognostic information than the World Health Organization (WHO)/American Joint Committee on Cancer (AJCC) TNM staging but may still fail to safely differentiate benign from malignant lesions. Poorly differentiated PNETs generally present with metastases and are rarely amenable for resection. Well-or intermediately differentiated tumors >= 2 cm with imaging evidence of malignancy or with a Ki-67 > 2% should be resected. It has been suggested that non-MEN related, nonfunctioning, and asymptomatic PNETs < 2 cm with a Ki-67 index >= 2% carry a low risk of metastasis and may be observed in the absence of clinical or radiologic criteria of malignancy or progression, especially in older patients. However, because metastases may occur with long delay with smaller PNETS, physicians should consider patient age, lesion location, and the risks of operation, and patients not undergoing surgery need to be closely followed closely.

  • 238.
    Hersi, Abdi-Fatah
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Västmanland Cty Hosp, Dept Surg, Västerås, Sweden.
    Eriksson, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Västmanland Cty Hosp, Dept Surg, Västerås, Sweden.
    Ramos, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Västmanland Cty Hosp, Dept Radiol, Västerås, Sweden.
    Abdsaleh, Shahin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Karakatsanis, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    A combined, totally magnetic technique with a magnetic marker for non-palpable tumour localization and superparamagnetic iron oxide nanoparticles for sentinel lymph node detection in breast cancer surgery2019In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 45, no 4, p. 544-549Article in journal (Refereed)
    Abstract [en]

    Background: Surgery for non-palpable breast cancer may often be a challenging procedure. Recently, a magnetic seed (Magseed®) used for tumour localization has been developed. Superparamagnetic iron oxide nanoparticles (SPIO) for sentinel lymph node (SN) detection is a novel tracer that may be injected up to four weeks preoperatively. This study is the first combining the magnetic seed and SPIO.

    Material and methods: Patients planned for breast conserving surgery and SN-biopsy (SNB) were recruited from two units in Sweden. Patients underwent lesion localization with Magseed® and SPIO injection (Magtrace™) by the breast radiologist in the preoperative period. Feasibility of successful lesion localization and excision together with a successful SNB detection was evaluated. Seed migration, number of SNs, specimen volume and calculated resection ratio (CRR) were reported.A survey of the physicians’ experience was conducted.

    Results: Localization was performed at a median of three days before surgery (range 0–25). All 32 patients underwent microscopically radical resection with a CRR of 1.49. No seed migration was noticed. SNB was successful in all patients. A median of two SNs was retrieved. Radiologists and surgeons reported the procedure easy to learn and outperformed guidewire localization in terms of localization and excision time. They thought the technique facilitated planning localization and surgery.

    Conclusions: The combined magnetic technique provided accuracy in tumour localization and SN detection without excess tissue excision and with promising results for flexibility in delivery of care. Larger studies are needed to confirm these findings.

  • 239.
    Hessman, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lindberg, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Carling, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Westin, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Mutation of the Multiple Endocrine Neoplasia Type 1 gene in nonfamilial, malignant tumors of the endocrine pancreas1998In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 58, no 3, p. 377-379Article in journal (Refereed)
    Abstract [en]

    Endocrine pancreatic tumors are rare neoplasms that occur sporadically or as part of a multiple endocrine neoplasia type 1 (MEN1) syndrome. Germ-line mutations of the MEN1 gene, located at 11q13, have been demonstrated in MEN1 kindreds, and loss of heterozygosity (LOH) on 11q13 together with somatic MEN1 mutations have been detected in 20% of nonfamilial parathyroid tumors. Here, we examine 11 non-MEN1 malignant tumors of the endocrine pancreas, 9 nonfunctioning tumors, and 2 glucagonomas. LOH of at least one informative locus on 11q13 was found in 70% of the tumors. Three tumors displayed somatic mutations of the MEN1 gene together with LOH on 11q13, whereas the corresponding germ-line DNA was normal. These findings support the hypothesis that MEN1 gene mutations contribute to the tumorigenesis of nonfamilial, malignant endocrine pancreatic tumors.

  • 240.
    Hessman, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    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.
    Multiple allelic deletions and intratumoral genetic heterogeneity in MEN1 pancreatic tumors2001In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 86, no 3, p. 1355-1361Article in journal (Refereed)
    Abstract [en]

    Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome with multiple tumors of the endocrine pancreas, the parathyroid, the pituitary, and other tissues. The MEN1 gene at 11q13 is homozygously mutated in the majority of MEN1 tumors. Here we present a genome-wide loss of heterozygosity (LOH) screening of 23 pancreatic lesions, one duodenal tumor, and one thymic carcinoid from 13 MEN1 patients. Multiple allelic deletions were found. Fractional allelic loss varied from 6-75%, mean 31%. All pancreatic tumors displayed LOH on chromosome 11, whereas the frequency of losses for chromosomes 3, 6, 8, 10, 18, and 21 was over 30%. Different lesions from individual patients had discrepant patterns of LOH. Intratumoral heterogeneity was revealed, with chromosome 6 and 11 deletions in most tumor cells, whereas other chromosomal loci were deleted in portions of the analyzed tumor. Chromosome 6 deletions were mainly found in lesions from patients with malignant features. Fractional allelic loss did not correlate to malignancy or to tumor size. Our findings indicate that MEN1 pancreatic tumors fail to maintain DNA integrity and demonstrate signs of chromosomal instability.

  • 241.
    Hessman, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Garske, Ulrike
    Rudberg, Claes
    Eriksson, Lars-Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Hellman, Per
    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.
    High success rate of parathyroid reoperation may be achieved with improved localization diagnosis2008In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 32, no 5, p. 774-81; discussion 782Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Because of the difficulty of reoperative parathyroid surgery, preoperative imaging studies have been increasingly adopted. We report the use of consistently applied localization diagnosis to yield high success rates in parathyroid reoperations. METHODS: Parathyroid reoperation was performed after previous parathyroid surgery in 144 patients with nonmalignant hyperparathyroidism (HPT) between 1962 and 2007. From the year 2000, 46 patients who underwent parathyroid reoperation and 14 patients who were subjected to thyroid surgery before primary parathyroid operation were investigated with sestamibi scintigraphy (MIBI), 11C-methionine PET/CT (met-PET), surgeon-performed ultrasound (US), US-guided fine-needle aspiration biopsy (US-FNA), and selective venous sampling (SVS) with rapid PTH (Q-PTH) analyses. When imaging was considered adequate, additional studies were generally not obtained. RESULTS: Reversal of hypercalcemia was achieved by reoperation in 134 of 144 (93%) of all patients with previous parathyroid surgery. In patients operated from year 2000, MIBI had 90% sensitivity and 88% predictive value, met-PET 79% sensitivity and 87% predictive value, and US 72% sensitivity and 93% predictive value. SVS with Q-PTH analyses provided accurate localization or regionalization in 11 of 11 recently selected patients. Q-PTH analyses in fine-needle aspirations verified parathyroid origin of excised specimens, and intraoperative Q-PTH helped decide when operations could be terminated. In patients subjected to the algorithm of imaging procedures, reversal of hypercalcemia and apparent cure was obtained after the reoperation in 45 of 46 patients with previous parathyroid surgery, implying a success rate of 98%, and in all patients with previous thyroid surgery. CONCLUSIONS: Reoperative parathyroid surgery is challenging. Results can be improved by consistently applied sensitive methods of preoperative imaging, and reoperative procedures may then achieve nearly the same success rates as primary operations.

  • 242.
    Hessman, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Westerdahl, J.
    Al-Suliman, N.
    Christiansen, P.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bergenfelz, A.
    Randomized clinical trial comparing open with video-assisted minimally invasive parathyroid surgery for primary hyperparathyroidism2010In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 97, no 2, p. 177-184Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous studies of video-assisted techniques for parathyroidectomy in patients with primary hyperparathyroidism have found similar or better results compared with bilateral neck exploration. The aim of the present study was to compare open minimally invasive parathyroidectomy with the video-assisted technique for primary hyperparathyroidism in a multicentre randomized trial. METHODS: Some 143 patients were randomized to open (n = 75) or video-assisted (n = 68) parathyroidectomy after positive sestamibi scintigraphy. There were no differences in preoperative data. The open operation was performed through a 15-mm incision. The video-assisted techniques used were minimally invasive video-assisted parathyroidectomy (MIVAP) or video-assisted parathyroidectomy using the lateral approach (VAPLA). Data were collected prospectively including postoperative pain scoring. RESULTS: The procedure was significantly quicker for the open compared to the video assisted operations: mean(s.d.) 60(35) versus 84(47) min (P = 0.001). Both groups of patients had similar conversion rates and the same outcome, with comparable incision lengths, low scores for postoperative neck discomfort, high cosmetic satisfaction and low complication rates. CONCLUSION: Open minimally invasive parathyroidectomy for primary hyperparathyroidism was quicker than either video-assisted technique.

  • 243.
    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.
    Allmän mammografi minskar dödlighet i bröstcancer2006In: Onkologi i Sverige, ISSN 1653-1582, Vol. 2, no 3, p. 46-48Article in journal (Refereed)
  • 244.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bristfälliga studier av diagnostiska cancertest: Varken systematiska översikter eller originalstudier håller måttet2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, no 17, p. 1308-1309Article in journal (Refereed)
    Abstract [sv]

    En genomgång av systematiska översikter av studier om diagnostiska test inom cancerområdet visar brister i både presentation och metoder.

    Genomgången talar för att det brister hos både författare och granskare vad gäller förståelsen av centrala metodfrågor. Standarden på denna forskning ligger långt efter de metodkrav som ställs på tex randomiserade kliniska prövningar av nya behandlingar.

    Det är en krävande forskningsprocess, både att göra en kritisk översikt av studier inom diagnosområdet och att genomföra en bra originalstudie av ett diagnostiskt test.

    Patientsäkerhet och utvecklande av kostnadseffektivitet inom diagnosområdet kräver att vi som läsare har krav på hög standard hos dessa processer.

  • 245.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Bröstsjukdomar2010In: Kirurgi / [ed] Bengt Jeppson, Lund: Studentlitteratur , 2010, 3Chapter in book (Other academic)
  • 246.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Obesity, Nutrition, and Prostate Cancer: Insights and Issues2013In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 63, no 5, p. 821-822Article in journal (Other academic)
  • 247.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Prostate cancer screening: the need for problem-solving that puts men's interests first2009In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 56, no 1, p. 34-37Article in journal (Refereed)
  • 248.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Reduction in breast cancer mortality from organized service screening with mammography: 1. Further confirmation with extended data2006In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, no 1, p. 45-51Article in journal (Refereed)
    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.

  • 249.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Reduction in breast cancer mortality from the organised service screening with mammography: 2. Validation with alternative analytic methods2006In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 15, no 1, p. 52-6Article in journal (Refereed)
    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.

  • 250.