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  • 251. Danad, Ibrahim
    et al.
    Raijmakers, Pieter G.
    Harms, Hendrik J.
    Heymans, Martijn W.
    van Royen, Niels
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Boellaard, Ronald
    van Rossum, Albert C.
    Lammertsma, Adriaan A.
    Knaapen, Paul
    Impact of anatomical and functional severity of coronary atherosclerotic plaques on the transmural perfusion gradient: a [O-15]H2O PET study2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no 31, p. 2094-U149Article in journal (Refereed)
    Abstract [en]

    Background Myocardial ischaemia occurs principally in the subendocardial layer, whereas conventional myocardial perfusion imaging provides no information on the transmural myocardial blood flow (MBF) distribution. Subendocardial perfusion measurements and quantification of the transmural perfusion gradient (TPG) could be more sensitive and specific for the detection of coronary artery disease (CAD). The current study aimed to determine the impact of lesion severity as assessed by the fractional flow reserve (FFR) on subendocardial perfusion and the TPG using [O-15]H2O positron emission tomography (PET) imaging in patients evaluated for CAD. Methods and results Sixty-six patients with anginal chest pain were prospectively enrolled and underwent [O-15] H2O myocardial perfusion PET imaging. Subsequently, invasive coronary angiography was performed and FFR obtained in all coronary arteries irrespective of the PET imaging results. Thirty (45%) patients were diagnosed with significant CAD(i.e. FFR <= 0.80), whereas on a per vessel analysis (n = 198), 53 (27%) displayed a positive FFR. Transmural hyperaemic MBF decreased significantly from 3.09 +/- 1.16 to 1.67 +/- 0.57 mL min(-1) g(-1) (P < 0.001) in non-ischaemic and ischaemic myocardium, respectively. The TPG decreased during hyperaemia when compared with baseline (1.20 +/- 0.14 vs. 0.94 +/- 0.17, P < 0.001), and was lower in arteries with a positive FFR (0.97 +/- 0.16 vs. 0.88 +/- 0.18, P < 0.01). ATPG threshold of 0.94 yielded an accuracy to detect CAD of 59%, which was inferior to transmural MBF with an optimal cutoff of 2.20 mL min(-1) g(-1) and an accuracy of 85% (P < 0.001). Diagnostic accuracy of subendocardial perfusion measurements was comparable with transmural MBF (83 vs. 85%, respectively, P = NS). Conclusion Cardiac [O-15]H2O PET imaging is able to distinguish subendocardial from subepicardial perfusion in the myocardium of normal dimensions. Hyperaemic TPG is significantly lower in ischaemic myocardium. This technique can potentially be employed to study subendocardial perfusion impairment in more detail. However, the diagnostic accuracy of subendocardial hyperaemic perfusion and TPG appears to be limited compared with quantitative transmural MBF, warranting further study.

  • 252. Danad, Ibrahim
    et al.
    Raijmakers, Pieter G.
    Harms, Hendrik J.
    van Kuijk, Cornelis
    van Royen, Niels
    Diamant, Michaela
    Lammertsma, Adriaan A.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    van Rossum, Albert C.
    Knaapen, Paul
    Effect of cardiac hybrid O-15-water PET/CT imaging on downstream referral for invasive coronary angiography and revascularization rate2014In: European Heart Journal Cardiovascular Imaging, ISSN 2047-2404, E-ISSN 2047-2412, Vol. 15, no 2, p. 170-179Article in journal (Refereed)
    Abstract [en]

    This study evaluates the impact of hybrid imaging on referral for invasive coronary angiography (ICA) and revascularization rates. A total of 375 patients underwent hybrid O-15-water positron emission tomography (PET)/computed tomography (CT)-based coronary angiography (CTCA) imaging for the evaluation of coronary artery disease (CAD). Downstream treatment strategy within a 60-day period after hybrid PET/CTCA imaging for ICA referral and revascularization was assessed. CTCA examinations were classified as showing no (obstructive) CAD, equivocal (borderline test result), or obstructive CAD, while the PET perfusion images were classified into normal or abnormal. On the basis of CTCA imaging, 182 (49) patients displayed no (obstructive) CAD. Only 10 (5) patients who showed no (obstructive) CAD on CTCA were referred for ICA, which were all negative. An equivocal CT study was observed in 80 (21) patients, among whom 56 (70) showed normal myocardial perfusion imaging (MPI), resulting in referral rates for ICA of 18 for normal MPI and 71 for abnormal MPI, respectively. No revascularizations were performed in the presence of normal MPI, while 59 of those with abnormal MPI were revascularized. CTCA indentified obstructive CAD in 113 (30) patients accompanied in 59 (52) patients with abnormal MPI. Referral rate for ICA was 57 for normal MPI and 88 for those with abnormal MPI, resulting in revascularization rates of 26 and 72, respectively. Hybrid O-15-water PET/CTCA imaging impacts clinical decision-making with regard to referral for ICA and revascularization procedures. Particularly, in the presence of an equivocal or abnormal CTCA, MPI could guide in the decision to refer for ICA and revascularization.

  • 253. Danad, Ibrahim
    et al.
    Raijmakers, Pieter G.
    Kamali, Parisa
    Harms, Hendrik J.
    de Haan, Stefan
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    van Kuijk, Cornelis
    Hoekstra, Otto S.
    Lammertsma, Adriaan A.
    Smulders, Yvo M.
    Heymans, Martijn W.
    Tulevski, Igor I.
    van Rossum, Albert C.
    Knaapen, Paul
    Carotid artery intima-media thickness, but not coronary artery calcium, predicts coronary vascular resistance in patients evaluated for coronary artery disease2012In: European Heart Journal: Cardiovascular Imaging, ISSN 2047-2404, Vol. 13, no 4, p. 317-323Article in journal (Refereed)
    Abstract [en]

    Aims There is growing evidence that coronary artery disease (CAD) affects not only the conduit epicardial coronary arteries, but also the microvascular coronary bed. Moreover, coronary microvascular dysfunction (CMVD) often precedes the stage of clinically overt epicardial CAD. Coronary artery calcium (CAC) and carotid intima-media thickness (C-IMT) measured with computed tomography (CT) and ultrasound, respectively, are among the available techniques to non-invasively assess atherosclerotic burden. An increased CAC score and C-IMT have also been associated with CMVD. It is therefore of interest to explore and compare the potential of CAC against C-IMT to predict minimal coronary vascular resistance (CVR). Methods and results We evaluated 120 patients (mean age 56 +/- 9 years, 58 men) without a documented history of CAD in whom and results obstructive CAD was excluded. All patients underwent C-IMT measurements, CAC scoring, and vasodilator stress O-15-water positron emission tomography (PET)/CT, during which the coronary flow reserve (CFR) and minimal CVR were analysed. Minimal CVR increased significantly with increasing tertiles of C-IMT (22 +/- 6, 27 +/- 11, and 28 +/- 9 mmHg mL(-1) min(-1) g(-1), P < 0.01), whereas the CFR was comparable across all C-IMT groups (P = 0.50). Minimal CVR increased significantly with an increase in CAC score (23 +/- 9, 27 +/- 8, 32 +/- 10, and 32 +/- 7 mmHg mL(-1) min(-1) g(-1). P < 0.01), whereas the CFR did not show a significant decrease with higher CAC scores (P = 0.18). Multivariable regression analysis revealed that C-IMT (P = 0.03), but not CAC, was independently associated with minimal CVR. Conclusion C-IMT, but not CAC score, independently predicts minimal CVR in patients with multiple cardiovascular risk factors and suspected of CAD.

  • 254. Danad, Ibrahim
    et al.
    Uusitalo, Valtteri
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Saraste, Antti
    Raijmakers, Pieter G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Lammertsma, Adriaan A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Heymans, Martijn W.
    Kajander, Sami A.
    Pietilae, Mikko
    James, Stefan K.
    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.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Knaapen, Paul
    Knuuti, Juhani
    Quantitative Assessment of Myocardial Perfusion in the Detection of Significant Coronary Artery Disease Cutoff Values and Diagnostic Accuracy of Quantitative [O-15]H2O PET Imaging2014In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 64, no 14, p. 1464-1475Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Recent studies have demonstrated improved diagnostic accuracy for detecting coronary artery disease (CAD) when myocardial blood flow (MBF) is quantified in absolute terms, but there are no uniformly accepted cutoff values for hemodynamically significant CAD. OBJECTIVES The goal of this study was to determine cutoff values for absolute MBF and to evaluate the diagnostic accuracy of quantitative [O-15]H2O positron emission tomography (PET). METHODS A total of 330 patients underwent both quantitative [O-15]H2O PET imaging and invasive coronary angiography in conjunction with fractional flow reserve measurements. A stenosis >90% and/or fractional flow reserve <= 0.80 was considered obstructive; a stenosis <30% and/or fractional flow reserve >0.80 was nonobstructive. RESULTS Hemodynamically significant CAD was diagnosed in 116 (41%) of 281 patients who fulfilled study criteria for CAD. Resting perfusion was 1.00 +/- 0.25 and 0.92 +/- 0.23 ml/min/g in regions supplied by nonstenotic and significantly stenosed vessels, respectively (p < 0.001). During stress, perfusion increased to 3.26 +/- 1.04 ml/min/g and 1.73 +/- 0.67 ml/min/g, respectively (p < 0.001). The optimal cutoff values were 2.3 and 2.5 for hyperemic MBF and myocardial flow reserve, respectively. For MBF, these cutoff values showed a sensitivity, specificity, and accuracy for detecting significant CAD of 89%, 84%, and 86%, respectively, at a per-patient level and 87%, 85%, and 85% at a per-vessel level. The corresponding myocardial flow reserve values were 86%, 72%, and 78% (per patient) and 80%, 82%, and 81% (per vessel). Age and sex significantly affected diagnostic accuracy of quantitative PET. CONCLUSIONS Quantitative MBF measurements with the use of [O-15]H2O PET provided high diagnostic performance, but both sex and age should be taken into account.

  • 255.
    Danfors, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    11C Molecular Imaging in Focal Epilepsy2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Epilepsy is a common neurological disease affecting 6 million people in Europe. Early prevention and accurate diagnosis and treatment are of importance to obtain seizure freedom. In this thesis new applications of carbon-11-labelled tracers in PET and autoradiographic studies were explored in focal epilepsy.

    Patients with low-grade gliomas often experience epileptic seizures. A retrospective PET-study assessing seizure activity, metabolic rate measured with 11C-methionine and other known prognostic factors was performed in patients with glioma. No correlation was found between seizure activity and uptake of methionine. The presence and termination of early seizures was a favourable prognostic factor.

    Activation of the neurokinin-1 (NK1) receptor by substance P (SP) induces epileptic activity. PET with the NK1 receptor antagonist GR205171 was performed in patients with temporal lobe epilepsy (TLE) and healthy controls. In TLE patients an increased NK1 receptor availability was found in both hemispheres, most pronounced in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptors and seizure frequency was observed in ipsilateral medial structures consistent with an intrinsic network using the NK1-SP receptor system for transmission of seizure activity.

    The uptake of 18F-fluoro-deoxy-glucose (FDG) is related to cerebral blood flow (CBF). Previously, methods to estimate blood flow from dynamic PET data have been described. A retrospective study was conducted in 15 patients undergoing epilepsy surgery investigation, including PET with 11C-FDG and 11C-Flumazenil (FMZ). The dynamic FMZ dataset and pharmacokinetic modeling with a multilinear reference tissue model were used to determine images of relative CBF. Agreement between data of FDG and CBF was analyzed showing a close association between interictal brain metabolism and relative CBF.

    Epilepsy often occurs after traumatic brain injuries. Changes in glia and inhibitory neuronal cells contribute to the chain of events leading to seizures. Autoradiography with 11C-PK11195, 11C-L-deprenyl and 11C-Flumazenil in an animal model of posttraumatic epilepsy studied the temporal and spatial distribution of microglia, astrocytes and GABAergic neurons. Results showed an instant increase in microglial activity that subsequently normalized, a late formation of astrogliosis and an instant and prolonged decease in GABA binding. The model can be used to visualize pathophysiological events during the epileptogenesis.

    List of papers
    1. Epileptic seizures and survival in early disease of grade 2 gliomas
    Open this publication in new window or tab >>Epileptic seizures and survival in early disease of grade 2 gliomas
    2009 (English)In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 16, no 7, p. 823-831Article in journal (Refereed) Published
    Abstract [en]

    Background and purpose

    The aims of this study were (i) to determine the correlation between seizure activity and the metabolic rate of the tumour measured by 11Cmethionine PET (MET PET) in patients with grade 2 gliomas, and (ii) to assess the prognostic impact of early seizure manifestations on patient survival.

    Methods

    In this retrospective review, early seizure manifestations were studied in 101 patients with supratentorial grade 2 gliomas subjected to MET PET as part of the pretreatment tumour investigation. Seizure manifestations as a variable was then used in multivariate survival analyses, together with established prognostic factors for this patient group.

    Results

    Of all 101 cases, 88 patients had seizures at tumour presentation. Fortyseven were seizure free at the early stage of the disease, whereas 54 had recurrent seizures. Patients with seizures at tumour presentation had a more favourable outcome before and after (P = 0.006) adjustment for conventional prognostic factors. However, for those who continued to have seizures early in the disease, the outcome was worse (P = 0.003). We found no significant correlation between MET PET and the seizure manifestations of the patients.

    Conclusion

    The presence and termination of early seizure manifestations may be favourable prognostic factors in patients with low-grade gliomas.

     

    Keywords
    11C methionine positron emission tomography, epileptic seizures, low-grade glioma, survival
    National Category
    Neurology
    Research subject
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-105434 (URN)10.1111/j.1468-1331.2009.02599.x (DOI)000266637000012 ()
    Available from: 2009-06-03 Created: 2009-06-03 Last updated: 2017-12-13Bibliographically approved
    2. Increased neurokinin-1 receptor availability in temporal lobe epilepsy: A positron emission tomography study using [(11)C]GR205171
    Open this publication in new window or tab >>Increased neurokinin-1 receptor availability in temporal lobe epilepsy: A positron emission tomography study using [(11)C]GR205171
    Show others...
    2011 (English)In: Epilepsy Research, ISSN 0920-1211, E-ISSN 1872-6844, Vol. 97, no 1-2, p. 183-189Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE: Activation of the neurokinin-1 (NK1) receptor by neuropeptide substance P (SP) induces and maintains epileptic activity in various experimental models of epilepsy. The primary objective of this study was to investigate whether neurobiological changes linked to NK1-SP receptor system are associated with hyperexcitability in patients with temporal lobe epilepsy (TLE). A secondary objective was to investigate the relationship between seizure frequency and NK1 receptor availability.

    METHODS: A positron emission tomography study was conducted with the selective NK1 receptor antagonist [(11)C]GR205171 in nine patients with TLE and 18 healthy control participants. Parametric PET images were generated using the Patlak graphical method, with cerebellum as reference region. Data analyses including group comparisons were performed using statistical parametric mapping.

    RESULTS: Patients with TLE showed increased NK1 receptor availability in both hemispheres with the most pronounced increase in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptor availability and seizure frequency was observed in the medial temporal lobe and in the lentiform nucleus ipsilateral to the seizure onset.

    CONCLUSION: Our results suggest that there is an intrinsic network using the NK1-SP receptor system for synaptic transmission and epileptiform activity in TLE.

    Keywords
    Epilepsy, PET, NK1, Substance P, TLE
    National Category
    Neurology
    Research subject
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-159946 (URN)10.1016/j.eplepsyres.2011.08.006 (DOI)00297873800021 ()21925840 (PubMedID)
    Available from: 2011-10-12 Created: 2011-10-12 Last updated: 2017-12-08Bibliographically approved
    3. Relative Cerbral Blood Flow Measurement using dynamic Flumazenil-PET may Replace Fluorodeoxyglucose-PET in Epilepsy Surgical Investigations
    Open this publication in new window or tab >>Relative Cerbral Blood Flow Measurement using dynamic Flumazenil-PET may Replace Fluorodeoxyglucose-PET in Epilepsy Surgical Investigations
    2012 (English)Article in journal (Other academic) Submitted
    National Category
    Neurosciences Other Basic Medicine
    Research subject
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-180846 (URN)
    Available from: 2012-09-11 Created: 2012-09-11 Last updated: 2018-01-12Bibliographically approved
    4. 11C-autoradiographic studies of dynamic changes in glial cells and benzodiazepine receptor binding in a model of posttraumatic epilepsy
    Open this publication in new window or tab >>11C-autoradiographic studies of dynamic changes in glial cells and benzodiazepine receptor binding in a model of posttraumatic epilepsy
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Neurosciences
    Identifiers
    urn:nbn:se:uu:diva-180847 (URN)
    Available from: 2012-09-11 Created: 2012-09-11 Last updated: 2018-06-18
  • 256.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Bergström, M
    Uppsala University PET Centre, University Hospital, Uppsala, Sweden.
    Feltelius, N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Westerberg, G
    Uppsala University PET Centre, University Hospital, Uppsala, Sweden.
    Långström, Bengt
    Uppsala University PET Centre, University Hospital, Uppsala, Sweden.
    Positron emission tomography with 11C-D-deprenyl in patients with rheumatoid arthritis. Evaluation of knee joint inflammation before and after intra-articular glucocorticoid treatment1997In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 26, no 1, p. 43-48Article in journal (Refereed)
    Abstract [en]

    Seven patients with arthritic disease and with clinical signs of inflammation of the knee joint, were investigated with positron emission tomography (PET) after injection of [N-methyl-11C]-D-deprenyl. Two healthy volunteers were included as controls. In five patients the investigation was repeated after an intra-articular injection of glucocorticoids. All patients showed very high uptake of the tracer in the paraarticular structures of the joint. After treatment there was approximately a 50% reduction of the uptake in the treated knees, both in the high uptake regions and in the surrounding soft tissues. No change was observed in the non-treated knees. In the healthy volunteers, only soft tissue surrounding the joint showed an uptake of the tracer, but at a magnitude which was 6-8 times lower than the high uptake regions in the arthritis patients. Although the mechanisms for the high uptake of 11C-D-deprenyl in affected joints of patients with arthritis is not clear, the present work points to a potential of PET for the assessment of disease intensity and monitoring of treatment.

  • 257.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Lubberink, Mark
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Relative Cerbral Blood Flow Measurement using dynamic Flumazenil-PET may Replace Fluorodeoxyglucose-PET in Epilepsy Surgical Investigations2012Article in journal (Other academic)
  • 258.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Velickaite, Vilma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Canto Moreira, Nuno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    The role of methionine positron emission tomography in the evaluation of central nervous system tumors in children2016In: Journal of Cerebral Blood Flow and Metabolism, ISSN 0271-678X, E-ISSN 1559-7016, Vol. 36, no Suppl. 1, p. 394-395, article id 538Article in journal (Other academic)
  • 259.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. neurologi.
    von Knorring, Anne-Liis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. BUP.
    Hartvig, Per
    Hospital Pharmacy.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Moulder, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Strömberg, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Torstenson, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Wester, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Watanabe, Yasuyoshi
    Department of Physiology, Osaka City University Graduate School of Medicine, Japan.
    Eeg-Olofsson, Orvar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Tetrahydrobiopterin in the treatment of children with autistic disorder. A double-blind placebo-controlled crossover study2005In: Journal of Clinical Psychopharmacology, ISSN 0271-0749, E-ISSN 1533-712X, Vol. 25, no 5, p. 485-489Article in journal (Refereed)
    Abstract [en]

    Twelve children, all boys, aged 4 to 7 years, with a diagnosis of autistic disorder and low concentrations of spinal 6R-l-erythro-5,6,7,8-tetrahydrobiopterin (tetrahydrobiopterin) were selected to participate in a double-blind, randomized, placebo-controlled, crossover study. The children received a daily dose of 3 mg tetrahydrobiopterin per kilogram during 6 months alternating with placebo. Treatment-induced effects were assessed with the Childhood Autism Rating Scale every third month. The results showed small nonsignificant changes in the total scores of Childhood Autism Rating Scale after 3- and 6-month treatment. Post hoc analysis looking at the 3 core symptoms of autism, that is, social interaction, communication, and stereotyped behaviors, revealed a significant improvement of the social interaction score after 6 months of active treatment. In addition, a high positive correlation was found between response of the social interaction score and IQ. The results indicate a possible effect of tetrahydrobiopterin treatment.

  • 260.
    Danfors, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Linnman, Clas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Kumlien, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Increased neurokinin-1 receptor availability in temporal lobe epilepsy: A positron emission tomography study using [(11)C]GR2051712011In: Epilepsy Research, ISSN 0920-1211, E-ISSN 1872-6844, Vol. 97, no 1-2, p. 183-189Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Activation of the neurokinin-1 (NK1) receptor by neuropeptide substance P (SP) induces and maintains epileptic activity in various experimental models of epilepsy. The primary objective of this study was to investigate whether neurobiological changes linked to NK1-SP receptor system are associated with hyperexcitability in patients with temporal lobe epilepsy (TLE). A secondary objective was to investigate the relationship between seizure frequency and NK1 receptor availability.

    METHODS: A positron emission tomography study was conducted with the selective NK1 receptor antagonist [(11)C]GR205171 in nine patients with TLE and 18 healthy control participants. Parametric PET images were generated using the Patlak graphical method, with cerebellum as reference region. Data analyses including group comparisons were performed using statistical parametric mapping.

    RESULTS: Patients with TLE showed increased NK1 receptor availability in both hemispheres with the most pronounced increase in anterior cingulate gyrus ipsilateral to seizure onset. A positive correlation between NK1 receptor availability and seizure frequency was observed in the medial temporal lobe and in the lentiform nucleus ipsilateral to the seizure onset.

    CONCLUSION: Our results suggest that there is an intrinsic network using the NK1-SP receptor system for synaptic transmission and epileptiform activity in TLE.

  • 261. Darreh-Shori, T.
    et al.
    Kadir, A.
    Almkvist, O.
    Grut, M.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Blomquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Eriksson, B.
    Långström, B.
    Nordberg, A.
    Inhibition of acetylcholinesterase in CSF versus brain assessed by 11C-PMP PET in AD patients treated with galantamine2008In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 29, no 2, p. 168-184Article in journal (Refereed)
    Abstract [en]

    The relationship between acetylcholinesterase (AChE) activity in the CSF and brain of patients with Alzheimer's disease (AD) was investigated in 18 mild AD patients following galantamine treatment. The first 3 months of the study had a randomized double-blind placebo-controlled design, during which 12 patients received galantamine (16-24 mg/day) and six patients placebo. This was followed by 9 months Galantamine treatment in all patients. Activities and protein levels of both the "read-through" AChE (AChE-R) and the synaptic (AChE-S) variants in CSF were assessed in parallel together with the regional brain AChE activity by C-11-PMP and PET. The AChE-S inhibition was 30-36% in CSF, which correlated well with the in vivo AChE inhibition in the brain. No significant AChE inhibition was observed in the placebo group. The increased level of the AChE-R protein was 16% higher than that of AChE-S. Both the AChE inhibition and the increased level of AChE-R protein positively correlated with the patient's performance in cognitive tests associated with visuospatial ability and attention. In conclusion, AChE levels in CSF closely mirror in vivo brain AChE levels prior to and after treatment with the cholinesterase inhibitors. A positive cognitive response seems to dependent on the AChE inhibition level, which is balanced by an increased protein level of the AChE-R variant in the patients.

  • 262. Dasu, Alexandru
    et al.
    Flejmer, Anna M.
    Dohlmar, Frida
    Josefsson, Dan
    Witt Nyström, Petra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    The Potential Benefit of Scanned Proton Beam Versus Intensity Modulated Photon Therapy as Adjuvant Radiation Therapy in Breast Cancer2014In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 10, p. 5873-5874Article in journal (Other academic)
  • 263. de Miranda, Noel F. C. C.
    et al.
    Georgiou, Konstantinos
    Chen, Longyun
    Wu, Chenglin
    Gao, Zhibo
    Zaravinos, Apostolos
    Lisboa, Susana
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Teixeira, Manuel R.
    Zeng, Yixin
    Peng, Roujun
    Pan-Hammarstrom, Qiang
    Exome sequencing reveals novel mutation targets in diffuse large B-cell lymphomas derived from Chinese patients2014In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, no 16, p. 2544-2553Article in journal (Refereed)
    Abstract [en]

    Next-generation sequencing studies on diffuse large B-cell lymphomas (DLBCLs) have revealed novel targets of genetic aberrations but also high intercohort heterogeneity. Previous studies have suggested that the prevalence of disease subgroups and cytogenetic profiles differ between Western and Asian patients. To characterize the coding genome of Chinese DLBCL, we performed whole-exome sequencing of DNA derived from 31 tumors and respective peripheral blood samples. The mutation prevalence of B2M, CD70, DTX1, LYN, TMSB4X, and UBE2A was investigated in an additional 105 tumor samples. We discovered 11 novel targets of recurrent mutations in DLBCL that included functionally relevant genes such as LYN and TMSB4X. Additional genes were found mutated at high frequency (>= 10%) in the Chinese cohort including DTX1, which was the most prevalent mutation target in the Notch pathway. We furthermore demonstrated that mutations in DTX1 impair its function as a negative regulator of Notch. Novel and previous unappreciated targets of somatic mutations in DLBCL identified in this study support the existence of additional/alternative tumorigenic pathways in these tumors. The observed differences with previous reports might be explained by the genetic heterogeneity of DLBCL, the germline genetic makeup of Chinese individuals, and/or exposure to distinct etiological agents.

  • 264. de Miranda, Noel F. C. C.
    et al.
    Peng, Roujun
    Georgiou, Konstantinos
    Wu, Chenglin
    Sörqvist, Elin Falk
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Berglund, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Chen, Longyun
    Gao, Zhibo
    Lagerstedt, Kristina
    Lisboa, Susana
    Roos, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    van Wezel, Tom
    Teixeira, Manuel R.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nilsson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Zeng, Yixin
    Kipling, David
    Pan-Hammarstrom, Qiang
    DNA repair genes are selectively mutated in diffuse large B cell lymphomas2013In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 210, no 9, p. 1729-1742Article in journal (Refereed)
    Abstract [en]

    DNA repair mechanisms are fundamental for B cell development, which relies on the somatic diversification of the immunoglobulin genes by V(D)J recombination, somatic hypermutation, and class switch recombination. Their failure is postulated to promote genomic instability and malignant transformation in B cells. By performing targeted sequencing of 73 key DNA repair genes in 29 B cell lymphoma samples, somatic and germline mutations were identified in various DNA repair pathways, mainly in diffuse large B cell lymphomas (DLBCLs). Mutations in mismatch repair genes (EXO1, MSH2, and MSH6) were associated with microsatellite instability, increased number of somatic insertions/deletions, and altered mutation signatures in tumors. Somatic mutations in nonhomologous end-joining (NHEJ) genes (DCLRE1C/ARTEMIS, PRKDC/DNA-PKcs, XRCC5/KU80, and XRCC6/KU70) were identified in four DLBCL tumors and cytogenetic analyses revealed that translocations involving the immunoglobulin-heavy chain locus occurred exclusively in NHEJ-mutated samples. The novel mutation targets, CHEK2 and PARP1, were further screened in expanded DLBCL cohorts, and somatic as well as novel and rare germline mutations were identified in 8 and 5% of analyzed tumors, respectively. By correlating defects in a subset of DNA damage response and repair genes with genomic instability events in tumors, we propose that these genes play a role in DLBCL lymphomagenesis.

  • 265. Deb, Siddhartha
    et al.
    Johansson, Ida
    Byrne, David
    Nilsson, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Constable, Leonie
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Dobrovic, Alexander
    Hedenfalk, Ingrid
    Fox, Stephen B.
    Nuclear HIF1A expression is strongly prognostic in sporadic but not familial male breast cancer2014In: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 27, no 9, p. 1223-1230Article in journal (Refereed)
    Abstract [en]

    Male breast cancer is poorly understood with a large proportion arising in the familial context particularly with the BRCA2 germline mutation. As phenotypic and genotypic differences between sporadic and familial male breast cancers have been noted, we investigated the importance of a hypoxic drive in these cancers as this pathway has been shown to be of importance in familial female breast cancer. Expression of two major hypoxia-induced proteins, the hypoxia-inducible factor-1 alpha (HIF1A) and the carbonic anhydrase IX (CA9), examined within a large cohort including 61 familial (3 BRCA1, 28 BRCA2, 30 BRCAX) and 225 sporadic male breast cancers showed that 31% of all male breast cancers expressed either HIF1A (25%) and/or CA9 (8%) in the combined cohort. Expression of HIF1A correlated with an increased incidence of a second-major malignancy (P=0.04), histological tumor type (P=0.005) and basal phenotype (P=0.02). Expression of CA9 correlated with age (P=0.004) in sporadic cases and an increased tumor size (P=0.003). Expression of HIF1A was prognostic for disease-specific survival in sporadic male breast cancers (HR: 3.8, 95% CI: 1.5-9.8, P=0.006) but not within familial male breast cancer, whereas CA9 was only prognostic in familial male breast cancers (HR: 358.0, 95% CI: 9.3-13781.7, P=0.002) and not in sporadic male breast cancer. This study found that hypoxic drive is less prevalent in male breast cancer compared with female breast cancer, possibly due to a different breast microenvironment. The prognostic impact of HIF1A is greatest in sporadic male breast cancers with an alternate dominant mechanism for the oncogenic drivers suggested in high risk familial male breast cancers.

  • 266.
    Degerman Gunnarsson, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lindau, M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Santillo, A F
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Engler, H
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Basun, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Re-evaluation of clinical dementia diagnoses with pittsburgh compound B positron emission tomography2013In: Dementia and geriatric cognitive disorders extra, ISSN 1664-5464, Vol. 3, no 1, p. 472-481Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    There is an overlap regarding Pittsburgh compound B (PIB) retention in patients clinically diagnosed as Alzheimer's disease (AD) and non-AD dementia. The aim of the present study was to investigate whether there are any differences between PIB-positive and PIB-negative patients in a mixed cohort of patients with neurodegenerative dementia of mild severity regarding neuropsychological test performance and regional cerebral glucose metabolism measured with [(18)F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET).

    METHODS:

    Eighteen patients clinically diagnosed as probable AD or frontotemporal dementia were examined with PIB PET, FDG PET and neuropsychological tests and followed for 5-9 years in a clinical setting.

    RESULTS:

    The PIB-positive patients (7 out of 18) had slower psychomotor speed and more impaired visual episodic memory than the PIB-negative patients; otherwise performance did not differ between the groups. The initial clinical diagnoses were changed in one third of the patients (6 out of 18) during follow-up.

    CONCLUSIONS:

    The subtle differences in neuropsychological performance, the overlap of hypometabolic patterns and clinical features between AD and non-AD dementia highlight the need for amyloid biomarkers and a readiness to re-evaluate the initial diagnosis.

  • 267. Degerman Gunnarsson, Malin
    et al.
    Lindau, Maria
    Santillo, Alexander
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Engler, Henry
    Lannfelt, Lars
    Basun, Hans
    Kilander, Lena
    Re-evaluation of clinical dementia diagnoses with PET-PIBManuscript (preprint) (Other academic)
    Abstract [en]

    Objectives: There is an overlap regarding Pittsburgh Compound-B (PIB) retention in patients clinically diagnosed as Alzheimer’s disease (AD) and non-AD dementia.  The aim of the present study was to investigate whether there are any differences between PIB+ and PIB PIB- patients in a mixed cohort of patients with neurodegenerative dementia of mild severity regarding neuropsychological test performance and regional cerebral glucose metabolism measured with 18 Fluoro-2-deoxy-d-glucose (FDG) PET.

    Methods: Eighteen patients clinically diagnosed as probable AD or frontotemporal dementia were examined with  PIB PET, FDG PET and neuropsychological tests and followed for 5-9 years in a clinical setting.

    Results:  The PIB+ patients (7/18) had slower psychomotor speed and more impaired visual episodic memory than the PIB- patients, otherwise performance did not differ between groups. The initial clinical diagnoses were changed in one third of the patients (6/18) during follow-up.  

    Conclusions: The subtle differences in neuropsychological performance, the overlap of hypometabolic patterns and clinical features between AD and non-AD dementia highlight the need of amyloid biomarkers and readiness to re-evaluate the initial diagnosis.

  • 268.
    Degerman Gunnarsson, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lindau, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Blennow, K
    Darreh-Shori, T
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Nordberg, A
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Basun, H
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Pittsburgh compound-B and Alzheimer's disease biomarkers in CSF, plasma and urine: An exploratory study2010In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, E-ISSN 1421-9824, Vol. 29, no 3, p. 204-212Article in journal (Refereed)
    Abstract [en]

    Background:

    The positron emission tomography (PET) radiotracer Pittsburgh Compound-B (PIB) is an in vivo ligand for measuring β-amyloid (Aβ) load. Associations between PET PIB and cerebrospinal fluid (CSF) Aβ1–42 and apolipoprotein E ε4 (APOE ε4) have been observed in several studies, but the relations between PIB uptake and other biomarkers of Alzheimer’s disease (AD) are less investigated.

    Method:

    PET PIB, PET 18Fluoro-2-deoxy-D-glucose and different AD biomarkers were measured twice in CSF, plasma and urine 12 months apart in 10 patients with a clinical diagnosis of mild to moderate AD.

    Results:

    PIB retention was constant over 1 year, inversely related to low CSF Aβ1–42 (p = 0.01) and correlated positively to the numbers of the APOE ε4 allele (0, 1 or 2) (p = 0.02). There was a relation between mean PIB retention and CSF ApoE protein (r = –0.59, p = 0.07), and plasma cystatin C (r = –0.56, p = 0.09).

    Conclusion:

    PIB retention is strongly related to CSF Aβ1–42, and to the numbers of the APOE ε4 allele.

  • 269.
    Delforoush, Maryam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Berglund, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Molecular Studies of Mechanisms of Drug Resistance in Malignant Cells With Focus on Lymphomas2012In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 48, no S5, p. S229-S229Article in journal (Refereed)
  • 270.
    Derosa, Savino
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Segelsjö, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Tannoia, Angela
    Pellegrini, Mariangela
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Perchiazzi, Gaetano
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Reabsorption atelectasis in a porcine model of ARDS: regional and temporal effects of airway closure, oxygen, and distending pressure2013In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, no 10, p. 1464-1473Article in journal (Refereed)
    Abstract [en]

    Little is known about the small airways dysfunction in acute respiratory distress syndrome (ARDS). By computed tomography (CT) imaging in a porcine experimental model of early ARDS, we aimed at studying the location and magnitude of peripheral airway closure and alveolar collapse under high and low distending pressures and high and low inspiratory oxygen fraction (FIO2). Six piglets were mechanically ventilated under anesthesia and muscle relaxation. Four animals underwent saline-washout lung injury, and two served as healthy controls. Beyond the site of assumed airway closure, gas was expected to be trapped in the injured lungs, promoting alveolar collapse. This was tested by ventilation with an FIO2 of 0.25 and 1 in sequence during low and high distending pressures. In the most dependent regions, the gas/tissue ratio of end-expiratory CT, after previous ventilation with FIO2 0.25 low-driving pressure, was significantly higher than after ventilation with FIO2 1; with high-driving pressure, this difference disappeared. Also, significant reduction in poorly aerated tissue and a correlated increase in nonaerated tissue in end-expiratory CT with FIO2 1 low-driving pressure were seen. When high-driving pressure was applied or after previous ventilation with FIO2 0.25 and low-driving pressure, this pattern disappeared. The findings suggest that low distending pressures produce widespread dependent airway closure and with high FIO2, subsequent absorption atelectasis. Low FIO2 prevented alveolar collapse during the study period because of slow absorption of gas behind closed airways.

  • 271. Dewdney, Alice
    et al.
    Cunningham, David
    Tabernero, Josep
    Capdevila, Jaume
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Cervantes, Andres
    Tait, Diana
    Brown, Gina
    Wotherspoon, Andrew
    de Castro, David Gonzalez
    Chua, Yu Jo
    Wong, Rachel
    Barbachano, Yolanda
    Oates, Jacqueline
    Chau, Ian
    Multicenter Randomized Phase II Clinical Trial Comparing Neoadjuvant Oxaliplatin, Capecitabine, and Preoperative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision in Patients With High-Risk Rectal Cancer (EXPERT-C)2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 14, p. 1620-1627Article in journal (Refereed)
    Abstract [en]

    Purpose To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer.

    Patients and Methods Patients with operable magnetic resonance imaging-defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX + C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis.

    Results One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX + C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [ HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX + C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX + C arm.

    Conclusion Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.

  • 272. Dias, M M
    et al.
    Pignon, J-P
    Karapetis, C S
    Boige, V
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Kweekel, D M
    Lara, P N
    Laurent-Puig, P
    Martinez-Balibrea, E
    Páez, D
    Punt, C J A
    Redman, M W
    Toffoli, G
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    McKinnon, R A
    Sorich, M J
    The effect of the UGT1A1*28 allele on survival after irinotecan-based chemotherapy: a collaborative meta-analysis2014In: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 14, no 5, p. 424-431Article in journal (Refereed)
    Abstract [en]

    To date, studies of irinotecan pharmacogenetics have mostly focused on the effect of the UGT1A1*28 allele on irinotecan-related toxicity. However, the clinical utility of routine UGT1A1*28 genotyping to pre-emptively adjust irinotecan dosage is dependent upon whether UGT1A1*28 also affects patient survival following irinotecan therapy. Previous observational studies evaluating the influence of UGT1A1*28 on survival have shown contradictory results. A systematic review and meta-analysis of both published and unpublished data were performed to summarize the available evidence of the relationship between the UGT1A1*28 allele and patient survival related to irinotecan therapy. Overall and progression-free survival meta-analysis data were available for 1524 patients and 1494 patients, respectively. The difference in the survival between patients of different UGT1A1*28 genotypes (homozygous, heterozygous or wild-type) who had received irinotecan was not found to be statistically significant. There was also no evidence of irinotecan dose, regimen or line of therapy having an impact on this association.

  • 273.
    Dimopoulou, Angeliki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    CT with 3D-Image Reconstructions in Preoperative Planning2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Computed tomography is one of the most evolving fields of modern radiology. The current CT applications permit among other things angiography, 3D image reconstructions, material decomposition and tissue characterization. CT is an important tool in the assessment of specific patient populations prior to an invasive or surgical procedure. The aim of this dissertation was to demonstrate the decisive role of CT with 3D-image reconstructions in haemodialysis patients scheduled to undergo fistulography, in patients undergoing surgical breast reconstructions with a perforator flap and in patients with complicated renal calculi scheduled to undergo percutaneous nephrolithotomy.

    CT Angiography with 3D image reconstructions was performed in 31 patients with failing arteriovenous fistulas and grafts, illustrating the vascular anatomy in a comprehensive manner in 93.5% of the evaluated segments and demonstrating a sensitivity of 95% compared to fistulography.

    In 59 mastectomy patients scheduled to undergo reconstructive breast surgery with a deep inferior epigastric perforator flap, the preoperative planning with CT Angiography with 3D image reconstructions of the anterior abdominal wall providing details of its vascular supply, reduced surgery time significantly (p< 0.001) and resulted in fewer complications.

    Dual Energy CT Urography with advanced image reconstructions in 31 patients with complicated renal calculi scheduled to undergo PNL, resulted in a new method of material characterisation (depicting renal calculi within excreted contrast) and in the possibility of reducing radiation dose by 28% by omitting the nonenhanced scanning phase. Detailed analysis of the changes renal calculi undergo when virtually reconstructed was performed and a comparison of renal calculi number, volume, height and attenuation between virtual nonenhanced and true nonenhanced images was undertaken. All parameters were significantly underestimated in the virtual nonenhanced images.

    CT with 3D-reconstructions is more than just “flashy images”. It is crucial in preoperative planning, optimizes various procedures and can reduce radiation dose. 

    List of papers
    1. MDCT angiography with 3D image reconstructions in the evaluation of failing arteriovenous fistulas and grafts in hemodialysis patients
    Open this publication in new window or tab >>MDCT angiography with 3D image reconstructions in the evaluation of failing arteriovenous fistulas and grafts in hemodialysis patients
    2011 (English)In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 52, no 9, p. 935-942Article in journal (Refereed) Published
    Abstract [en]

    Background: Arteriovenous fistulas and grafts are the methods of choice for vascular access in renal failure patients in need of hemodialysis. Their major complication, however, is stenosis, which might lead to thrombosis.

    Purpose: To demonstrate the usefulness of 16-MDCTA with 3D image reconstructions, in long-term hemodialysis patients with dysfunctional arteriovenous fistulas and grafts (AVF and AVG).

    Material and Methods: During a 17-month period, 31 patients with dysfunctional AVF and AVG (24 AVF and seven AVG) were examined with MDCTA with 3D image postprocessing. Parameters such as comprehension of the anatomy, quality of contrast enhancement, and pathological vascular changes were measured. DSA was then performed in 24 patients.

    Results: MDCTA illustrated the anatomy of the AVF/AVG and the entire vascular tree to the heart, in a detailed and comprehensive manner in 93.5% of the evaluated segments, and depicted pathology of AVF/AVG or pathology of the associated vasculature. MDCTA demonstrated a total of 38 significant stenoses in 25 patients. DSA verified 37 stenoses in 24 patients and demonstrated two additional stenoses. MDCTA had thus a sensitivity of 95%. All 24 patients were treated with percutaneous transluminal angioplasty (PTA) with good technical results.

    Conclusion: MDCTA with 3D reconstructions of dysfunctioning AVFs and AVGs in hemodialysis patients is an accurate and reliable diagnostic method helping customize future intervention.

    Keywords
    CT angiography; hemodialysis; arteriovenous fistula; arteriovenous grafts; 3D reconstructions
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-160999 (URN)10.1258/ar.2011.110255 (DOI)000297489200001 ()21969710 (PubMedID)
    Available from: 2011-11-04 Created: 2011-11-04 Last updated: 2017-12-08Bibliographically approved
    2. Preoperative CT angiography reduces surgery time in perforator flap reconstruction
    Open this publication in new window or tab >>Preoperative CT angiography reduces surgery time in perforator flap reconstruction
    Show others...
    2009 (English)In: Journal of plastic, reconstructive & aesthetic surgery : JPRAS, ISSN 1748-6815, Vol. 62, no 9, p. 1112-1117Article in journal (Refereed) Published
    Abstract [en]

    The use of perforator flaps in breast reconstructions has increased considerably in the past decade. A disadvantage of the perforator flap is difficult dissection, which results in a longer procedure. During spring 2006, we introduced CT angiography (CTA) as part of the diagnostic work-up in perforator flap reconstructions to visualise each perforator more accurately. The main objectives were to reduce surgery time and the number of complications. A chart review was conducted 1 year after CTA introduction to investigate if these objectives were met. MATERIALS AND METHODS: Patients with a deep inferior epigastric perforator (DIEP) flap who underwent preoperative analysis through CTA were retrospectively evaluated. The population <0.001) than in the control group, 264 min (SD+/-62) versus 354 min (SD+/-83), respectively. There was a tendency for fewer complications in the CTA group compared with the control group. All flaps were successful in the CTA group. In the control group, one flap failed and partial necrosis occurred in three flaps. The differences were not statistically significant. CONCLUSIONS: Preoperative CTA in the assessment of vascular anatomy during perforator flap reconstruction was safe and reliable. It helped reduce surgery time, and may prevent the number of postoperative complications.

    Keywords
    DIEP, Perforator flap, CT angiography, Surgery time
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-108874 (URN)10.1016/j.bjps.2007.12.090 (DOI)000270162600002 ()18675605 (PubMedID)
    Available from: 2009-10-01 Created: 2009-10-01 Last updated: 2013-01-23Bibliographically approved
    3. A new technique for visualisation of complex renal calculi using Dual Energy CT and image merging, in the preoperative work-up of patients undergoing Percutaneous Nephrolithotomy
    Open this publication in new window or tab >>A new technique for visualisation of complex renal calculi using Dual Energy CT and image merging, in the preoperative work-up of patients undergoing Percutaneous Nephrolithotomy
    (English)Manuscript (preprint) (Other academic)
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:uu:diva-182092 (URN)
    Available from: 2012-10-03 Created: 2012-10-03 Last updated: 2013-01-23
    4. Dual Energy CT in patients with complicated renal calculi undergoing Percutaneous Nephrolithotomy: virtual nonenhanced images vs. true nonenhanced images; correlation on calculi number, volume, size and attenuation
    Open this publication in new window or tab >>Dual Energy CT in patients with complicated renal calculi undergoing Percutaneous Nephrolithotomy: virtual nonenhanced images vs. true nonenhanced images; correlation on calculi number, volume, size and attenuation
    (English)Manuscript (preprint) (Other academic)
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Research subject
    Radiology
    Identifiers
    urn:nbn:se:uu:diva-182094 (URN)
    Available from: 2012-10-03 Created: 2012-10-03 Last updated: 2013-01-23
  • 274.
    Dimopoulou, Angeliki
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Raland, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    MDCT angiography with 3D image reconstructions in the evaluation of failing arteriovenous fistulas and grafts in hemodialysis patients2011In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 52, no 9, p. 935-942Article in journal (Refereed)
    Abstract [en]

    Background: Arteriovenous fistulas and grafts are the methods of choice for vascular access in renal failure patients in need of hemodialysis. Their major complication, however, is stenosis, which might lead to thrombosis.

    Purpose: To demonstrate the usefulness of 16-MDCTA with 3D image reconstructions, in long-term hemodialysis patients with dysfunctional arteriovenous fistulas and grafts (AVF and AVG).

    Material and Methods: During a 17-month period, 31 patients with dysfunctional AVF and AVG (24 AVF and seven AVG) were examined with MDCTA with 3D image postprocessing. Parameters such as comprehension of the anatomy, quality of contrast enhancement, and pathological vascular changes were measured. DSA was then performed in 24 patients.

    Results: MDCTA illustrated the anatomy of the AVF/AVG and the entire vascular tree to the heart, in a detailed and comprehensive manner in 93.5% of the evaluated segments, and depicted pathology of AVF/AVG or pathology of the associated vasculature. MDCTA demonstrated a total of 38 significant stenoses in 25 patients. DSA verified 37 stenoses in 24 patients and demonstrated two additional stenoses. MDCTA had thus a sensitivity of 95%. All 24 patients were treated with percutaneous transluminal angioplasty (PTA) with good technical results.

    Conclusion: MDCTA with 3D reconstructions of dysfunctioning AVFs and AVGs in hemodialysis patients is an accurate and reliable diagnostic method helping customize future intervention.

  • 275.
    Dimopoulou, Angeliki
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Dual Energy CT in patients with complicated renal calculi undergoing Percutaneous Nephrolithotomy: virtual nonenhanced images vs. true nonenhanced images; correlation on calculi number, volume, size and attenuationManuscript (preprint) (Other academic)
  • 276.
    Dimopoulou, Angeliki
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Åslund, Per-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Medical Physics.
    Magnusson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    A new technique for visualisation of complex renal calculi using Dual Energy CT and image merging, in the preoperative work-up of patients undergoing Percutaneous NephrolithotomyManuscript (preprint) (Other academic)
  • 277. Du, Likun
    et al.
    Peng, Roujun
    Björkman, Andrea
    Filipe de Miranda, Noel
    Rosner, Cornelia
    Kotnis, Ashwin
    Berglund, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Liu, Chonghai
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Hematology and Immunology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Hojjat-Farsangi, Mohammad
    Rabbani, Hodjattallah
    Teixeira, Manuel R
    Revy, Patrick
    Durandy, Anne
    Zeng, Yixin
    Gennery, Andrew R
    de Villartay, Jean-Pierre
    Pan-Hammarström, Qiang
    Cernunnos influences human immunoglobulin class switch recombination and may be associated with B cell lymphomagenesis2012In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 209, no 2, p. 291-305Article in journal (Refereed)
    Abstract [en]

    Cernunnos is involved in the nonhomologous end-joining (NHEJ) process during DNA double-strand break (DSB) repair. Here, we studied immunoglobulin (Ig) class switch recombination (CSR), a physiological process which relies on proper repair of the DSBs, in B cells from Cernunnos-deficient patients. The pattern of in vivo generated CSR junctions is altered in these cells, with unusually long microhomologies and a lack of direct end-joining. The CSR junctions from Cernunnos-deficient patients largely resemble those from patients lacking DNA ligase IV, Artemis, or ATM, suggesting that these factors are involved in the same end-joining pathway during CSR. By screening 269 mature B cell lymphoma biopsies, we also identified a somatic missense Cernunnos mutation in a diffuse large B cell lymphoma sample. This mutation has a dominant-negative effect on joining of a subset of DNA ends in an in vitro NHEJ assay. Translocations involving both Ig heavy chain loci and clonal-like, dynamic IgA switching activities were observed in this tumor. Collectively, our results suggest a link between defects in the Cernunnos-dependent NHEJ pathway and aberrant CSR or switch translocations during the development of B cell malignancies.

  • 278.
    Dubois, Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Andersson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Asplund, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Björkelund, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Evaluating real-time immunohistochemistry on multiple tissue samples, multiple targets and multiple antibody labeling methods2013In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 6, p. 542-Article in journal (Refereed)
    Abstract [en]

    Background

    Immunohistochemistry (IHC) is a well-established method for the analysis of protein expression in tissue specimens and constitutes one of the most common methods performed in pathology laboratories worldwide. However, IHC is a multi-layered method based on subjective estimations and differences in staining and interpretation has been observed between facilities, suggesting that the analysis of proteins on tissue would benefit from protocol optimization and standardization. Here we describe how the emerging and operator independent tool of real-time immunohistochemistry (RT-IHC) reveals a time resolved description of antibody interacting with target protein in formalin fixed paraffin embedded tissue. The aim was to understand the technical aspects of RT-IHC, regarding generalization of the concept and to what extent it can be considered a quantitative method.

    Results

    Three different antibodies labeled with fluorescent or radioactive labels were applied on nine different tissue samples from either human or mouse, and the results for all RT-IHC analyses distinctly show that the method is generally applicable. The collected binding curves showed that the majority of the antibody-antigen interactions did not reach equilibrium within 3 hours, suggesting that standardized protocols for immunohistochemistry are sometimes inadequately optimized. The impact of tissue size and thickness as well as the position of the section on the glass petri dish was assessed in order for practical details to be further elucidated for this emerging technique. Size and location was found to affect signal magnitude to a larger extent than thickness, but the signal from all measurements were still sufficient to trace the curvature. The curvature, representing the kinetics of the interaction, was independent of thickness, size and position and may be a promising parameter for the evaluation of e.g. biopsy sections of different sizes.

    Conclusions

    It was found that RT-IHC can be used for the evaluation of a number of different antibodies and tissue types, rendering it a general method. We believe that by following interactions over time during the development of conventional IHC assays, it becomes possible to better understand the different processes applied in conventional IHC, leading to optimized assay protocols with improved sensitivity.

  • 279. Dueland, Svein
    et al.
    Guren, Tormod K.
    Hagness, Morten
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Line, Pal-Dag
    Pfeiffer, Per
    Foss, Aksel
    Tveit, Kjell M.
    Chemotherapy or Liver Transplantation for Nonresectable Liver Metastases From Colorectal Cancer?2015In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 261, no 5, p. 956-960Article in journal (Refereed)
    Abstract [en]

    Objective: The primary objective was to compare overall survival (OS) in patients with colorectal cancer (CRC) with nonresectable liver-only metastases treated by liver transplantation or chemotherapy. Background: CRC is the third most common cancer worldwide. About 50% of patients will develop metastatic disease primarily to the liver and the lung. The majority of patients with liver metastases receive palliative chemotherapy, with a median OS of trial patients of about 2 years, and less than 10% are alive at 5 years. Methods: Patients with nonresectable liver-only CRC metastases underwent liver transplantation in the SECA study (n = 21). Disease-free survival (DFS) and OS of patients included in the SECA study were compared with progression-free survival (PFS) and OS in a similar cohort of CRC patients with liver-only disease included in a first-line chemotherapy study, the NORDIC VII study (n = 47). PFS/DFS and OS were estimated by the Kaplan-Meier method. Results: DFS/PFS in both groups were 8 to 10 months. However, a dramatic difference in OS was observed. The 5-year OS rate was 56% in patients undergoing liver transplantation compared with 9% in patients starting first-line chemotherapy. The reason for the large difference in OS despite similar DFS/PFS is likely different metastatic patterns at relapse/progression. Relapse in the liver transplantation group was often detected as small, slowly growing lung metastases, whereas progression of nonresectable liver metastases was observed in the chemotherapy group. Conclusions: Compared with chemotherapy, liver transplantation resulted in a marked increased OS in CRC patients with nonresectable liver-only metastases.

  • 280. Dueland, Svein
    et al.
    Kyrre, Tormod
    Hagness, Guren Morten
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Line, Pal-Dag
    Pfeiffer, Per
    Foss, Aksel
    Tveit, Kjell Magne
    Outcome after liver transplantation compared with chemotherapy in colorectal cancer patients with nonresectable liver-only disease.2014In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, no 3Article in journal (Other academic)
  • 281.
    Duvernoy, Olov
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Borowiec, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Helmius, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Erikson, Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Complications of percutaneous pericardiocentesis under fluoroscopic guidance1992In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 33, no 4, p. 309-313Article in journal (Refereed)
    Abstract [en]

    Complications in 352 cases of fluoroscopy-guided percutaneous pericardiocentesis accomplished through an indwelling catheter were reviewed following surgery and non-surgery. Thirteen major complications were found, namely 3 cardiac perforations, 2 cardiac arrhythmias, 4 cases of arterial bleeding, 2 cases of pneumothorax in children, one infection, and one major vagal reaction. No significant difference in complications was found between pericardiocenteses for pericardial effusions after cardiac surgery (n = 208) and those for effusions of non-surgical (n = 144) origin. Fluoroscopy-guided pericardiocentesis by the subxiphoid approach with placement of an indwelling catheter is a safe method for achieving pericardial drainage in both surgical and non-surgical effusions. Accidental cardiac perforation with a fine needle is a minor complication as long as the needle is directed towards the anterior diaphragmatic border of the right ventricle and drainage is achieved with a reliable indwelling catheter.

  • 282.
    Ebeling Barbier, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Several sources of error in estimation of left ventricular mass with M-mode echocardiography in elderly subjects2011In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 116, no 4, p. 258-64Article in journal (Refereed)
    Abstract [en]

    Introduction. M-mode echocardiography estimates of the left ventricular mass (LVM) were greater than magnetic resonance imaging (MRI) estimates. There are substantial differences between the methods both in the means of measuring and the calculation formula. The aim of this study was to investigate whether any difference in estimates of LVM between M-mode echocardiography and MRI is due to the means of measuring or to the calculation formula, using MRI as the gold standard.

    Material and methods. M-mode echocardiography and MRI were performed on 229 randomly selected 70-year-old community-living subjects. LVM was calculated from echocardiography (LVM(echo)) and from MRI (LVM(MRI)) measurements using standard techniques. Additionally LVM was calculated with the echocardiography formula from echo-mimicking measurements made on MR images (LVM(MRI/ASE)).

    Results. There were significant differences between all three LVM estimates in women, in men, and in the entire population. Echocardiography estimated LVM to be larger than did MRI, and the LVM(MRI/ASE) estimate was larger than the LVM(MRI). The difference between LVM(MRI) and LVM(MRI/ASE) was larger than the difference between LVM(echo) and LVM(MRI/ASE). There was a low correlation between LVM(echo) and LVM(MRI) (R(2) = 0.46) as well as between LVM(MRI/ASE) and LVM(MRI) (R(2) = 0.65).

    Conclusion. The means of measuring and the calculation formula both independently add to the error in LVM estimation with M-mode echocardiography. The error of the calculation formula seems to be greater than the error of the means of measuring in a population of community-living elderly men and women.

  • 283.
    Ebeling Barbier, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lundin, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Melki, Vilyam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    James, Stefan K.
    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.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Percutaneous Closure in Transfemoral Aortic Valve Implantation: A Single-Centre Experience2015In: Cardiovascular and Interventional Radiology, ISSN 0174-1551, E-ISSN 1432-086X, Vol. 38, no 6, p. 1438-1443Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To report the experience of a percutaneous closure device used for transfemoral transcatheter aortic valve implantation (TAVI) in an unselected patient and operator population.

    MATERIALS AND METHODS: Eighty-two consecutive patients (32 women, 50 men) who underwent transfemoral TAVI between September 2009 and February 2014 at our hospital were retrospectively reviewed for percutaneous closure device (PCD) failure, vascular complications, and bleeding. The diameter and calcification of the common femoral artery (CFA) and the thickness of the subcutaneous fat layer in the groin were assessed on computed tomography images.

    RESULTS: The incidences of PCD failure and minor and major vascular complications were 19.5 % (n = 16/82), 19.5 % (n = 16/82), and 7 % (n = 6/82) respectively. 8.5 % (n = 7/82) had a minor perioperative bleeding, 6 % (n = 5/82) had a major bleeding, and none had any life-threatening bleeding. When PCD failed, haemostasis was obtained with fascia suturing, covered stent placement, or with surgical cutdown. Thirty-day mortality and 1-year all-cause mortality were 8.5 % (n = 7/82) and 19.5 % (n = 16/82), respectively. In a multiple regression analysis, the CFA diameter and the presence of severe calcification were independently related to PCD failure (correlation coefficient = -0.24, p = 0.027 and correlation coefficient = 0.23, p = 0.036, respectively).

    CONCLUSION: PCD failure was related to a small CFA diameter and to a severely calcified CFA. Failure could largely be managed with minimally invasive techniques such as covered stents or fascia suturing.

  • 284.