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  • 201.
    Canto Moreira, Nuno
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ribeiro, Valentina
    Hospital S. Antonio, Porto, Portugal.
    Teixeira, João
    Hospital S. Antonio, Porto, Portugal.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Visualisation of the fetal lip and palate: is brain-targeted MRI reliable?2011In: Neurology, ISSN 0028-3878, E-ISSN 1526-632XArticle in journal (Other academic)
    Abstract [en]

    Introduction: The purpose of the study was to evaluate the ability of brain-targeted MRI to assess the anatomy of the fetal upper lip and palate.

     

    Methods: Two independent readers made a blind retrospective review of 60 MRI of fetuses of 20 to 38 gestational weeks (GW). Fifty-five fetuses had normal post-natal follow-up.  Five fetuses had oro-facial anomalies at post-natal follow-up, including five cleft lips (two bilateral, three unilateral), four cleft primary palates (two bilateral, two unilateral) and two cleft secondary palates.

    The upper lip, primary palate, secondary palate and nasal septum were scored into four levels, from evidently normal to evidently abnormal. In case of a suspected pathology, the readers attempted a diagnosis.

     

    Results: Interobserver agreement (weighted kappa) was 0.79 for the upper lip, 0.70 for the primary palate, 0.86 for the secondary palate, and 0.90 for the nasal septum. The scoring levels of the readers did not change significantly across gestational age.

    The readers identified 100% of all pathological cases. The normality was correctly scored in 96-100% of the normal lips and primary palates and in 93-97% of the normal secondary palates depending on the reader. A deviated septum was only scored in two fetuses with unilateral cleft palates.

     

    Conclusion:  MRI in experienced hands seems reliable for assessment of the fetal lip and palate, even in brain-targeted examinations. Attention should therefore be paid to the lip and palate in all fetal MRI examinations, since unsuspected clefts may be revealed.

     

     

  • 202.
    Canto Moreira, Nuno
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Teixeira, J.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    The ear in fetal MRI: What can we really see?2011In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 53, no Suppl 1, p. S23-Article in journal (Refereed)
  • 203.
    Canto Moreira, Nuno
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Teixeira, João
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    The ear in fetal MRI: what can we really see?2011In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 53, no 12, p. 1001-1008Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The aim of this study was to investigate the ability to depict the components of the ear on brain-oriented fetal MRI studies.

    METHODS: Retrospective evaluation of the ear in MRI studies was performed post-mortem in 16 fetuses ranging from 15 to 22 gestation weeks (GW), and in 122 examinations in vivo of fetuses ranging from 20 to 38 GW. The cochlea, vestibular apparatus, middle ear, and external auditory canal were separately graded according to the components that were delineated.

    RESULTS: The components of the inner and middle ear were fully delineated in 100% of the post-mortem examinations, but the external auditory canals were only seen in only 25%. In the in vivo group, the imaging detail was much lower. Cochlear turns could be identified in 75% of the fetuses, the vestibule and the lateral semicircular canals in 72% andossicles in 70%. Before 25 GW, the ability to identify these individual parts was 50%, 30%, and 33%, respectively, and above it was 89%, 93%, and 90% . In most cases, the external auditory canals could only be seen after 29 GW.

    CONCLUSION: In fetal MRI studies in vivo, it is possible to depict the components of the ear in the majority of the fetuses, in such a manner as to exclude major malformations. However, MRI might not provide enough detail to rule out pathology of the ear before 25 GW, this being a critical age for pregnancy management in many countries.

  • 204.
    Canto Moreira, Nuno
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Teixeira, João
    Department of Neuroradiology, H. G. S. Antonio, Porto, Portugal.
    Themudo, Raquel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Amini, Hashem
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Raininko, Raili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Measurements of the normal fetal brain at gestation weeks 17 to 23: a MRI study2011In: Neuroradiology, ISSN 0028-3940, E-ISSN 1432-1920, Vol. 53, no 1, p. 43-48Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: To obtain measurements of the normal fetal brain before 24 weeks of gestation (GW), a deadline for medical decisions on fetal viability in a large number of countries. METHODS: We retrospectively reviewed 70 normal MR examinations of fetuses aged GW 17 to 23. The fronto-occipital diameter, the cerebral bi-parietal diameter, the transverse cerebellar diameter, the vermian height, and antero-posterior diameter were measured. RESULTS: The median, maximum, and minimum values for each parameter were displayed for each individual GW. CONCLUSION: The recorded data might contribute to a better assessment of fetal health by providing normal boundaries for the brain growth.

  • 205. Caplin, Martyn
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nillson, Ola
    Baum, Richard P
    Klose, Klaus J
    Kelestimur, Fahrettin
    Plöckinger, Ursula
    Papotti, Mauro
    Salazar, Ramon
    Pascher, Andreas
    ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: colorectal neuroendocrine neoplasms2012In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 95, no 2, p. 88-97Article in journal (Refereed)
  • 206. Carlson, K
    et al.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Simonsson, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    MR imaging of multiple myeloma in tumour mass measurement at diagnosis and during treatment1995In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 36, no 1, p. 9-14Article in journal (Refereed)
    Abstract [en]

    The bone marrow of the spine, pelvis and proximal femora was examined with MR imaging at diagnosis in 30 cases of multiple myeloma (MM), and during treatment on 69 occasions. The MR pattern was normal, focal or diffuse and correlated to stage. A tumour mass index (TMI) was calculated by estimating the total myeloma mass visualised at MR imaging. The TMI correlated significantly with stage, lytic bone lesions, serum calcium, serum beta-2-microglobulin and survival. No abnormalities were seen at MR investigation in 4 of 6 patients classified as stage II because of osteoporosis only. Therapy efficacy evaluation with MR imaging corresponded to clinical evaluation on 54 of the 69 occasions. MR examination of bone marrow in MM patients can be used for tumour mass assessment, both at diagnosis and during follow-up. Valuable information can be obtained when the tumour mass is difficult to estimate using clinical criteria, e.g. in non-secretory MM or when osteoporosis is the only variable indicating an increase in the tumour mass.

  • 207.
    Carlsson, J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Shen, L.
    Xiang, J.
    Xu, J.
    Wei, Q.
    Tendencies for higher co-expression of EGFR and HER2 and downregulation of HER3 in prostate cancer lymph node metastases compared with corresponding primary tumors2013In: Oncology Letters, ISSN 1792-1074, Vol. 5, no 1, p. 208-214Article in journal (Refereed)
    Abstract [en]

    The epidermal growth factor receptor (EGFR) family members are potential targets for therapy using extracellular domain receptor binding agents, such as the antibodies trastuzumab and cetuximab, or antibodies labeled with therapeutically useful radionuclides or toxins. This is especially the case when the tumor cells are resistant to chemotherapy and tyrosine kinase inhibitors. Studies concerning the expression of these receptors in prostate cancer vary in the literature, possibly due to differences in patient inclusion, sample preparations and scoring criteria. In our study, EGFR, HER2 and HER3 expression was analyzed in prostate cancer samples from primary tumors and corresponding lymph node metastases from 12 patients. The expression of HER2 and EGFR was scored from immunohistochemical preparations and the HercepTest criteria (0, 1+, 2+ or 3+), while HER3 expression was scored as no, weak or strong staining. There were 5 EGER-positive (2+ or 3+) primary tumors and 6 EGFR-positive lymph node metastases, and there was EGFR upregulation in one metastasis. Only 4 of the 12 patients had marked HER2 expression (2+ or 3+) in their primary tumors and there was one downregulation and 5 cases of upregulation in the metastases. Thus, a total of 8 out of 12 analyzed metastases were HER2-positive. Of the 12 primary tumors, 9 expressed HER3 while only 2 of the lymph node metastases expressed recognizable HER3 staining, so 7 metastases appeared to have downregulated HER3 expression. In one of the primary tumors there was positive co-expression of EGFR and HER2, while this co-expression was observed in 4 of the metastases. Thus, there were tendencies for upregulation of HER2, increased co-expression of EGFR and HER2 and downregulation of HER3 in the prostate cancer lymph node metastases in comparison to the primary tumors. The results are encouraging for studies involving more patients. Possible strategies for EGFR- and HER2-targeted therapy are briefly discussed in the present study, especially with regard to the expression and co-expression of EGFR and HER2 in metastases.

  • 208.
    Carlsson, Jorgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Imaging ff HER2-Expression in Breast Cancer Metastases (Review)2014In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 10, p. 5855-5855Article in journal (Other academic)
  • 209.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Potential for clinical radionuclide-based imaging and therapy of common cancers expressing EGFR-family receptors2012In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 33, no 3, p. 653-659Article in journal (Refereed)
    Abstract [en]

    High expression of epidermal growth factor receptor (EGFR)-family receptors, especially EGFR, HER2, and HER3, makes them interesting for targeted radionuclide-based imaging and therapy of disseminated cancer. The expression in some commonly occurring cancers such as breast, prostate, colorectal, and urinary bladder cancers is summarized. Possible strategies for radionuclide-based imaging and therapy are briefly discussed, especially in relation to the receptor expression in metastases.

  • 210. Caroli, A.
    et al.
    Prestia, A.
    Galluzzi, S.
    Ferrari, C.
    van der Flier, W. M.
    Ossenkoppele, R.
    Van Berckel, B.
    Barkhof, F.
    Teunissen, C. E.
    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.
    Carter, S. F.
    Scholl, M.
    Choo, I. H.
    Grimmer, T.
    Nordberg, A.
    Scheltens, P.
    Drzezga, A.
    Frisoni, G. B.
    Mild cognitive impairment with suspected non AD pathology (SNAP): prediction of progression to dementia2014In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 261, no S1, p. S14-S14, article id OS1103Article in journal (Other academic)
  • 211. Caroli, A.
    et al.
    Prestia, A.
    Galluzzi, S.
    Ferrari, C.
    van der Flier, W. M.
    Ossenkoppele, R.
    Van Berckel, B.
    Barkhof, F.
    Teunissen, C. E.
    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.
    Carter, S. F.
    Scholl, M.
    Choo, I. H.
    Grimmer, T.
    Nordberg, A.
    Scheltens, P.
    Drzezga, A.
    Frisoni, G. B.
    Mild cognitive impairment with suspected non AD pathology (SNAP): prediction of progression to dementia2014In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 21, p. 19-19Article in journal (Other academic)
  • 212. Caroli, Anna
    et al.
    Prestia, Annapaola
    Galluzzi, Samantha
    Ferrari, Clarissa
    van der Flier, Wiesje M.
    Ossenkoppele, Rik
    Van Berckel, Bart
    Barkhof, Frederik
    Teunissen, Charlotte
    Wall, Anders E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Carter, Stephen F.
    Schoell, Michael
    Choo, Il Han
    Grimmer, Timo
    Redolfi, Alberto
    Nordberg, Agneta
    Scheltens, Philip
    Drzezga, Alexander
    Frisoni, Giovanni B.
    Mild cognitive impairment with suspected nonamyloid pathology (SNAP) Prediction of progression2015In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 84, no 5, p. 508-515Article in journal (Refereed)
    Abstract [en]

    Objectives:The aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non-Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI).Methods:We measured markers of amyloid pathology (CSF -amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [F-18]-fluorodeoxyglucose-PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A+/A- and N+/N- based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A-N+ cases.Results:The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71% (60/85) in A-N-, A+N-, SNAP, and A+N+, respectively; the proportion of APOE epsilon 4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A+N- and A+N+ groups (p 0.005). Hypometabolism in SNAP patients was comparable to A+N+ patients (p = 0.154), while hippocampal atrophy was more severe in SNAP patients (p = 0.002). Compared with A-N-, SNAP and A+N+ patients had significant risk of progressive cognitive deterioration (hazard ratio = 2.7 and 3.8, p = 0.016 and p < 0.001), while A+N- patients did not (hazard ratio = 1.13, p = 0.771). In A+N- and A+N+ groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r = 0.42, p = 0.073).Conclusions:Our findings support the notion that patients with SNAP MCI feature a specific risk progression profile.

  • 213. Carter, Stephen F.
    et al.
    Scholl, Michael
    Almkvist, Ove
    Wall, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Engler, Henry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Nordberg, Agneta
    Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by (11)C-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining (11)C-Pittsburgh Compound B and (18)F-FDG2012In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 53, no 1, p. 37-46Article in journal (Refereed)
    Abstract [en]

    Astrocytes colocalize with fibrillar amyloid-beta (A beta) plaques in postmortem Alzheimer disease (AD) brain tissue. It is therefore of great interest to develop a PET tracer for visualizing astrocytes in vivo, enabling the study of the regional distribution of both astrocytes and fibrillar A beta. A multitracer PET investigation was conducted for patients with mild cognitive impairment (MCI), patients with mild AD, and healthy controls using (11)C-deuterium-L-deprenyl ((11)C-DED) to measure monoamine oxidase B located in astrocytes. Along with (11)C-DED PET, (11)C-Pittsburgh compound B ((11)C-PIB; fibrillar A beta deposition), (18)F-FDG (glucose metabolism), T1 MRI, cerebrospinal fluid, and neuropsychologic data were acquired from the patients. Methods: (11)C-DED PET was performed in MCI patients (n = 8; mean age 6 SD, 62.6 +/- 7.5 y; mean Mini Mental State Examination, 27.5 +/- 2.1), AD patients (n = 7; mean age, 65.1 +/- 6.3 y; mean Mini Mental State Examination, 24.4 +/- 5.7), and healthy age-matched controls (n = 14; mean age, 64.7 +/- 3.6 y). A modified reference Patlak model, with cerebellar gray matter as a reference, was chosen for kinetic analysis of the (11)C-DED data. (11)C-DED data from 20 to 60 min were analyzed using a digital brain atlas. Mean regional (18)F-FDG uptake and (11)C-PIB retention were calculated for each patient, with cerebellar gray matter as a reference. Results: ANOVA analysis of the regional (11)C-DED binding data revealed a significant group effect in the bilateral frontal and bilateral parietal cortices related to increased binding in the MCI patients. All patients, except 3 with MCI, showed high (11)C-PIB retention. Increased (11)C-DED binding in most cortical and subcortical regions was observed in MCI (11)C-PIB+ patients relative to controls, MCI (11)C-PIB (negative) patients, and AD patients. No regional correlations were found between the 3 PET tracers. Conclusion: Increased (11)C-DED binding throughout the brain of the MCI (11)C-PIB+ patients potentially suggests that astrocytosis is an early phenomenon in AD development.

  • 214.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Ehrsson, H
    Wallin, I
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Pharmacokinetics of cisplatin during hyperthermic intraperitoneal treatment of peritoneal carcinomatosis2013In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 69, no 3, p. 533-540Article in journal (Refereed)
    Abstract [en]

    Purpose

    Cisplatin during hyperthermic intraperitoneal chemotherapy (HIPEC) has not previously been measured with a selective technique. The primary aims were to examine the pharmacokinetics of active cisplatin and its monohydrated complex (MHC) during HIPEC using a specific measuring technique, to compare cisplatin’s systemic absorption with oxaliplatin, and to compare active cisplatin levels to that of total platinum.

    Methods

    Ten patients treated with cytoreductive surgery and HIPEC (cisplatin 50 mg/m2,doxorubicin 15 mg/m2) were recruited. Blood and perfusate samples were drawn during and after HIPEC. Cisplatin analysis was conducted using liquid chromatography (LC) with post-column derivatization with diethyldithiocarbamate and compared with inductively coupled plasma-mass spectrometry (ICP-MS).

    Results

    The mean half-life (t1/2) of perfusate cisplatin was 18.4 min, with area under the time-concentration curve (AUC) 0–90 min of 2.87 mM·min and estimated 0–60 min of 2.45 mM·min. The absorption t1/2 was 9.0 min for cisplatin and 18.2 min for oxaliplatin. The ratio of total platinum to active cisplatin increased in a linear manner by time of perfusion.

    Conclusions

    Cisplatin is absorbed quicker than oxaliplatin. Lowering the perfusion time to 60 min does not significantly change the pharmacokinetics of cisplatin, and is therefore to be considered. As the HIPEC perfusion progresses, the ICP-MS technique does not adequately reflect active cisplatin levels in the perfusate

  • 215.
    Cashin, Peter H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Comparison of Prognostic Scores for Patients with Colorectal Cancer Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy2013In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 20, no 13, p. 4183-4189Article in journal (Refereed)
    Abstract [en]

    Background. There are three prognostic scores for the cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment of colorectal cancer peritoneal metastases: the newly introduced COREP (colorectal peritoneal) score, the peritoneal surface disease severity score (PSDS), and the prognostic score (PS). The aim was to determine which prognostic score had the best prognostic value. Methods. Between 2006 and 2010, a total of 77 patients with peritoneal metastases fromcolorectal cancer underwent CRS/HIPEC treatment. The COREP, PSDS, and PS scores were successfully applied to 56 patients (73 %) having sufficient data. The end points were prediction of open-and-close cases (n = 9), R1 resections (n = 41), and survival of <12 months (n = 18). Area under the receiver operating characteristic curves (accuracy) was compared. Subgroup analysis was performed on patients not previously used for the development of the COREP score (n = 24). Multivariable logistic regressions of the three end points were performed as well as Cox regression for overall survival. Furthermore, COREP and peritoneal cancer index were compared. Results. For open-and-close case prediction, accuracy for the whole group (n = 56) and subgroup (n = 24) was 87 and 88 %, respectively for COREP; 66 and 77 % for PSDS; and 68 and 78 % for PS. For R1 resection prediction, accuracy was 81 and 81 %, 76 and 78 %, and 75 and 77 %, respectively. For prediction of survival of <12 months, accuracy was 83 and 84, 54 and 67 %, and 55 and 56 %, respectively. The COREP score was the only independent prognostic factor in all four multivariable analyses. A COREP score of >= 6 identified patients with poor survival more accurately than a PCI of >20. Conclusions. The COREP score predicted open-and-close cases, R1 resections, and poor survival better than PSDS and PS. COREP better identifies patients with poor survival than intraoperative PCI.

  • 216.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Prognosis and Treatment of Recurrences in a Cohort Study2012In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, no 6, p. 509-515Article in journal (Refereed)
    Abstract [en]

    Background

    Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal carcinomatosis (PC) is gaining acceptance, but controversy remains. The primary aims were to analyze the outcome and prognostic variables of colorectal PC patients treated with CRS and IPC, and to report on the outcome of additional surgical treatments of subsequent recurrences.

    Methods

    Patients referred for treatment of colorectal PC between 1996 and 2010 were included in a cohort. The following data was collected: clinicopathological parameters, survival, recurrences, perioperative chemotherapy and type of IPC (hyperthermic intraperitoneal chemotherapy, HIPEC; or sequential postoperative intraperitoneal chemotherapy, SPIC). Multivariable analyses were conducted on potential prognostic factors for overall survival (OS).

    Results

    In the 151-patient cohort, the median OS was 34months (range: 2-77) for CRS and HIPEC with five-year survival predicted at 40% (five-year disease-free survival 32%). For CRS and SPIC, the OS was 25months (range: 2-188) with five-year survival at 18%.  Open-and-close patients survived 6months (range: 0-14) with no five-year survival (HIPEC vs. SPIC p=0.047, SPIC vs. open-and-close p<0.001). Adjuvant systemic chemotherapy was a noteworthy independent prognostic factor in the multivariable analysis. OS for patients undergoing additional surgical treatment of recurrences was 25months vs. 10months with best supportive care or palliative chemotherapy (p=0.01).

    Conclusion

    Substantial long-term survival is possible in patients with colorectal PC. HIPEC was associated with better OS than SPIC and adjuvant systemic chemotherapy may improve the outcome in patients. Good OS is achievable in selected patients undergoing additional surgical treatment of isolated liver or peritoneal recurrences after prior complete CRS.

  • 217.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no 3, p. 647-652Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Cytoreductive surgery and intraperitoneal chemotherapy has improved prognosis in patients with peritoneal carcinomatosis. The main modes of intraperitoneal chemotherapy treatment are peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic sequential postoperative intraperitoneal chemotherapy (SPIC). The aim of this study was to compare HIPEC and SPIC with respect to overall survival, disease-free survival, morbidity, and mortality in patients with peritoneal carcinomatosis from colon cancer.

    PATIENTS AND METHODS:

    A matched case-control study was conducted in patients with surgical macroscopic complete removal of carcinomatosis; matching was according to the peritoneal cancer index score. Thirty-two patients were included, 16 in each group (HIPEC and SPIC). Overall survival, disease-free survival, morbidity, mortality, and clinicopathological parameters were compared.

    RESULTS:

    Median overall survival was 36.5 months in the HIPEC group and 23.9 months in the SPIC group (P = 0.01). Median disease-free survival for these groups was 22.8 (HIPEC) and 13.0 months (SPIC; P = 0.02). Morbidity was not statistically different, 19% in SPIC and 37% in HIPEC. Postoperative mortality was observed in one patient in each group.

    CONCLUSION:

    HIPEC was associated with improved overall survival and disease-free survival compared with SPIC at similar morbidity and mortality, suggesting that HIPEC is the treatment of choice in colonic peritoneal carcinomatosis.

  • 218.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study2012In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 256, no 6, p. 1078-1083Article in journal (Refereed)
    Abstract [en]

    Objective: There were 2 objectives: first, to investigate how many patients were excluded from surgery on the basis of the radiological extent of the peritoneal carcinomatosis (PC) or the clinical examination; and second, to develop a score based primarily on serum tumor markers (STMs) that could predict short cancer-specific survival (<12 months). Background: Patient selection and prediction of prognosis is crucial for successful treatment of colorectal PC. Methods: All patients with colorectal PC referred for cytoreductive surgery and intraperitoneal chemotherapy (2005-2008) at Uppsala University hospital were included. Patients were divided into 2 groups-nonsurgery and surgery. Clinicopathological and laboratory parameters were collected in the surgery group. A Corep (COloREctal-Pc) score was developed using hazard ratios from histology, hematological status, serial serum tumor markers (STMs), and STM changes over time. Sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were calculated in a second validating dataset (n = 24) with a survival cutoff of less than 12 months. Results: A total of 107 patients were included in the study, 42 in the nonsurgery group and 65 in the surgery group. In the nonsurgery group, 2 patients were excluded solely on the basis of the radiological extent of PC and 7 patients on clinical examination. The Corep score ranged from 0 to 18. A score of 6 or more showed a validated sensitivity of 80%, specificity 100%, PPV 1.0, and NPV 0.93. Conclusions: Radiological extent of PC was not a main deciding factor for treatment decisions and had less impact than the clinical examination. The Corep score identified patients with short cancer-specific survival that may not be suitable for treatment.

  • 219.
    Cashin, Peter H.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Response to comments on 'Cytoreductive surgery and intraperitoneal chemotherapy'2012In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, no 10, p. 1012-1012Article in journal (Refereed)
  • 220.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Karlsson, Henning
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer2013In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, p. 435-Article in journal (Refereed)
    Abstract [en]

    Background: The optimal choice of cytotoxic drugs for intraperitoneal chemotherapy (IPC) in conjunction with cytoreductive surgery (CRS) for treatment of peritoneal carcinomatosis(PC) is poorly defined. We investigated drug sensitivity ex vivo in patient samples of various PC tumor types and correlated clinical outcome to drug sensitivity within the subset of PC fromcolorectal cancer (CRC). 

    Methods: PC tissue samples (n = 174) from mesothelioma, pseudomyxoma peritonei (PMP), ovarian cancer, CRC or appendix cancer were analyzed ex vivo for sensitivity to oxaliplatin, cisplatin, mitomycin C, melphalan, irinotecan, docetaxel, doxorubicin and 5-FU. Clinicopathological variables and outcome data were collected for the CRC subset. 

    Results: Mesothelioma and ovarian cancer were generally more drug sensitive than CRC, appendix cancer and PMP. Oxaliplatin showed the most favorable ratio between achievable IPC concentration and ex vivo drug sensitivity. Drug sensitivity in CRC varied considerably between individual samples. Ex vivo drug sensitivity did not obviously correlate to time-to-progression (TTP) in individual patients. 

    Conclusions: Drug-sensitivity varies considerably between PC diagnoses and individual patients arguing for individualized therapy in IPC rather than standard diagnosis-specific therapy. However, in the current paradigm of treatment according to diagnosis, oxaliplatin is seemingly the preferred drug for IPC from a drug sensitivity and concentration perspective. Inthe CRC subset, analysis of correlation between ex vivo drug sensitivity and TTP was inconclusive due to the heterogeneous nature of the data.

  • 221.
    Cashin, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Andréasson, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Appendiceal Adenocarcinoids with Peritoneal Carcinomatosis Treated with Cytoreductive Surgery and Intraperitoneal Chemotherapy: a retrospective study of in vitro drug sensitivity and survival2011In: Clinical Colorectal Cancer, ISSN 1533-0028, Vol. 10, no 2, p. 108-112Article in journal (Refereed)
    Abstract [en]

    Purpose: The purpose of this study was to present results on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) of appendiceal adenocarcinoid (MC) with peritoneal carcinomatosis (PC), to assess drug sensitivity of AAC, as compared with colorectal cancer (CRC), and to report any discordant histopathology.

    Methods: Ten patients were treated with CRS and HIPEC. Treatment, drug sensitivity profiles, histopathology, and survival data were recorded and matched with potential prognostic indicators. Drug sensitivity was assessed with short-term fluorometric microculture cytotoxicity assay and compared with peritoneal metastases from CRC.

    Results: Patients with completeness of cytoreduction score (CC) 1 (16.4 months). In the CC 1 group. For standard drugs, tumor cells from MC and CRC were equally sensitive; except for docetaxel, to which MC was more sensitive than CRC.

    Conclusion: The CC-score correlated with overall survival. Candidates for this type of treatment should be referred early for evaluation in order to reach a better CC score. Drugs used for CRC also seem adequate for treatment of MC, although other drugs, eg, docetaxel, might be more active.

  • 222. Castano, J. P.
    et al.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Maecke, H. R.
    Villabona, C.
    Vazquez-Albertino, R.
    Navarro, E.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Gastrointestinal neuroendocrine tumors (NETs): new diagnostic and therapeutic challenges2014In: Cancer Metastasis Review, ISSN 0167-7659, E-ISSN 1573-7233, Vol. 33, no 1, p. 353-359Article, review/survey (Refereed)
    Abstract [en]

    This paper summarizes the current understanding of the biology of somatostatin receptor (sst), role of immunotherapy in neuroendocrine tumor (NET), new agents for PPRT, and methods to assess response and clinical benefit in NET. One of the most interesting aspects of sst biology is the recent discovery of truncated variants of the sst5 receptor subtype with unique tissue distribution and response to somatostatin (SST). These truncated receptors are associated with bad patient prognosis, decreased response to SST analogs, and may be new targets for diagnoses and treatment. IFN remains a cost-effective agent, particularly in classic mid gut carcinoids, and there is interest to continue examining immunotherapy's in this disease. PRRT remains a key strategy for treatment and imaging. In addition to the classic agents, there are a series of new agents targeting other receptors such as the incretin receptors (GLP-1R; GIPR) and other G-protein coupled receptors with great potential. With regards to therapy monitoring, the most commonly used criteria are Response Criteria Evaluation in Solid Tumors (RECIST). However, for different reasons, these criteria are not very useful in NET. Incorporation of other criteria such as Choi as well as functional imaging assessment with PET would be of great interest in this area.

  • 223.
    Cavalli-Björkman, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Factors Influencing Selection of Treatment for Colorectal Cancer Patients2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In Sweden and elsewhere there is evidence of poorer cancer survival for patients of low socioeconomic status (SES), and in some settings differences in treatment by SES have been shown.

    The aim of this thesis was to explore factors which influence cancer treatment decisions, such as knowledge reaped from clinical trials, patient-related factors, and physician-related factors. In a register study of colorectal cancer, all stages, patients were stratified for SES-factors. Differences were seen with regards to clinical investigation, surgical and oncological treatment and survival, with the highly educated group being favored. Survival was better for highly educated patients in stages I, II and III but not in stage IV.

    In a Scandinavian cohort of newly metastasized colorectal cancer patients, recruitment to clinical trials was studied. Patients entering clinical trials had better performance status and fewer cancer symptoms than those who were treated with chemotherapy outside of a clinical trial. Median survival was 21.3 months for trial-patients and 15.2 months for those treated with chemotherapy outside a  trial. Those not treated with chemotherapy had a median survival of just 2.1 months. Patients in clinical trials are highly selected and conclusions drawn from studies cannot be applied to all patients.

    In the same cohort, treatment and survival were stratified for education, smoking and indicators of social structure. Highly educated patients did not have a survival advantage. Patients who lived alone were offered less combination chemotherapy and surgery of metastases than other patients and had 4 months shorter survival than those who lived with a spouse or child. In a fourth study, 20 Swedish gastrointestinal oncologists were interviewed on which factors they considered when deciding on oncological treatment. Oncologists feared chemotherapy complications due to lack of social support, and ordered less combination chemotherapy for patients living alone. Highly educated patients were seen as well-read and demanding, and giving in to these patients’ requests for treatment was regarded as a way of pleasing patients and relatives and of avoiding conflict.

    List of papers
    1.
    The record could not be found. The reason may be that the record is no longer available or you may have typed in a wrong id in the address field.
    2. Clinical trial enrollment, patient characteristics, and survival differences in prospectively registered metastatic colorectal cancer patients
    Open this publication in new window or tab >>Clinical trial enrollment, patient characteristics, and survival differences in prospectively registered metastatic colorectal cancer patients
    Show others...
    2009 (English)In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 115, no 20, p. 4679-87Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Trial accrual patterns were examined to determine whether metastatic colorectal cancer (mCRC) patients enrolled in trials are representative of a general cancer population concerning patient characteristics and survival.

    METHODS: A total of 760 mCRC patients referred for their first oncological consideration at 3 hospitals in Scandinavia covering defined populations were registered consecutively during 2003 to 2006. Clinical trial enrollment, patient characteristics, and treatment were recorded prospectively, and the follow-up was complete.

    RESULTS: Palliative chemotherapy was initiated in 61% of the patients. Approximately one-third (36%) of patients receiving chemotherapy were included in a trial. The main reason for nonparticipation was failed eligibility criteria (69%). The median survival after chemotherapy was 15.8 months for all patients, and 18 months after combination chemotherapy. Trial patients had better prognostic characteristics and significantly longer survival than nontrial patients: 21.3 months versus 15.2 months when receiving combination chemotherapy. Poor performance status was the main reason for giving best supportive care only, and the median survival was then only 2.1 months. The median survival for all 760 nonresectable mCRC patients was 10.7 months.

    CONCLUSIONS: mCRC patients enrolled into clinical trials differ in characteristics from patients receiving chemotherapy outside protocol and have better survival, even when given the same treatment. Although trial patients have a median survival close to 2 years, survival is lower for all patients receiving chemotherapy and much lower for all patients diagnosed with mCRC. Studies that better accept the heterogeneity of the population with mCRC are needed.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-113895 (URN)10.1002/cncr.24527 (DOI)000270740900007 ()19562777 (PubMedID)
    Available from: 2010-02-04 Created: 2010-02-04 Last updated: 2017-12-12Bibliographically approved
    3. Lower treatment intensity and poorer survival in metastatic colorectal cancer patients who live alone
    Open this publication in new window or tab >>Lower treatment intensity and poorer survival in metastatic colorectal cancer patients who live alone
    Show others...
    2012 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 107, no 1, p. 189-194Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Socioeconomic status (SES) and social support influences cancer survival. If SES and social support affects cancer treatment has not been thoroughly explored. METHODS: A cohort consisting of all patients who were initially diagnosed with or who developed metastatic colorectal cancer (mCRC, n = 781) in three Scandinavian university hospitals from October 2003 to August 2006 was set up. Clinical and socioeconomic data were registered prospectively. RESULTS: Patients living alone more often had synchronous metastases at presentation and were less often treated with combination chemotherapy than those cohabitating (HR 0.19, 95% CI 0.04-0.85, P = 0.03). Surgical removal of metastases was less common in patients living alone (HR 0.29, 95% CI 0.10-0.86, P = 0.02) but more common among university-educated patients (HR 2.22, 95% CI 1.10-4.49, P = 0.02). Smoking, being married and having children did not influence treatment or survival. Median survival was 7.7 months in patients living alone and 11.7 months in patients living with someone (P < 0.001). Living alone remained a prognostic factor for survival after correction for age and comorbidity. CONCLUSION: Patients living alone received less combination chemotherapy and less secondary surgery. Living alone is a strong independent risk factor for poor survival in mCRC. 

    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-172517 (URN)10.1038/bjc.2012.186 (DOI)000305888400029 ()
    Available from: 2012-04-11 Created: 2012-04-11 Last updated: 2017-12-07Bibliographically approved
    4. Equal cancer treatment regardless of education level and family support?: A qualitative study of oncologists’ decision-making
    Open this publication in new window or tab >>Equal cancer treatment regardless of education level and family support?: A qualitative study of oncologists’ decision-making
    2012 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, no 4, p. e001248-Article in journal (Refereed) Published
    Abstract [en]

    Objective: Treatment gradients by socioeconomic status have been observed within cancer care in several countries. The objective of this study was to explore whether patients' educational level and social network influence oncologists' clinical decision-making. Design: Semi-structured interviews on factors considered when deciding on treatment for cancer patients. Interviews were transcribed and analysed using inductive qualitative content analysis. Setting: Oncologists in Swedish university-and non-university hospitals were interviewed in their respective places of work. Participants: Twenty Swedish clinical oncologists selected through maximum-variation sampling. Primary and secondary outcome measures: Elements which influence oncologists' decision-making process were explored with focus on educational level and patients' social support systems. Results: Oncologists consciously used less combination chemotherapy for patients living alone, fearing treatment toxicity. Highly educated patients were considered as well-read, demanding and sometimes difficult to reason with. Patients with higher education, those very keen to have treatment and persuasive relatives were considered as challenges for the oncologist. Having large groups of relatives in a room made doctors feel outnumbered. A desire to please patients and relatives was posed as the main reason for giving in to patients' demands, even when this resulted in treatment with limited efficacy. Conclusions: Oncologists tailor treatment for patients living alone to avoid harmful side-effects. Many find patients' demands difficult to handle and this may result in strong socioeconomic groups being over-treated.

    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-172518 (URN)10.1136/bmjopen-2012-001248 (DOI)000315049300078 ()
    Available from: 2012-04-11 Created: 2012-04-11 Last updated: 2017-12-07Bibliographically approved
  • 224.
    Cavalli-Björkman, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Implications of patients' socioeconomic status - what oncologists should be aware of2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 2, p. 161-163Article in journal (Other academic)
  • 225.
    Cavalli-Björkman, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Strang, Peter
    Equal cancer treatment regardless of education level and family support?: A qualitative study of oncologists’ decision-making2012In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, no 4, p. e001248-Article in journal (Refereed)
    Abstract [en]

    Objective: Treatment gradients by socioeconomic status have been observed within cancer care in several countries. The objective of this study was to explore whether patients' educational level and social network influence oncologists' clinical decision-making. Design: Semi-structured interviews on factors considered when deciding on treatment for cancer patients. Interviews were transcribed and analysed using inductive qualitative content analysis. Setting: Oncologists in Swedish university-and non-university hospitals were interviewed in their respective places of work. Participants: Twenty Swedish clinical oncologists selected through maximum-variation sampling. Primary and secondary outcome measures: Elements which influence oncologists' decision-making process were explored with focus on educational level and patients' social support systems. Results: Oncologists consciously used less combination chemotherapy for patients living alone, fearing treatment toxicity. Highly educated patients were considered as well-read, demanding and sometimes difficult to reason with. Patients with higher education, those very keen to have treatment and persuasive relatives were considered as challenges for the oncologist. Having large groups of relatives in a room made doctors feel outnumbered. A desire to please patients and relatives was posed as the main reason for giving in to patients' demands, even when this resulted in treatment with limited efficacy. Conclusions: Oncologists tailor treatment for patients living alone to avoid harmful side-effects. Many find patients' demands difficult to handle and this may result in strong socioeconomic groups being over-treated.

  • 226.
    Cavalli-Björkman, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lambe, Mats
    Eaker, Sonja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Sandin, Fredrik
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Differences according to educational level in the management and survival of colorectal cancer in Sweden2011In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 47, no 9, p. 1398-1406Article in journal (Refereed)
    Abstract [en]

    Socioeconomic status (SES) affects survival after a cancer diagnosis. The extent to which differences in management can explain this is not known. Record-linkage between two Swedish Regional Clinical Quality Registers of colorectal cancer and a socio-economic database generated a dataset with information on diagnostic procedures, treatment and survival in patients of different educational background. Three thousand eight hundred and ninety-nine rectal cancer patients from the years 1995 to 2006 and 5715 colon cancer patients from 1997 to 2006 were evaluated. Compared to patients with high education, those with shorter education had poorer relative and overall survival (57.9% 5-year relative survival versus 63.8% in colon cancer, 58.7% versus 69.1% in rectal cancer). There were also differences in diagnostic activity with preoperative computer tomography (40% versus 47.3%) and colonoscopy (56.3% versus 62.8%) being more frequent in highly educated groups (p = 0.001 and 0.037, respectively). Surgery resulting in colostomy was performed in 26.9% of rectal cancer patients of high education compared to 35.5% of those with low education (p = 0.005). Although rectal cancer has poorer prognosis than colon cancer, it was noted that among the highly educated, rectal cancer patients had better survival than colon cancer patients (69.1% versus 63.8% 5-year relative survival). It thus appears that improved rectal cancer management has benefited mainly patients of middle and higher educational levels. We conclude that socioeconomic differences exist in diagnostic activity and management of colorectal cancer, which may affect survival.

  • 227.
    Cavalli-Björkman, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Qvortrup, Camilla
    Sebjørnssen, Sigrunn
    Pfeiffer, Per
    Wentzel-Larsen, Tore
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sorbye, Halfdan
    Lower treatment intensity and poorer survival in metastatic colorectal cancer patients who live alone2012In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 107, no 1, p. 189-194Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Socioeconomic status (SES) and social support influences cancer survival. If SES and social support affects cancer treatment has not been thoroughly explored. METHODS: A cohort consisting of all patients who were initially diagnosed with or who developed metastatic colorectal cancer (mCRC, n = 781) in three Scandinavian university hospitals from October 2003 to August 2006 was set up. Clinical and socioeconomic data were registered prospectively. RESULTS: Patients living alone more often had synchronous metastases at presentation and were less often treated with combination chemotherapy than those cohabitating (HR 0.19, 95% CI 0.04-0.85, P = 0.03). Surgical removal of metastases was less common in patients living alone (HR 0.29, 95% CI 0.10-0.86, P = 0.02) but more common among university-educated patients (HR 2.22, 95% CI 1.10-4.49, P = 0.02). Smoking, being married and having children did not influence treatment or survival. Median survival was 7.7 months in patients living alone and 11.7 months in patients living with someone (P < 0.001). Living alone remained a prognostic factor for survival after correction for age and comorbidity. CONCLUSION: Patients living alone received less combination chemotherapy and less secondary surgery. Living alone is a strong independent risk factor for poor survival in mCRC. 

  • 228.
    Cederblad, Lena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Thunberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Engström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Castro, Juan
    Rutqvist, Lars Erik
    Laytragoon-Lewin, Nongnit
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    The Combined Effects of Single-Nucleotide Polymorphisms, Tobacco Products, and Ethanol on Normal Resting Blood Mononuclear Cells2013In: Nicotine & tobacco research, ISSN 1462-2203, E-ISSN 1469-994X, Vol. 15, no 5, p. 890-895Article in journal (Refereed)
    Abstract [en]

    Introduction: Tobacco and ethanol consumption are crucial factors in the development of various diseases including cancer. In this investigation, we evaluated the combined effects of a number of single nucleotide polymorphisms (SNPs), with ethanol and tobacco products on healthy individuals. Methods: Pure nicotine, cigarette smoke extract, and Swedish snuff (snus) extract were used. The effects were examined by means of in vitro cell cycle progression and cell death of peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. Results: After 3 days, in vitro, resting PBMCs entered the S and G2 stage in the presence of 100 mu M nicotine. The PBMCs only proceeded to S stage, in the presence of 0.2% ethanol. The nicotine- and ethanol-induced normal cell cycle progression correlated to a number of SNPs in the IL12RB2, Rad 52, XRCC2, P53, CCND3, and ABCA1 genes. Certain SNPs in Caspases 8, IL12RB2, Rad 52, MMP2, and MDM2 genes appeared to significantly influence the effects of EtOH-, snus-, and snus + EtOH-induced cell death. Importantly, the highest degree of cell death was observed in the presence of smoke + EtOH. The amount of cell death under this treatment condition also correlated to specific SNPs, located in the MDM2, ABCA1, or GASC1 genes. Conclusions: Cigarette smoke in combination with ethanol strongly induced massive cell death. Long-term exposure to smoke and ethanol could provoke chronic inflammation, and this could be the initiation of disease including the development of cancer at various sites.

  • 229. Cerhan, James R.
    et al.
    Berndt, Sonja I.
    Vijai, Joseph
    Ghesquieres, Herve
    McKay, James
    Wang, Sophia S.
    Wang, Zhaoming
    Yeager, Meredith
    Conde, Lucia
    de Bakker, Paul I. W.
    Nieters, Alexandra
    Cox, David
    Burdett, Laurie
    Monnereau, Alain
    Flowers, Christopher R.
    De Roos, Anneclaire J.
    Brooks-Wilson, Angela R.
    Lan, Qing
    Severi, Gianluca
    Melbye, Mads
    Gu, Jian
    Jackson, Rebecca D.
    Kane, Eleanor
    Teras, Lauren R.
    Purdue, Mark P.
    Vajdic, Claire M.
    Spinelli, John J.
    Giles, Graham G.
    Albanes, Demetrius
    Kelly, Rachel S.
    Zucca, Mariagrazia
    Bertrand, Kimberly A.
    Zeleniuch-Jacquotte, Anne
    Lawrence, Charles
    Hutchinson, Amy
    Zhi, Degui
    Habermann, Thomas M.
    Link, Brian K.
    Novak, Anne J.
    Dogan, Ahmet
    Asmann, Yan W.
    Liebow, Mark
    Thompson, Carrie A.
    Ansell, Stephen M.
    Witzig, Thomas E.
    Weiner, George J.
    Veron, Amelie S.
    Zelenika, Diana
    Tilly, Herve
    Haioun, Corinne
    Molina, Thierry Jo
    Hjalgrim, Henrik
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Adami, Hans-Olov
    Bracci, Paige M.
    Riby, Jacques
    Smith, Martyn T.
    Holly, Elizabeth A.
    Cozen, Wendy
    Hartge, Patricia
    Morton, Lindsay M.
    Severson, Richard K.
    Tinker, Lesley F.
    North, Kari E.
    Becker, Nikolaus
    Benavente, Yolanda
    Boffetta, Paolo
    Brennan, Paul
    Foretova, Lenka
    Maynadie, Marc
    Staines, Anthony
    Lightfoot, Tracy
    Crouch, Simon
    Smith, Alex
    Roman, Eve
    Diver, W. Ryan
    Offit, Kenneth
    Zelenetz, Andrew
    Klein, Robert J.
    Villano, Danylo J.
    Zheng, Tongzhang
    Zhang, Yawei
    Holford, Theodore R.
    Kricker, Anne
    Turner, Jenny
    Southey, Melissa C.
    Clavel, Jacqueline
    Virtamo, Jarmo
    Weinstein, Stephanie
    Riboli, Elio
    Vineis, Paolo
    Kaaks, Rudolph
    Trichopoulos, Dimitrios
    Vermeulen, Roel C. H.
    Boeing, Heiner
    Tjonneland, Anne
    Angelucci, Emanuele
    Di Lollo, Simonetta
    Rais, Marco
    Birmann, Brenda M.
    Laden, Francine
    Giovannucci, Edward
    Kraft, Peter
    Huang, Jinyan
    Ma, Baoshan
    Ye, Yuanqing
    Chiu, Brian C. H.
    Sampson, Joshua
    Liang, Liming
    Park, Ju-Hyun
    Chung, Charles C.
    Weisenburger, Dennis D.
    Chatterjee, Nilanjan
    Fraumeni, Joseph F., Jr.
    Slager, Susan L.
    Wu, Xifeng
    de Sanjose, Silvia
    Smedby, Karin E.
    Salles, Gilles
    Skibola, Christine F.
    Rothman, Nathaniel
    Chanock, Stephen J.
    Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 11, p. 1233-1238Article in journal (Refereed)
    Abstract [en]

    Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 x 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 x 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 x 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 x 10(-13) and 3.63 x 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.

  • 230.
    Chabok, Abbas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Smedh, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Nilsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Stenson, Marianne
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    CT-colonography in the follow-up of acute diverticulitis: patient acceptance and diagnostic accuracy2013In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, no 8, p. 979-986Article in journal (Refereed)
    Abstract [en]

    Objective. The aim of this study was to assess CT-colonography (CTC) in the follow-up of diverticulitis regarding patient acceptance and diagnostic accuracy for diverticular disease, adenomas and cancer, with colonoscopy as a reference standard. Methods. A prospective comparative study where half of the patients underwent colonoscopy first, followed immediately by CTC. The other half had the examinations in the reverse order. Patient experiences and findings were registered after every examination, blinded to the examiner. Results. Of a total of 110 consecutive patients, 108 were included in the study, with a median age of 56 years (range 27-84). The success rate was 91% for colonoscopy and 86% for CTC. Examination time was 25 mm for both methods. The mean time for CTC evaluation was 20 mm. Eighty-three per cent of the patients received sedation during colonoscopy. Despite this, patients experienced colonoscopy as more painful (p < 0.001) and uncomfortable (p < 0.001). Diverticulosis and polyps were detected in 94% and 20% with colonoscopy and in 94% and 29% with CTC, respectively. Sensitivity and specificity for CTC in the detection of diverticulosis was 99% and 67%, with a good agreement (kappa = 0.71). Regarding detection of polyps, the sensitivity and specificity were 47% and 75%, with a poor agreement (kappa = 0.17). No cancer was found. Conclusion. CTC was less painful and unpleasant and can be used for colonic investigation in the follow-up of diverticulitis. CTC detected diverticulosis with good accuracy while the detection accuracy of small polyps was poor. CTC is a viable alternative, especially in case of incomplete colonoscopy or in a situation with limited colonoscopy resources.

  • 231. Choo, Il Han
    et al.
    Ni, Ruiqing
    Scholl, Michael
    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.
    Almkvist, Ove
    Nordberg, Agneta
    Combination of F-18-FDG PET and Cerebrospinal Fluid Biomarkers as a Better Predictor of the Progression to Alzheimer's Disease in Mild Cognitive Impairment Patients2013In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 33, no 4, p. 929-939Article in journal (Refereed)
    Abstract [en]

    The biomarker-based new diagnostic criteria have been proposed for Alzheimer's disease (AD) spectrum. However, any biomarker alone has not been known to have satisfactory AD predictability. We explored the best combination model with baseline demography, neuropsychology, F-18-fluorodeoxyglucose positron emission tomography (FDG-PET), cerebrospinal fluid (CSF) biomarkers, and apolipoprotein E (APOE) genotype evaluation to predict progression to AD in mild cognitive impairment (MCI) patients. Alongitudinal clinical follow-up (mean, 44 months; range, 1.6-161.7 months) of MCI patients was done. Among 83 MCI patients, 26 progressed to AD (MCI-AD) and 51 did not deteriorate (MCI-Stable). We applied that univariate and multivariate logistic regression analyses, and multistep model selection for AD predictors including biomarkers. In univariate logistic analysis, we selected age, Rey Auditory Verbal Retention Test, parietal glucose metabolic rate, CSF total tau, and presence or not of at least one APOE epsilon 4 allele as predictors. Through multivariate stepwise logistic analysis and model selection, we found the combination of parietal glucose metabolic rate and total tau representing the best model for AD prediction. In conclusion, our findings highlight that the combination of regional glucose metabolic assessment by PET and CSF biomarkers evaluation can significantly improve AD predictive diagnostic accuracy of each respective method.

  • 232. Ciesielski, Krzysztof Chris
    et al.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Saha, Punam K.
    Efficient algorithm for finding the exact minimum barrier distance2014In: Computer Vision and Image Understanding, ISSN 1077-3142, E-ISSN 1090-235X, Vol. 123, p. 53-64Article in journal (Refereed)
  • 233.
    Ciray, Ipek
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lindman, H
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Wanders, A
    Bergh, J
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Effect of granulocyte colony-stimulating factor (G-CSF)-supported chemotherapy on MR imaging of normal red bone marrow in breast cancer patients with focal bone metastases2003In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 44, no 5, p. 472-484Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the effect of granulocyte colony-stimulating factor (G-CSF)-supported chemotherapy on normal red bone marrow MR imaging in breast cancer patients with focal bone metastases.

    MATERIAL AND METHODS: Fifteen breast cancer patients who were examined before and after chemotherapy with T1-weighted-SE and long echo-time inversion-recovery turbo-spin-echo (long TE IR-TSE) sequences in the thoracolumbar spine and pelvis were retrospectively studied. Nine of them received G-CSF therapy after the administration of each chemotherapy course. Of these 9 patients, the MR follow-ups were performed during G-CSF in 4 patients and after G-CSF therapy in 5 patients. Six patients did not receive G-CSF. Signal intensity (SI) changes in normal bone marrow were evaluated visually in all patients and quantitatively in 13 patients.

    RESULTS: In all 4 patients investigated during G-CSF therapy a diffuse, homogeneous SI increase on long TE IR-TSE was observed visually and quantitatively in initially normal bone marrow. This change obscured some focal lesions in 2 patients. No such SI change was visible after G-CSF therapy (p = 0.008) or in patients not receiving G-CSF. On T1-weighted images an SI decrease was found both during and after G-CSF therapy, but an increase occurred in patients not receiving G-CSF.

    CONCLUSION: G-CSF-supported chemotherapy can induce diffuse SI changes in normal red bone marrow on MR imaging. On long TE IR-TSE, the changes are visible during G-CSF treatment and can lead to misinterpretations in the response evaluation of bone metastases to therapy.

  • 234.
    Ciray, Ipek
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bergh, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Early response of breast cancer bone metastases to chemotherapy evaluated with MR imaging2001In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 42, no 2, p. 198-206Article in journal (Other academic)
    Abstract [en]

    PURPOSE:

    To compare T1-weighted spin-echo and fat-suppressed long echo time inversion recovery turbo spin-echo (long TE IR-TSE) MR images in the evaluation of early response of breast cancer bone metastases to chemotherapy.

    MATERIAL AND METHODS:

    Eighteen breast cancer patients with known bone metastases were investigated prospectively by MR, using T1-weighted and long TE IR-TSE sequences on the sternum, spine, pelvis and proximal femora, before and after a median of 6 courses of chemotherapy. Therapeutic response evaluation with MR was based on change in tumor size assessed quantitatively by measuring all focal metastases, and change in pattern and signal intensity (SI) of the metastases, assessed visually. Combined response evaluation based on clinical findings, conventional radiography, and scintigraphy was used as reference.

    RESULTS:

    Progressive disease (2 patients) and no change (4 patients) were assessed equally well on both MR sequences. Long TE IR-TSE demonstrated partial response with higher accuracy than T1-weighted images, 58% (7/12 patients) vs. 17% (2/12 patients). In patients without progression there was an SI increase in or around the metastases in 6 patients on T1-weighted images and in 7 patients on long TE IR-TSE images.

    CONCLUSION:

    The long TE IR-TSE sequence demonstrated early partial response of breast cancer bone metastases to chemotherapy more accurately than the T1-weighted sequence.

  • 235.
    Ciray, Ipek
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Andréasson, I
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Edekling, T
    Hansen, J
    Bergh, J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Evaluation of new sclerotic bone metastases in breast cancer patients during treatment2000In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 41, no 2, p. 178-182Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    According to the World Health Organization (WHO) criteria for response of bone metastases to therapy, new lesions indicate progressive disease. We intended to prove that a new sclerotic lesion on conventional radiography may also be a sign of a positive therapeutic response in a previously undetectable lytic metastasis.

    MATERIAL AND METHODS:

    In a previous placebo-controlled clinical trial of clodronate (Ostac) therapy, 139 breast cancer patients with bone metastases underwent both conventional radiography and bone scan every 6 months for 2 years with 99mTc before and during clodronate treatment. WHO criteria were applied for therapy response evaluation.

    RESULTS:

    In 24 patients, 52 new sclerotic lesions observed during therapy were selected for re-evaluation of conventional radiographs and bone scans. In 8 of the 24 patients, 17 of 52 new sclerotic lesions (33%) had showed positive uptake on previous bone scans. These lesions were possibly misinterpreted as new when applying WHO criteria.

    CONCLUSION:

    For better assessment of new sclerotic lesions during treatment, more sensitive techniques, e.g. bone scan, are needed as a complement to conventional radiography.

  • 236.
    Ciray, Ipek
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Assessment of suspected bone metastases: CT with and without clinical information compared to CT-guided bone biopsy1997In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 38, no 5, p. 890-895Article in journal (Refereed)
    Abstract [en]

    PURPOSE:

    To evaluate the role of CT with and without clinical information as compared to CT-guided bone biopsy in the assessment of suspected bone metastases.

    MATERIAL AND METHODS:

    The study comprised 51 consecutive patients with suspected bone metastases who had undergone CT-guided bone biopsies with an eccentric drill system. CT of the targets, clinical information, and histopathology were scored separately as malignant, uncertain or benign. The results of CT alone and CT in combination with clinical information were compared to the results of histopathology.

    RESULTS:

    Histopathology diagnosed 45/51 lesions (88%), 23 as malignant and 22 as benign. CT correctly depicted 17 of these 23 malignant lesions. The remaining 6 malignant lesions were CT-scored as uncertain (n = 5) or benign (n = 1). CT correctly depicted only 3 of the 22 benign lesions. The remaining 19 benign lesions were CT-scored as malignant (n = 2) or uncertain (n = 17). When uncertain CT scores were combined with clinical scores, the true-positive and true-negative results for malignancy increased from 44% to 82%.

    CONCLUSION:

    In most cases, CT in combination with clinical information gives enough information about the nature-malignant or benign-of a skeletal lesion. In uncertain cases, diagnostic accuracy can be improved by means of CT-guided bone biopsy.

  • 237.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Hahn, Andreas
    Ganger, Sebastian
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bannbers, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Oreland, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Epperson, C Neill
    Lanzenberger, Rupert
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Emotional fronto-cingulate cortex activation and brain derived neurotrophic factor polymorphism in premenstrual dysphoric disorder2014In: Human Brain Mapping, ISSN 1065-9471, E-ISSN 1097-0193, Vol. 35, no 9, p. 4450-4458Article in journal (Refereed)
    Abstract [en]

    Premenstrual dysphoric disorder (PMDD) is the prototypical sex-specific disorder in which symptom onset and offset require a particular hormonal milieu and for which there is moderate heritability. The present study investigated brain emotion processing in PMDD and healthy controls, as well as functional polymorphisms in two candidate genes for PMDD, the serotonin transporter (5-HTT) and brain derived neurotrophic factor (BDNF). The 5-HTT linked polymorphic region (5-HTTLPR) and BDNF Val66Met polymorphisms were genotyped in 31 patients with PMDD and 31 healthy controls. A subset of 16 patients and 15 controls participated in two functional magnetic resonance imaging-sessions performing an emotion processing task; once in the mid-follicular, and once in the late luteal phase which corresponds with maximum severity of mood symptoms. Genotypes were not directly associated with PMDD. A main effect of group was found in the whole brain analysis, with patients having lower activation of the pre-genual anterior cingulate and ventro-medial prefrontal cortex, independent of menstrual cycle phase. Post-hoc functional ROI analyses in the fronto-cingulate cluster showed no effect of 5-HTTLPR genotype but a genotype-by-group-by-phase interaction effect of BDNF Val66Met. Women with PMDD who were carriers of the Met-allele had lower fronto-cingulate cortex activation in the luteal phase compared to Met-allele carrying controls. The results provide suggestive evidence of impaired emotion-induced fronto-cingulate cortex activation in PMDD patients. Although limited by a small sample, the potential influence of BDNF Val66Met in PMDD is in line with preclinical findings. Hum Brain Mapp, 2014. 

  • 238.
    Covaciu, Lucian
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Weis, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bengtsson, Caroline
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Allers, M
    Lunderquist, A
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Brain temperature in volunteers subjected to intranasal cooling2011In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 37, no 8, p. 1277-1284Article in journal (Refereed)
    Abstract [en]

    Intranasal cooling can be used to initiate therapeutic hypothermia. However, direct measurement of brain temperature is difficult and the intra-cerebral distribution of temperature changes with cooling is unknown. The purpose of this study was to measure the brain temperature of human volunteers subjected to intranasal cooling using non-invasive magnetic resonance (MR) methods. Intranasal balloons catheters circulated with saline at 20A degrees C were applied for 60 min in ten awake volunteers. No sedation was used. Brain temperature changes were measured and mapped using MR spectroscopic imaging (MRSI) and phase-mapping techniques. Heart rate and blood pressure were monitored throughout the experiment. Rectal temperature was measured before and after the cooling. Mini Mental State Examination (MMSE) test and nasal inspection were done before and after the cooling. Questionnaires about the subjects' personal experience were completed after the experiment. Brain temperature decrease measured by MRSI was -1.7 +/- A 0.8A degrees C and by phase-mapping -1.8 +/- A 0.9A degrees C (n = 9) at the end of cooling. Spatial distribution of temperature changes was relatively uniform. Rectal temperature decreased by -0.5 +/- A 0.3A degrees C (n = 5). The physiological parameters were stable and no shivering was reported. The volunteers remained alert during cooling and no cognitive dysfunctions were apparent in the MMSE test. Postcooling nasal examination detected increased nasal secretion in nine of the ten volunteers. Volunteers' acceptance of the method was good. Both MR techniques revealed brain temperature reductions after 60 min of intranasal cooling with balloons circulated with saline at 20A degrees C in awake, unsedated volunteers.