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  • 101.
    Jansson, Agneta
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Carlsson, Jonas
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, The Institute of Technology.
    Olsson, Anette
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Storm, Petter
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Margolin, Sara
    Department of Oncology, Karolinska University Hospital/ Södersjukhuset, Stockholm, Sweden.
    Gunnarsson, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Medical Genetics. Linköping University, Faculty of Health Sciences.
    Stenmark Askmalm, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Lindblom, Annika
    Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Persson, Bengt
    Linköping University, Department of Physics, Chemistry and Biology, Bioinformatics. Linköping University, The Institute of Technology.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    A new polymorphism in the coding region of exon four in HSD17B2 in relation to risk of sporadic and hereditary breast cancer2007In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 106, no 1, p. 57-64Article in journal (Refereed)
    Abstract [en]

    In situ synthesis of oestrogens is of great importance in the development and progression of breast cancer. 17β-hydroxysteroid dehydrogenase (17HSD) type 2 catalyses oxidation from oestradiol to oestrone, and thereby protects the breast epithelial cells from oestradiol. Low expression of 17HSD type 2 has been associated with decreased survival in breast cancer, but no studies have investigated the mechanism behind the low expression. The 17HSD type 2 gene (HSD17B2) was screened for mutations with Single Stranded Conformation Polymorphism (SSCP)-DNA sequencing in 59 sporadic breast cancer cases, 19 hereditary breast cancer cases and seven breast cancer cell lines. DNA samples from 226 healthy individuals were used to identify if changes were previously unknown polymorphisms. No mutation was detected and therefore mutations in HSD17B2 do not explain why some breast tumours exhibit low 17HSD type 2 expression. However, a previously unknown polymorphism was found in exon four (Met226Val). Using molecular modelling, we found that the substituted residue is located at the outer part of the steroid binding site, probably causing minor alterations in the substrate binding. We further studied if the polymorphism contributes to breast cancer susceptibility in a larger material, but did not find an increased risk in the group of 317 sporadic breast cancer patients, 188 breast cancer patients with two close relatives with breast cancer or 122 hereditary breast cancer patients, compared to the healthy control group. We suggest that the detected polymorphism does not contribute to a higher risk of developing breast cancer.

  • 102.
    Jansson, Agneta
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Emterling, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Arbman, Gunnar
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Noxa in colorectal cancer: A study on DNA, mRNA and protein expression2003In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 22, no 30, p. 4675-4678Article in journal (Refereed)
    Abstract [en]

    Noxa is a BH3-only member of the Bcl-2 family, upregulated by p53 as a response to DNA damage. Mutations in the BH3-only region of other BH3-only members lead to an inactive protein. We have investigated the mRNA expression of Noxa with real-time PCR in 94 unselected colorectal adenocarcinomas and the corresponding normal mucosa. Among them, Noxa protein expression was investigated with immunohistochemistry in 16 tumors and six corresponding normal mucosa samples. Further, we searched for Noxa mutations in all the cases using single-stranded conformation polymorphism and DNA sequencing. The mRNA expression of Noxa was weak in 9% and strong in 2% of the tumors, and decreased in 9% and increased in 16% of the tumors compared with the normal mucosa, however, these changes did not have any clinical or pathological significance. The protein level in most of the cases investigated was correlated with the mRNA level. We did not find any mutations in the Noxa gene. Thus, we suggest that Noxa may not be of importance in the development of colorectal cancer.

  • 103.
    Jansson, Agneta
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Gentile, Massamiliano
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    p53 mutations are present in colorectal cancer with cytoplasmic p53 accumulation2001In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 92, no 3, p. 338-341Article in journal (Refereed)
    Abstract [en]

    Previous studies have shown that nuclear p53 over-expression is an indicator of p53 mutations whereas cytoplasmic p53 accumulation is related to wild-type p53 in several kinds of tumors. Cytoplasmic p53 accumulation has been demonstrated to be an independent prognostic factor in colorectal adenocarcinomas. The purpose was to examine whether mutations occur in cases with p53 accumulated in the cytoplasm and whether there are any differences in the frequency and characteristics of p53 mutations in different staining patterns. In the present study, we identified p53 mutations using PCR single-strand conformation polymorphism (SSCP) and DNA sequencing in 75 primary colorectal adenocarcinomas with different staining patterns (negative, nucleus, cytoplasm, nucleus and cytoplasm). The results show that the frequency and nature of mutations in tumors with cytoplasmic p53 accumulation were similar to those with nuclear p53 expression. However, the tumors with accumulation in both the nucleus and cytoplasm demonstrated a higher mutation rate. We suppose that the role of cytoplasmic p53 accumulation in predicting prognosis in patients with colorectal cancer may be dependent on both mutational and non-mutational mechanisms.

  • 104.
    Jansson, Agneta
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Gunnarsson, Cecilia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Cohen, Maja
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Sivik, Tove
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    17β-hydroxysteroid dehydrogenase 14 affects estradiol levels in breast cancer cells and is a prognostic marker in estrogen receptor-positive breast cancer2006In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 66, no 23, p. 11471-11477Article in journal (Refereed)
    Abstract [en]

    Estrogens have an important role in the progression of breast cancer. The 17β-hydroxysteroid dehydrogenase (17HSD) family has been identified to be of significance in hormone-dependent tissues. 17HSD1 and 17HSD2 are the main 17HSD enzymes involved in breast cancer investigated this far, but it is possible that other hormone-regulating enzymes have a similar role. 17HSD5 and 17HSD12 are associated with sex steroid metabolism, and 17HSD14 is a newly discovered enzyme that may be involved in the estrogen balance. The mRNA expression of 17HSD5, 17HSD12, and 17HSD14 were analyzed in 131 breast cancer specimens by semiquantitative real-time PCR. The results were compared with recurrence-free survival and breast cancer-specific survival of the patients. The breast cancer cell lines MCF7, SKBR3, and ZR75-1 were transiently transfected with 17HSD14 to investigate any possible effect on estradiol levels. We found that high 17HSD5 was related to significantly higher risk of late relapse in estrogen receptor (ER)-positive patients remaining recurrence-free later than 5 years after diagnosis (P = 0.02). No relation to 17HSD12 expression was found, indicating that 17HSD12 is of minor importance in breast cancer. Patients with ER-positive tumors with high expression levels of 17HSD14 showed a significantly better prognosis about recurrence-free survival (P = 0.008) as well as breast cancer-specific survival (P = 0.01), confirmed by multivariate analysis (P = 0.04). Transfection of 17HSD14 in the human breast cancer cells MCF7 and SKBR3 significantly decreased the levels of estradiol, presenting an effect of high expression levels of the enzyme. ©2006 American Association for Cancer Research.

  • 105.
    Jansson, Agneta
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Gunnarsson, Cecilia
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Proliferative responses to altered 17β-hydroxysteroid dehydrogenase (17HSD) type 2 expression in human breast cancer cells are dependent on endogenous expression of 17HSD type 1 and the oestradiol receptors2006In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 13, no 3, p. 875-884Article in journal (Refereed)
    Abstract [en]

    The primary source of oestrogen in premenopausal women is the ovary but, after menopause, oestrogen biosynthesis in peripheral tissue is the exclusive site of formation. An enzyme group that affects the availability of active oestrogens is the 17β-hydroxysteroid dehydrogenase (17HSD) family. In breast cancer, 17HSD type 1 and type 2 have been mostly investigated and seem to be the principal 17HSD enzymes involved thus far. The question whether 17HSD type 1 or type 2 is of greatest importance in breast tumour development is still not clear. The aim of this study was to investigate how the loss of 17HSD type 2 expression, using siRNA in the non-tumour breast epithelial cells HMEC (human mammal epithelial cells) and MCF10A, and gain of 17HSD type 2 expression, using transient transfection in the breast cancer derived cell lines MCF7 and T47D, affect oestradiol conversion and proliferation rate measured as S-phase fraction. We further investigated how this was related to the endogenous expression of 17HSD type 1 and oestradiol receptors in the examined cell lines. The oestradiol level in the medium changed significantly in the MCF7 transfected cells and the siRNA-treated HMEC cells, but not in T47D or MCF10A. The S-phase fraction decreased in the 17HSD type 2-transfected MCF7 cells and the siRNA-treated HMEC cells. The results seemed to be dependent on the endogenous expression of 17HSD type 1 and the oestradiol receptors. In conclusion, we found that high or low levels of 17HSD type 2 affected the oestradiol concentration significantly. However, the response was dependent on the endogenous expression of 17HSD type 1. Expression of 17HSD type 1 seems to be dominant to 17HSD type 2. Therefore, it may be important to investigate a ratio between 17HSD type 1 and 17HSD type 2.

  • 106.
    Jansson, Agneta K.
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Emterling, Anna M.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Department of Surgery, Vrinnevi Hospital, Norrköping, Sweden.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    The BH3-only member Noxa may not be involved in the development of unselected colorectal cancerManuscript (preprint) (Other academic)
    Abstract [en]

    Noxa is an BH3-only member of the Bcl-2 family, upregulated by p53 as a response to DNA damage. Mutations in the BH3-only region of other BH3-only members lead to an inactive protein. We have investigated the mRNA expression of Noxa with real-time PCR in 94 unselected colorectal adenocarcinomas and the corresponding normal mucosa. Further, we searched for mutations in the Noxa gene using single stranded conformation polymorphism and DNA sequencing. The mRNA expression of Noxa was weak in 9% and strong in 2% of the tumours and decreased in 9% and increased in 16% of the tumours compared to the normal mucosa, but these changes did not have any clinical or pathological significance. We did not find any mutations in the gene. Thus, our observations suggest that the variations in Noxa gene may not be of particular importance in the development of unselected colorectal cancer.

  • 107.
    Jansson, Agneta
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Bax expression decreases significantly from primary tumor to metastasis in colorectal cancer2002In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 20, no 3, p. 811-816Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Bax is a proapoptotic member of the bcl-2 family. Previous studies about Bax have shown that the expression increases from normal to tumor tissue, but the clinical significance is contradictory. Our aims were to analyze the expression of Bax from normal mucosa to primary tumor and to metastases in colorectal cancer patient. We further investigated whether low Bax expression in the primary tumor or changed expression from normal mucosa to primary tumor and to metastases had biologic and clinical significance.

    PATIENTS AND METHODS: The study included 135 patients with primary colorectal adenocarcinoma, of whom 31 had metastases in the lymph nodes and 75 had normal mucosa. Immunohistochemistry, DNA sequencing, and microsatellite analysis were used to detect Bax expression, mutations, and microsatellite instability.

    RESULTS: The protein was observed in 132 of 135 tumors, all normal epithelial cells and metastases. The frequencies of weak expression were greater from well/moderately to poorly differentiated and to mucinous carcinomas. Bax expression was stronger from normal to tumor tissue, but subsequently decreased in metastases. The matched cases with lower expression in the metastases than in the primary tumor showed a more infiltrative growth pattern and more distal metastases.

    CONCLUSION: The association of Bax expression with tumor differentiation/histologic types and a decreased expression in the metastases, suggests that Bax expression may be involved in tumor differentiation/histologic types and metastatic progression. We also propose the novel notion that changed Bax expression in the metastases compared with the primary tumors might provide information to determine the clinicopathologic characteristics of the tumor.

  • 108. Jayson, Gordon
    et al.
    Zweit, Jamal
    Jackson, Alan
    Mulatero, Clive
    Julyan, Peter
    Ranson, Malcolm
    Broughton, Lynn
    Wagstaff, John
    Håkansson, Leif
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Groenewegen, Gerard
    Bailey, John
    Smith, Nigel
    Hastings, David
    Lawrence, Jeremy
    Haroon, Hamied
    Ward, Tim
    McGown, Alan
    Tang, Meina
    Levitt, Dan
    Marreaud, Sandrine
    Lehmann, Frederic
    Herold, Manfred
    Zwierzina, Heinz
    Molecular imaging and biological evaluation of HuMV833 anti-VEGF antibody: Implications for trial design of antiangiogenic antibodies2002In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 94, no 19, p. 1484-1493Article in journal (Refereed)
    Abstract [en]

    Background: Vascular endothelial growth factor (VEGF) is a potent angiogenic cytokine, and various inhibitory agents, including specific antibodies, have been developed to block VEGF-stimulated angiogenesis. We developed HuMV833, a humanized version of a mouse monoclonal anti-VEGF antibody (MV833) that has antitumor activity against a number of human tumor xenografts, and investigated the distribution and biologic effects of HuMV833 in patients in a phase I trial. Methods: Twenty patients with progressive solid tumors were treated with various doses of HuMV833 0.3, 1, 3, or 10 mg/kg). Positron emission tomography with 124I-HuMV833 was used to measure the antibody distribution in and clearance from tissues. Magnetic resonance imaging was used to measure the vascular permeability surface area product with a first-pass pharmacokinetic model (Kfp) to determine tumor vascular permeability. Results: The antibody was generally well tolerated, although the incremental dose, phase I study design, and pharmacodynamic end-points could not identify the optimum biologically active dose. Antibody distribution and clearance were markedly heterogeneous between and within patients and between and within individual tumor. HuMV833 distribution to normal tissues also varied among patients, but the antibody was cleared from these tissues in a homogeneous fashion. Permeability was strongly heterogeneous between and within patients and between and within individual tumors. All tumors showed a reduction in kfp 48 hours after the first treatment (median = 44%, range = 4%-91%). Conclusions: Because of the heterogeneity in tumor biology with respect to anti-body uptake and clearance, we suggest that either intrapatient dose escalation approaches or larger, more precisely defined patient cohorts would be preferable to conventional strategies in the design of phase I studies with anitiangiogenic compounds like HuMV833.

  • 109.
    Jerevall, Piiha-Lotta
    et al.
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Ahmadi, Ahmad
    Linköping University, Department of Biomedicine and Surgery, Division of cell biology. Linköping University, Faculty of Health Sciences.
    Bergman, Malin
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Wingren, Sten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of cell biology.
    Sulfotransferase1A1 and risk of postmenopausal breast cancer2005In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 25, no 3 C, p. 2515-2517Article in journal (Refereed)
    Abstract [en]

    The detoxification enzyme sulfotransferase1A1 (SULT1A1) is implicated in the inactivation of estrogens and the activation of promutagens andprocarcinogens. SULT1A1 activity varies among individuals, and this difference in phenotype is, in part, controlled by genetic polymorphism (Arg→His in codon 213). It is hypothesized that the His allele contributes to the risk of postmenopausal breast cancer. Frequencies of the Arg/His alleles were estimated in 229 postmenopausal breast cancer patients and 227 age-matched controls using a PCR-RFLP assay. Allele frequencies and genotype distributions were not statistically different between postmenopausal breast cancer patients and the population-based controls, i.e. neither of the alleles is associated with an increased risk of breast cancer in the present study.

  • 110.
    Jirström, K
    et al.
    Division of Pathology Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden .
    Rydén, L
    Division of Pathology Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden .
    Anagnostaki, L
    Division of Pathology Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden .
    Nordenskjöld, Bo
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Thorstenson, S
    Department of Pathology and Cytology, Kalmar County Hospital, Kalmar, Sweden .
    Chebil, G
    Department of Pathology, Helsingborg Hospital, Helsingborg, Sweden.
    Jönsson, P-E
    Department of Surgery, Helsingborg Hospital.
    Fernö, M
    Department of Oncology, Lund University Hospital, Lund, Sweden.
    Landberg, G
    Division of Pathology Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden .
    Pathology parameters and adjuvant tamoxifen response in a randomised premenopausal breast cancer trial2005In: Journal of Clinical Pathology, ISSN 0021-9746, E-ISSN 1472-4146, Vol. 58, no 11, p. 1135-1142Article in journal (Refereed)
    Abstract [en]

    Background: Subgroups of breast cancer that have an impaired response to endocrine treatment, despite hormone receptor positivity, are still poorly defined. Breast cancer can be subdivided according to standard pathological parameters including histological type, grade, and assessment of proliferation. These parameters are the net result of combinations of genetic alterations effecting tumour behaviour and could potentially reflect subtypes that respond differently to endocrine treatment.

    Aims: To investigate the usefulness of these parameters as predictors of the response to tamoxifen in premenopausal women with breast cancer.

    Materials/methods: Clinically established pathological parameters were assessed and related to the tamoxifen response in 500 available tumour specimens from 564 premenopausal patients with breast cancer randomised to either two years of tamoxifen or no treatment with 14 years of follow up. Proliferation was further evaluated by immunohistochemical Ki-67 expression.

    Results: Oestrogen receptor positive ductal carcinomas responded as expected to tamoxifen, whereas the difference in recurrence free survival between control and tamoxifen treated patients was less apparent in the relatively few lobular carcinomas. For histological grade, there was no obvious difference in treatment response between the groups. The relation between proliferation and tamoxifen response seemed to be more complex, with a clear response in tumours with high and low proliferation, whereas tumours with intermediate proliferation defined by Ki-67 responded more poorly.

    Conclusions: Clinically established pathology parameters seem to mirror the endocrine treatment response and could potentially be valuable in future treatment decisions for patients with breast cancer.

  • 111.
    Jirström, Karin
    et al.
    Division of Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.
    Stendahl, Maria
    Division of Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.
    Rydén, Lisa
    Division of Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.
    Kronblad, Åsa
    Division of Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.
    Bendahl, Pär-Ola
    Department of Oncology, University Hospital, Lund, Sweden.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Landberg, Göran
    Division of Pathology, Department of Laboratory Medicine, Lund University, Malmö University Hospital, Malmö, Sweden.
    Adverse effect of adjuvant tamoxifen in premenopausal breast cancer with cyclin D1 gene amplification2005In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 65, no 17, p. 8009-8016Article in journal (Refereed)
    Abstract [en]

    Cyclins D1 and A2 are cell cycle regulators that also have the ability to interact with the estrogen receptor (ER) and consequently interfere with antiestrogen treatment in breast cancer. Experimental data support this concept, but the clinical relevance needs to be further established. In this study, we evaluated cyclin D1 and A2 protein expression by immunohistochemistry and cyclin D1 gene (CCND1) amplification by fluorescence in situ hybridization in 500 primary breast cancers arranged in tissue microarrays. Patients had been randomized to 2 years of adjuvant tamoxifen or no treatment with a median follow-up of 14 years, allowing for subgroup analysis of treatment response defined by cyclin status. We found that both cyclin D1 and A2 protein overexpression was associated with an impaired tamoxifen response, although not significant in multivariate interaction analyses, whereas tamoxifen-treated patients with CCND1-amplified tumors had a substantially increased risk for disease recurrence after tamoxifen treatment in univariate analyses [relative risk (RR), 2.22; 95% confidence interval (95% CI), 0.94-5.26; P = 0.06] in contrast to nonamplified tumors (RR, 0.39; 95% CI, 0.23-0.65; P < 0.0001). Consequently, a highly significant interaction between tamoxifen treatment and CCND1 amplification could be shown regarding both recurrence-free survival (RR, 6.38; 95% CI, 2.29-17.78; P < 0.001) and overall survival (RR, 5.34; 95% CI, 1.84-15.51; P = 0.002), suggesting an agonistic effect of tamoxifen in ER-positive tumors. In node-positive patients, the disparate outcome according to gene amplification status was even more accentuated. In summary, our data implicate that despite a significant correlation to cyclin D1 protein expression, amplification status of the CCND1 gene seems a strong independent predictor of tamoxifen response, and possibly agonism, in premenopausal breast cancer.

  • 112.
    Johansson, Malin
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Årstrand, Kerstin
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Håkansson, Annika
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Lindholm, C
    Department of Oncology, Ryhov County Hospital, Jönköping, Sweden.
    Kågedal, Bertil
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Quantitative analysis of tyrosinase and tyrosinase-related protein-2 mRNA from melanoma cells in blood by real-time polymerase chain reaction2000In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 10, no 3, p. 213-222Article in journal (Refereed)
    Abstract [en]

    Several studies have evaluated the use of polymerase chain reaction (PCR) amplification of tyrosinase mRNA to detect melanoma cells in blood. However, contradictory results have been obtained from different groups. We therefore have developed and validated a quantitative PCR method for tyrosinase and tyrosinase-related protein-2 (TRP-2) mRNA. An important methodological finding was that high concentrations of reverse transcriptase or RNA sample inhibited the following PCR. This could be abolished by dilution of the cDNA sample before the PCR. Standard curves with a linear range over at least five logs were obtained with dilutions of melanoma cell cDNA. Controls (RNA and cDNA) consisting of melanoma cells (1000/ml) added to blood were analysed repeatedly over 3 months, resulting in means between 880 and 1074 AU/ml. The RNA controls were stable, whereas the cDNA controls, as well as the calibrators, showed a tendency to change over time. The variation in the RNA controls was 25% for tyrosinase and 22% for TRP-2. Seven stage III-IV melanoma patients were tested for tyrosinase and TRP-2 transcripts in blood drawn from a peripheral vein and from a Port-a-cath. Tyrosinase mRNA was found in three patients (0.8-12.4 AU/ml). For TRP-2, the same amount was found in the patients as in healthy donors. No differences were seen between blood from a peripheral vein and from the Port-a-cath. We here present fast and sensitive methods for the quantification of tyrosinase and TRP-2 mRNA in blood.

  • 113.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Common cytogenetic abnormalities2004In: Chronic lymphocytic leukemia. Molecular genetics, biology, diagnosis, and management / [ed] Guy B. Faguet, Totowa, New Jersey: Humana Press Inc. , 2004, p. 163-171Chapter in book (Other academic)
    Abstract [en]

    A comprehensive and critical review of the latest scientific advances in our understanding of the molecular genetics and biology of CLL and their application to the best management of CLL. The authors focus on diagnosis, prognosis, multifaceted treatment options, and complications. Among the diverse treatments considered are chemotherapy, autologous and allogenic transplantations, monoclonal antibody therapy, immunotoxin therapy, gene therapy, and several new therapeutic strategies. Familial and juvenile chronic lymphocytic leukemia are also discussed

  • 114.
    Juliusson, Gunnar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Theorin, Niklas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Karlsson, Karin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Frödin, U
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Subcutaneous alemtuzumab vs ATG in adjusted conditioning for allogeneic transplantation: Influence of Campath dose on lymphoid recovery, mixed chimerism and survival2006In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 37, no 5, p. 503-510Article in journal (Refereed)
    Abstract [en]

    Sixty-nine consecutive patients (median age 54 years) were prospectively enrolled in a single-institution protocol for allogeneic transplantation with adjusted non-myeloablative fludarabine-melfalan-based conditioning including cyclosporin A and MMF, and one of three modes of serotherapy. Thirty-one donors (45%) were unrelated. The first cohort of 29 had ATG (Thymoglobulin 2 mg/kg × 3 days), the subsequent 26 had Campath 30 mg × 3 days subcutaneously, and the final cohort of 14 had 30 mg Campath once. The groups were similar as regards age, diagnosis and risk factors. Campath-patients had no acute toxicity, fewer days with fever and antibiotics, and required fewer transfusions than ATG-treated patients. 3-d-Campath patients showed lower lymphocyte counts from day + 4, and CD4 +, CD8 +, CD19 + and NK cells recovered slower than in ATG-treated patients. More Campath patients developed mixed chimerism that required DLI. 3-d-Campath induced more serious and opportunistic infections than ATG, which resulted in a greater non-relapse mortality and an impaired overall survival despite a low tumor-related mortality. The change of the Campath dosing schedule to one dose abrogated the deleterious effect of 3-d-Campath on immune recovery, severe infections and survival. Subcutaneous Campath is simple and provides strong immune suppression with no early toxicity, but dose limitation to 30 mg once is recommended. © 2006 Nature Publishing Group. All rights reserved.

  • 115. Karlsson, Lasse
    et al.
    Håkansson, Anders
    Nordenskjöld, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Opportunistisk cancerscreening i primärvård2002In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, p. 2636-2638Article in journal (Other academic)
  • 116.
    Karlsson, Margareta
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    DNA ploidy, proliferation markers and prognosis in malignant melanoma1995Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Malignant melanoma is a serious disease when metastases occur. It is therefore important to investigate possible tools for prediction to the outcome of the disease. In the present investigation 265 patients with cutaneous malignant melanoma and uveal melanoma was investigated with flow cytometry.

    In 82 patients with stage Ill cutaneous melanoma we found that the DNA ploidy and S-phase fraction on the primacy tumours and the time to the first metastases predicted the post-recurrence survival. Patients with diploid melanoma cells, low S-phase fraction and a long recurrence free interval had a rather favourable prognosis despite presence of regional metastases. In 55 subjects a significantly higher frequency of aneuploidy was found in metastases compared to the primary tumour of the same patients, suggesting a higher growth potential in metastases.

    A high S-phase fraction measured on the last histologically metastases before chemotherapy treatment was associated with an objective response and a longer survival in 87 patients with disseminated melanoma. The anatomical location of the metastases also predicted objective response, and together with a high S-phase fraction, a large number of metastatic sites and objective response were associated with survival.

    DNA ploidy together with histopathologic type and tumour size could predict the survival in 96 patients with uveal melanoma. A small, diploid tumour of spindle-cell type gave a significantly longer survival than a large, aneuploid tumour of epithelioid-cell type. In univariate statistical analysis the S-phase fraction predicted survival, but did not remain as a prognostic factor after adjustments for ploidy, histologic type and tumoursize. DNA ploidy and S-phase fraction were correlated with well-known histopathologic features. The proliferation marker Ki-67 was correlated with well-known histopathological features and associated with survival in 79 patients. This was not the case with the proliferation marker PCNA. Patients with uveal melanomas containing a high percentage of Ki-67 positive nuclei had a significant shorter survival than those with a low percentage.

  • 117.
    Knutsen Holmqvist, Annica
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Adell, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Inflammatory infiltration, fibrosis, necrosis and mucinous content in relation to clinicopathological and molecular factors in rectal cancers with or without preoperative radiotherapy.2006In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 16, no 2, p. 321-327Article in journal (Refereed)
    Abstract [en]

    The association between inflammatory infiltration, fibrosis, necrosis and mucinous content in rectal cancers, and their relationship to preoperative radiotherapy (RT) clinicopathological and biological factors (p53, apoptosis and Cox-2) is not fully characterised. We analysed these histopathological parameters and their relationships in rectal cancer patients who participated in a clinical trial of preoperative RT. One hundred and forty-eight preoperative biopsies and 153 surgically resected tumours were examined. Of the surgical specimens, 81 had surgery alone and 72 received RT before surgery. A higher grade of inflammatory infiltration was related to favourable survival in the whole group of patients (p=0.004, for multivariate analysis p=0.01) as well as in the subgroups of patients with (p=0.04) or without RT (p=0.01). After RT, tumours showed a decreased infiltration (p=0.0003) and increased necrosis (p=0.006), strong necrosis was related to favourable survival (p=0.046). Necrosis (p=0.054) and fibrosis (p=0.06) tended to be increased in p53-negative tumours after RT. Inflammatory infiltration was a strong prognostic factor in rectal cancer patients, regardless of RT. RT tended to induce necrosis and fibrosis in p53-negative tumours.

  • 118. Koul, A
    et al.
    Bendahl, P-O
    Borg, Å
    Fernö, M
    Fredstorp Lidebring, M
    Högberg, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Långström Einarsson, M
    Ridderheim, M
    Willén, R
    TP53 protein expression analysis by luminometric immunoassay in comparison with gene mutation status and prognostic factors in early stage endometrial cancer2002In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 12, no 4, p. 362-371Article in journal (Refereed)
    Abstract [en]

    Mutations in the TP53 tumor suppressor gene have been shown to significantly correlate with poor prognosis in endometrial cancer. In the present study we have evaluated a luminometric immunoassay (LIA) for quantitative estimation of TP53 protein expression in 65 cytosol preparations from endometrial cancer, previously analyzed for mutations in TP53 exons 4-10. LIA showed high (= 0.6 ng/mg protein) expression of TP53 protein in all eight tumors with missense mutation, but high protein levels were also detected in 15 tumors with normal TP53 sequence. All four tumors with nonsense or frameshift mutations had low or no TP53 protein expression. LIA was further evaluated in a retrospective study of 201 cytosol samples from endometrial cancer. TP53 overexpression (>= 0.6 ng/mg protein) was observed in 22% of the tumors and correlated with nonendometrioid histology types (P = 0.005), poorly differentiated tumors (P = 0.001), higher FIGO grade (P = 0.001), DNA nondiploidy (P = 0.002), and high S-phase fraction (P = 0.03). After a median follow-up time of 6.8 years (range 0.7-9.9 years), 22 (13%) progressions were observed in the 175 patients with early stage (I-II) disease. TP53 overexpression (P = 0.04), FIGO grade 3 vs. 1 + 2 (P = 0.01), higher age (P = 0.02), and DNA nondiploidy (P < 0.001) showed significant correlation to shorter progression-free survival in these patients. We conclude that TP53 protein analysis by LIA provides an incomplete correlation to mutation status and cannot substitute for mutation analysis in assessment of prognosis in endometrial carcinoma. In comparison to TP53 overexpression and higher FIGO grades, DNA nonploidy status seems to be a better prognostic indicator to define a subset of early stage endometrial cancer patients who may benefit by adjuvant chemotherapy/radiotherapy.

  • 119. Kronblad, A
    et al.
    Jirström, K
    Rydén, L
    Nordenskjöld, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Landberg, G
    Hypoxia inducible factor-1α is a prognostic marker in premenopausal patients with intermediate to highly differentiated breast cancer but not a predictive marker for tamoxifen response2006In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 118, no 10, p. 2609-2616Article in journal (Refereed)
    Abstract [en]

    Hypoxia is common in many solid tumours, including breast cancer. Hypoxia triggers the expression of hypoxia inducible factor-1α (HIF-1α), and HIF-1α has been associated with an impaired prognosis in breast cancer and down-regulation of the oestrogen receptor (ER), potentially affecting the treatment efficiency of antioestrogens. The role of HIF-1α regarding prognostic and treatment predictive information in breast cancer has not been established and we therefore analyzed HIF-1α using immunohistochemistry in a cohort of 377 premenopausal stage II breast cancers arranged in a tissue microarray. The patients were included in a randomized trial with either 2 years of tamoxifen or no adjuvant treatment. The tamoxifen treatment effect could be studied in subgroups of breast cancer and pure prognostic information could be scrutinized for untreated control patients. HIF-1α was scored as positive in 24% of the tumours and correlated positively to tumour size, Nottingham histological grade (NHG), Ki-67, Her2 and cyclin E expression and negatively to lymph node status, cyclin D1, ER and PR (progesterone receptor) expression. Surprisingly, there was no difference in tamoxifen response for patients with high or low HIF-1α expressing tumours. In lymph node-positive patients as well as NHG 1/2 tumours, high HIF-1α protein expression was significantly associated with an impaired recurrence-free survival (p = 0.014, 0.018). When analyzing the subgroup of NHG 1/2 tumours, a high HIF-1α expression was the only independent significant prognostic marker in multivariate analysis, including standard prognostic markers, suggesting that HIF-1α might be a useful prognostic marker in this subgroup of breast cancer, with a rather good but diverse prognosis. © 2005 Wiley-Liss, Inc.

  • 120.
    Kågedal, Bertil
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Farnebäck, Malin
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Håkansson, Annika
    Department of Oncology, University Hospital MAS and Lund University, Malmö, Sweden.
    Gustafsson, Bertil
    Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Cytology. Linköping University, Faculty of Health Sciences.
    Håkansson, Leif
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    How useful are housekeeping genes?: variable expression in melanoma metastases2007In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 45, no 11, p. 1481-1487Article in journal (Refereed)
    Abstract [en]

    Background: There is a certain difference in opinion regarding the optimal choice of housekeeping genes used as normalization factors in gene expression analysis. We have therefore examined the suitability of three housekeeping genes, hypoxanthine phosphoribosyl transferase, β-glucuronidase and β2-micro-globulin, for normalization of expression data from melanoma metastases.

    Methods: The expression of the three housekeeping genes was quantified by quantitative reverse transcription PCR in snap-frozen sections from 44 melanoma metastases, of which 19 were from patients treated with cisplatinum, dacarbazine and interferon-α2b.

    Results: The expression of each housekeeping gene varied considerably between the different metastases. Histopathological examination of the tissue sections revealed variation in the amount of tumor cells in the tissue, necrosis, varying degrees of lymphocyte infiltration, and lymph node remnants. Based on this examination, 16 biopsies were omitted from further analysis because they had cracked, contained empty or necrotic areas, or were dominated by lymph node tissue. Even in sections with more than 90% tumor cells, a wide variation in the expression of the three housekeeping genes was found. The amount of lymphatic infiltrate in the tumors can have an effect on the expression of housekeeping genes in the meta-stases, whereas treatment did not seem to influence the expression.

    Conclusions: We conclude that the choice of housekeeping genes can have great impact on the normalization of specific genes in melanoma metastases. Furthermore, in the analysis of mRNA expression in tumor tissue, microscopic examination is of great importance to evaluate the integrity and cellular composition of the biopsy.

  • 121. Lacombe, D
    et al.
    Fumoleau, P
    Zwierzina, H
    Twelves, C
    Håkansson, Leif
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Jayson, G
    Lehmann, F
    Verweij, J
    The EORTC and drug development2002In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 38, p. 19-23Article in journal (Refereed)
  • 122.
    Lewander, Andreas
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Kumar Reddy Butchi, Anil
    Gao, Jingfang
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    He, Lu-Jun
    Lindblom, Annika
    Arbman, Gunnar
    Carstensen, John
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Department of Health and Society, Tema Health and Society.
    Zhang, Zhi-Yong
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Polymorphism in the promoter region of the NFKB1 gene increases the risk of sporadic colorectal cancer in Swedish but not in Chinese populations2007In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 11, p. 1332-1338Article in journal (Refereed)
    Abstract [en]

    Objective. An insertion/deletion polymorphism (-94ins/delATTG) in the promoter region of the NFKB1 gene correlates to an increased risk of ulcerative colitis, a known risk factor for colorectal cancer, but this polymorphism has not been studied in colorectal cancer patients. The purpose of this study was to investigate whether this polymorphism is related to colorectal cancer risk and clinicopathological variables. Material and methods. Case samples were taken from four groups of Swedish patients: 193 unselected patients, 90 patients with ≥3 affected 1st-degree relatives, 85 patients with 2 affected 1st-degree relatives, and 109 sporadic cancer patients, and one group of 193 unselected Chinese patients. Controls included 439 Swedish and 458 Chinese healthy individuals. Genotypes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Results. The deletion increased the risk of colorectal cancer among Swedish unselected patients (OR=3.81, 95% CI: 2.17-6.69, p<0.0001 for heterozygote deletion, and OR=4.65, 95% CI: 2.43-8.89, p<0.0001 for homozygote deletion) and sporadic cancer patients (OR=7.73, 95% CI: 3.06-19.57, p<0.0001 for heterozygote deletion, and OR=6.58, 95% CI: 2.35-18.43, p<0.0001 for homozygote deletion) compared to homozygote insertion (wild-type), but not among the other Swedish or Chinese patients (p>0.05). Similar evidence was seen in age-adjusted analyses (p<0.0001). The polymorphism did not correlate to clinicopathological variables (p>0.05). Conclusions. Deletion of the polymorphism was associated with increased susceptibility to sporadic colorectal cancers in the Swedish population, but not in the Swedish patients with a family history of colorectal cancer or in Chinese patients. © 2007 Taylor & Francis.

  • 123. Lindemalm, S
    et al.
    Liliemark, J
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Larsson, R
    Albertioni, F
    Cytotoxicity and pharmacokinetics of cladribine metabolite, 2-chloroadenine in patients with leukemia2004In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 210, no 2, p. 171-177Article in journal (Refereed)
    Abstract [en]

    The nucleoside analog 2-chlorodeoxyadenosine (Cladribine, CdA) is used in the treatment of patients with several hematological malignancies. After administration of CdA, the major catabolite measured in plasma and urine is 2-chloroadenine (CAde). This study was performed to determine the pharmacokinetics after oral and intravenous (iv) infusion of CdA in patients treated for chronic lymphocytic leukemia and to evaluate the toxicity of CAde to leukemia cells in vitro. CdA and CAde were also determined in plasma from 31 patients and in urine from 16 patients with reversed-phase high-performance liquid chromatographic. The toxicity of CdA and CAde was also determined in leukemic cells from 7 patients by fluorometric microculture cyotoxicity assay. Five times more CAde was quantified after oral treatment compared with an iv infusion of CdA. After iv infusion, the half-life was the same for CdA and CAde, but after oral administration the half-life was doubled for CAde. Excreted amount of CAde in urine constituted about 1.1% after iv infusion and 4.7% after oral CdA treatment. In vitro exposure of leukemia cells to CAde showed that it was eight times less toxic as compared to CdA. We conclude that CAde has a lower cytotoxic effect than CdA but may contribute significantly to the cytotoxicity after oral administration.

  • 124. Lindholm, Christer
    et al.
    Andersson, Ronny
    Dufmats, Monika
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Hansson, Johan
    Ingvar, Christian
    Möller, Torgil
    Sjödin, Helena
    Stierner, Ulrika
    Wagenius, Gunnar
    Invasive cutaneous malignant melanoma in Sweden, 1990-1999: A prospective, population-based study of survival and prognostic factors2004In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 101, no 9, p. 2067-2078Article in journal (Refereed)
    Abstract [en]

    BACKGROUND. The objective of the current study was to compile prospective, population-based data on cutaneous invasive melanomas in Sweden during the period from 1990 to 1999, to describe and analyze survival data and prognostic factors, and to make comparisons with previously published Swedish and international data. METHODS. Twelve thousand five hundred thirty-three patients, which included 97% of all registered melanomas in Sweden, were included and described. Among these, 9515 patients with clinical Stage I and II melanoma were included in an analysis of survival and in a univariate analysis, and 6191 patients were included in a multivariate analysis of prognostic factors. RESULTS. There was no significant change in melanoma incidence during 1990-1999. Favorable prognostic factors were found, especially in younger and female patients, resulting in a relative 5-year survival rate of 91.5%. In the multivariate analysis, significant factors that had a negative effect on survival were Clark level of invasion, Breslow thickness, ulceration, older patient age, trunk location, greatest tumor dimension, nodular histogenetic type, and male gender. CONCLUSIONS. During the period from 1990 to 1999, the 5-year survival of patients with malignant melanoma in Sweden was better compared with the previously reported rates in published, population-based studies from Sweden, probably as a result of better secondary prevention due to better knowledge and awareness by both patients and the medical profession. The more favorable prognostic factors and the change in melanoma location found in younger patients, compared with earlier reports, may reflect changes in clothing as well as tanning habits, however, a decrease also was found in Clark Level II and thin melanomas for the same patient group. The authors concluded that further improvements can be achieved with better access to health care and with the use of early melanoma detection campaigns.

  • 125.
    Lotfi, Kourosh
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Letter: Monitoring oral cyclosporine therapy2005In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 36, p. 367-367Article in journal (Other academic)
  • 126.
    Lundin, Anna-Carin
    et al.
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Eriksson, Birgitta
    Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
    Bergman-Jungeström, Malin
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Wingren, Sten
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Association of breast cancer progression with a vitamin D receptor gene polymorphism1999In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 59, no 10, p. 2332-2334Article in journal (Refereed)
    Abstract [en]

    The vitamin D3 receptor gene (VDR) contains a TaqI RFLP that is associated with increased VDR mRNA stability, increased serum levels of 1α,25-dihydroxyvitamin D3 (1,25-D3), and decreased risk for prostate cancer. Determination of the TaqI genotype, in a group of young women with breast cancer (n = 111; age, <37 years) and a control population (n = 130), revealed no overall association to risk for breast cancer. However, patients without TaqI site (TT genotype) showed a significantly increased risk for lymph node metastasis (relative risk, 1.8, 95% confidence interval, 1.3- 2.6). Furthermore, a tendency toward an increased survival was found among estrogen receptor-positive, tamoxifen-treated patients who were homozygous for the TaqI site (P = 0.075). We conclude that polymorphism in the VDR gene may influence tumor progression and tamoxifen treatment response in early- onset breast carcinomas.

  • 127.
    Malmström, Henric
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Intraperitoneal Chemotherapy of Ovarian Cancer1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ovarian cancer is still the most common cause of death among gynecologic malignancies in spite of the fact that newer and more effective drugs and/or administration techniques have been developed in the last decade. However, substantial improvements in response rate andprogression-free survival have been reported in many studies.

    In this study the efficacy, toxicity and feasibility of different drugs administered IP were evaluated in patients with ovarian cancer. The maximum tolerated dose of carboplatin administered IP was determined to be 500 mg!m2 This dose was given adjuvantly in a phase IT study to 47 women with early-stage disease. There were 10 patients in this study who developed recurrent disease. The toxicity was acceptable, the major dose-limiting toxic effect being hematologic, especially thrombocytopenia. One patient developed grade 3 nephrotoxicity after the second course. There was no incidence of treatment-related death.

    Thirty-five patients with advanced ovarian cancer were treated with an aggressive combination regimen (cisplatin/etoposide) intraperitoneally with IV sodium thiosulphate as antidote. The dose-limiting toxic effect was hematologic. Two patients developed severe nephrotoxicity. The median progression-free interval was 13 months and the survival at closing point 31% with a median follow-up of 16 months.

    The patient acceptance and feasibility of using subcutaneously implantable peritoneal access devices were analyzed in 125 patients. Port-A-Cath was used in 98% of the patients, 465 IP courses were administered and 27 (21.6%) severe or moderate complications related to Port-A-Cath were registered.

    The incidence of nephrotoxicity in patients treated IP with platinum-containing regimens was analysed. Six of 135 patients (4%) developed severe nephrotoxicity; impairment of renal function, as judged by serum creatinine, was seen in most patients. This was cumulative during treatment and not completely reversible. Young age was a predictive factor for severe nephrotoxicity.

  • 128. Marchand, M
    et al.
    Punt, CJA
    Aamdal, S
    Escudier, B
    Kruit, WHJ
    Keilholz, U
    Håkansson, Leif
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    van Baren, N
    Humblet, Y
    Mulders, P
    Avril, M-F
    Eggermont, AMM
    Scheibenbogen, C
    Uiters, J
    Wanders, J
    Delire, M
    Boon, T
    Stoter, G
    Immunisation of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2: A clinical report2003In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 39, no 1, p. 70-77Article in journal (Refereed)
    Abstract [en]

    Fifty-seven patients with MAGE-3-positive measurable metastatic cancer, most of them with melanoma, were vaccinated with escalating doses of a recombinant MAGE-3 protein combined with a fixed dose of the immunological adjuvant SBAS-2, which contained MPL and QS21. The immunisation schedule included 4 intramuscular (i.m.) injections at 3-week intervals. Patients whose tumour stabilised or regressed after 4 vaccinations received 2 additional vaccinations at 6-week intervals. The vaccine was generally well tolerated. Among the 33 melanoma patients who were evaluable for tumour response, we observed 2 partial responses, 2 mixed responses and 1 stabilisation. Time to progression in these 5 patients varied from 4 to 29 months. In addition, a partial response lasting 10 months was observed in 1 of the 3 metastatic bladder cancer patients included. None of the tumour responses described above involved visceral metastases. Immunological responses to the vaccine will be reported separately. ⌐ 2002 Elsevier Science Ltd. All rights reserved.

  • 129.
    Matthiesen, Leif
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Berg, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Håkansson, L
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Lymphocyte subsets and mitogen stimulation of blood lymphocytes in preeclampsia.1999In: American Journal of Reproductive Immunology and Microbiology, ISSN 8755-8920, Vol. 41, p. 192-203Article in journal (Refereed)
  • 130. Mattsson, Sören
    et al.
    Brahme, Anders
    Carlsson, Jörgen
    Denekamp, Juliana
    Forssell-Aronsson, Eva
    Hellström, Mikael
    Johansson, Karl-Axel
    Kjellén, Elisabeth
    Littbrand, Bo
    Nordenskjöld, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Stenerlöw, Bo
    Turesson, Ingela
    Zackrisson, Björn
    Glimelius, Bengt
    Swedish Cancer Society radiation therapy research investigation2002In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 41, no 7-8, p. 596-603Article in journal (Refereed)
    Abstract [en]

    In an investigation by the Swedish Cancer Society, the present status, critical issues and future aspects and prospects were described by an expert group for each of nine major areas of radiation research. A summary of the investigation is presented in this report. A more extensive summary (in Swedish) can be found at www.Cancerfonden.se. It is concluded that radiation therapy plays an increasingly important role in curative and palliative tumour treatment and presents a considerable challenge to research. Several suggestions are made that could improve the possibilities for high-quality radiation therapy research in Sweden.

  • 131. Meng, Wen-Jian
    et al.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Tian, Chao
    Wang, Ling
    Yu, Yong-Yang
    Zhou, Bing
    Gu, Jun
    Xia, Qing-Jie
    Li, Yuan
    Wang, Rong
    Zheng, Xue-Lian
    Zhou, Zong-Guang
    Microsatellite instability did not predict individual survival in sporadic stage II and III rectal cancer patients2007In: Oncology, ISSN 0890-9091, Vol. 72, no 1-2, p. 82-88Article in journal (Refereed)
    Abstract [en]

    Objectives: Tumors with high-frequency microsatellite instability (MSI-H) have unique biological behavior and the predictive role of microsatellite instability (MSI) status on survival of colorectal cancer is still debated. The prognostic significance of MSI status in sporadic stage II and III rectal cancer patients needs to be more precisely defined. So we investigated the relationship between MSI status and clinicopathological features and prognosis in these patients. Methods: DNAs from fresh-frozen paired samples of tumors and corresponding normal tissue from 128 stage II and III rectal cancer patients were analyzed for MSI by PCR amplification using markers recommended by a National Cancer Institute workshop on MSI. To assess prognostic significance, Cox proportional hazards modeling was used. Results: Twelve (9.3%) tumors in our study were MSI-H, 28 (21.9%) were low-frequency MSI (MSI-L) and 88 (68.8%) were microsatellite stable (MSS). Most of the MSI-H tumors compared with MSI-L and MSS tumors were found in female patients (p = 0.031), had mucinous histology (p = 0.023), high grade of differentiation (p = 0.002) and high level of preoperative serum carcinoembryonic antigen (p = 0.005). Rectal cancer patients with MSI-H did not show a better clinical outcome than those with MSI-L/MSS, neither in all cases (p = 0.986) nor in stage II and stage III disease analyzed separately (p = 0.705 and p = 0.664, respectively). Conclusions: Data provided here demonstrated there was high incidence of MSI-H and MSI was not a prognostic factor in sporadic stage II and III rectal cancers from the Chinese Han population included in this study. Tumor stage is more suitable than MSI status for prediction of individual survival in sporadic stage II and III rectal cancer patients. Copyright © 2007 S. Karger AG.

  • 132. Meng, Wen-Jian
    et al.
    Wang, Ling
    Tian, Chao
    Yu, Yong-Yang
    Zhou, Beng
    Gu, Yun
    Xia, Qing-Jie
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Li, Yuan
    Wang, Rong
    Zheng, Xue-Lian
    Zhou, Zong-Guang
    Novel mutations and sequence variants in exons 3-9 of human T Cell Factor-4 gene in sporadic rectal cancer patients stratified by microsatellite instability2007In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 13, no 27, p. 3747-3751Article in journal (Refereed)
    Abstract [en]

    Aim: To establish the role of human T Cell Factor-4 (hTCF-4) gene exons 3-9 mutation status in association with sporadic rectal cancer with microsatellite instability (MSI). Methods: Microsatellite markers were genotyped in 93 sporadic rectal cancer patients. Eleven cases were found to be high-frequency MSI (MSI-H). Sequence analysis of the coding region of the exons 3-9 of hTCF-4 gene was carried out for the 11 MSI-H cases and 10 controls (5 microsatellite stability (MSS) cases and 5 cases with normal mucosa). The sequencing and MSI identification were used. Results: Several novel mutations and variants were revealed. In exon 4, one is a 4-position continuous alteration which caused amino acid change from Q131T and S132I (391insA, 392 G > A, 393 A > G and 395delC) and another nucleotide deletion (395delC) is present in MSI-H cases (5/10 and 4/10, respectively) but completely absent in the controls. Conclusion: Novel mutations in exon 4 of hTCF-4 gene were revealed in this study, which might be of importance in the pathogenesis of sporadic rectal cancer patients with MSI-H. © 2007 WJG. All rights reserved.

  • 133. Merup, M
    et al.
    Lazarevic, V
    Nahi, H
    Andreasson, B
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Nilsson, L
    Brune, M
    LeBlanc, K
    Kutti, J
    Birgegard, G
    Different outcome of allogeneic transplantation in myelofibrosis using conventional or reduced-intensity conditioning regimens2006In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 135, no 3, p. 367-373Article in journal (Refereed)
    Abstract [en]

    Allogeneic haematopoietic stem cell transplantation remains the only curative treatment of myelofibrosis with myeloid metaplasia (MMM). Previous reports have indicated significant treatment-related mortality (TRM) for patients transplanted after myeloablative conditioning but superior survival has been reported after reduced-intensity conditioning (RIC). We report the results of a survey of all allogeneic transplantations for MMM performed in Sweden at six transplant units between 1982 and 2004. Twenty-seven patients were transplanted, 17 with a myeloablative conditioning regimen and 10 with RIC. The median age was 50 years (5-63 years) at transplantation. After a median follow up of 55 months, 20 patients are alive. TRM was 10% in the RIC group and 30% in the myeloablative group. There was no difference in survival for high or low-risk patients according to Cervantes score or between sibling and unrelated donor transplantations. © 2006 The Authors.

  • 134.
    Moparhti, Satish Babu
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Arbman, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Wallin, Åsa
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Kayed, Hany
    General Surgery, University of Heidelberg, Heidelberg, Germany.
    Kleeff, Jörg
    General Surgery, University of Heidelberg, Heidelberg, Germany.
    Zentgraf, Hanswalter
    Applied Tumor Virology, University of Heidelberg, Heidelberg, Germany.
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Expression of MAC30 protein is related to survival and biological variables in primary and metastatic colorectal cancers2007In: International Journal of Oncology, ISSN 1019-6439, Vol. 30, no 1, p. 91-95Article in journal (Refereed)
    Abstract [en]

    MAC30 is highly expressed in several types of tumors including colorectal cancers, however, its clinicopathological and biological significance in colorectal cancers is currently not known. The aim of our study was to investigate MAC30 expression in distant normal mucosa, adjacent normal mucosa, primary tumors and metastases of colorectal cancer, and to determine the relationship between MAC30 expression and clinicopathological and biological variables. MAC30 expression was immunohistochemically examined in distant normal mucosa (n = 54), adjacent normal mucosa (n = 123), primary tumors (n = 217) and lymph node metastases (n = 56) from colorectal cancer patients. MAC30 cytoplasmic expression was increased from distant normal mucosa to primary tumor and to metastasis (p < 0.0001-0.04). Furthermore, 40% primary and 37% metastatic tumors showed stronger cytoplasmic expression of MAC30 at the tumor invasive margins compared to inner tumor areas. Strong cytoplasmic expression of MAC30 in the metastasis was related to a poor prognosis (p = 0.04). MAC30 cytoplasmic expression was positively related to expression of proliferating cell nuclear antigen (p = 0.04), p53 (p = 0.04), nucleoporin 88 (p = 0.001), legumain (p = 0.004) and particularly interesting new cysteine-histidine rich protein (p = 0.004). However, MAC30 expression in the nucleus and stroma did not have any clinicopathological and biological significance (p > 0.05). In conclusion, MAC30 protein may play a role in development of colorectal cancer, and can be considered as a prognostic factor.

  • 135. Murthy, RV
    et al.
    Arbman, G
    Gao, Jingfang
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Roodman, D
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Legumain expression in relation to clinicopathologic and biological variables in colorectal cancer2005In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 11, no 6, p. 2293-2299Article in journal (Refereed)
    Abstract [en]

    Purpose: Legumain, a novel asparaginyl endopeptidase, has been observed to be highly expressed in several types of tumors including colorectal cancer. However, there is no study examining the relationship of legumain expression to clinocopatbologic and biological variables in colorectal cancers. Experimental Design: We investigated legumain expression in 164 primary colorectal cancers, 34 corresponding distant normal mucosa samples, 89 adjacent normal mucosa samples, and 33 lymph node metastases using immunohistochemistry. We also did Western blotting analysis on three additional colorectal cancers and three colonic cell lines. Results: Legumain expression was increased in primary tumors compared with distant or adjacent normal mucosa (P < 0.05), but there was no significant change between primary tumors and metastases (P > 0.05). Legumain expression was positively related to poorer differentiation/ mucinous carcinoma (P = 0.04), higher degree of necrosis (P = 0.03) and apoptosis (P < 0.0001), positive proliferating cell nuclear antigen (P < 0.0001) and p53 expression (P = 0.049), and had a positive tendency towards stromelysin 3 (P = 0.058) and PINCH positivity (P = 0.05). The patients with tumors that showed both weak and lower percentage of the legumain expression, either in tumor (P = 0.01) or in stroma (P = 0.04), had a better prognosis. Conclusions: The legumain expression may be involved in colorectal cancer development and have a prognostic value in the patients. ©2005 American Association for Cancer Research.

  • 136.
    Myrelid, Pär
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Dufmats, Monika
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Lilja, Ingela
    Grännö, C
    Lannerstad, O
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Atopic manifestations are more common in patients with Crohn disease than in the general population2004In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 39, no 8, p. 731-736Article in journal (Refereed)
    Abstract [en]

    Background: The role of TNF-α in Crohn disease is now well established and anti-TNF-α is frequently used as a second- or third-line treatment. Tumor necrosis factor-α (TNF-α) is traditionally associated with macrophages but has recently also been found in mast cells of the ileal wall in patients with Crohn disease. As it is well known that mast cells and TNF-α play important roles in atopic manifestations like asthma, allergic rhinitis, and eczema the aim of this study was to investigate whether these are seen more commonly in Crohn patients than in the general population. Methods: Patients with Crohn disease (n = 308), aged 18-50 years, living in the Linköping region in southeast Sweden, were asked to answer a questionnaire regarding the presence of any kind of atopic manifestations. The questionnaire was also sent to 930 controls collected from the Southeastern Region Population Registry. The controls were matched according to age, sex, and place of residence. Results: The response rate among the Crohn patients was 91% (280/308) and among controls 84% (779/930). Eczema was a significantly more frequent manifestation, being almost twice as common in Crohn patients (27%) as in the general population (16%). Adjustment by logistic regression for place of residence, gender, age and coexistence of any other atopic manifestation did not change the odds ratios significantly. Conclusion: Atopic manifestations as a group, and eczema as a single manifestation, are significantly more frequent in Crohn patients than in the general population.

  • 137.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology. Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    On the measurement of evaporative water loss: methods and clinical applications1977Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The new method for measurement of water loss by evaporation from the skin described in paper I, offers a high degree of accuracy and improved sensitivity in comparison with devices reported previously. Rapid recordings can be made by technically untrained persons both in clinical departments and in the laboratory.

    Using this method, the average insensible perspiration from the skin of healthy adult subjects at rest was found to be 381, 526 and 695 gr per day at ambient temperatures of 22°, 27° and 30°C, respectively. On the head, hands and feet the evaporation rate was high, while on other body surface areas more moderate values were recorded,

    In a clinical study on newborn infants, a linear relationship between the evaporative water loss from the skin and the ambient humidity was found. At an ambient temperature of 34.5°c and an ambient relative humidity of 50% the average transepidermal water loss was calculated to be 8.1 g/m2h.

    In burned patients high evaporation rates from about 140 g/m2h to over 220 g/m2h were recorded on the injured skin surfaces. Biological dressings were only slightly permeable to water vapour, while the permeability of the artificial dressings tested was generally high.

    By recording the rate of increase in vapour concentration in a closed measurement chamber placed over the exposed abdominal cavity during surgery, the water loss by evaporation from wounds and exteriorized viscera was determined. At incisions of minor extent the evaporative water loss was low, while at larger incisions with exteriorized viscera the water loss by evaporation from the wound exceeded the basal cutaneous perspiration of healthy adult subjects.

  • 138. Nordengren, J
    et al.
    Fredstorp Lidebring, M
    Bendahl, P-O
    Brunner, N
    Fero, M
    Högberg, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Stephens, RW
    Willén, RW
    Casslén, B
    High tumor tissue concentration of plasminogen activator inhibitor-2 (PAI-2) is an independent marker for shorter progression-free survival of patients with early stage endometrial cancer2002In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 97, p. 379-385Article in journal (Refereed)
  • 139.
    Nordenskjöld, Bo
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Rosell, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Rutqvist, Lars-Erik
    Department of Oncology, Södersjukhuset Hospital, Stockholm, Sweden.
    Malmström, Per-Olof
    Department of Oncology, Lund University Hospital, Lund, Sweden.
    Bergh, Jonas
    Department of Oncology, Karolinska Hospital, Stockholm, Sweden.
    Bengtsson, Nils-Olof
    Department of Oncology, Umeå University Hospital, Umeå, Sweden.
    Hatschek, Thomas
    Department of Oncology, Karolinska Hospital, Stockholm, Sweden.
    Wallgren, Arne
    Department of Oncology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Carstensen, John
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Department of Health and Society, Tema Health and Society.
    Coronary heart disease mortality after 5 years of adjuvant tamoxifen therapy: Results from a randomized trial2005In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 97, no 21, p. 1609-1610Article in journal (Refereed)
    Abstract [en]

    From January 1, 1983, through December 31, 1992, a total of 4610 patients entered a randomized trial that compared mortality among patients receiving 2 years of adjuvant tamoxifen therapy with that in patients receiving 5 years of adjuvant tamoxifen therapy, 4175 of whom were recurrence free after 2 years of tamoxifen therapy. Among the 2046 patients randomly assigned to the 5-year group all-cause mortality, breast cancer-specific mortality, and the incidence of contralateral breast cancer were reduced, compared with those among 2129 patients randomized in the 2-year group, but the incidence of endometrial cancer was increased. In addition, mortality from coronary heart disease was statistically significantly reduced in the 5-year group, compared with that in the 2-year group (hazard ratio = 0.67, 95% confidence interval = 0.47 to 0.94, P = .022 [two-sided Wald test]). Ten years after surgery, 2.1% of the patients in the 5-year group and 3.5% of those in the 2-year group had died from coronary heart disease. No statistically significant increases in mortality from other heart diseases, cerebrovascular diseases, or other vascular diseases were observed. © The Author 2005. Published by Oxford University Press. All rights reserved.

  • 140.
    Nordström, Marie
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Hardell, Lennart
    Fredriksson, Mats
    Previous medical history and medications as risk factors for hairy cell leukemia.1999In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 6, p. 415-419Article in journal (Refereed)
  • 141. Nyström, Lennarth
    et al.
    Andersson, Ingvar
    Bjurstam, Nils
    Frisell, Jan
    Nordenskjöld, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Rutqvist, Lars Erik
    Long-term effects of mammography screening: Updated overview of the Swedish randomised trials2002In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 359, no 9310, p. 909-919Article in journal (Refereed)
    Abstract [en]

    Background: There has been much debate about the value of screening mammography. Here we update the overview of the Swedish randomised controlled trials on mammography screening up to and including 1996. The Kopparberg part of the Two-County trial was not available for the overview, but the continuation of the Malm÷ trial (MMST II) has been added. The article also contains basic data from the trials that have not been presented before. Methods: The trials (n=247 010, invited group 129 750, control group 117 260) have been followed up by record linkage to the Swedish Cancer and Cause of Death Registers. The relative risks (RR) for breast cancer death and mortality were calculated for the invited and the control groups. The trial-specific as well as the age-specific effects were analysed. RRs were calculated by the density method, with total person-time experience of the cohort by time interval of follow-up as a basis for estimating mortality rates. We calculated weighted RRs and 95% CI with the Mantel-Haenszel procedure. Findings: The median trial time - the time from randomisation until the first round was completed for the control group or if the control group was not invited, until end of follow-up - was 6.5 years (range 3.0-18.1). The median follow-up time, the time from randomisation, to the end of follow-up, was 15.8 years (5.8-20.2). There were 511 breast cancer deaths in 1 864 770 women-years in the invited groups and 584 breast cancer deaths in 1 688 440 women-years in the control groups, a significant 21% reduction in breast cancer mortality (RR=0.79, 95% CI 0.70-0.89). The reduction was greatest in the age group 60-69 years at entry (33%). Looking at 5-year age groups, there were statistically significant effects in the age groups 55-59, 60-64, and 65-69 years (RR=0.76, 0.68, and 0.69, respectively). There was a small effect in women 50-54 years at randomisation (RR=0.95). The benefit in terms of cumulative breast cancer mortality started to emerge at about 4 years after randomisation and continued to increase to about 10 years. Thereafter the benefit in absolute terms was maintained throughout the period of observation. The age-adjusted relative risk for the total mortality was 0.98 (0.96-1.00). Interpretation: The advantageous effect of breast screening on breast cancer mortality persists after long-term follow-up. The recent criticism against the Swedish randomised controlled trials is misleading and scientifically unfounded.

  • 142. Olsson-Strömberg, U
    et al.
    Höglund, M
    Björkholm, M
    Braide, I
    Carlson, K
    Gahrton, G
    Grimfors, G
    Hast, R
    Lerner, r
    Linder, O
    Ljungman, P
    Löfvenberg, E
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Nilsson, PG
    Paul, c
    Rodjer, s
    Stenke, L
    Tidefeldt, U
    Turesson, I
    Uden, AM
    Wahlin, A
    Vilén, L
    Winqvist, I
    Zettervall, O
    Öberg, G
    Simonsson, B
    Successful mobilization of Ph-negative blood stem cells with intensive chemotherapy+ G-CSF in patients with chronic myelogenous leukemia in first chronic phase2006In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 47, no 9, p. 1768-1773Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to investigate the feasibility of mobilizing Philadelphia chromosome negative (Ph-) blood stem cells (BSC) with intensive chemotherapy and lenograstim (G-CSF) in patients with CML in first chronic phase (CP1). During 1994-1999 12 centers included 37 patients <56 years. All patients received 6 months' IFN, stopping at median 36 (1-290) days prior to the mobilization chemotherapy. All received one cycle of daunorubicin 50 mg/m2 and 1 hour infusion on days 1-3, and cytarabine (ara-C) 200 mg/m2 24 hours' i.v. infusion on days 1-7 (DA) followed by G-CSF 526 μg s.c. once daily from day 8 after the start of chemotherapy. Leukaphereses were initiated when the number of CD 34+ cells was >5/μ blood. Patients mobilizing poorly could receive a 4-day cycle of chemotherapy with mitoxantrone 12 mg/m2/day and 1 hour i.v infusion, etoposide 100 mg/m2/day and 1 hour i.v. infusion and ara-C 1 g/m2/twice a day with 2 hours' i.v infusion (MEA) or a second DA, followed by G-CSF 526 μg s.c once daily from day 8 after the start of chemotherapy. Twenty-seven patients received one cycle of chemotherapy and G-CSF, whereas 10 were mobilized twice. Twenty-three patients (62%) were successfully (MNC >3.5 × 108/kg, CFU-GM >1.0 × 104/kg, CD34+ cells >2.0 × 106/kg and no Ph+ cells in the apheresis product) [n = 16] or partially successfully (as defined above but 1-34% Ph+ cells in the apheresis product) [n = 7] mobilized. There was no mortality during the mobilization procedure. Twenty-one/23 patients subsequently underwent auto-SCT. The time with PMN <0.5 × 109/l was 10 (range 7-49) and with platelets <20 × 109/l was also 10 (2-173) days. There was no transplant related mortality. The estimated 5-year overall survival after auto-SCT was 68% (95% CI 47-90%), with a median follow-up time of 5.2 years. We conclude that in a significant proportion of patients with CML in CP 1, intensive chemotherapy combined with G-CSF mobilizes Ph - BSC sufficient for use in auto-SCT.

  • 143. Olsson-Strömberg, Ulla
    et al.
    Simonsson, Bengt
    Ahlgren, Tomas
    Björkholm, Magnus
    Carlsson, Karin
    Gahrton, Gösta
    Hast, Robert
    Löfvenberg, Eva
    Linder, Olle
    Ljungman, Per
    Malm, Claes
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Paul, Christer
    Rödjer, Stig
    Turesson, Ingemar
    Udén, Ann-Mari
    Wahlin, Anders
    Killander, Andreas
    Wadman, Bengt
    Westin, Jan
    Vikrot, Olle
    Zettervall, Olle
    Öberg, Gunnar
    Comparison of busulphan, hydroxyurea and allogeneic bone marrow transplantation (BMT) in chronic myeloid leukaemia: BMT prolongs survival2004In: The Hematology Journal, ISSN 1466-4860, E-ISSN 1476-5632, Vol. 5, no 6, p. 462-466Article in journal (Refereed)
    Abstract [en]

    Introduction: Whether busulphan-treated patients develop blastic transformation earlier than hydroxyurea treated has been a controversial issue. In a randomised prospective study, we examined the busulphan versus hydroxyurea influence on time to blast crisis and on survival. When we opened our study in 1984, the clinical benefit of allogeneic bone marrow transplantation (BMT) was not well known, to follow up the long-time outcome of this treatment was therefore of great interest. Materials and methods: Previously untreated CML patients were randomly started on either hydroxyurea (30 mg/kg/day) or busulphan (0.1 mg/kg/day). The end points of the study were overall survival and time to blast crisis. A total of 26 patients subsequently underwent BMT. Results: A total of 179 patients were randomised, 90 to hydroxyurea, and 89 to busulphan treatment. There was no significant difference in survival between hydroxyurea- and busulphan-treated patients (P = 0.46), median survival was 3.5 and 3.2 years, respectively. In all, 85 of the patients were subsequently diagnosed with blast crisis, 41 in the busulphan and 44 in the hydroxyurea group. There was no significant difference between the two groups (P=0.91). The 26 patients who were allotransplanted survived significantly longer than those who were not transplanted (P=0.0001). The 5-year-survival rates were 50 and 22% and the 10-year-survival rates were 46 and 2%, respectively. The median survival was 4.7 years for the transplanted and 3.3 years for the nontransplanted patients. Conclusion: We did not find any difference between hydroxyurea and busulphan treatment, either in overall survival or in blast crisis-free survival, transplanted patients survived significantly longer than nontransplanted patients. © 2004 The European Hematology Association All rights reserved.

  • 144. Pachkoria, Ketevan
    et al.
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology.
    Adell, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Jarlsfelt, Ingvar
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Significance of Cox-2 expression in rectal cancers with or without preoperative radiotherapy2005In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 63, no 3, p. 739-744Article in journal (Refereed)
    Abstract [en]

    Purpose: Radiotherapy has reduced local recurrence of rectal cancers, but the result is not satisfactory. Further biologic factors are needed to identify patients for more effective radiotherapy. Our aims were to investigate the relationship of cyclooxygenase-2 (Cox-2) expression to radiotherapy, and clinicopathologic/biologic variables in rectal cancers with or without radiotherapy. Methods and Materials: Cox-2 expression was immunohistochemically examined in distal normal mucosa (n = 28), in adjacent normal mucosa (n = 107), in primary cancer (n = 138), lymph node metastasis (n = 30), and biopsy (n = 85). The patients participated in a rectal cancer trial of preoperative radiotherapy. Results: Cox-2 expression was increased in primary tumor compared with normal mucosa (p < 0.0001), but there was no significant change between primary tumor and metastasis. Cox-2 positivity was or tended to be related to more p53 and Ki-67 expression, and less apoptosis (p ≤ 0.05). In Cox-2-negative cases of either biopsy (p = 0.01) or surgical samples (p = 0.02), radiotherapy was related to less frequency of local recurrence, but this was not the case in Cox-2-positive cases. Conclusion: Cox-2 expression seemed to be an early event involved in rectal cancer development. Radiotherapy might reduce a rate of local recurrence in the patients with Cox-2 weakly stained tumors, but not in those with Cox-2 strongly stained tumors. © 2005 Elsevier Inc.

  • 145.
    Persson, Anders
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Department of Medicine and Care, Radiology. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Volume imaging of the abdomen: three-dimensional visualisation of tubular structures in the body with CT and MRI2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The overwhelming amount of image-based information in modem medicine makes it crucial to develop methods to handle and analyze images and make them comprehensible for users. The aim of this thesis was to study the radiological practice of three-dimensional (3D) visualization of tubular structures in the body with CT and MRI. All the studies cancern 3D imaging of tubular structures with camputed tomography (CT) and magnetic resonance imaging (MRI). The first three studies examine the abdominal aorta; the two later ones the, bile ducts.

    Study I compared measurements of aorta diameters taken from MR images presented using two visualization methods - maximum intensity projection (MlP) and volume rendering (VRT) - with invasive angiography (DSA) and CT as reference methods. Mean diameters of MR images were smaller than those from DSA and CT when MlP was used, but in general not when VRT was used.

    Study II evaluated the dependence on the observer and the choice of method and settings during rendering using the same material as in Study 1. In both MlP and VRT, the choice of settings had significant influence on the results. With DSA as the reference method, VRT gave larger measurement errors than MIP when the rendering parameters were set to fixed values, but not if the user was allowed to select the settings freely.

    Study III evaluated three new techniques for standardizing VRT protocols for MRA. Inter-reader variability and agreement with DSA were studied by comparing diameter measurements of the abdominal aorta obtained by the three new techniques, by VRT with freely chosen parameters and by MlP. All three new methods were significantly better than MlP and VRT with freely chosen parameters conceming inter-observer agreement. Agreement with DSA was significantly better for one of the methods. Standardized protocols seem to have a potential to make VRT a clinically useful alternative to MlP for MR angiography measurements.

    Study IV evaluated CT imaging of the bile ducts after drip intravenous infusion of the contrast medium iotroxate (CT cholangiography) in terms of adverse effects and visibility. With infusion time adjusted for individual variation in serum bilirubin concentration, a total side-effect frequency of less than 1% was found. A systematic review of previously published studies indicated a frequency of 2.3%. Good contrast excretion and visualization of bile ducts even in patients with elevated bilirubin levels were noted.

    Study V evaluated the diagnostic benefits of the same imaging method by comparing it with findings from surgery and endoscopic retrograde cholangiopancreatography (ERCP). The consensus sensitivity and specificity for diagnosing biliary stones was 88% and 94%, respectively. The use of VRT improved diagnostic certainty in 14% of the evaluatians, and the visualization of ductal stones was improved in 38% of the positive cases.

    In conclusion, volume rendering technique with standardized parameters may become a clinically useful tool in the clinical MRI environment. DIC-CT with bilirubin-governed infusion time and volume rendering post-processing produces detailed images of the biliary tree, resulting in good sensitivity and specificity. Moreover the safety is acceptable.

    List of papers
    1. Measurements before endovascular repair of abdominal aortic aneurysms: MR imaging with MRA vs. angiography and CT
    Open this publication in new window or tab >>Measurements before endovascular repair of abdominal aortic aneurysms: MR imaging with MRA vs. angiography and CT
    Show others...
    2003 (English)In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 44, no 2, p. 177-184Article in journal (Refereed) Published
    Abstract [en]

    Purpose: 1) To compare measurements obtained with MR imaging (MRI)/contrast-enhanced MR angiography (CE MRA) with measurements obtained with angiography (DSA) and CT, for stent-graft sizing of abdominal aortic aneurysms (AAA). 2) To compare MRA measurements obtained with the two post processing techniques MIP (maximum intensity projection) and VRT (3D volume rendering technique).

    Material and Methods: The prospective study included 20 consecutive patients with AAA identified by DSA and CT as suitable for endovascular repair. For the study, MRI/CE MRA was performed. Five measurement variables for stent-graft sizing were chosen. Comparisons were made between MRI/CE MRA, DSA and CT, and between observers. Comparisons were also made between MIP and VRT.

    Results: Significantly shorter lengths were obtained with MRA-MIP than with DSA. Three out of six diameter measurements were significantly smaller on MRI/CE MRA than on DSA and CT. No significant differences were found between the observers. One diameter measurement was significantly smaller on MIP than on VRT, while the other measurements showed no significant differences.

    Conclusion: The length measurements obtained with MRA-MIP were probably more correct than those with DSA. For more reliable diameter measurements with CE MRA, improvements of the technique, including VRT reconstructions and a standardized determination of the vessel boundaries, are needed.

    Keywords
    Abdominal aortic aneurysm, Angiography, CT, Endograft sizing, MR angiography, Volume rendering technique
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:liu:diva-46720 (URN)10.1034/j.1600-0455.2003.00029.x (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved
    2. Volume rendering compared with maximum intensity projection for magnetic resonance angiography measurements of the abdominal aorta
    Open this publication in new window or tab >>Volume rendering compared with maximum intensity projection for magnetic resonance angiography measurements of the abdominal aorta
    Show others...
    2004 (English)In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 45, no 4, p. 453-459Article in journal (Refereed) Published
    Abstract [en]

    Purpose: To compare the volume rendering technique (VRT) with maximum intensity projection (MIP) for aortic diameter measurements in MR angiography (MRA) data sets.

    Material and Methods: Existing contrast-enhanced 3-dimensional MRA and digital subtraction angiography (DSA) data sets from 20 patients were analyzed. In each MRA data set, two aortic diameters were measured using MIP and VRT. Agreement with DSA measurements, dependence on rendering parameters, and interobserver agreement were assessed.

    Results: Diameters measured on MIP with fixed parameters showed no significant difference compared with DSA and with freely selected parameters a slight overestimation relative to DSA. Diameters measured on VRT were larger than on DSA. For both MIP and VRT, the measurements depended on the chosen parameters. The error relative to DSA was larger for VRT than for MIP with fixed parameters but not with freely chosen parameters. Interobserver agreement did not differ significantly.

    Conclusions: VRT is not suitable for diameter measurements of the abdominal aorta with fixed parameter settings but may be useful with user-selected settings.

    Keywords
    Abdominal aortic aneurysm AAA, angiography, magentic resonance angiography MRA, maximum intensity projection MIP, under dependence, volume rendering technique VRT
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-24036 (URN)10.1080/02841850410006876 (DOI)3592 (Local ID)3592 (Archive number)3592 (OAI)
    Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
    3. Standardized volume rendering for magnetic resonance angiography measurements in the abdominal aorta
    Open this publication in new window or tab >>Standardized volume rendering for magnetic resonance angiography measurements in the abdominal aorta
    Show others...
    2006 (English)In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 47, no 2, p. 172-178Article in journal (Refereed) Published
    Abstract [en]

    Purpose: To compare three methods for standardizing volume rendering technique (VRT) protocols by studying aortic diameter measurements in magnetic resonance angiography (MRA) datasets.

    Material and Methods: Datasets from 20 patients previously examined with gadolinium-enhanced MRA and with digital subtraction angiography (DSA) for abdominal aortic aneurysm were retrospectively evaluated by three independent readers. The MRA datasets were viewed using VRT with three different standardized transfer functions: the percentile method (Pc-VRT), the maximum-likelihood method (ML-VRT), and the partial range histogram method (PRH-VRT). The aortic diameters obtained with these three methods were compared with freely chosen VRT parameters (F-VRT) and with maximum intensity projection (MIP) concerning inter-reader variability and agreement with the reference method DSA.

    Results: F-VRT parameters and PRH-VRT gave significantly higher diameter values than DSA, whereas Pc-VRT gave significantly lower values than DSA. The highest interobserver variability was found for F-VRT parameters and MIP, and the lowest for Pc-VRT and PRH-VRT. All standardized VRT methods were significantly superior to both MIP and F-VRT in this respect. The agreement with DSA was best for PRH-VRT, which was the only method with a mean error below 1 mm and which also had the narrowest limits of agreement (95% of cases between 2.1 mm below and 3.1 mm above DSA).

    Conclusion: All the standardized VRT methods compare favorably with MIP and VRT with freely selected parameters as regards interobserver variability. The partial range histogram method, although systematically overestimating vessel diameters, gives results closest to those of DSA.

    Keywords
    Abdominal aortic aneurysm (AAA); angiography; magnetic resonance angiography (MRA); maximum intensity projection (MIP); volume rendering technique (VRT); user dependence
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-14591 (URN)10.1080/02841850500445298 (DOI)000236669500010 ()
    Available from: 2007-08-24 Created: 2007-08-24 Last updated: 2017-12-13Bibliographically approved
    4. Three-dimensional drip infusion CT cholangiography in patients with suspected obstructive biliary disease: a retrospective analysis of feasibility and adverse reaction to contrast material
    Open this publication in new window or tab >>Three-dimensional drip infusion CT cholangiography in patients with suspected obstructive biliary disease: a retrospective analysis of feasibility and adverse reaction to contrast material
    2006 (English)In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 6, no 1Article in journal (Refereed) Published
    Abstract [en]

    Background

    Computed Tomography Cholangiography (CTC) is a fast and widely available alternative technique to visualise hepatobiliary disease in patients with an inconclusive ultrasound when MRI cannot be performed. The method has previously been relatively unknown and sparsely used, due to concerns about adverse reactions and about image quality in patients with impaired hepatic function and thus reduced contrast excretion. In this retrospective study, the feasibility and the frequency of adverse reactions of CTC when using a drip infusion scheme based on bilirubin levels were evaluated.

    Methods

    The medical records of patients who had undergone upper abdominal spiral CT with subsequent three-dimensional rendering of the biliary tract by means of CTC during seven years were retrospectively reviewed regarding serum bilirubin concentration, adverse reaction and presence of visible contrast media in the bile ducts at CT examination. In total, 153 consecutive examinations in 142 patients were reviewed.

    Results

    Contrast media was observed in the bile ducts at 144 examinations. In 110 examinations, the infusion time had been recorded in the medical records. Among these, 42 examinations had an elevated bilirubin value (>19 umol/L). There were nine patients without contrast excretion; 3 of which had a normal bilirubin value and 6 had an elevated value (25–133 umol/L). Two of the 153 examinations were inconclusive. One subject (0.7%) experienced a minor adverse reaction – a pricking sensation in the face. No other adverse effects were noted.

    Conclusion

    We conclude that drip infusion CTC with an infusion rate of the biliary contrast agent iotroxate governed by the serum bilirubin value is a feasible and safe alternative to MRC in patients with and without impaired biliary excretion.

    In this retrospective study the feasibility and the frequency of adverse reactions when using a drip infusion scheme based on bilirubin levels has been evaluated.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-34913 (URN)10.1186/1471-2342-6-1 (DOI)24035 (Local ID)24035 (Archive number)24035 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13Bibliographically approved
    5. Volume rendering of three-dimensional drip infusion CT cholangiography in patients with suspected obstructive biliary disease: a retrospective study
    Open this publication in new window or tab >>Volume rendering of three-dimensional drip infusion CT cholangiography in patients with suspected obstructive biliary disease: a retrospective study
    2005 (English)In: British Journal of Radiology, ISSN 0007-1285, E-ISSN 1748-880X, Vol. 78, no 936, p. 1078-1085Article in journal (Refereed) Published
    Abstract [en]

    The purpose of this study was to evaluate the diagnostic potential of prolonged drip infusion CT cholangiography (DIC-CT) using meglumine iotroxate (Biliscopin®) and 3D volume rendering in patients with suspected obstructive biliary disease. From a material of 142 patients who had undergone a drip infusion CT, all cases with a verified surgical or endoscopic retrograde cholangiography (ERC) diagnosis (n=33) were selected. Age-matched controls were selected from the remaining examinations. Three radiologists reviewed all 66 examinations in retrospect, independently as well as in consensus. The image quality and the estimated diagnostic quality were rated as good or moderate in 91% of the 198 reviews. The consensus sensitivity and specificity for diagnosing biliary stones was 88% and 94%, respectively (with sensitivities ranging from 88% to 94% for individual observers, and specificities from 86% to 96%). Two out of three strictures were observed. No false positive strictures were described. The use of volume rendering technique (VRT) improved diagnostic certainty in 28/198 (14%) of the evaluations. The visualization of ductal stones was improved in 18/48 (38%). No differences in diagnostic quality between single and multislice CT were observed. We conclude that a detailed image of the biliary tree with good sensitivity and specificity can be obtained by means of bilirubin-governed infusion time DIC-CT with volume rendering reconstruction.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-30833 (URN)10.1259/bjr/14176682 (DOI)16483 (Local ID)16483 (Archive number)16483 (OAI)
    Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2017-12-13Bibliographically approved
  • 146. Pfeiffer, P
    et al.
    Sörbye, H
    Ehrsson, H
    Fokstuen, T
    Mortensen, JP
    Baltesgard, L
    Tveit, KM
    Ögreid, D
    Starkhammar, Hans
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Wallin, I
    Qvortrup, C
    Glimelius, B
    Short-time infusion of oxaliplatin in combination with capecitabine (XELOX30) as second-line therapy in patients with advanced colorectal cancer after failure to irinotecan and 5-fluorouracil2006In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 17, no 2, p. 252-258Article in journal (Refereed)
    Abstract [en]

    Background: The efficacy of oxaliplatin combined with capecitabine (XELOX) as second-line therapy in patients with advanced colorectal cancer (ACRC) resistant to irinotecan is not well established. Oxaliplatin induces acute, cold-induced neuropathy in most patients. The incidence is claimed to be infusion rate-dependent and therefore a 2-h infusion is recommended. Patients and methods: For practical and economic reasons, but also for patient's convenience, we performed a phase II study to examine XELOX30 (capecitabine 1000 mg/m2 orally twice daily on days 1-14 and oxaliplatin 130 mg/m2 as a 30 min infusion on day 1) in patients with ACRC resistant to irinotecan. In addition the pharmacokinetics of oxaliplatin was studied. Results: From November 2002 to September 2003, 70 patients with ACRC were treated with XELOX30. Median age was 62 (range 33-74 years) years and median performance status was 1 (range 0-2). The median number of courses was four (range 1-12) and median cumulative dose of oxaliplatin was 530 (range 125-1560) mg/m2. The response rate was 17% (95% CI 10-23), median time to progression (TTP) was 5.4 months (95% CI 4.6-6.4) and median survival 9.5 months (95% CI 8.5-11.2). White blood cell count (WBC) and performance status were significantly correlated to TTP. Neurotoxicity was moderate: grade 1 56%, grade 2 17% and grade 3 6%. Other grade 3 toxicities were nausea/ vomiting 9%, diarrhoea 14% and PPE 8%. The maximum blood concentration and total body clearance of oxaliplatin was higher than previously reported in studies examining 2-h infusions, but the volume of distribution and terminal half-life was in close agreement with previous results. Conclusion: XELOX30 is a very convenient second-line regimen in ACRC with an activity and safety profile similar to other oxaliplatin schedules. © 2005 European Society for Medical Oncology.

  • 147.
    Rosenberg, Per
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    On the prognosis and treatment of early stage endometrial carcinoma: Studies with special reference to uterine papillary serous carcinoma1992Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The prognosis and therapy in the subgroup of endometrial malignancies called Uterine Papillary Serous Carcinoma (UPSC) was investigated. This entity constitutes about 6-8 % of all endometrial carcinomas clinical stage I but, as has been shown here, accounts for one third of the cancer mortality in the early stages of endometrial carcinoma.

    -The prognostic significance of nuclear atypia, FIGO grade and age was determined in patients with clinical stage 1-11 Uterine Papillary Serous Carcinoma.

    -DNA-index and S-phase fraction, determined by flow cytometry on formalin-fixed, paraffin-embedded endometrial curettage material was evaluated in relation to nuclear atypia, FIGO grade and age in early stage endometrial carcinoma.

    -A new method of minimizing the dilution of non-epithelial cells in the malignant curettage material when performing flow cytometry was developed.

    -The survival and pattern of metastasis in a population-based patient material was investigated -The effects on survival of a new aggressive treatment regimen was assessed.

    The results show that: Patients with uterine papillary serous carcinoma have a much worse prognosis than do patients with ordinary endometrial carcinoma.

    DNA ploidy and S-phaseratederived from flow cytometryperformed on disintegrated, previously paraffinembedded, endometrial curettings are important prognostic factors.

    It is possible to exclude contaminating non-epithelial cells from the DNA analysis by the use of an anticytokeratin antibody, Patients with uterine papillary serous carcinoma clinical stage I have a significantly higher risk of recurrence than patients with non-UPSC. The localisation of the recurrences among the UPSC patients is more similar to that of serous papillary ovarian carcinoma than that of ordinary adenocarcinoma of the endometrium. A primary treatment ofUPSC with a more extensive surgery, adjuvant external radiation and platinum-based chemotherapy seems to improve the outcome.

  • 148.
    Rosenberg, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Andersson, H
    Boman, K
    Ridderheim, M
    Sorbe, B
    Puistola, U
    Parö, G
    Randomized trial of single agent paclitaxel given weekly versus every three weeks and with peroral versus intravenous steroid premedication to patients with ovarian cancer previously treated with platinum2002In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 41, no 5, p. 418-424Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate the efficacy and toxicity of paclitaxel given at the same dose intensity and administered weekly (arm A) or every 3 weeks (arm B), and to assess the safety of intravenous steroids versus standard peroral premedication. Two hundred and eight patients with advanced ovarian cancer previously treated with no more than one platinum-containing regimen were randomized to receive either a weekly infusion of paclitaxel or an infusion every 3 weeks. The median delivered dose intensity was 77.6 mg/m2/week in the weekly arm, and 72.7 mg/m2/week in the every 3 weeks arm. WHO grade 3-4 hematological and non-hematological toxicity occurred more frequently in arm B. No difference in number of severe events of hypersensitivity, response rate, time to progression or survival between arms was observed. Weekly paclitaxel at a dose of 67 mg/m2/week was found to have a better safety profile and seemed to be as effective as the equivalently dosed schedule every 3 weeks. Intravenous steroids are a safe alternative to oral steroids.

  • 149.
    Rydén, Lisa
    et al.
    Department of Surgery, Helsingborgs Lasarett, Helsingborg, Sweden and Department of Laboratory Medicine, div of Pathology, University Hospital, Malmö.
    Jönsson, Per-Ebbe
    Department of Surgery, Helsingborgs Lasarett, Helsingborg, Sweden.
    Chebil, Gunilla
    Department of Pathology, Helsingborgs Lasarett, Helsingborg.
    Dufmats, Monika
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Fernö, Mårten
    Department of Oncology, University Hospital, Lund.
    Jirström, Karin
    Department of Laboratory Medicine, div of Pathology, University Hospital, Malmö.
    Källström, Ann-Christine
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Landberg, Göran
    Department of Laboratory Medicine, div of Pathology, University Hospital, Malmö.
    Stål, Olle
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Thorstenson, Sten
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Nordenskjöld, Bo
    Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
    Two years of adjuvant tamoxifen in premenopausal patients with breast cancer: a randomised, controlled trial with long-term follow-up2005In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 41, no 2, p. 256-264Article in journal (Refereed)
    Abstract [en]

    Adjuvant tamoxifen treatment increases recurrence-free survival (RFS) and overall survival (OS) in early breast cancer, although in premenopausal patients the number of studies comparing tamoxifen vs no treatment are limited. We report herein the effect on RFS of adjuvant tamoxifen treatment in a multicentre trial of premenopausal patients with stage II breast cancer patients randomised between 1986 and 1991 to 2 years of tamoxifen treatment (n = 276) or no treatment (n = 288). The receptor status of the tumour was known for 541 (96%) of the patients included. Tamoxifen treatment significantly increased RFS in patients with hormone receptor-positive (oestrogen receptor-positive (ER+) and/or progesterone receptor-positive (PR+)) tumours (Relative Risk (RR) 0.65; 95% Confidence Interval (CI): 0.48–0.89, P = 0.006), and the beneficial effect of tamoxifen was extended to patients with indicators of poor prognosis, such as young age and nodal-positivity. PR status was a significant predictor of response to tamoxifen in multivariate models with testing of interactions of hormone receptor status and adjuvant therapy.

  • 150. Salahshor, S
    et al.
    Hou, H
    Diep, CB
    Loukala, A
    Zhang, Hong
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology.
    Liu, T
    Chen, J
    Iselius, L
    Rubio, C
    Lothe, RA
    Aaltonen, L
    Sun, Xiao-Feng
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology.
    Lindmark, G
    Lindblom, A
    A germline E-cadherin mutation in a family with gastric and colon cancer.2001In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 8, p. 439-443Article in journal (Refereed)
12345 101 - 150 of 213
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