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  • 251.
    Schoultz, Ida
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Verma, Deepti
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Halfvarsson, Jonas
    Örebro University Hospital.
    Torkvist, Leif
    Karolinska University Hospital.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine . Linköping University, Faculty of Health Sciences.
    Sjoqvist, Urban
    Karolinska University Hospital.
    Lordal, Mikael
    Karolinska University Hospital.
    Tysk, Curt
    Örebro University Hospital.
    Lerm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Combined Polymorphisms in Genes Encoding the Inflammasome Components NALP3 and CARD8 Confer Susceptibility to Crohns Disease in Swedish Men2009In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 104, no 5, p. 1180-1188Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES : Crohns disease (CD) is characterized by overproduction of proinflammatory cytokines like interleukin (IL)-1 beta. Production of mature IL-1 beta is dependent on a caspase-1-activating protein complex called the NALP3 inflammasome, composed of NALP3, ASC, and CARD8. NALP3 shares structural similarities with Nod2, and both of these proteins are required for bacteria-induced IL-1 beta secretion. The combination of the polymorphisms CARD8 (C10X) and NALP3 (Q705K) was recently shown to be associated with rheumatoid arthritis. Our aim was to investigate whether these combined polymorphisms play a role in the susceptibility to CD.

    METHODS: The study included 498 CD patients in two cohorts from different regions and 742 control individuals from a Swedish population. DNA was isolated from whole blood. Polymorphisms of (Q705K) NALP3 and (C10X) CARD8, as well as the Nod2 variants, R702W and G908R, were genotyped using the Taqman single nucleotide polymorphism assay. The Nod2 frameshift mutation, L1007fs, was detected by Megabace SNuPe genotyping.

    RESULTS: Our results show that men who have both the C10X and Q705K alleles in CARD8 and NALP3, and who express wild-type alleles of Nod2 are at an increased risk of developing CD (odds ratio, OR: 3.40 range: 1.32-8.76); P = 0.011). No association with these polymorphisms was found in women (OR: 0.89 (range: 0.44-1.77); P = 0.74).

    CONCLUSIONS: We suggest a role for combined polymorphisms in CARD8 and NALP3 in the development of CD in men, with obvious sex differences in the genetic susceptibility pattern. These findings give further support to the importance of innate immune responses in CD.

  • 252.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Macrophage antigen expression in breast and colorectal cancers: A consequence of macrophage - tumour cell fusion?2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Carcinogenesis is a sophisticated biological process consisting of a series of progressive changes in somatic cells from premalignant to malignant phenotype. Despite the vast information available about cancer cells, the origin of cancer and cause of metastasis still remain enigmatic. The hypothesis of cell fusion is one of several models explaining the evolution of neoplasia into clinically significant cancer. This theory states that cancer cells through heterotypic fusion with host cells generate hybrids expressing traits from both parental cells, and acquire metastatic potentials and growth-promoting properties. The cell fusion theory is still unproven and speculative, but cell fusion is a common biological process in normal tissue. Accumulated evidence shows that macrophage-cancer cell fusion occurs in vitro and in vivo and produces hybrids with metastatic potential, but the clinical significant of cell fusion is unclear. The aim of this thesis is to test this hypothesis in clinical patient materials and to explore the clinical significance of macrophage phenotype traits in solid tumours.

    Paraffin-embedded cancer and normal tissue specimens from patients with breast cancer (n=133) and colorectal cancer (two different patient materials with totally 240 patients) were immunostained for the macrophage-specific antigen, CD163. The expression of CD163 was tested in relation to macrophage infiltration and tumour stage, survival time, irradiation, DNA ploidy, cancer cell proliferation and apoptosis.

    Phenotypic macrophage traits, such as the expression of CD163, were seen in both breast and colorectal cancers, and were correlated to advanced tumour stages and poor survival. CD163 expression was more frequent in rectal cancer after irradiation and was associated with decreased apoptosis. Cancer cell proliferation was correlated to both macrophage infiltration and CD163 expression. Multivariate analysis showed that CD163 is a significant prognostic factor in both breast and colorectal cancers.

    In an attempt to examine factors related to the function of macrophage fusion, the expression of the signalling adaptor protein DAP12 was tested and related to CD163 expression in breast cancers from 133 patients. DAP12 was shown to occur in breast cancer cells and was related to high histologic tumour grade, skeletal and liver metastasis, and poor prognosis. The findings in this thesis support the cell fusion theory and illustrate its clinical impact on tumour progression and metastasis.

    List of papers
    1. Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival
    Open this publication in new window or tab >>Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival
    Show others...
    2008 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 123, no 4, p. 780-786Article in journal (Refereed) Published
    Abstract [en]

    Cells of the monocyte/macrophage lineage are important for tumour cell migration, invasion and metastasis. Fusion between macrophages and cancer cells in animal models in vitro and in vivo causes hybrids with increased metastatic potential. Primary breast cancer cells were characterized for macrophage antigens to test if phenotypic resemblance to macrophages is related to early distant recurrence. Immunostaining for CD163, MAC387 and CD68 was performed in a breast cancer tissue micro array from 127 patients consequently followed up for a median of 13 years. Tumour-associated macrophages expressed all 3 antigens. The breast cancers expressed CD163 to 48%, MAC387 to 14% while CD68 was not expressed. TGF-β staining intensity was positively related to both CD163 and MAC387 expression. Expression of CD163 in the cancer cells was compared to their DNA ploidy, Nottingham Histological Grade, TNM-stage, node state, presence of estrogen receptors and occurrence of distant metastases and survival. Cancers of a more advanced histological grade expressed CD163 to a higher extent. Cells expressing MAC387 were more common in cancers with a high proportion of CD163 positive cells. Multivariate analysis showed that expression of the macrophage antigen CD163 in breast cancer cells has a prognostic impact on the occurrence of distant metastases and reduced patient survival time.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-43420 (URN)10.1002/ijc.23527 (DOI)73820 (Local ID)73820 (Archive number)73820 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
    2. Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time.
    Open this publication in new window or tab >>Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time.
    2009 (English)In: International journal of cancer. Journal international du cancer, ISSN 1097-0215, Vol. 125, no 8, p. 1826-1831Article in journal (Refereed) Published
    Abstract [en]

    Expression of the macrophage antigen CD163 in breast cancer cells is recently shown to be related to early distant recurrence and shortened survival. In this study, 163 patients with rectal cancer, included in the Swedish rectal cancer trial and followed up for a median of 71 months, were examined for the expression of CD163 in the primary tumors. The cancer cells expressed CD163 in the primary tumors in 23% (n = 32) of the patients. In pretreatment biopsies from 101 patients, 10 had CD163-positive cancers and these patients had earlier local recurrence (p < 0.044) and reduced survival time (p < 0.045) compared with those with CD163-negative tumors. When studying surgical specimens from 61 patients randomized to preoperative irradiation (5 x 5 Gy delivered in 1 week), it was found that 31% were CD163 positive whereas the corresponding figure was only 17% for 78 patients who were nonirradiated (p < 0.044), which tentatively may be consistent with X-rays inducing fusion. In CD163-positive tumors there was a reduced apoptotic activity as measured with the Termina deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) technique (p = 0.018). There tended also to be an increased proliferation activity measured as an expression of Ki-67 non significant (NS). It is concluded that primary rectal cancers may express CD-163, and this phenotypic macrophage trait is related to early local recurrence, shorter survival time and reduced apoptosis. Furthermore, the expression of CD163 is more common after irradiation.

    Keywords
    rectal cancer • macrophages • metastasis • survival • cell fusion • radiotherapy
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-21408 (URN)10.1002/ijc.24506 (DOI)19582880 (PubMedID)
    Available from: 2009-10-01 Created: 2009-10-01 Last updated: 2010-04-14
    3. Tumor cell expression of CD163 is an independent prognostic factor in colorectal cancer patients
    Open this publication in new window or tab >>Tumor cell expression of CD163 is an independent prognostic factor in colorectal cancer patients
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    CD163 is a macrophage specific marker. Recent studies have shown that CD163 expression in breast and rectal cancer cells is associated with poor prognosis. This study was conducted to evaluate the relationship between CD163 expression, as a macrophage trait, and macrophage infiltration and their clinical-pathological significance in colorectal cancer. The hypothesis of macrophage-cancer cell fusion may explain the expression of CD163 in cancer cells.

    Immune-staining of CD163 and macrophage infiltration were evaluated in paraffinembedded specimens, earlier analyzed for Ki-67, CD31 and D2-40 and S-phase fraction, from primary tumors and normal colorectal mucosa of 77 patients with colorectal carcinoma. The outcomes were analyzed in relation to clinical-pathological data.

    CD163 is positive in cancer cells in 16-18% of the patients and it is related to advanced tumor stages (stage III-IV) and unfavorable prognosis. High macrophage infiltration may be related to lower survival but this relation was not statistically significant. The prognostic significance of CD163 expression is independent of tumor stage (p=0,015) and macrophage density in tumor stroma (p=0,007).

    The expression of macrophage phenotype in colorectal cancer cells is associated with poor prognosis independently of tumor stage and macrophage density in the tumour stroma. Macrophages may promote tumour growth and progression by an autocrine interaction with cancer cells. Macrophage – cancer cell fusion may occur in colorectal cancer and contribute to tumour progression and metastasis.

    Keywords
    Colorectal cancer, tumour associated macrophages, macrophage infiltration, CD163, cell fusion
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54818 (URN)
    Available from: 2010-04-14 Created: 2010-04-14 Last updated: 2010-04-14Bibliographically approved
    4. DAP12, a macrophage fusion receptor, is expressed in breast cancer cells and associated with skeletal and liver metastases and poor survival
    Open this publication in new window or tab >>DAP12, a macrophage fusion receptor, is expressed in breast cancer cells and associated with skeletal and liver metastases and poor survival
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    DAP12 is a transmembrane receptor present in myeloid cells and is essential for the development of functionally mature osteoclasts and microglia, and for integrin signaling in macrophages and neutrophils. The macrophage specific antigen CD163 is expressed in breast and colorectal cancer and is associated with early cancer recurrence and poor prognosis. We hypothesize that macrophage traits in cancer cells may be explained by fusion between cancer cells and tumor associated macrophages. The role of DAP12 in the fusion between cancer cells and macrophages is not known. This study was performed to investigate the expression of DAP12 in breast cancer cells and its´ relation to macrophage trait manifested by CD163 expression.

    Immunostaining of DAP12, CD163 and MAC387 were evaluated in paraffinembedded specimens from totally 133 patients with breast cancer. The outcomes were analyzed in relation to clinicopathological data.

    DAP12 expression was positive in the majority of cases (64%) with breast cancer and associated with advanced tumor grade (p= 0.015) and liver metastasis (p= 0.0465) but not lung metastasis (0.997). It tended to correlate with skeletal metastases (p=0.0673). Patients with breast cancer expressing high DAP12 had poor prognosis with higher rates of skeletal (p=0.023) and liver metastases (p=0.028) and overall shorter distant recurrence free survival (p=0.0028). DAP12 expression was neither correlated to CD163 nor MAC387 expression. To our knowledge, this is the first study where DAP12 expression is reported in breast cancer.

    In conclusion, DAP12 is expressed in breast cancer and is significantly related to skeletal and liver metastasis as well as poor prognosis. We hypothesize that DAP12 expression may promote fusion between breast cancer cells and macrophages. It may even promote homing of cancer cells in bone and liver tissue and result in increased metastasis at these sites.

    Keywords
    Breast cancer, tumour associated macrophages, DAP12, CD163, metastasis, cell fusion
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54819 (URN)
    Available from: 2010-04-14 Created: 2010-04-14 Last updated: 2010-04-14
  • 253.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Tumor cell expression of CD163 is an independent prognostic factor in colorectal cancer patientsManuscript (preprint) (Other academic)
    Abstract [en]

    CD163 is a macrophage specific marker. Recent studies have shown that CD163 expression in breast and rectal cancer cells is associated with poor prognosis. This study was conducted to evaluate the relationship between CD163 expression, as a macrophage trait, and macrophage infiltration and their clinical-pathological significance in colorectal cancer. The hypothesis of macrophage-cancer cell fusion may explain the expression of CD163 in cancer cells.

    Immune-staining of CD163 and macrophage infiltration were evaluated in paraffinembedded specimens, earlier analyzed for Ki-67, CD31 and D2-40 and S-phase fraction, from primary tumors and normal colorectal mucosa of 77 patients with colorectal carcinoma. The outcomes were analyzed in relation to clinical-pathological data.

    CD163 is positive in cancer cells in 16-18% of the patients and it is related to advanced tumor stages (stage III-IV) and unfavorable prognosis. High macrophage infiltration may be related to lower survival but this relation was not statistically significant. The prognostic significance of CD163 expression is independent of tumor stage (p=0,015) and macrophage density in tumor stroma (p=0,007).

    The expression of macrophage phenotype in colorectal cancer cells is associated with poor prognosis independently of tumor stage and macrophage density in the tumour stroma. Macrophages may promote tumour growth and progression by an autocrine interaction with cancer cells. Macrophage – cancer cell fusion may occur in colorectal cancer and contribute to tumour progression and metastasis.

  • 254.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    DAP12, a macrophage fusion receptor, is expressed in breast cancer cells and associated with skeletal and liver metastases and poor survivalManuscript (preprint) (Other academic)
    Abstract [en]

    DAP12 is a transmembrane receptor present in myeloid cells and is essential for the development of functionally mature osteoclasts and microglia, and for integrin signaling in macrophages and neutrophils. The macrophage specific antigen CD163 is expressed in breast and colorectal cancer and is associated with early cancer recurrence and poor prognosis. We hypothesize that macrophage traits in cancer cells may be explained by fusion between cancer cells and tumor associated macrophages. The role of DAP12 in the fusion between cancer cells and macrophages is not known. This study was performed to investigate the expression of DAP12 in breast cancer cells and its´ relation to macrophage trait manifested by CD163 expression.

    Immunostaining of DAP12, CD163 and MAC387 were evaluated in paraffinembedded specimens from totally 133 patients with breast cancer. The outcomes were analyzed in relation to clinicopathological data.

    DAP12 expression was positive in the majority of cases (64%) with breast cancer and associated with advanced tumor grade (p= 0.015) and liver metastasis (p= 0.0465) but not lung metastasis (0.997). It tended to correlate with skeletal metastases (p=0.0673). Patients with breast cancer expressing high DAP12 had poor prognosis with higher rates of skeletal (p=0.023) and liver metastases (p=0.028) and overall shorter distant recurrence free survival (p=0.0028). DAP12 expression was neither correlated to CD163 nor MAC387 expression. To our knowledge, this is the first study where DAP12 expression is reported in breast cancer.

    In conclusion, DAP12 is expressed in breast cancer and is significantly related to skeletal and liver metastasis as well as poor prognosis. We hypothesize that DAP12 expression may promote fusion between breast cancer cells and macrophages. It may even promote homing of cancer cells in bone and liver tissue and result in increased metastasis at these sites.

  • 255.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Olsson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time.2009In: International journal of cancer. Journal international du cancer, ISSN 1097-0215, Vol. 125, no 8, p. 1826-1831Article in journal (Refereed)
    Abstract [en]

    Expression of the macrophage antigen CD163 in breast cancer cells is recently shown to be related to early distant recurrence and shortened survival. In this study, 163 patients with rectal cancer, included in the Swedish rectal cancer trial and followed up for a median of 71 months, were examined for the expression of CD163 in the primary tumors. The cancer cells expressed CD163 in the primary tumors in 23% (n = 32) of the patients. In pretreatment biopsies from 101 patients, 10 had CD163-positive cancers and these patients had earlier local recurrence (p < 0.044) and reduced survival time (p < 0.045) compared with those with CD163-negative tumors. When studying surgical specimens from 61 patients randomized to preoperative irradiation (5 x 5 Gy delivered in 1 week), it was found that 31% were CD163 positive whereas the corresponding figure was only 17% for 78 patients who were nonirradiated (p < 0.044), which tentatively may be consistent with X-rays inducing fusion. In CD163-positive tumors there was a reduced apoptotic activity as measured with the Termina deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) technique (p = 0.018). There tended also to be an increased proliferation activity measured as an expression of Ki-67 non significant (NS). It is concluded that primary rectal cancers may express CD-163, and this phenotypic macrophage trait is related to early local recurrence, shorter survival time and reduced apoptosis. Furthermore, the expression of CD163 is more common after irradiation.

  • 256.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Olsson, Hans
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Doré, Siv
    Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Breast cancer expression of CD163, a macrophage scavenger receptor, is related to early distant recurrence and reduced patient survival2008In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 123, no 4, p. 780-786Article in journal (Refereed)
    Abstract [en]

    Cells of the monocyte/macrophage lineage are important for tumour cell migration, invasion and metastasis. Fusion between macrophages and cancer cells in animal models in vitro and in vivo causes hybrids with increased metastatic potential. Primary breast cancer cells were characterized for macrophage antigens to test if phenotypic resemblance to macrophages is related to early distant recurrence. Immunostaining for CD163, MAC387 and CD68 was performed in a breast cancer tissue micro array from 127 patients consequently followed up for a median of 13 years. Tumour-associated macrophages expressed all 3 antigens. The breast cancers expressed CD163 to 48%, MAC387 to 14% while CD68 was not expressed. TGF-β staining intensity was positively related to both CD163 and MAC387 expression. Expression of CD163 in the cancer cells was compared to their DNA ploidy, Nottingham Histological Grade, TNM-stage, node state, presence of estrogen receptors and occurrence of distant metastases and survival. Cancers of a more advanced histological grade expressed CD163 to a higher extent. Cells expressing MAC387 were more common in cancers with a high proportion of CD163 positive cells. Multivariate analysis showed that expression of the macrophage antigen CD163 in breast cancer cells has a prognostic impact on the occurrence of distant metastases and reduced patient survival time.

  • 257.
    Shabo, Ivan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Svanvik, Joar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Expression of Macrophage Antigens by Tumor Cells2011In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 714, p. 141-150Article in journal (Refereed)
    Abstract [en]

    Macrophages are a heterogeneous cell population of the myeloid linage derived from monocytes. These cells show two different polarization states, M1 and M2 macrophages in response to different micro environmental signals. Tumor associated macrophages (TAM) represent the M2 type and promote tumor progression. These cells express antigens that more or less are specific for macrophages like: CD14, CD68, MAC387, CD 163, and DAP12. In a series of recent studies it is shown that cancer cells may express these antigens and CD I 63, MAC387 and DAP12 may be expressed by e.g. breast cancer cells. Thus, 48% of the breast cancers expressed CD163 that is a scavenger receptor normally expressed by macrophages alone. The corresponding figure for rectal cancer is 31%. The expression of CD163 is correlated to early distant recurrence in breast cancer and local recurrence in rectal cancer and reduced survival time in both conditions. Expression of macrophage antigens in breast- and colorectal-cancers may have a prognostic relevance in clinical praxis. One explanation to these findings is that resemblance with macrophages may indicate a more invasive phenotype due to genetic exchange between the primary tumor cells and associated macrophages. This is further supported by the finding that expression of DAP12, a macrophage fusion receptor, in breast cancer is associated with an advanced tumor grade and higher rates of skeletal and liver metastases and overall shorter distant recurrence free survival. Another explanation to the changed phenotype is a genetic exchange between the cells by exosome-mediated transfer.

  • 258.
    Shen, Yang-mei
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Olsson, Birgit
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Overexpression of GLUT1 in colorectal cancer is independently associated with poor prognosis2011In: International Journal of Biological Markers, ISSN 0393-6155, E-ISSN 1724-6008, Vol. 26, no 3, p. 166-172Article in journal (Refereed)
    Abstract [en]

    Background: To investigate the expression of glucose transporter 1 (GLUT1) in colorectal cancer (CRC) and its relationship to clinicopathological variables. Methods: The expression of GLUT1 in 163 primary tumors together with the corresponding normal mucosa, and 36 liver metastases was examined using real-time PCR. Results: The mean value of GLUT1 was higher in primary tumors (50.390 +/- 68.648) than in the corresponding normal mucosa (20.437 +/- 28.703, p less than 0.0001), while there was no significant difference in GLUT1 expression between CRC and liver metastasis (50.390 +/- 68.648 vs 52.277 +/- 52.482, p = 0.190). In CRCs, GLUT1 expression was higher in poorly differentiated than in well and moderately differentiated tumors (p = 0.022), and higher in stage III + IV than in stage I + II tumors (p = 0.035). The patients with high-expressed GLUT1 had a worse prognosis than those with low-expressed GLUT1 independently of gender, age, tumor site, stage and differentiation (p = 0.026, RR 2.737, 95% CI 1.126-6.651) in stage I-III CRCs. In liver metastasis, GLUT1 expression was higher in larger tumors than in smaller ones (p = 0.025). Conclusions: Overexpression of GLUT1 in stage I-III CRCs was independently associated with poor prognosis.

  • 259.
    Shen, Yang-mei
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Arbman, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Gullstrand, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Wei, Yu-Quan
    Sichuan University.
    Zhang, Hong
    University of Skövde.
    Rosell, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Olsson, Birgit
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Peng, Feng
    Sichuan University.
    Yang, Han-Shuo
    Sichuan University.
    Wang, Chun-Ting
    Sichuan University.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Novel gene hBiot2 is an independent prognostic factor in colorectal cancer patients2012In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 27, no 2, p. 376-382Article in journal (Refereed)
    Abstract [en]

    The present study investigated the expression of the novel gene hBiot2 in colorectal cancer (CRC) and its relationships with clinicopathological variables in CRC patients. The expression of hBiot2 in 163 primary CRCs together with the corresponding normal mucosa, 36 liver metastases and 5 colon cancer cell lines was examined using real-time PCR. In situ hybridization (ISH) was performed to evaluate the localization of hBiot2 expression in CRC and normal mucosa. hBiot2 expression at the RNA level was localized in the nucleus of tumor cells and normal epithelial cells. The mean expression of hBiot2 in the CRCs (243.571 +/- 564.569) was higher compared to the normal mucosa (107.252 +/- 413.635, Pandlt;0.0001) and liver metastasis samples (42.002 +/- 40.809, P=0.0002). hBiot2 expression was increased from stages I + II to III (P=0.047), and no difference in the expression was found in stages III and IV (P=0.452). A high value of hBiot2 was associated with a poorer prognosis compared with a low value independently of gender, age, tumor site, stage and differentiation (P=0.007, RR 7.519, 95% Cl 1.729-32.704). Liver metastasis, smaller tumors, non-local recurrence and primary liver surgery alone were associated with a higher value of hBiot2 compared to larger tumors, local recurrence and repeated liver surgery (P=0.003, 0.044 and 0.026, respectively). An inverse relationship was found between hBiot2 expression and the metastatic potential of the colon cancer cell lines. Thus, increased expression of hBiot2 may be an early and interim event in the development of CRC. A higher expression of hBiot2 in primary CRC patients independently indicates a poorer prognosis.

  • 260.
    Silva, M.A.
    et al.
    Department of Pathology and Molecular Medicine, McMaster University, Health Science Centre 3N5C, 1200 Main St. West, Hamilton, ON L8N 3Z5, Canada.
    Quera, R.
    Internal Medicine Department, University of Chile Clinical Hospital, Clínica Las Condes, Santiago, Chile.
    Valenzuela, J.
    Internal Medicine Department, University of Chile Clinical Hospital, Clínica Las Condes, Santiago, Chile.
    Salim, Sa´ad
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery .
    Söderholm, Johan D
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Perdue, M.H.
    Department of Pathology and Molecular Medicine, McMaster University, Health Science Centre 3N5C, 1200 Main St. West, Hamilton, ON L8N 3Z5, Canada.
    Dendritic cells and toll-like receptors 2 and 4 in the ileum of Crohn's disease patients2008In: Digestive Diseases and Sciences, ISSN 0163-2116, E-ISSN 1573-2568, Vol. 53, no 7, p. 1917-1928Article in journal (Refereed)
    Abstract [en]

    We investigated myeloid-dendritic cell (DC) marker and Toll-like receptor (TLR)-2 and 4 distributions in ileal samples from Crohn's disease (CD) patients (n = 14) and controls (n = 13). In controls, no TLR-2+ cells were observed, and higher numbers of TLR-4+ and DC-SIGN+ cells (P < 0.01) were detected in ileal samples when compared versus colonic tissues. In non-inflamed CD ileum, TLR-4+ and DC-SGN+ cells were depleted from superficial areas of the villus, and a significant CD1a+ cell infiltration (P < 0.01) was observed when compared to ileal controls and non-inflamed colonic CD samples. In inflamed CD ileum, DC-SIGN+, CD1a+, TLR-4+ and few TLR-4 +DC-SIGN+ cells were detected as well as CD83 depletion. No correlation between TLR-2 and DC markers was detected in CD samples. A unique distribution of myeloid-DC markers characterized the CD ileum. Also, the presence of significant amounts of ileal CD1a+ cells may provide a relevant DC-mediated mechanism for antigen recognition in the pathogenesis of CD. © 2007 Springer Science+Business Media, LLC.

  • 261.
    Sjodahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Proposal: a score to select patients for fistulotomy2010In: COLORECTAL DISEASE, ISSN 1462-8910, Vol. 12, no 5, p. 487-489Article in journal (Refereed)
    Abstract [en]

    Traditionally the distance between the inner opening and the anal verge is considered when making the decision to lay open an anal fistula or not. In contrast to this, the score presented here includes the distance to the upper border of the puborectalis muscle or to the external sphincter (anteriorly). In addition this score also takes various aspects of bowel function into consideration.

  • 262.
    Sjöberg, Folke
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Larsen, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences.
    Bak, Zoltan
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Samuelsson, Anders
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Intensive Care UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Iredahl, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences.
    Thorfinn, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Huss, Fredrik
    Brännskadecentrum, Akademiska sjukhuset, Uppsala.
    Rousseau, Andreas
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Psychiatry. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Hyperbar syrgasbehandling kan vara skadlig vid kolmonoxidförgiftning2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 32-33, p. 1506-Article in journal (Refereed)
  • 263.
    Sjödahl, Rune
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Schulz, C
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Myrelid, Pär
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Andersson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Long-term quality of life in patients with permanent sigmoid colostomy2012In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 14, no 6, p. E335-E338Article in journal (Refereed)
    Abstract [en]

    Aim The study aimed to assess quality of life (QoL) in patients with a sigmoid colostomy using a simple general and disease-specific instrument. A subgroup not doing well was identified and examined further. Method The Short Health Scale (SHS) is a four-item instrument exploring severity of symptoms, function in daily life, worry, and general well-being, using visual analogue scales ranging from 0 to 100 where 100 is the worst possible situation. The SHS was delivered to 206 patients with a sigmoid colostomy. It was returned by 181 (87.9%) patients [88 men; median age 73 (3391) years]. Follow-up was 61 (10484) months for 178 (86.4%) patients returning usable questionnaires. A subgroup of 16 patients scoring more than 50 in all four items of the SHS was further examined with StomaQOL where 100 is best possible. Results The median score for severity of symptoms was 18 (295), function in daily life 21 (095), worry 17 (398) and general well-being 22 (099). A score of andlt; 50 in the SHS was recorded in 84.9%, 82.1%, 79.9% and 70.5% respectively. In the group scoring more than 50 in all four items patients diagnosed with irritable bowel syndrome constituted 43.8% to compare with 5.6% in the entire study group (P andlt; 0.001). Median score for StomaQOL was 37 (2262) in this group. Conclusion Most patients with a permanent sigmoid colostomy have a good QoL consistent with previous findings. However, this is reduced in a subgroup of patients diagnosed with irritable bowel syndrome.

  • 264.
    Sjödahl, Rune
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Thorelius, Lars
    Copenhagen University Hospital.
    Hallböök, Olof
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Ultrasonographic findings in patients with peristomal bulging2011In: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, ISSN 0036-5521, Vol. 46, no 6, p. 745-749Article in journal (Refereed)
    Abstract [en]

    Aim. The aim of this study was to obtain a classification of peristomal bulging based on findings at ultrasonography in patients with a sigmoid colostomy. Methods. The patient material comprised 30 men and 33 women. The median age was 69 years (28--90) and the median time between stoma creation and investigation was 68 months (3--426). Any bulging was measured, and the abdominal opening for the stoma bowel was evaluated at the clinical examination. At the ultrasonographic investigation, the patients were first investigated in the supine position to measure the transverse and vertical diameter of the abdominal opening and the thickness of the abdominal muscles. Results. Three types of ultrasonographic findings were identified. In ultra-I, the stoma bowel was completely fixed or showed telescoping-like movement through the abdominal opening. In ultra-II, fatty tissue was prolapsed together with the stoma bowel forming a bend in the subcutaneous tissue. In ultra-III, another bowel segment or fatty tissue passed beside the stoma bowel through the abdominal opening into the abdominal wall. A normal finding without any bulging at the clinical examination was associated with a smaller area and a smaller diameter of the abdominal opening than the area and diameter in patients with a visible peristomal bulging. There was no difference in the thickness of the muscle layer of the abdominal wall between patients with and without bulging. Conclusions. Ultrasonography can make a dynamic diagnosis of parastomal hernia. In patients with visible peristomal bulging, the area of the abdominal opening is increased but there is no decrease in the thickness of the muscles of the abdominal wall.

  • 265.
    Sjöwall, Johanna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Carlsson, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery.
    Vaarala, Outi
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics.
    Bergstrom, S.
    Bergström, S., Department of Microbiology, University of Umeå, Umeå, Sweden.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Innate immune responses in Lyme borreliosis: Enhanced tumour necrosis factor-a and interleukin-12 in asymptomatic individuals in response to live spirochetes2005In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 141, no 1, p. 89-98Article in journal (Refereed)
    Abstract [en]

    Innate immunity is important for early defence against borrelia spirochetes and should play a role in the clinical outcome of the infection. In order to study early cytokine responses, in vitro differentiated dendritic cells (DCs) and whole blood cells from 21 patients with different clinical outcomes of Lyme neuroborreliosis were stimulated with live borrelia spirochetes. The borrelia-induced secretion of interleukin (IL)-4, IL-10, IL-12p70, Interferon (INF)-? and tumour necrosis factor (TNF)-a in DCs and IL-1ß, IL-6, IL-8, IL-10, IL-12p70, TNF-a, regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1a, MIP-1ß and eotaxin in whole blood cells was measured by enzyme-linked immunospot (ELISPOT) and multiplex arrays, respectively. We found increased numbers of TNF-a-secreting DCs (P = 0.018) in asymptomatic seropositive individuals compared to patients with subacute neuroborreliosis and seronegative controls. Asymptomatic individuals were also found to have elevated levels of IL-12p70 (P = 0.031) in whole blood cell supernatants compared to seronegative controls. These results are in line with previous experiments using cells of the adaptive immune response, indicating that strong T helper type 1 (Th1) proinflammatory responses might be associated with a successful resolution of Lyme disease. © 2005 British Society for Immunology.

  • 266.
    Smeds, Staffan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Kald, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Lofstrom, L
    Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Chronic pain after open inguinal hernia repair: a longitudinal self-assessment study2010In: HERNIA, ISSN 1265-4906, Vol. 14, no 3, p. 249-252Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to assess the variation of self-reported pain over a period of 2 years in three groups of patients with no, moderate and severe pain at 3 months after primary open inguinal hernia repair. In two cohorts of patients from 2004 (n = 272) and 2005 (n = 292) who had given a self-report of postoperative pain at 3 months, 79 randomly selected patients without pain (box visual analogue scale [VAS] level 10) and all patients with moderate (Box VAS level 7-9) and severe pain (Box VAS level 1-6), 91 and 9, respectively, were included in the case series. The self-assessments were repeated for all patients 1-1.5 and 2-2.5 years after surgery (November 2006). It was observed that moderate pain reappeared among the pain-free patients in 28 and 23% after 1-1.5 and 2-2.5 years, respectively. Of those patients with moderate pain at 3 months, 39 and 49% reported no pain at 1-1.5 and 2-2.5 years, respectively, after surgery. A worsening from moderate pain to severe pain was reported by 22% of patients after 1-1.5 years and by 15% of patients after 2-2.5 years. Hernia recurrence (n = 3) was observed only in patients with increased pain. All nine patients with severe pain at 3 months reported less pain, but only one was pain-free at 2-2.5 years after surgery. The study shows that a significant proportion of the patients developed pain later than 3 months after the operation. It further points to a difference in pain evolvement in patients with moderate pain and those with severe postoperative pain at 3 months. Pain can increase in intensity from moderate to severe, both with and without the presence of a clinical recurrence.

  • 267.
    Smeds, Staffan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Löfström, L
    Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Eriksson, Olle
    Linköping University, Department of Computer and Information Science, Statistics. Linköping University, Faculty of Arts and Sciences.
    Influence of nerve identification and the resection of nerves at risk on postoperative pain in open inguinal hernia repair2010In: HERNIA, ISSN 1265-4906, Vol. 14, no 3, p. 265-270Article in journal (Refereed)
    Abstract [en]

    Surgical strategy regarding nerve identification and resection in relation to chronic postoperative pain remains controversial. A central question is whether nerves in the operation field, when identified, should be preserved or resected. In the present study, the hypotheses that the identification and consequent resection of nerves at risk have no influence on postoperative pain has been tested. A single-centre study was conducted in 525 patients undergoing Lichtenstein hernioplasty. One surgeon (364 operations, Group A) consequently resected nerves at risk for being injured and nine surgeons (161 operations, Group B) adhered to the general routine of nerve preservation. All cases were ambulatory surgery on anaesthetised patients and the groups were similar with regard to age, body mass index (BMI) and preoperative pain. Self-reported pain at 3 months was recorded on a 10-box visual analogue scale (VAS). The identification and resection of nerves were continuously registered. Statistical calculations were performed with Fishers exact test and ordinal logistic regression. There was no significant difference in the number of identified nerves in the two groups of patients (iliohypogastricus, P = 0.555; ilioinguinalis, P = 0.831; genital branch, P = 0.214). However, the number of resected nerves was significantly higher in Group A for the iliohypogastric nerve, P andlt; 0.001, but not for ilioinguinalis, P = 0.064, and genital branch, P = 0.362. Non-identification of the ilioinguinal nerve correlated to the highest level of self-reported postoperative pain at 3 months. Patients in Group A, who had nerves at risk resected from the operation field, reported significantly less postoperative pain at 3 months, P = 0.007. This register study confirms the importance of nerve identification. Nerve resection strategy with the consequent removal of nerves at risk gives a significantly better outcome in Lichtenstein hernioplasty.

  • 268.
    Smeds, Staffan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Löfström, Lars
    Sergelkliniken Linköping.
    Kald, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Not to hurt the patient--do we live up to this in hernia surgery? A self-assessment method tested to answer the question2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 21, p. 1582-1584Article in journal (Refereed)
    Abstract [en]

       

  • 269.
    Sommar, Pehr
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Junker, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Strandenes, Eivind
    Haukeland Hospital, Norway .
    Ness, Charlotte
    Haukeland Hospital, Norway .
    Hansson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Johnson, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Kratz, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Osteogenically-induced human dermal fibroblasts as a tool to regenerate bone2013In: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 47, no 1, p. 8-13Article in journal (Refereed)
    Abstract [en]

    Engineering of bone tissue could help to overcome the need for extensive reconstruction and associated donor site morbidity, and it has been proposed that osteogenic biomaterials, which are scaffolds that contain osteocompetent cells, could be used to fill large bone defects. This study investigated the potential of osteogenically-induced human dermal fibroblasts cultured on gelatin microcarriers combined with platelet-rich plasma in a model of a femoral defect in athymic rats. Defects were transplanted with one of the following six combinations: 1 = sodium chloride, 2 = platelet-rich plasma, 3 = microcarriers + platelet-rich plasma, 4 = human dermal fibroblasts on microcarriers + platelet-rich plasma, 5 = human osteoblasts on microcarriers + platelet-rich plasma, and 6 = osteogenically induced human dermal fibroblasts on microcarriers + platelet-rich plasma. The femoral defects were assessed 4 weeks postoperatively with computed tomography (CT), routine histological staining, fluorescence in situ hybridisation, and polyclonal antibodies directed towards osteocalcin and osteonectin. Radiographs of all groups taken 4 weeks postoperatively showed unhealed defects. Femoral defects transplanted with osteogenically-induced human dermal fibroblasts on microcarriers (group 6) contained dense clusters of cells with large quantities of extracellular matrix. These clusters were exclusive to this group and stained strongly for osteocalcin and osteonectin. Fluorescence in situ hybridisation showed viable human cells in femoral defects that had been transplanted with microcarriers seeded with cells, which confirmed the survival of implanted cells. In conclusion, osteogenically-induced human dermal fibroblasts survived in this new niche, and bone-like structures were apparent in the defects.

  • 270.
    Sommar, Pehr
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Plastic Surgery, Hand Surgery and Burns . Linköping University, Faculty of Health Sciences.
    Pettersson, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Ness, Charlotte
    Department of Surgery, Section of Plastic Surgery and Burn Centre, Haukeland University Hospital, Bergen, Norway.
    Johnson, Hans
    Department of Surgery, Section of Plastic Surgery and Burn Centre, Haukeland University Hospital, Bergen, Norway.
    Kratz, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Plastic Surgery, Hand Surgery and Burns . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Junker, Johan P E
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Engineering three-dimensional cartilage- and bone-like tissues using human dermal fibroblasts and macroporous gelatine microcarriers2010In: Journal of plastic, reconstructive & aesthetic surgery : JPRAS, ISSN 1878-0539, Vol. 63, no 6, p. 1036-1046Article in journal (Refereed)
    Abstract [en]

    The creation of tissue-engineered cartilage and bone, using cells from an easily available source seeded on a suitable biomaterial, may have a vast impact on regenerative medicine. While various types of adult stem cells have shown promising results, their use is accompanied by difficulties associated with harvest and culture. The proposed inherent plasticity of dermally derived human fibroblasts may render them useful in tissue-engineering applications. In the present study, human dermal fibroblasts cultured on macroporous gelatine microcarriers encapsulated in platelet-rich plasma into three-dimensional constructs were differentiated towards chondrogenic and osteogenic phenotypes using specific induction media. The effect of flow-induced shear stress on osteogenic differentiation of fibroblasts was also evaluated. The generated tissue constructs were analysed after 4, 8 and 12 weeks using routine and immunohistochemical stainings as well as an enzyme activity assay. The chondrogenic-induced tissue constructs were composed of glycosaminoglycan-rich extracellular matrix, which stained positive for aggrecan. The osteogenic-induced tissue constructs were composed of mineralised extracellular matrix containing osteocalcin and osteonectin, with cells showing an increased alkaline phosphatase activity. Increased osteogenic differentiation was seen when applying flow-induced shear stress to the culture. Un-induced fibroblast controls did not form cartilage- or bone-like tissues. Our findings suggest that primary human dermal fibroblasts can be used to form cartilage- and bone-like tissues in vitro when cultured in specific induction media.

  • 271.
    Stinner, B
    et al.
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Bauhofer, A
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Lorenz, W
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Rothmund, M
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Plaul, U
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Torossian, A
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Celik, I
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Sitter, H
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Koller, M
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Black, A
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Duda, D
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Encke, A
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Greger, B
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    van Goor, H
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Hanisch, E
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Hesterberg, R
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Klose, KJ
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Lacaine, F
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Lorijn, RHW
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Margolis, C
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Neugebauer, E
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Nyström, Per-Olof
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Reemst, PHM
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Schein, M
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Solovera, J
    Univ Marburg, Inst Theoret Surg, D-35033 Marburg, Germany Univ Marburg, Dept Gen Surg, D-35032 Marburg, Germany Univ Marburg, Dept Anaesthesia & Intens Care Med, D-35032 Marburg, Germany Bristol Royal Infirm, Dept Anaesthesia, Bristol, Avon, England Rot Kreuz Clin, Dept Surg, Kassel, Germany Univ Frankfurt, Dept Surg, D-6000 Frankfurt, Germany Dept Surg, Lichtenfels, Germany Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands Knappschafts Clin, Dept Surg, Dortmund, Germany St Hildegardes Clin, Dept Anaesthesia, Mainz, Germany Univ Marburg, Dept Radiol, D-35032 Marburg, Germany Hosp Tenon, Dept Surg, Paris, France Amgen Inc Europe, Lucerne, Switzerland Ben Gurion Univ Negev, Fac Hlth Sci, Ctr Med Descis Making, IL-84105 Beer Sheva, Israel Univ Cologne, Dept Surg 2, Biochem & Expt Div, D-5000 Cologne 41, Germany Linkoping Univ, Dept Med Surg Gastroenterol, S-58183 Linkoping, Sweden Diakonissenhuis, Dept Surg, Eindhoven, Netherlands Cornell Univ, New York Methodist Hosp, Dept Surg, Ithaca, NY 14853 USA.
    Granulocyte-colony stimulating factor in the prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4) - Protocol of a controlled clinical trial developed by consensus of an international study group Part three: individual patient, complication algorithm and quality management2001In: Inflammation Research, ISSN 1023-3830, E-ISSN 1420-908X, Vol. 50, no 5, p. 233-248Article, review/survey (Refereed)
    Abstract [en]

    General design: Presentation of a new type of a study protocol for evaluation of the effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of postoperative infectious complications and of sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). A randomised placebo controlled, double-blinded, single-centre study is performed at an University Hospital (n = 40 patients for each group). This part presents the course of the individual patient and a complication algorithm for the management of anastomotic leakage and quality management. Objective: In part three of the protocol, the three major sections include: - The course of the individual patient using a comprehensive graphic display, including the perioperative period, hospital stay and post discharge outcome. - A center based clinical practice guideline for the management of the most important postoperative complication anastomotic leakage - including evidence based support for each step of the algorithm. - Data management, ethics and organisational structure. Conclusions: Future studies with immune modifiers will also fail if not better structured (reduction of variance) to achieve uniform patient management in a complex clinical scenario. This new type of a single-centre trial aims to reduce the gap between animal experiments and clinical trials or - if it fails - at least demonstrates new ways for explaining the failures.

  • 272.
    Sundquist, M
    et al.
    Kalmar County Hospital.
    Arnesson, Lars-Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Brudin, L
    Kalmar County Hospital.
    Fohlin, H
    Tejler , G
    Västervik Hospital.
    When do locoregional recurrencies occur and how common is contralateral breast cancer?2009In: in CANCER RESEARCH, vol 18, 2009, Vol. 18, p. S76-S76Conference paper (Refereed)
  • 273.
    Svanvik, Joar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Laparoscopic cholecystectomy for acute cholecystitis2000In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 165, p. 16-17Article in journal (Refereed)
    Abstract [en]

    Acute cholecystitis was initially considered a contra-indication for laparoscopic cholecystectomy, but today the laparoscopic route is generally used even for severe acute cholecystitis. Several studies have shown that this is possible, although the conversion and complication rates are high, but there are no randomised controlled trials that evaluate the complications and costs of this technique compared with conventional open techniques. The timing of a laparoscopic cholecystectomy for acute cholecystitis is also a matter of debate as well as its use in elderly patients with this condition.

  • 274.
    Svanvik, Joar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Results of laparoscopic compared with open cholecystectomy2000In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 165, p. 12-15Article in journal (Refereed)
    Abstract [en]

    Laparoscopic cholecystectomy was introduced in 1985 and diffused within a few years throughout the world. The avalanche-like spread resulted in this procedure not being scientifically supported by results of controlled clinical trials. By 1997 there were just 13 randomised controlled trials and 150 prospective studies that followed a research protocol, while there were more than 1500 retrospective analyses of series of operations in a country, in a specific hospital, or by a specific surgeon. Comparisons with the conventional laparotomy technique and with minilaparotomy techniques are complicated by the fact that the variables compared, such as operation times, complication rates, and costs, varied over time.

  • 275.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Intestinal permeability in NEUROGASTROENTEROLOGY AND MOTILITY, vol 24, issue , pp 11-112012In: NEUROGASTROENTEROLOGY AND MOTILITY, Blackwell Publishing , 2012, Vol. 24, p. 11-11Conference paper (Refereed)
    Abstract [en]

    n/a

  • 276.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Mast Cells and Mastocytosis2009In: DIGESTIVE DISEASES, ISSN 0257-2753, Vol. 27, p. 129-136Article in journal (Refereed)
    Abstract [en]

    Mast cells (MCs) typically reside at barrier sites of the body, including the intestinal mucosa, and play a vital role in innate host defence. Activated MCs release a wide variety of bioactive mediators. These include preformed mediators stored in the granules (e. g. histamine and tryptase) and newly synthesised mediators (e. g. prostaglandins, leukotrienes and cytokines). MCs are present in all layers throughout the gastrointestinal (GI) tract and there is a close bi-directional connection between MCs and enteric nerves that is of vital importance in the regulation of GI functions. Some gain-of-function mutations in c-kit, encoding the tyrosine kinase-receptor for stem cell factor, are associated with the rare disease entity, systemic mastocytosis. These patients present symptoms arising from MC mediator release or infiltration. GI manifestations are common in this patient group, mainly abdominal pain and diarrhoea. Endoscopy with biopsies reveals MC infiltration in the mucosa. Other diagnostic tools include bone marrow biopsy and serum tryptase. Treatment is symptomatic with antihistamines or cromoglycate in mild cases, whereas severe cases need cytoreductive therapy that should be managed with expert haematologists. From a day-to-day clinical perspective, the important role of MCs in neuroimmune interaction has been implicated in the intestinal response to stress, in alterations of mucosal and neuromuscular function in irritable bowel syndrome or inflammatory bowel disease, and in the pathogenesis of nonerosive oesophageal reflux disease. Thus, MCs have important regulatory and protective roles in innate defence, in addition to being a potential mediator of mucosal pathophysiology in GI diseases. We need to learn how to balance the response of these volatile cells to be able to benefit from their versatility.

  • 277.
    Söderholm, Johan D
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Stress-related changes in oesophageal permeability: Filling the gaps of GORD?2007In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 56, no 9, p. 1177-1180Article, review/survey (Refereed)
    Abstract [en]

    Albeit remaining a controversial issue, it has become increasingly recognised that psychological stress has a major impact on gut mucosal function and affects the course of gastrointestinal disorders. Research during the last decade has shown that stress causes barrier dysfunction of the gastrointestinal mucosa by mechanisms that mainly involve neuropeptides and mast cells. Moreover, accumulating evidence implicates increased permeability as a pathogenic factor in gastroesophageal reflux disease (GORD). Recent data demonstrating that psychological stress may induce a permeability defect in stratified epithelia, including the oesophagus, shed new light on the pathophysiological events leading to heartburn and GORD.

  • 278.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Juliusson, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oncology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Haematology UHL.
    Sjödahl, Rune
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Long-term endoscopic remission in a case of Crohn's disease after autologous bone marrow transplantation.2000In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 118, no 4, p. 4212-Conference paper (Other academic)
  • 279.
    Söderholm, Johan D
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Pettersson, S.
    Institutionen för mikrobiologi, tumör- och cellbiologi (MTC), Karolinska institutet, Stockholm, Sweden.
    Polygenetisk störning i första linjens mukosaförsvar2009In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 106, no 45, p. 2974-2978Article in journal (Refereed)
    Abstract [en]

    [No abstract available]

  • 280.
    Söderholm, Johan D
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Wiren, M
    Linkoping Univ, Linkoping, Sweden McMaster Univ, Hamilton, ON, Canada.
    Franzén, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology . Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Perdue, MH
    Linkoping Univ, Linkoping, Sweden McMaster Univ, Hamilton, ON, Canada.
    Olaison, Gunnar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    "Topical" phase effects of acetysalicylic acid on human small bowel epithelium: Inhibition of oxidative phosphorylation and increased tight junction permeability.2000In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 118, no 4, p. 4298-Conference paper (Other academic)
  • 281.
    Tesselaar, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences.
    Bergkvist, Max
    Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Polarized Light Spectroscopy for Measurement of the Microvascular Response to Local Heating at Multiple Skin Sites2012In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 19, no 8, p. 705-713Article in journal (Refereed)
    Abstract [en]

    Objective: To evaluate whether TiVi, a technique based on polarized light, could measure the change in RBC concentration during local heating in healthy volunteers. Methods: Using a custom-made transparent heater, forearm skin was heated to 42 degrees C for 40 minutes while the change in RBC concentration was measured with TiVi. The perfusion response during local heating was measured at the same time with Laser Doppler flowmetry. Results: Mean RBC concentration increased (91 +/- 34 vs. 51 +/- 34 A.U. at baseline, p less than 0.001). The spatial heterogeneity of the RBC concentration in the measured skin areas was 26 +/- 6.4% at baseline, and 23 +/- 4.6% after 40 minutes of heating. The mean RBC concentrations in two skin sites were highly correlated (0.98 at baseline and 0.96 after 40 minutes of heating). The change in RBC concentration was less than the change in perfusion, measured with LDF. Unlike with LDF, a neurally mediated peak was not observed with TiVi in most of the test subjects. Conclusions: TiVi is a valuable technique for measuring the microvascular response to local heating in the skin, and offers a high reproducibility for simultaneous measurements at different skin sites, provided carefully controlled experiments are ensured.

  • 282.
    Tesselaar, Erik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Measurement of red blood cell concentration in skin during vascular provocations using polarization light spectroscopy imaging in JOURNAL OF VASCULAR RESEARCH, vol 48, issue , pp 164-1642011In: JOURNAL OF VASCULAR RESEARCH, Karger , 2011, Vol. 48, p. 164-164Conference paper (Refereed)
    Abstract [en]

    n/a

  • 283.
    Thor, Johan
    et al.
    Högskolan i Jönköping.
    Lundgren, Charlotte
    Linköping University, Department of Culture and Communication, Language and Culture. Linköping University, Department of Culture and Communication, Swedish Studies and Comparative Literature. Linköping University, Faculty of Arts and Sciences.
    Batalden, Paul
    The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth Medical School, Lebanon, New Hampshire, USA.
    Andersson Gäre, Boel
    Landstinget i Jönköpings län.
    Henriks, Göran
    Landstinget i Jönköpings län.
    Sjödahl, Rune
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Gabrielsson Järhult, Felicia
    Högskolan i Jönköping, Institutionen för gerontologi.
    Collaborative improvement of cancer care in southeastern Sweden – striving for better patient and population health, better care, and better professional development2012In: Sustainably improving health care: creatively linking care outcomes, system performance and professional development / [ed] Batalden, Paul and Foster, Tina, London: Radcliffe Publishing, 2012Chapter in book (Other academic)
  • 284.
    Thorfinn, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL.
    Angelidis, I K
    Stanford University.
    Gigliello, L
    Stanford University.
    Pham, H M
    Stanford University.
    Lindsey, D
    Stanford University.
    Chang, J
    Stanford University.
    Bioreactor optimization of tissue engineered rabbit flexor tendons in vivo2012In: JOURNAL OF HAND SURGERY-EUROPEAN VOLUME, ISSN 1753-1934, Vol. 37E, no 2, p. 109-114Article in journal (Refereed)
    Abstract [en]

    Tissue-engineered rabbit flexor tendons reseeded with cells are stronger in vitro after culture in a bioreactor. It is not known whether this effect persists in vivo. Tenocytes from New Zealand white rabbits were seeded onto rabbit rear paw flexor tendons that were deprived of cells and exposed to cyclic strain in a bioreactor. Reseeded constructs that were kept unloaded in a medium for 5 days were used as controls. The tendons were implanted to bridge a zone II defect in the rabbit. After explantation 4 weeks later, the ultimate tensile strength (UTS) and elastic modulus (EM) were determined. Tendon constructs that were exposed to cyclic strain had significantly improved UTS and EM. Histology showed that cellularity was increased in the bioreactor tendons.

  • 285.
    Thorfinn, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Saber, Sepideh
    Stanford University Medical Center.
    Angelidis, Ioannis
    Stanford University Medical Center.
    Ki, Sae
    Stanford University Medical Center.
    Zhang, Andrew
    Stanford University Medical Center.
    Chong, Alphonsus
    Stanford University Medical Center.
    Pham, Hung
    Stanford University Medical Center.
    Lee, Gordon
    Stanford University Medical Center.
    Chang, James
    Stanford University Medical Center.
    Flexor Tendon Tissue Engineering: Temporal Distribution of Donor Tenocytes versus Recipient Cells2009In: Plastic and reconstructive surgery (1963), ISSN 0032-1052, E-ISSN 1529-4242, Vol. 124, no 6, p. 2019-2026Article in journal (Refereed)
    Abstract [en]

    Background: Tissue-engineered tendon material may address tendon shortages in mutilating hand injuries. Tenocytes from rabbit flexor tendon can be successfully seeded onto acellularized tendons that are used as tendon constructs. These constructs in vivo exhibit a population of tenocyte-like cells; however, it is not known to what extent these cells are of donor or recipient origin. Furthermore, the temporal distribution is also not known. Methods: Tenocytes from New Zealand male rabbits were cultured and seeded onto acellularized rabbit forepaw flexor tendons (n = 48). These tendon constructs were transplanted into female recipients. Tendons were examined after 3, 6, 12, and 30 weeks using fluorescent in situ hybridization to detect the Y chromosome in the male donor cells. One unseeded, acellularized allograft in each animal was used as a control. Results: The donor male tenocytes populate the epitenon and endotenon of the grafts at greater numbers than the recipient female tenocytes at 3 and 6 weeks. The donor and recipient tenocytes are present jointly in the grafts until 12 weeks. At 30 weeks, nearly all cells are recipient tenocyte-like cells. Conclusions: Donor male cells survive in decreasing numbers over time until 30 weeks. The presence of cells in tissue-engineered tendon grafts has been shown in prior studies to add to the strength of the constructs in vitro. This study shows that recipient cells can migrate into and repopulate the tendon construct. Cell seeding onto tendon material may create stronger constructs that will allow the initiation of motion earlier. (Plast. Reconstr. Surg. 124: 2019, 2009.)

  • 286.
    Thorfinn, Johan
    et al.
    Department of Plastic Surgery, Hand Surgery and Burns Linköpings Universitet.
    Tarpila, Erkki
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Intravesical self-tying knots in suprapubic catheters: A report of two cases2008In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 42, no 1, p. 86-87Article in journal (Refereed)
    Abstract [en]

    We present two cases in which intravesical, self-tying knots occurred when the Cystofix catheter was used for suprapubic catheterization in two male boys admitted for hypospadias surgery. This complication of suprapubic catheterization is most likely due to the pigtail end of the catheter, and should be considered when removal is difficult. © 2008 Taylor & Francis.

  • 287.
    Tibbling, Lita
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Gezelius, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Franzen, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Factors influencing lower esophageal sphincter relaxation after deglutition2011In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 17, no 23, p. 2844-2847Article in journal (Refereed)
    Abstract [en]

    AIM: To study the relationship between upper esophageal sphincter (UES) relaxation, peristaltic pressure and lower esophageal sphincter (LES) relaxation following deglutition in non-dysphagic subjects. METHODS: Ten non-dysphagic adult subjects had a high-resolution manometry probe passed transnasally and positioned to cover the UES, the esophageal body and the LES. Ten water swallows in each subject were analyzed for time lag between UES relaxation and LES relaxation, LES pressure at time of UES relaxation, duration of LES relaxation, the distance between the transition level (TL) and the LES, time in seconds that the peristaltic wave was before (negative value) or after the TL when the LES became relaxed, and the maximal peristaltic pressure in the body of the esophagus. RESULTS:Relaxation of the LES occurred on average 3.5 s after the bolus had passed the UES and in most cases when the peristaltic wave front had reached the TL. The LES remained relaxed until the peristaltic wave faded away above the LES. CONCLUSION: LES relaxation seemed to be caused by the peristaltic wave pushing the bolus from behind against the LES gate.

  • 288.
    Tiveljung, Annika
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Borch, Kurt
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Jonasson, Jon
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Mårdh, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Petersson, Fredrik
    Ryhov Hospital, Jönköping.
    Monstein, Hans-Jürg
    Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology.
    Identification of Helicobacter in gastric biopsies by PCR based on 16S rDNA sequences: a matter of little significance for the prediction of H. pylori-associated gastritis?1998In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 47, no 8, p. 695-704Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to correlate molecular evidence of the presence of Helicobacter pylori in gastric biopsy samples, based on analysis of 16S rDNA, vacuolating toxin (vacA), urease A (ureA) and cagA genes, with the clinical, histological and serological findings in patients with H. pylori-associated gastritis. Fresh biopsy samples were collected from the gastric antrum and corpus of 22 asymptomatic volunteers with or without H. pylori-associated gastritis. Total DNA was extracted from the biopsy material and subjected to 16S rDNA PCR amplification, Southern blotting and 16S rDNA sequence analysis of the PCR products. The vacA, ureA and cagA genes were characterised by PCR amplification and Southern blot analysis. Based on partial 16S rDNA sequence analysis, DNA belonging to the genus Helicobacter was detected in gastric biopsy samples from 20 of 22 subjects, including seven of nine histologically and serologically normal controls. Six of 20 partial 16S rDNA sequences revealed variations within variable regions V3 and V4 that deviated from those of the H. pylori type strain ATCC 4350T and, therefore, possibly represented other species of Helicobacter. VacA genes identical with those of the type strain were found predominantly in the subjects with H. pylori gastritis, and all the patients except one were found to be cagA-positive. There was no evidence of false positive PCR reactions. In conclusion, the PCR-based molecular typing methods used here were apparently too sensitive when applied to the detection of H. pylori in human gastric tissues. The lack of quantitative analysis makes them inappropriate as clinical tools for the diagnosis of H. pylori-associated gastritis, despite the fact that they provide a qualitative and sensitive tool for the detection and characterisation of H. pylori in the gastrointestinal tract.

  • 289.
    Tjomsland, Vegard
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Niklasson, Lina
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Borch, Kurt
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Druid, Henrik
    Department of Oncology-pathology, Karolinska Institutet, Stockholm, Sweden.
    Bratthall, Charlotte
    Division of Oncology, Kalmar hospital, Kalmar, Sweden.
    Messmer, Davorka
    Cancer Center, University of California San Diego, La Jolla, USA.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Spångeus, Anna
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Pancreatic cancer microenvironment has a high degree of inflammation and infiltrating immune cells in its stroma2010Manuscript (preprint) (Other academic)
    Abstract [en]

    Tumor microenvironment is composed of tumor cells, fibroblasts, and infiltrating immune cells, and other cellular components, which work together and create an inflammatory environment favoring tumor progression. The present study aimed to characterize the expression and location of immune cells and investigate inflammatory factors that influence pancreatic ductal adenocarcinoma (PDAC).

    Methods: qPCRs and immunohistological stainings were performed for inflammatory factors and immune cells localized in tumor tissues from patients with PDAC (N=30).

    Results: All PDAC tissues had significant increased levels of inflammatory and chemotactic factors such as IL-1α, COX-2, CXCL8, CCL2, and CCL20 as compared to controls. The PDAC stroma, i.e. the fibrosis surrounding the tumor, was the main producer of these factors with the exception of IL-1α, which was expressed by tumor cells and some infiltrating immune cells. The gene expression for immune cell specific markers CD163, CD1c, CD303, and CD8, corresponding to macrophages, myeloid dendritic cells (DCs), plasmacytoid DCs, and cytotoxic T lymphocytes (CTL), respectively, were all significantly increased in PDAC tissues. Immunostaining of the tumor tissue confirmed the elevated levels of infiltrating macrophages, DCs, mature DCs, and cytotoxic T lymphocytes (CTL). The different immune cells were in nearly all cases localized in the fibrotic tissue adjacent to tumor nests. Production of CXCL8 mRNA and protein by the stroma was dependent on the tumor expression of IL-1α. Of importance, we found a correlation in expression of the proinflammatory factor IL-1α and the PDAC patients’ survival time.

    Conclusion: PDAC cells seem to take advantage of IL-1α to create an inflammatory microenvironment with high degree of fibrosis and the ability to both recruit and activate immune cells and the level of inflammation in this environment influenced the clinical outcome for the patients. Therapies targeting the inflammation might be beneficial for the survival of patients with PDAC.

  • 290.
    Tjomsland, Vegard
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Niklasson, Lina
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Borch, Kurt
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Druid, Henrik
    Karolinska Institute.
    Bratthall, Charlotte
    Kalmar Hospital.
    Messmer, Davorka
    University of Calif San Diego.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Spångeus, Anna
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    The Desmoplastic Stroma Plays an Essential Role in the Accumulation and Modulation of Infiltrated Immune Cells in Pancreatic Adenocarcinoma2011In: Clinical & Developmental Immunology, ISSN 1740-2522, E-ISSN 1740-2530, Vol. 2011, no 212810Article in journal (Refereed)
    Abstract [en]

    Tumor microenvironment is composed of tumor cells, fibroblasts, and infiltrating immune cells, which all work together and create an inflammatory environment favoring tumor progression. The present study aimed to investigate the role of the desmoplastic stroma in pancreatic ductal adenocarcinoma (PDAC) regarding expression of inflammatory factors and infiltration of immune cells and their impact on the clinical outcome. The PDAC tissues examined expressed significantly increased levels of immunomodulatory and chemotactic factors (IL-6, TGF beta, IDO, COX-2, CCL2, and CCL20) and immune cell-specific markers corresponding to macrophages, myeloid, and plasmacytoid dendritic cells (DCs) as compared to controls. Furthermore, short-time survivors had the lowest levels of DC markers. Immunostainings indicated that the different immune cells and inflammatory factors are mainly localized to the desmoplastic stroma. Therapies modulating the inflammatory tumor microenvironment to promote the attraction of DCs and differentiation of monocytes into functional DCs might improve the survival of PDAC patients.

  • 291.
    Tjomsland, Vegard
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Spangeus, Anna
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences.
    Messmer, Davorka
    University of California.
    Emilsson, Johan
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Falkmer, Ursula
    Jonköping Hospital.
    Falkmer, Sture
    Jonköping Hospital.
    Magnusson, Karl-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Borch, Kurt
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
    Pancreatic adenocarcinoma exerts systemic effects on the peripheral blood myeloid and plasmacytoid dendritic cells: an indicator of disease severity?2010In: BMC CANCER, ISSN 1471-2407, Vol. 10, no 87Article in journal (Refereed)
    Abstract [en]

    Background: Dendritic cells (DCs) isolated from tumor bearing animals or from individuals with solid tumors display functional abnormalities and the DC impairment has emerged as one mechanism for tumor evasion from the control of the immune system. Ductal pancreatic adenocarcinoma (PDAC), the most common pancreatic cancer, is recognized as a very aggressive cancer type with a mortality that almost matches the rate of incidence. Methods: We examined the systemic influence ductal pancreatic adenocarcinoma ( PDAC) exerted on levels of peripheral blood DCs and inflammatory mediators in comparison to the effects exerted by other pancreatic tumors, chronic pancreatitis, and age-matched controls. Results: All groups examined, including PDAC, had decreased levels of myeloid DCs (MDC) and plasmacytoid DCs (PDC) and enhanced apoptosis in these cells as compared to controls. We found elevated levels of PGE2 and CXCL8 in subjects with PDAC, and chronic pancreatitis. Levels of these inflammatory factors were in part restored in PDAC after tumor resection, whereas the levels of DCs were impaired in the majority of these patients similar to 12 weeks after tumor removal. Our results prove that solid pancreatic tumors, including PDAC, systemically affect blood DCs. The impairments do not seem to be tumor-specific, since similar results were obtained in subjects with chronic pancreatitis. Furthermore, we found that PDAC patients with a survival over 2 years had significant higher levels of blood DCs compared to patients with less than one year survival. Conclusions: Our findings points to the involvement of inflammation in the destruction of the blood MDCs and PDCs. Furthermore, the preservation of the blood DCs compartment in PDAC patients seems to benefit their ability to control the disease and survival.

  • 292.
    Tjomsland, Vegard
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Spångeus, Anna
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Borch, Kurt
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Messmer, Davorka
    University of California San Diego, CA 92093, USA.
    Larsson, Marie
    University of California San Diego, CA 92093, USA.
    Semi Mature Blood Dendritic Cells Exist in Patients with Ductal Pancreatic Adenocarcinoma Owing to Inflammatory Factors Released from the Tumor2010In: PLOS ONE, ISSN 1932-6203, Vol. 5, no 10Article in journal (Refereed)
    Abstract [en]

    Background: Much evidence exists regarding the fact that blood DCs, both myeloid DCs (MDCs) and plasmacytoid DCs (PDCs), are negatively affected in different types of cancer, with both reduced numbers and impaired functionality. Functional impairment of DCs in patients with pancreatic ductal adenocarcinoma (PDAC), may contribute to the poor clinical outcome. The aim of this study was to examine the effects PDAC had on blood DCs and elucidate the underlying mechanism responsible for the DC impairment. Methodology/Principal Findings: We examined the systemic influence PDAC exerted on blood DCs by ex vivo measuring numerous activation and maturation markers expressed on these cells. Furthermore, the effect patient plasma and the inflammatory factors CXCL8 and PGE(2) had on purified MDCs and PDCs from healthy donors was assessed and compared to the DCs existing in PDAC patients. We found a partial maturation of the blood MDCs and PDCs in PDAC patients with significantly enhanced expression of CD83, CD40, B7H3, PDL-1, CCR6, and CCR7 and decreased expression of ICOSL, and DCIR. These changes lead to impairment in their immunostimulatory function. Furthermore, chronic pancreatitis gave rise to DCs with similar semi-mature phenotype as seen in PDAC. Low expression of ICOSL was associated with poor prognosis. We found that the mechanism underlying this semi-maturation of DCs was inflammatory factors existing in the PDAC patients plasma. Of note, PGE2, which is elevated PDAC patient plasma, was one contributing factor to the changes seen in MDCs and PDCs phenotype. Conclusion/Significance: Our findings point to a role for the systemic inflammation in transforming blood MDCs and PDCs into semi-mature cells in PDAC patients and we show a correlation between maturation status and clinical outcome. Thus, means to preserve a functional blood DC compartment in PDAC patients by diminishing the inflammation could facilitate their ability to control the disease and improve survival.

  • 293.
    Tjomsland, Vegard
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Spångeus, Anna
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Välilä, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Borch, Kurt
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Druid, Henrik
    Department of Oncology-pathology, Karolinska Institutet, Stockholm, Sweden.
    Falkmer, Sture
    Department of Clinical Pathology, County Hospital Ryhov, Jönköping, Sweden.
    Falkmer, Ursula
    Department of Oncology, County Hospital Ryhov, Jönköping, Sweden.
    Messmer, Davorka
    Cancer Center, University of California San Diego, La Jolla, USA.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    IL-1α Sustains the Inflammation in Human Pancreatic Cancer Microenvironment by Targeting Cancer Associated Fibroblasts2010Manuscript (preprint) (Other academic)
    Abstract [en]

    The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is dynamic with an extensive interaction between the stroma and tumor cells. Our aim for this study was to delineate the cross-talk between PDAC and cancer-associated fibroblasts (CAFs) with focus on the mechanism creating the chronic inflammatory tumor milieu. We assessed the effect cross talk between primary PDAC and CAF cell lines propagated from tumors had on the creation and sustenance of an inflammatory environment and what factors that were involved in establishing the inflammation.

    The coculture of PDAC and CAF cell lines, propagated from tumor tissues, enhanced the levels of inflammatory factors including IL-1α, IL-6, CXCL8, VEGFA, CCL20, and COX-2. The production of these factors correlated with the expression detected in vivo in PDAC tissues. The key producers of nearly all inflammatory factors were the CAFs and not the tumor cells.

    IL-1α was produced by the tumor cell lines, whereas almost all IL-1RI was expressed by CAFs thus corresponding to their in vivo expression profile in PDAC tissues, indicating a role for the IL-1 signaling cascade in a tumor favorable microenvironment. Neutralization of the IL-1α pathway efficiently diminished the cross talk induced production of inflammatory factors, both in stroma and tumor cells. These data suggest that the cross-talk between PDAC cells and the main stroma cell type, i.e. CAFs, is one contributing factor in the formation of the inflammatory tumor environment and we propose that the neutralization of IL-1α pathway might be a potential therapy for this cancer.

  • 294.
    Tjomsland, Vegard
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Spångeus, Anna
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Välilä, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Sandström, Per
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Borch, Kurt
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Druid, Henrik
    Department of Oncology – Pathology, Karolinska Institutet, Stockholm.
    Falkmer, Sture
    Department of Clinical Pathology, County Hospital Ryhov, Jönköping.
    Falkmer, Ursula
    Department of Oncology, Aalborg University Hospital, Aalborg, Denmark.
    Messmer, Davorka
    Moores Cancer Center, University California San Diego, La Jolla, CA, USA.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    Interleukin 1α sustains the expression of inflammatory factors in human pancreatic cancer microenvironment by targeting cancer-associated fibroblasts2011In: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 13, no 8, p. 664-675Article in journal (Refereed)
    Abstract [en]

    The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) is dynamic with an extensive interaction between the stroma and tumor cells. The aim for this study was to delineate the cross-talk between PDAC and cancer-associated fibroblasts (CAFs) with focus on the mechanism creating the chronic inflammatory tumor milieu. We assessed the effects of the cross-talk between primary PDAC and CAF cell lines on the creation and sustenance of the inflammatory tumor microenvironment in pancreatic cancer. The coculture of primary PDAC and CAF cell lines enhanced the levels of inflammatory factors including IL-1á, IL-6, CXCL8, VEGFA, CCL20, and COX-2. CAFs were superior to tumor cells regarding the production of most inflammatory factors and tumor cell associated IL-1á was established as the initiator of the enhanced production of inflammatory factors through the binding of IL-1á to the active IL-1 receptor (IL-1R1) expressed predominantly by CAFs. Furthermore, we found a positive correlation between IL-1á and CXCL8 expression levels in PDAC tissues and correlation between IL-1á expression and the clinical outcome of the patients. This confirmed an important role for the IL-1 signaling cascade in the creation and sustenance of a tumor favorable microenvironment. Neutralization of the IL-1á signaling efficiently diminished the cross-talk induced production of inflammatory factors. These data suggest that the cross-talk between PDAC cells and the main stroma cell type, i.e. CAFs, is one essential factor in the formation of the inflammatory tumor environment and we propose that neutralization of the IL-1á signaling might be a potential therapy for this cancer.

  • 295.
    Trulsson, Lena
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery .
    Gasslander, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Permerth, J
    Svanvik, Joar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    The balance of mitogenesis and apoptosis in the rat pancreas in response to CCK-8.2000In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 118, no 4, p. 5324-Conference paper (Other academic)
  • 296.
    Turegano, F
    et al.
    Hospital Gen Gregorio Maranon, Spain .
    Lennquist, Sten
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Teaching and Research in Disaster Medicine and Traumatology.
    Editorial Material: Untitled2013In: European Journal of Trauma and Emergency Surgery, ISSN 1863-9933, E-ISSN 1863-9941, Vol. 39, no 2, p. 105-106Article in journal (Other academic)
    Abstract [en]

    n/a

  • 297.
    Uranus, S.
    et al.
    Uranüs, S., Department of Surgery, Karl-Franzens Univ. Sch. of Medicine, Graz, Austria, Department of Surgery, Karl-Franzens Univ. Sch. of Medicine, Auenbruggerplatz 29, AT-8036 Graz, Austria.
    Lennquist, Sten
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Centre for Teaching and Research in Disaster Medicine and Traumatology.
    Trauma management and education in Europe: A survey of twelve geographically and socioeconomically diverse European countries2002In: European Journal of Surgery, ISSN 1102-4151, E-ISSN 1741-9271, Vol. 168, no 12, p. 730-735Article in journal (Refereed)
    Abstract [en]

    Objective: To record the current standards of management and education in trauma surgery in 12 geographically and socioeconomically diverse countries in Europe. Design: Questionnaire study. Setting: Teaching hospital, Austria. Intervention: Questionnaire sent to experts on trauma in Austria, France, Germany, Italy, The Netherlands, Norway, Portugal, Romania, Spain, Sweden, Turkey, and the United Kingdom. Main outcome measure: Comparison of management of patients before, during, and after admission to hospital, and opportunities for initial and in-service training. Results: Management of patients and opportunities for training varied considerably from country to country, ranging from an organised trauma service throughout with specialised training to a haphazard and variable service that depended more on individual hospitals, doctors and patients. Conclusions: Standardisation of management and training would be desirable, and should be possible at least in countries that are members of the European Union.

  • 298.
    Van Assche, Gert
    et al.
    University Hospital Gasthuisberg.
    Dignass, Axel
    Frankfurter Diakonie Kliniken.
    Reinisch, Walter
    AKH Wien, Vienna, Austria .
    Janneke van der Woude, C
    Erasmus MC, Rotterdam, Netherlands .
    Sturm, Andreas
    Ghent University Hospital.
    Guslandi, Mario
    IRCCS San Raffaele, Milan, Italy .
    Oldenburg, Bas
    Tel Aviv University.
    Marteau, Philippe
    Lariboisiere Hospital, Paris.
    Ardizzone, Alessandro
    Osped L Sacco, Milan, Italy .
    C Baumgart, Daniel
    Humboldt University.
    DHaens, Geert
    Imelda GI Clin Research Centre, Bonheiden, Belgium .
    Gionchetti, Paolo
    University Bologna.
    Portela, Francisco
    Coimbra University Hospital.
    Vucelic, Boris
    University Hospital Rebro.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Escher, Johanna
    Erasmus MC, Sophia Childrens Hospital, Rotterdam, Netherlands .
    Koletzko, Sibylle
    Dr V Haunersches Kinderspital, Munich, Germany .
    Kolho, Kaija-Leena
    Hospital Children and Adolescents, Helsinki, Finland .
    Lukas, Milan
    Clin Centre ISACRE Lighthouse, Prague.
    Mottet, Christian
    University Lausanne Hospital.
    Tilg, Herbert
    Bezirkskrankenhaus Hall Tirol, Hall In Tirol, Austria .
    Vermeire, Severine
    University Hospital Gasthuisberg.
    Carbonnel, Frank
    Besancon University Hospital.
    Cole, Andrew
    Derby Hospital NHS Fdn Trust.
    Novacek, Gottfried
    Med University Vienna.
    Reinshagen, Max
    Klinikum Braunschweig.
    Tsianos, Epameinondas
    University Ioannina.
    Herrlinger, Klaus
    Robert Bosch Krankenhaus.
    Oldenburg, Bas
    University Med Centre Utrecht.
    Bouhnik, Yoram
    Beaujon Hospital.
    Kiesslich, Ralf
    Johannes Gutenberg University Mainz.
    Stange, Eduard
    Robert Bosch Krankenhaus.
    Travis, Simon
    John Radcliffe Hospital.
    Lindsay, James
    Barts and London NHS Trust.
    The second European evidence-based Consensus on the diagnosis and management of Crohns disease: Special situations2010In: JOURNAL OF CROHNS and COLITIS, ISSN 1873-9946, Vol. 4, no 1, p. 63-101Article in journal (Refereed)
    Abstract [en]

    n/a

  • 299.
    Vanheel, H
    et al.
    Katholieke University of Leuven, Belgium .
    Vicario, M
    Institute Recerca, Spain .
    Martinez, C
    Institute Recerca, Spain .
    Vanuytsel, T
    Katholieke University of Leuven, Belgium .
    Pardon, N
    Katholieke University of Leuven, Belgium .
    Santos, J
    Institute Recerca, Spain .
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Östergötland.
    Tack, J
    Katholieke University of Leuven, Belgium .
    Farre, R
    Katholieke University of Leuven, Belgium .
    Duodenal low-grade inflammation and impaired mucosal integrity in functional dyspepsia patients in NEUROGASTROENTEROLOGY AND MOTILITY, vol 24, issue , pp 24-252012In: NEUROGASTROENTEROLOGY AND MOTILITY, Blackwell Publishing , 2012, Vol. 24, p. 24-25Conference paper (Refereed)
    Abstract [en]

    n/a

  • 300.
    Velin Keita, Åsa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Ericson, Ann-Charlott
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Braaf, Ylva
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Wallon, Conny
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Increased antigen and bacterial uptake in follicle-associated epithelium induced by chronic psychological stress in rats2004In: Gut, ISSN 0017-5749, Vol. 53, no 4, p. 494-500Article in journal (Refereed)
    Abstract [en]

    Background: Chronic stress affects the course of inflammatory bowel disease and experimental colitis, and may also initiate intestinal inflammation in rats.

    Aim: To investigate the effects of stress on the M cell containing follicle associated epithelium, specialised in antigen uptake.

    Subjects and methods: Wistar rats were submitted to acute water avoidance stress for one hour or chronic water avoidance stress for 1 hour/day for 10 consecutive days. Permeability to 51Cr-EDTA, horseradish peroxidase, and chemically killed Escherichia coli K-12 was studied in both villus and follicle associated epithelium in Ussing chambers. Segments were further examined by light, electron, and confocal microscopy.

    Results: Acute stress increased horseradish peroxidase flux in villus as well as in follicle associated epithelium. Chronic stress further increased permeability to horseradish peroxidase in villus and follicle associated epithelium, in the latter by almost fourfold. Moreover, chronic stress induced over 30 times increased E coli passage in follicle associated epithelium whereas there was no significant increase in villus epithelium. Bacterial uptake was confirmed by confocal microscopy showing fluorescent bacteria penetrating and passing through the epithelial surface.

    Conclusions: These results show that the barrier function of follicle associated epithelium can be modulated, and that chronic stress enhances the uptake of luminal antigens and bacteria via the follicle associated epithelium. This can increase antigen exposure in Peyer’s patches thereby having implications in the initiation of proinflammatory immune responses within the intestinal mucosa.

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