liu.seSearch for publications in DiVA
Change search
Refine search result
1 - 11 of 11
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Green, Henrik
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Rosenberg, Per
    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.
    Mirghani, Rajaa A
    Karolinska University .
    Rymark, Per
    Västerås Hospital.
    Åvall Lundqvist, Elisabeth
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Karolinska University Hospital.
    Peterson, Curt
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Pharmacogenetic Studies of Paclitaxel in the Treatment of Ovarian Cancer2009In: Basic & Clinical Pharmacology & Toxicology, ISSN 1742-7835, E-ISSN 1742-7843, Vol. 104, no 2, p. 130-137Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to evaluate the role of sequence variants in the CYP2C8, ABCB1 and CYP3A4 genes and the CYP3A4 phenotype for the pharmacokinetics and toxicity of paclitaxel in ovarian cancer patients. Thirty-eight patients were treated with paclitaxel and carboplatin. The genotypes of CYP2C8*1B, *1C, *2, *3, *4, *5, *6, *7, *8 and P404A, ABCB1 G2677T/A and C3435T, as well as CYP3A4*1B, were determined by pyrosequencing. Phenotyping of CYP3A4 was performed in vivo with quinine as a probe. The patients were monitored for toxicity and 23 patients underwent a more extensive neurotoxicity evaluation. Patients heterozygous for G/A in position 2677 in ABCB1 had a significantly higher clearance of paclitaxel than most other ABCB1 variants. A lower clearance of paclitaxel was found for patients heterozygous for CYP2C8*3 when stratified according to the ABCB1 G2677T/A genotype. In addition, the CYP3A4 enzyme activity in vivo affected which metabolic pathway was dominant in each patient, but not the total clearance of paclitaxel. The exposure to paclitaxel correlated to the degree of neurotoxicity. Our findings suggest that interindividual variability in paclitaxel pharmacokinetics might be predicted by ABCB1 and CYP2C8 genotypes and provide useful information for individualized chemotherapy.

  • 2.
    Hogberg, Thomas
    et al.
    Lund University.
    Signorelli, Mauro
    A Manzoni Hospital.
    Freire de Oliveira, Carlos
    University Hospital, Coimbra, Portugal .
    Fossati, Roldano
    Mario Negri Institute for Pharmacological Research.
    Lissoni, Andrea Alberto
    S Gerardo Hospital.
    Sorbe, Bengt
    Örebro University Hospital.
    Andersson, Hakan
    Gothenburg University Hospital.
    Grenman, Seija
    Turku University Hospital.
    Lundgren, Caroline
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre.
    Boman, Karin
    Umeå University Hospital.
    Tholander, Bengt
    Karolinska Hospital.
    Scambia, Giovanni
    Gemelli Hospital.
    Reed, Nicholas
    University of Glasgow.
    Cormio, Gennaro
    University of Bari.
    Tognon, Germana
    Spedali Civil Brescia.
    Clarke, Jackie
    Belfast City Hospital.
    Sawicki, Tomasz
    Medical University of Gdansk.
    Zola, Paolo
    Mauriziano Hospital.
    Kristensen, Gunnar
    Norwegian Radium Hospital.
    Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer - Results from two randomised studies2010In: EUROPEAN JOURNAL OF CANCER, ISSN 0959-8049, Vol. 46, no 13, p. 2422-2431Article in journal (Refereed)
    Abstract [en]

    Introduction: Endometrial cancer patients with high grade tumours, deep myometrial invasion or advanced stage disease have a poor prognosis. Randomised studies have demonstrated the prevention of loco-regional relapses with radiotherapy (RT) with no effect on overall survival (OS). The possible additive effect of chemotherapy (CT) remains unclear. Two randomised clinical trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival (PFS) in high-risk endometrial cancer. The two studies were pooled. Methods: Patients (n = 540; 534 evaluable) with operated endometrial cancer International Federation of Obstetrics and Gynaecology (FIGO) stage I-III with no residual tumour andprognostic factors implying high-risk were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy. Results: In the NSGO/EORTC study, the combined modality treatment was associated with 36% reduction in the risk for relapse or death (hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.41-0.99; P = 0.04); two-sided tests were used. The result from the Gynaecologic Oncology group at the Mario Negri Institute (MaNGO)-study pointed in the same direction (HR 0.61), but was not significant. In the combined analysis, the estimate of risk for relapse or death was similar but with narrower confidence limits (HR 0.63, CI 0.44 0.89; P = 0.009). Neither study showed significant differences in the overall survival. In the combined analysis, overall survival approached statistical significance (HR 0.69, CI 0.46-1.03; P = 0.07) and cancer-specific survival (CSS) was significant (HR 0.55, CI 0.35-0.88; P = 0.01). Conclusion: Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and a high-risk profile. A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results.

  • 3.
    Khoshnoud, Mahmoud R
    et al.
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Lofdahl, Britta
    Department of Pathology, Uppsala University Hospital, Sweden.
    Fohlin, Helena
    Östergötlands Läns Landsting, Centre of Surgery and Oncology, Oncology Centre. Linköping University, Faculty of Health Sciences.
    Fornander, Tommy
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Stål, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Skoog, Lambert
    Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
    Bergh, Jonas
    Cancer Center, Karolinska Institute, Stockholm Sweden and Medical Breast Unit, Christie Hospital, Manchester, UK.
    Nordenskjöld, Bo
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
    Immunohistochemistry compared to cytosol assays for determination of estrogen receptor and prediction of the long-term effect of adjuvant tamoxifen2011In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 126, no 2, p. 421-430Article in journal (Refereed)
    Abstract [en]

    The purpose of this study is to compare immunohistochemistry (IHC) and cytosol-based assays for determination of estrogen receptor (ER) and prediction of response to adjuvant tamoxifen treatment in postmenopausal women with early-stage invasive breast cancer. The Stockholm Breast Cancer Study Group conducted a randomized trial during 1976 through 1990 comparing adjuvant tamoxifen versus control. The patients were stratified according to tumor size and lymph node status in high-risk and low-risk groups. In this study we evaluated 683 patients with “low risk” breast cancer (size ≤30 mm, lymph node-negative) for whom ER status had been determined by both the cytosol assays and IHC at one pathology laboratory. The median follow-up was 17 years. Six hundred eighty-three patients had tumors with ER determined by both methods, 536 (78.5%) were ER-positive by cytosol assays using the cutoff level at ≥0.05 fmol/μg DNA and 539 patients were ER-positive (79%) by IHC using the cutoff level at ≥10% cell stained. Thirty-nine tumors (5.7%) were ER-positive by cytosol but not by IHC, whereas the opposite pattern was found for 42 cases (6.1%). Only seven tumors had stained cells between 0 and 9% by IHC. The concordance between IHC and cytosol assays was high (88%). The kappa statistic was 0.65, 95% CI 0.58–0.72. Among patients classified as ER-negative no therapeutic benefit from tamoxifen was observed. Among patients with ER-expressing tumors, tamoxifen resulted in significantly better recurrence-free survival irrespective of the method (IHC: HR, 0.53, P < 0.001; cytosol: HR, 0.53, P < 0.001). The effect on overall survival was not statistically significant probably due to the limited sample size. Both IHC and cytosol assay accurately predict long-term response to adjuvant tamoxifen.

  • 4.
    Myrelid, Pär
    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.
    Surgery and immuno modulation in Crohn’s disease2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Crohn’s disease is a chronic inflammatory bowel disease with unknown origin. This study investigates the combined use of surgery and immuno modulation in Crohn’s disease. The outcome of medication and surgery in 371 operations on 237 patients between 1989 and 2006 were evaluated. Moreover the effects of prednisolone, azathioprine and infliximab on the healing of colo-colonic anastomosis in 84 mice with or without colitis were evaluated.

    The use of thiopurines after abdominal surgery in selected cases of severe Crohn’s disease was found to prolong the time to clinical relapse of the disease from 24 to 53 months. Patients on postoperative maintenance therapy with azathioprine had a decreased symptomatic load over time and needed fewer steroid courses.

    The use of thiopurines was found to be a risk factor of anastomotic complications in abdominal surgery for Crohn’s disease together with pre-operative intra-abdominal sepsis and colo-colonic anastomosis. The risk for anastomotic complications increased from 4 % in those without any of these risk factors to 13 % in those with any one and 24 % if two or three risk factors were present.

    In patients with two or more of these, or previously established, risk factors prior to surgery one should consider refraining from anastomosis or doing a proximal diverting stoma. Another possibility is to use a split stoma in which both ends of a future delayed anastomosis are brought out in the same ostomy hole of the abdominal wall. This method was found to significantly decrease the number of risk factors prior to the actual anastomosis as well as decreasing the risk of anastomotic complications, without increasing the number of operations or the time spent in hospital.

    In the animal model all three medications had an ameliorating effect on the colitis compared with placebo. Only prednisolone was found to interfere with the healing of the colo-colonic anastomoses with significantly decreased bursting pressure compared with placebo as well as azathioprine and infliximab.

    The association between azathioprine therapy and anastomotic complications may be due to a subgroup of patients with a more severe form of the disease who have an increased risk of such complications and also are more prone to receive intense pharmacological therapy.

    List of papers
    1. Azathioprine as a postoperative prophylaxis reduces symptoms in aggressive Crohn's disease
    Open this publication in new window or tab >>Azathioprine as a postoperative prophylaxis reduces symptoms in aggressive Crohn's disease
    Show others...
    2006 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 41, no 10, p. 1190-1195Article in journal (Refereed) Published
    Abstract [en]

    Objective. Recurrence of Crohn's disease (CD) after surgery is common. Azathioprine/6-mercaptopurine (Aza/6-MP) is effective in controlling medically induced remission but, so far, has only been sparsely investigated after surgically induced remission. This study comprises a subset of CD patients considered to have an aggressive disease course and chosen for treatment with Aza postoperatively. Material and methods. In 1989-2000, a total of 100 patients with CD were given Aza/6-MP as a postoperative prophylaxis. Fourteen Aza/6-MP-intolerant patients were compared with 28 Aza-tolerant patients, matched for gender, age, and duration of disease. Patients were prospectively registered for symptoms using a modified Crohn's disease activity index (CDAI) and perceived health was assessed on a visual analogue scale (VAS). The primary outcome variable was the modified CDAI postoperatively integrated over time, other variables were time to first relapse (modified CDAI ≥ 150), time to first repeated surgery, number of courses of steroids, and repeated surgery per year of follow-up. Patients were followed for a median of 84.7months (23.2-140). Results. The modified CDAI integrated over time was 93 for Aza-treated patients compared with 184 for controls (p = 0.01) and time to first relapse was 53 and 24 months, respectively (p < 0.05). Aza-treated patients needed fewer courses of corticosteroids (p = 0.05) compared with controls. Perceived health did not differ between the groups, nor did need of repeated surgery. Time to first repeat operation was 53 and 37 months, respectively. Conclusions. In CD patients considered to have an aggressive disease course, Aza reduced symptoms after surgery and prolonged the time to symptomatic relapse. The findings support a role for Aza as a postoperative maintenance treatment in CD. © 2006 Taylor & Francis.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-35679 (URN)10.1080/00365520600587378 (DOI)28126 (Local ID)28126 (Archive number)28126 (OAI)
    Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
    2. Thiopurine Therapy Is Associated with Postoperative Intra-Abdominal Septic Complications in Abdominal Surgery for Crohns Disease
    Open this publication in new window or tab >>Thiopurine Therapy Is Associated with Postoperative Intra-Abdominal Septic Complications in Abdominal Surgery for Crohns Disease
    Show others...
    2009 (English)In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 52, no 8, p. 1387-1394Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE: Thiopurines are important as maintenance therapy in Crohns disease, but there have been concerns whether thiopurines increase the risk for anastomotic complications. The present study was performed to assess whether thiopurines alone, or together with other possible risk factors, are associated with postoperative intra-abdominal septic complications after abdominal surgery for Crohns disease.

    METHODS: Prospectively registered data regarding perioperative factors were collected at a single tertiary referral center from 1989 to 2002. Data from 343 consecutive abdominal operations on patients with Crohns disease were entered into a multivariate analysis to evaluate risk factors for intra-abdominal septic complications. All operations involved either anastomoses, strictureplasties, or both; no operations, however, involved proximal diversion.

    RESULTS: Intra-abdominal septic complications occurred in 26 of 343 operations (8%). Thiopurine therapy was associated with an increased risk of intra-abdominal septic complications (16% with therapy; 6% without therapy; P = 0.044). Together with established risk factors such as pre-operative intra-abdominal sepsis (18% with sepsis; 6% without sepsis; P = 0.024) and colocolonic anastomosis (16% with such anastomosis; 6% with other types of anastomosis; P = 0.031), thiopurine therapy was associated with intra-abdominal septic complications in 24% if any 2 or all 3 risk factors were present compared with 13% if any 1 factor was present, and only 4% in patients if none of these factors were present (P andlt; 0.0001).

    CONCLUSIONS: Thiopurine therapy is associated with postoperative intra-abdominal septic complications. The risk for intra-abdominal septic complications was related to the number of identified risk factors. This increased risk should be taken into consideration when planning surgery for Crohns disease.

    Keywords
    Crohns disease, Immunosuppression, Surgery, Postoperative complications, Anastomosis, surgical
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-53691 (URN)10.1007/DCR.0b013e3181a7ba96 (DOI)
    Available from: 2010-02-01 Created: 2010-02-01 Last updated: 2017-12-12
    3. Split Stoma in Resectional Surgery of High Risk Patients with Ileocolonic Crohn’s Disease
    Open this publication in new window or tab >>Split Stoma in Resectional Surgery of High Risk Patients with Ileocolonic Crohn’s Disease
    2012 (English)In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 14, no 2, p. 188-193Article in journal (Refereed) Published
    Abstract [en]

    Objectives: Surgery for Crohn’s disease (CD) is at high risk of anastomotic complications, with severe postoperative morbidity and even mortality. This retrospective study of high risk CD patients compared the outcome of primary anastomosis (PA) with that of split stoma (SS) and delayed anastomosis (DA).

    Methods: We performed 146 operations for ileocolonic CD from 1995-2006. Patient data were obtained from a prospectively registered data base. Patients with ≥2 preoperative risk factors (n=76) constituted high risk patients. Outcomes following PA or SS with DA were assessed.

    Results: The number of risk factors (mean) was 2.4 in the PA group and 3.5 in the SS group at time of resection and 0.2 (p<0.0001) at time of DA after 5.0 (2.3-12.6) months. Anastomotic complications occurred in 19 % (11/57) after PA compared with 0 % (0/19) after DA (p=0.038). The total number of operations and in-hospital time was 1.9 (±1.5) and 20.9 (±35.6) days after PA compared with 2.0 (±0.2) and 17.8 (±10.4) days after DA (p=0.70 and p=0.74).

    Conclusions: SS in high risk ileocolonic resections for CD, reduces the number of risk factors at the time of DA and the risk for anastomotic complications, compared to PA, without adding inhospital time or number of operations.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2012
    Keywords
    Crohn’s Disease; Stoma, Surgical; Surgery; Postoperative Complications; Anastomosis, Surgical
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54812 (URN)10.1111/j.1463-1318.2011.02578.x (DOI)000298944800019 ()
    Available from: 2010-04-14 Created: 2010-04-14 Last updated: 2017-12-12Bibliographically approved
    4. Effects of Anti-Inflammatory Therapy on Bursting Pressure of colonic Anastomosis in Dextran Sulfate Sodium Induced Colitis in Mice
    Open this publication in new window or tab >>Effects of Anti-Inflammatory Therapy on Bursting Pressure of colonic Anastomosis in Dextran Sulfate Sodium Induced Colitis in Mice
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: The aim of this experimental study was to evaluate the effect of colitis and anti inflammatory therapies, respectively, on the healing of colonic anastomoses in mice.

    Methods: Eighty four female C57BL/6 mice where randomized into eight groups; four groups continued receiving plain tap water and four groups receiving dextran sulfate sodium. Intraperitoneal treatment was given for 14 days with placebo, prednisolone (2 mg/kg bodyweight), azathioprine (5 mg/kg bodyweight) or infliximab (5 mg/kg bodyweight) until surgery with transsection of the colon and an end to end colonic anastomosis was performed. All mice were sacrificed on day 2 and bursting pressure measurements were recorded.

    Results: In the DSS group the mice receiving placebo (n=4) had a more active inflammation with a bowel weight of 12.8 (10.6-15.0) mg/mm, which differed significantly from all the other therapy arms; prednisolone 8.1 (7.5-9.1) mg/mm (p=0.014), azathioprine 8.2 (7.0-8.5) mg/mm (p=0.0046), infliximab 6.7 (6.4-7.9) mg/mm (p=0.0055). Bursting pressure for the placebo group was 90.0 (71.5-102.8) mmHg and did not differ from the azathioprine or infliximab groups, 84.4 (70.5-112.5) and 92.3 (75.8-122.3) mmHg respectively. In contrast bursting pressure for the prednisolone-treated group was decreased compared to placebo, 55.5 (42.8-73.0) mmHg (p=0.0004), as well as compared with azathioprine (p=0.0004) and infliximab (p=0.0015).

    Conclusions: All given therapies had effect on the DSS-induced colitis. A severe decrease in bursting pressure of a colonic anastomosis was seen after preoperative steroids but we found no effect of azathioprine or infliximab. Thus, AZA and IFX may not increase the risk for anastomotic complications per se; the need for these therapies may rather be seen as markers of severe IBD with increased risk of surgical complications.

    Keywords
    Inflammatory Bowel Disease; Surgery; Postoperative Complications; Anastomosis, Surgical; Colitis, DSS
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54815 (URN)
    Available from: 2010-04-14 Created: 2010-04-14 Last updated: 2010-04-14Bibliographically approved
  • 5.
    Myrelid, Pär
    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.
    Salim, Sa’ad
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Melgar, Silvia
    Biosciences Institute, University College Cork, Cork City, Ireland.
    Pruteanu, Mihaela
    Biosciences Institute, University College Cork, Cork City, Ireland.
    Andersson, Peter
    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.
    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, Oncology Centre.
    Effects of Anti-Inflammatory Therapy on Bursting Pressure of colonic Anastomosis in Dextran Sulfate Sodium Induced Colitis in MiceManuscript (preprint) (Other academic)
    Abstract [en]

    Background: The aim of this experimental study was to evaluate the effect of colitis and anti inflammatory therapies, respectively, on the healing of colonic anastomoses in mice.

    Methods: Eighty four female C57BL/6 mice where randomized into eight groups; four groups continued receiving plain tap water and four groups receiving dextran sulfate sodium. Intraperitoneal treatment was given for 14 days with placebo, prednisolone (2 mg/kg bodyweight), azathioprine (5 mg/kg bodyweight) or infliximab (5 mg/kg bodyweight) until surgery with transsection of the colon and an end to end colonic anastomosis was performed. All mice were sacrificed on day 2 and bursting pressure measurements were recorded.

    Results: In the DSS group the mice receiving placebo (n=4) had a more active inflammation with a bowel weight of 12.8 (10.6-15.0) mg/mm, which differed significantly from all the other therapy arms; prednisolone 8.1 (7.5-9.1) mg/mm (p=0.014), azathioprine 8.2 (7.0-8.5) mg/mm (p=0.0046), infliximab 6.7 (6.4-7.9) mg/mm (p=0.0055). Bursting pressure for the placebo group was 90.0 (71.5-102.8) mmHg and did not differ from the azathioprine or infliximab groups, 84.4 (70.5-112.5) and 92.3 (75.8-122.3) mmHg respectively. In contrast bursting pressure for the prednisolone-treated group was decreased compared to placebo, 55.5 (42.8-73.0) mmHg (p=0.0004), as well as compared with azathioprine (p=0.0004) and infliximab (p=0.0015).

    Conclusions: All given therapies had effect on the DSS-induced colitis. A severe decrease in bursting pressure of a colonic anastomosis was seen after preoperative steroids but we found no effect of azathioprine or infliximab. Thus, AZA and IFX may not increase the risk for anastomotic complications per se; the need for these therapies may rather be seen as markers of severe IBD with increased risk of surgical complications.

  • 6.
    Myrelid, Pär
    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.
    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, Oncology Centre.
    Sjödahl, Rune
    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.
    Andersson, Peter
    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.
    Split Stoma in Resectional Surgery of High Risk Patients with Ileocolonic Crohn’s Disease2012In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 14, no 2, p. 188-193Article in journal (Refereed)
    Abstract [en]

    Objectives: Surgery for Crohn’s disease (CD) is at high risk of anastomotic complications, with severe postoperative morbidity and even mortality. This retrospective study of high risk CD patients compared the outcome of primary anastomosis (PA) with that of split stoma (SS) and delayed anastomosis (DA).

    Methods: We performed 146 operations for ileocolonic CD from 1995-2006. Patient data were obtained from a prospectively registered data base. Patients with ≥2 preoperative risk factors (n=76) constituted high risk patients. Outcomes following PA or SS with DA were assessed.

    Results: The number of risk factors (mean) was 2.4 in the PA group and 3.5 in the SS group at time of resection and 0.2 (p<0.0001) at time of DA after 5.0 (2.3-12.6) months. Anastomotic complications occurred in 19 % (11/57) after PA compared with 0 % (0/19) after DA (p=0.038). The total number of operations and in-hospital time was 1.9 (±1.5) and 20.9 (±35.6) days after PA compared with 2.0 (±0.2) and 17.8 (±10.4) days after DA (p=0.70 and p=0.74).

    Conclusions: SS in high risk ileocolonic resections for CD, reduces the number of risk factors at the time of DA and the risk for anastomotic complications, compared to PA, without adding inhospital time or number of operations.

  • 7.
    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
  • 8.
    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.

  • 9.
    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.

  • 10.
    Winbladh, Anders
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Björnsson, Bergthor
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Trulsson, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Bojmar, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Gullstrand, Per
    Linköping University, Department of Clinical and Experimental 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, Oncology Centre.
    N-Acetylcysteine Improves Glycogenesis after Segmental Liver Ischemia and Reperfusion Injury in PigsManuscript (preprint) (Other academic)
    Abstract [en]

    Objective: N-Acetylcysteine (NAC) is an antioxidative molecule known to protect liver tissue from oxygen radical species generated during ischemia and reperfusion. Nutritional and toxicology studies have shown that NAC also improves glucose metabolism and glycogen stores. We hypothesized that NAC improves glycogenesis and that impaired glycogenesis is a key element in ischemia-reperfusion injury.

    Material and Methods: In an experimental model, 80 minutes of segmental liver ischemia was induced in 16 pigs and the reperfusion was followed for 360 minutes. Eight animals received NAC 150 mg/kg as a bolus injection followed by an infusion of NAC 50 mg/kg/h intravenously.

    Results: AST and leukocyte density were lower in the NAC-treated animals, unrelated to the glutathione levels or apoptosis. Glycogen stores returned to a higher degree in the NAC treated animals and microdialysis revealed lower levels of lactate during the reperfusion phase. Nitrite/Nitrate levels in the NAC group were lower in both serum and microdialysate, indicating that NAC scavenges radical nitrosative species (RNS).

    Conclusions: NAC treatment improves glycogenesis after liver ischemia and reperfusion injury and reduces the level of intraparenchymal lactate during reperfusion, possibly due to the scavenging of RNS.

  • 11.
    Winbladh, Anders
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Björnsson, Bergthor
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Trulsson, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Offenbartl, Karsten
    Höglandssjukhuset, Eksjö.
    Gullstrand, Per
    Linköping University, Department of Clinical and Experimental 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, Oncology Centre.
    Ischemic Preconditioning Prior to Intermittent Pringles Maneuver in Liver Resections2012In: Journal of Hepato-Biliary-Pancreatic Sciences, ISSN 1868-6982, Vol. 19, no 2, p. 159-170Article in journal (Refereed)
    Abstract [en]

    Background: Continuous inflow vascular occlusion during liver resections causes less severe ischemia and reperfusion injury (IRI) if it is preceded by ischemic preconditioning (IP) or if intermittent inflow occlusion is used during the resection. No previous clinical trial has studied the effects of adding IP to intermittent inflow occlusion.

    Methods: Consecutive patients (n=32) with suspicion of malignant liver disease had liver resections (minimum 2 segments) performed with inflow occlusion 15/5. Half of the patients were randomized to receive IP (10/10). The patients were stratified according to volume of resection and none had chronic liver disease. The patients were followed for 5 days with microdialysis (μD).

    Results: All patients completed the study and there were no deaths. No differences were seen between the groups regarding demographics or perioperative parameters (bleeding, duration of ischemia, resection volume, complications and serum lab tests). There were no differences in ALT, AST, Bilirubin or PT-INR levels, but μD revealed lower levels of lactate, pyruvate and glucose in the IP group having major liver resections (ANOVA). Nitrite and nitrate levels in μD decreased postoperatively but no differences were seen between the groups. In one patient an elevated μDglycerol curve was seen before the diagnosis of a stroke was made.

    Conclusions: IP before intermittent vascular occlusion does not reduce the serum parameters used to assess IRI. IP seems to improve aerobic glucose metabolism as the levels of glucose, pyruvate and lactate locally in the liver were reduced compared to controls in patients having resected >3 segments. μD may be used to monitor metabolism locally.

1 - 11 of 11
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf