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  • 1.
    Fredriksson, Fanny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Outcome and prevention strategies in peritoneal adhesion formation2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Peritoneal adhesions occur in up to 93% of adults after peritoneal trauma during surgery. Most adhesions are asymptomatic but can cause female infertility, small bowel obstruction (SBO) and chronic abdominal pain. Adhesion prophylaxis is needed to reduce the significant morbidity and increased health care costs resulting from peritoneal adhesions. This thesis aims to establish a relevant and reproducible experimental adhesion model to simultaneously study the healing processs and adhesion formation and later to examine whether carbazate-activated polyvinyl alcohol (PVAC), an aldehyde-carbonyl scavenger, can reduce adhesion formation or not; and, in a long-term follow-up, to investigate the incidence of and identify risk factors for adhesive SBO requiring surgical treatment after laparotomy during infancy and to survey the prevalence of self-reported chronic abdominal pain and female infertility. Male Sprague-Dawley rats were subjected to laparotomy, cecal abrasion, and construction of a small bowel anastomosis and examined at various time points after surgery. Early elevation of IL-6, IL-1β and TNF-α concentrations in peritoneal fluid but not in plasma correlate to adhesion formation in this rodent adhesion model, indicating that anti-adhesion treatment should be early, local and not systemic. The animals were treated with either peritoneal instillation of PVAC, or the anastomosis was sutured with PVAC-impregnated resorbable polyglactin sutures. At day 7, bursting pressure of the anastomosis was measured and adhesions were blindly evaluated using Kennedy- and Nair scoring systems. PVAC-impregnated sutures reduced adhesion formation without reducing bursting pressure. Infants who underwent laparotomy between 1976 and 2011 were identified (n=1185) and 898 patients were included with a median follow-up time of 14.7 (range 0.0-36.0) years. The median age at first laparotomy was 6 (range 1.0-365.0) days. There were 113 patients (12.6%) with adhesive SBO, with the highest incidence found in patients with Hirschsprung’s disease (19 of 65, 29%), malrotation (13 of 45, 29%), intestinal atresia (11 of 40, 28%) and necrotizing enterocolitis (16 of 64, 25%). Lengthy duration of surgery (hazard ratio (HR) 1.25, 95% CI, 1.07 to 1.45), stoma formation (HR 1.72, 1.15 to 2.56) and postoperative complications (HR 1.81, 1.12 to 2.92) were independent risk factors. Chronic abdominal pain was reported in 180 (24.0%) of 750 patients, and 17 (13.8%) of 123 women reported infertility. The morbidity after laparotomy in neonates and infants is high. Awareness of the risk factors may promote changes in surgical practice.

    List of papers
    1. Locally increased concentrations of inflammatory cytokines in an experimental intraabdominal adhesion model
    Open this publication in new window or tab >>Locally increased concentrations of inflammatory cytokines in an experimental intraabdominal adhesion model
    2014 (English)In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 49, no 10, p. 1480-1484Article in journal (Refereed) Published
    Abstract [en]

    Background: Peritoneal adhesions may cause bowel obstruction, infertility, and pain. This study investigated cytokines, proteins and growth factors thought to promote formation of adhesions in an experimental intraabdominal adhesion model. Methods: Male Sprague-Dawley rats were subjected to laparotomy, cecal abrasion, and construction of a small bowel anastomosis and examined at various time points after surgery. Concentrations of cytokines and growth factors in plasma and peritoneal fluid were analyzed using electrochemoluminescence and quantitative sandwich enzyme immunoassay technique. Results: Concentrations of interleukin-6 (IL-6), interleukin-1beta (IL-1 beta), and tumor necrosis factor alpha (TNF-alpha) increased in peritoneal fluid from 6 h after incision. Plasma concentrations of IL-6 increased at 6 h, but plasma concentrations of IL-1 beta and TNF-alpha remained low. Peritoneal fluid concentrations of platelet-derived growth factor-BB (PDGF- BB), transforming growth factor beta1 (TGF-beta 1), vascular endothelial growth factor (VEGF), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were below detection levels at all time points. Conclusion: Early elevations of IL-6, IL-1 beta, and TNF-alpha concentrations in peritoneal fluid correlated to adhesion formation in this rodent model. Our model is relevant and reproducible, suitable for intervention, and indicates that antiadhesion strategies should be early, local and not systemic.

    Keywords
    Peritoneal adhesions, Rat, Inflammatory cytokines
    National Category
    Pediatrics Surgery
    Identifiers
    urn:nbn:se:uu:diva-236557 (URN)10.1016/j.jpedsurg.2014.03.010 (DOI)000343140200008 ()25280650 (Scopus ID)
    Available from: 2014-11-24 Created: 2014-11-19 Last updated: 2017-12-05Bibliographically approved
    2. Sutures impregnated with an aldehyde-carbonyl scavenger reduce peritoneal adhesions
    Open this publication in new window or tab >>Sutures impregnated with an aldehyde-carbonyl scavenger reduce peritoneal adhesions
    Show others...
    (English)Article in journal (Refereed) Submitted
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-282118 (URN)
    Available from: 2016-04-02 Created: 2016-04-02 Last updated: 2016-06-01
    3. Adhesive small bowel obstruction after laparotomy during infancy
    Open this publication in new window or tab >>Adhesive small bowel obstruction after laparotomy during infancy
    2016 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 103, no 3, p. 284-289Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Intra-abdominal adhesions can cause adhesive small bowel obstruction, chronic abdominal pain and female infertility. Reports on long-term outcomes following laparotomy during infancy are scarce. The aims of this study were to investigate the incidence of and risk factors for long-term adhesive small bowel obstruction and associated morbidity after laparotomy during infancy.

    METHODS: Infants who underwent laparotomy between 1976 and 2011 were identified. Data were extracted from medical records and a questionnaire was sent to the patients.

    RESULTS: Some 898 of 1185 eligible patients were included, with a median follow-up time of 14·7 (range 0·0-36·0) years. Median age at first laparotomy was 6 (range 1·0-365·0) days. There were 113 patients (12·6 per cent) with adhesive small bowel obstruction who underwent relaparotomy, 79 (69·9 per cent) occurring during the first 2 years after the initial laparotomy. The highest incidence of small bowel obstruction was found in patients with Hirschsprung's disease (19 of 65, 29 per cent), malrotation (13 of 45, 29 per cent), intestinal atresia (11 of 40, 28 per cent) and necrotizing enterocolitis (16 of 64, 25 per cent). Lengthy duration of surgery (hazard ratio (HR) 1·25, 95 per cent c.i. 1·07 to 1·45), stoma formation (HR 1·72, 1·15 to 2·56) and postoperative complications (HR 1·81, 1·12 to 2·92) were independent risk factors. Chronic abdominal pain was reported in 180 (24·0 per cent) of 750 patients, and 17 (13·8 per cent) of 123 women reported infertility.

    CONCLUSION: The incidence of adhesive small bowel obstruction after laparotomy in infants is high.

    National Category
    Surgery Pediatrics
    Identifiers
    urn:nbn:se:uu:diva-273906 (URN)10.1002/bjs.10072 (DOI)000368804700016 ()26667204 (PubMedID)
    Available from: 2016-01-19 Created: 2016-01-19 Last updated: 2017-11-30Bibliographically approved
  • 2.
    Fredriksson, Fanny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Christofferson, Rolf H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Transplantation and regenerative medicine.
    Lilja, Helene Engstrand
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Locally increased concentrations of inflammatory cytokines in an experimental intraabdominal adhesion model2014In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 49, no 10, p. 1480-1484Article in journal (Refereed)
    Abstract [en]

    Background: Peritoneal adhesions may cause bowel obstruction, infertility, and pain. This study investigated cytokines, proteins and growth factors thought to promote formation of adhesions in an experimental intraabdominal adhesion model. Methods: Male Sprague-Dawley rats were subjected to laparotomy, cecal abrasion, and construction of a small bowel anastomosis and examined at various time points after surgery. Concentrations of cytokines and growth factors in plasma and peritoneal fluid were analyzed using electrochemoluminescence and quantitative sandwich enzyme immunoassay technique. Results: Concentrations of interleukin-6 (IL-6), interleukin-1beta (IL-1 beta), and tumor necrosis factor alpha (TNF-alpha) increased in peritoneal fluid from 6 h after incision. Plasma concentrations of IL-6 increased at 6 h, but plasma concentrations of IL-1 beta and TNF-alpha remained low. Peritoneal fluid concentrations of platelet-derived growth factor-BB (PDGF- BB), transforming growth factor beta1 (TGF-beta 1), vascular endothelial growth factor (VEGF), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were below detection levels at all time points. Conclusion: Early elevations of IL-6, IL-1 beta, and TNF-alpha concentrations in peritoneal fluid correlated to adhesion formation in this rodent model. Our model is relevant and reproducible, suitable for intervention, and indicates that antiadhesion strategies should be early, local and not systemic.

  • 3.
    Fredriksson, Fanny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Christofferson, Rolf H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lilja, Helene Engstrand
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Adhesive small bowel obstruction after laparotomy during infancy2016In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 103, no 3, p. 284-289Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Intra-abdominal adhesions can cause adhesive small bowel obstruction, chronic abdominal pain and female infertility. Reports on long-term outcomes following laparotomy during infancy are scarce. The aims of this study were to investigate the incidence of and risk factors for long-term adhesive small bowel obstruction and associated morbidity after laparotomy during infancy.

    METHODS: Infants who underwent laparotomy between 1976 and 2011 were identified. Data were extracted from medical records and a questionnaire was sent to the patients.

    RESULTS: Some 898 of 1185 eligible patients were included, with a median follow-up time of 14·7 (range 0·0-36·0) years. Median age at first laparotomy was 6 (range 1·0-365·0) days. There were 113 patients (12·6 per cent) with adhesive small bowel obstruction who underwent relaparotomy, 79 (69·9 per cent) occurring during the first 2 years after the initial laparotomy. The highest incidence of small bowel obstruction was found in patients with Hirschsprung's disease (19 of 65, 29 per cent), malrotation (13 of 45, 29 per cent), intestinal atresia (11 of 40, 28 per cent) and necrotizing enterocolitis (16 of 64, 25 per cent). Lengthy duration of surgery (hazard ratio (HR) 1·25, 95 per cent c.i. 1·07 to 1·45), stoma formation (HR 1·72, 1·15 to 2·56) and postoperative complications (HR 1·81, 1·12 to 2·92) were independent risk factors. Chronic abdominal pain was reported in 180 (24·0 per cent) of 750 patients, and 17 (13·8 per cent) of 123 women reported infertility.

    CONCLUSION: The incidence of adhesive small bowel obstruction after laparotomy in infants is high.

  • 4.
    Fredriksson, Fanny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Engstrand Lilja, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Survival rates for surgically treated necrotising enterocolitis have improved over the last four decades2019In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, no 9, p. 1603-1608Article in journal (Refereed)
    Abstract [en]

    Aim Improved survival rates for premature infants have also increased the population at risk of necrotising enterocolitis (NEC). This study evaluated the outcomes of surgically treated NEC and identified risk factors for mortality, intestinal failure (IF) and IF associated liver disease (IFALD). Methods This was a retrospective observational study of 131 infants with surgically treated NEC from 1976 to 2016 in a Swedish tertiary referral centre: 20 in 1976-1996, 33 in 1997-2006 and 78 in 2007-2016. Data were extracted from medical records, and the Cox regression model was used to identify risk factors. Results When the first and last periods were compared, they showed decreases in both gestational age, from 30 to 26 weeks, and mortality rates, from 45% to 29%. IF was found in 67 patients (56%), IFALD in 41 patients (34%) and short bowel syndrome (SBS) in 13 (19%). The incidence of IF was high, even in infants without SBS. Low gestational age was an independent risk factor for mortality. No risk factors were identified for IF or IFALD. Conclusion Survival rates for NEC improved from 1976-2016, despite a decrease in gestational age. Clinicians should be particularly aware of the risk of infants without SBS developing IF.

  • 5.
    Fredriksson, Fanny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Engstrand, Thomas
    Christofferson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Bowden, Tim
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Lilja, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Sutures impregnated with an aldehyde-carbonyl scavenger reduce peritoneal adhesionsArticle in journal (Refereed)
  • 6.
    Fredriksson, Fanny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Nordborg, Claes
    Dept of Pathology, Institute of Biomedicine, Gothenburg University, Sweden.
    Hallén, Tobias
    Dept of Neurosurgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Haemangiopericytoma presenting with acute intracerebral haemorrhage: a case report and literature review2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 4, p. 753-758Article, review/survey (Refereed)
    Abstract [en]

    Background.

    Intracranial haemangiopericytoma (HPC), a rare malignant tumour, should be distinguished from meningioma and solitary fibrous tumour, which have been considered as separate entities since 1993, according to histopathology and clinical characteristics.

    Methods.

    A PUBMED search for "Intracranial Haemangiopericytoma" yielded 176 articles, where 26 were of particular interest for this review article.

    Case report.

    Our patient, a 27-year-old man with HPC of grade III according to WHO, presents with an acute intracerebral haematoma, which is extremely rare.

    Results.

    Surgery (total resection) is the primary treatment. Long-term close clinical and radiological follow-up is crucial due to the high rate of recurrence and tendency for development of metastasis.

    Discussion.

    The effects of postoperative radiotherapy need further investigation. Besides neurosurgery, radiotherapy should always be considered in both patients with these highly malignant tumours (WHO grade III) and in patients with partial resection or inoperable cases (WHO grade II).

  • 7.
    Fredriksson, Fanny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Sellberg, Felix
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Bowden, Tim
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Engstrand, T.
    Karolinska Univ Hosp, Dept Reconstruct Plast Surg, SE-17176 Stockholm, Sweden.;Karolinska Inst, SE-17176 Stockholm, Sweden..
    Berglund, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Engstrand Lilja, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
    Sutures impregnated with carbazate-activated polyvinyl alcohol reduce intraperitoneal adhesions2017In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 52, no 11, p. 1853-1858Article in journal (Refereed)
    Abstract [en]

    Background: Intraperitoneal adhesions cause significant morbidity. They occur after peritoneal trauma, which induces oxidative stress with production of inflammatory cytokines, peroxidized proteins (carbonyls) and lipids (aldehydes). This study aimed to investigate if carbazate-activated polyvinyl alcohol (PVAC), an aldehyde-carbonyl inhibitor, can reduce intraperitoneal adhesions in an experimental model.

    Material and methods: Male Sprague-Dawley rats (n = 110) underwent laparotomy, cecal abrasion and construction of a small bowel anastomosis. They either were treated with intraperitoneal instillation of PVAC or were sutured with PVAC-impregnated sutures. Thromboelastography analysis was performed using human blood and PVAC. The lipid peroxidation product malondialdehyde (MDA) and inflammatory cytokines IL-1 beta and IL-6 were quantified in peritoneal fluid. At day 7, bursting pressure of the anastomosis was measured and adhesions were blindly scored.

    Results: PVAC in human blood decreased the production of the fibrin-thrombocyte mesh without affecting the coagulation cascade. MDA, IL-1 beta and IL-6 were increased after 6 h without significant difference between the groups. PVAC-impregnated sutures reduced intraperitoneal adhesions compared to controls (p = 0.0406) while intraperitoneal instillation of PVAC had no effect. Anastomotic bursting pressure was unchanged.

    Conclusions: Intervention with an aldehyde-carbonyl inhibitor locally in the wound by PVAC-impregnated sutures might be a new strategy to reduce intraperitoneal adhesions.

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