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  • 1.
    Ahlström, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Christofferson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Lörelius, L-E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Vascularization of the continuous human colonic cancer cell line LS 174 T deposited subcutaneously in nude rats1988In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 96, no 8, p. 701-710Article in journal (Refereed)
    Abstract [en]

    The macro- and microvasculature of the human colonic cancer cell line LS 174 T, 2-8 weeks after subcutaneous deposition in both hind legs of congenitally athymic rats was investigated by light microscopy, angiography, and microvascular corrosion casting with analysis in a scanning electron microscope. The tumour blood vessels were connected to branches of the femoral artery. Only the outer 200-500 micron of the tumour was extensively vascularized, with several concentric, incomplete layers of tortuous vessels, resembling onion skin. Light microscopy revealed necrosis and bleeding in the centre of the tumour, especially in the older tumours, which corresponded well to the central avascularity observed in the casts. There was an increase in venular and capillary density and tortousity towards the tumour in the adjacent muscular fascia. It is concluded that the cell line LS 174 T grows invasively inwards and recruits its vessels from the nude rat host. The overall tumour vascular pattern was unorganized, suggesting limited control of new vessel formation. Extravasations of resin, which were encountered in all cast tumours, can be a rough indicator of enhanced vascular permeability.

  • 2.
    Al-Mashhadi, Ammar Nadhom Farman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Checa, Antonio
    Karolinska Institute.
    Wåhlin, Nils
    Karolinska Institute.
    Nevéus, Tryggve
    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), Paediatric Inflammation Research.
    Fossum, Magdalena
    Karolinska institute.
    Wheelock, Craig E.
    Karolinska Institute.
    Karanikas, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Stenberg, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Persson, A. Erik G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlström, Mattias
    Karolinska Institute.
    Changes in arterial pressure and markers of nitric oxide homeostasis and oxidative stress following surgical correction of hydronephrosis in children2018In: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 33, no 4, p. 639-649Article in journal (Refereed)
    Abstract [en]

    Objective Recent clinical studies have suggested an increased risk of elevated arterial pressure in patients with hydronephrosis. Animals with experimentally induced hydronephrosis develop hypertension, which is correlated to the degree of obstruction and increased oxidative stress. In this prospective study we investigated changes in arterial pressure, oxidative stress, and nitric oxide (NO) homeostasis following correction of hydronephrosis.

    Methods Ambulatory arterial pressure (24 h) was monitored in pediatric patients with hydronephrosis (n = 15) before and after surgical correction, and the measurements were compared with arterial pressure measurements in two control groups, i.e. healthy controls (n = 8) and operated controls (n = 8). Markers of oxidative stress and NO homeostasis were analyzed in matched urine and plasma samples.

    Results The preoperative mean arterial pressure was significantly higher in hydronephrotic patients [83 mmHg; 95% confidence interval (CI) 80–88 mmHg] than in healthy controls (74 mmHg; 95% CI 68–80 mmHg; p < 0.05), and surgical correction of ureteral obstruction reduced arterial pressure (76 mmHg; 95% CI 74–79 mmHg; p < 0.05). Markers of oxidative stress (i.e., 11- dehydroTXB2, PGF2α, 8-iso-PGF2α, 8,12-iso-iPF2α-VI) were significantly increased (p < 0.05) in patients with hydronephrosis compared with both control groups, and these were reduced following surgery (p < 0.05). Interestingly, there was a trend for increased NO synthase activity and signaling in hydronephrosis, which may indicate compensatory mechanism(s).

    Conclusion This study demonstrates increased arterial pressure and oxidative stress in children with hydronephrosis compared with healthy controls, which can be restored to normal levels by surgical correction of the obstruction. Once reference data on ambulatory blood pressure in this young age group become available, we hope cut-off values can be defined for deciding whether or not to correct hydronephrosis surgically.

    Keywords Blood pressure . Hydronephrosis . Hypertension . Nitric oxide . Oxidative stress . Ureteral obstruction 

  • 3.
    Angsten, Gertrud
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Danielson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Kassa, Ann-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Lilja, Helene Engstrand
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Outcome of laparoscopic versus open gastrostomy in children2015In: Pediatric surgery international (Print), ISSN 0179-0358, E-ISSN 1437-9813, Vol. 31, no 11, p. 1067-1072Article in journal (Refereed)
    Abstract [en]

    Laparoscopic gastrostomy (LAPG) has gained popularity in children. The aim of this study was to compare the outcome of LAPG versus open gastrostomy (OG) in children with focus on complications, operative times and postoperative length of stay. Retrospective study of children who had gastrostomies inserted at our tertiary Pediatric Surgery Center from 2000 until 2013. The indications for a gastrostomy were an anticipated need for enteral support for at least 6 months. Totally 243 children were included in the study, 83 with LAPG and 160 with OG. We found a significant difference in postoperative length of stay, 3 days in the LAPG group versus 4 days in the OG group but no difference in a sub-group analysis from 2010 to 2013 when both techniques were used. There was no difference in median operative time or complications rates. Granuloma was the dominating complication in both groups. These two feeding-access techniques are comparable regarding complications, operative times and postoperative length of stay. The choice of surgical method should be individualized based on the patient's characteristics and the experience of the surgeon. The favorable results with LAPG in adults are not necessarily transferable to children since there are physiological and anatomical differences.

  • 4.
    Angsten, Gertrud
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Finkel, Yigael
    Lucas, Steven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kassa, Ann-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Paulsson, Mattias
    Engstrand Lilja, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Improved outcome in neonatal short bowel syndrome using parenteral fish oil in combination With ω-6/9 Lipid Emulsions2012In: JPEN - Journal of Parenteral and Enteral Nutrition, ISSN 0148-6071, E-ISSN 1941-2444, Vol. 36, no 5, p. 587-595Article in journal (Refereed)
    Abstract [en]

    Background:

    Newborn infants with short bowel syndrome (SBS) represent a high risk group of developing intestinal failure-associated liver disease (IFALD) which may be fatal. However, infants have a great capacity for intestinal growth and adaptation if IFALD can be prevented or reversed. A major contributing factor to IFALD may be the soybean oil-based intravenous lipid emulsions used since the introduction of parenteral nutrition (PN) 40 years ago.

    Methods:

    This retrospective study compares the outcome in 20 neonates with SBS treated with parenteral fish oil (Omegaven) in combination with omega-6/9 lipid emulsions (ClinOleic) with the outcome in a historical cohort of 18 patients with SBS who received a soybean oil-based intravenous lipid emulsion (Intralipid).

    Results:

    Median gestational age was 26 weeks in the treatment group and 35.5 weeks in the historical group. All patients were started on PN containing Intralipid that was switched to ClinOleic/Omegaven in the treatment group at a median age of 39 gestational weeks. In the treatment group, direct bilirubin levels were reversed in all 14 survivors with cholestasis (direct bilirubin >50 umol/). Median time to reversal was 2.9 months. Only 2 patients died of liver failure (10%).  In the historical cohort, 6 patients (33%) died of liver failure and only 2 patients showed normalization of bilirubin levels.

    Conclusions:

    Parenteral fish oil in combination with omega-6/9 lipid emulsions was associated with improved outcome in premature neonates with SBS. When used instead of traditional soybean-based emulsions, this mixed lipid emulsion may facilitate intestinal adaptation by increasing the IFALD-free period.

  • 5.
    Arnell, Kai
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Wester, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Treatment of cerebrospinal fluid shunt infections in children using systemic and intraventricular antibiotic therapy in combination with externalization of the ventricular catheter: efficacy in 34 consecutively treated infections2007In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 107, no 3, p. 213-219Article in journal (Refereed)
    Abstract [en]

    OBJECT: There are no randomized studies comparing the efficacy of different antibiotic regimens for the treatment of cerebrospinal fluid (CSF) shunt infections, and in the studies that have been reported, efficacy data are limited. The aim of this study was therefore to report the authors' experience using a specific protocol for the management of shunt infections in children. Standard treatment included a two-stage procedure involving externalization of the ventricular catheter in combination with intraventricular and systemic administration of antibiotic medication followed by shunt replacement. Intraventricular treatment consisted of daily instillations of vancomycin or gentamicin with trough concentrations held at high levels of 7 to 17 mg/L for both antibiotic agents. METHODS: During a 13-year study period, the authors treated 34 consecutive intraventricular shunt infections in 30 children. Infections with coagulase-negative staphylococci predominated, and Gram-negative bacterial infection occurred in five children. Ten of the children were initially treated with intravenous antibiotic therapy for at least 3 days, but this treatment did not sterilize the CSF. After externalization of the ventricular catheter, high-dose intraventricular treatment was given for a median of 8 days (range 3-17 days) before shunt replacement. RESULTS: The CSF was found to be sterile (cultures were negative for bacteria) in one of three, seven of eight, 20 of 20, and six of six cases after 1, 2, 3, and more than 3 days' treatment, respectively. In no case was any subsequent culture positive after a negative result had been obtained. Clinical symptoms resolved in parallel with the sterilization of the CSF. There were no relapses or deaths during the 6-month follow-up period, and there have been none as of April 2007. CONCLUSIONS: Despite the ventricular catheter being left in place and the short duration of therapy, the treatment regimen described by the authors resulted in quick sterilization of the CSF, a low relapse rate, and survival of all patients in this series.

  • 6.
    Arnell, Kai
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Olsen, L.
    Wester, T.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Hydrocephalus2008In: Pediatric surgery: Diagnosis and management, Berlin: Springer Verlag , 2008, p. 418-426Chapter in book (Other (popular science, discussion, etc.))
  • 7.
    Asif, Sana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ekdahl, Kristina N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Fromell, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Gustafson, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Barbu, Andreea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Le Bland, Katarina
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Teramura, Yuji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Heparinization of cell surfaces with short pepetide-conjugated PEG-lipid regulates thromboinflammation in thransplantation of human MSCs and hepatocytes2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 35, p. 194-205Article in journal (Refereed)
    Abstract [en]

    Infusion of therapeutic cells into humans is associated with immune responses, including thromboinflammation, which result in a large loss of transplanted cells\ To address these problems, heparinization of the cell surfaces was achieved by a cell-surface modification technique using polyethylene glycol conjugated phospholipid (PEG-lipid) derivatives. A short heparin-binding peptide was conjugated to the PEG-lipid for immobilization of heparin conjugates on the surface of human mesenchymal stem cells (hMSCs) and human hepatocytes. Here three kinds of heparin-binding peptides were used for immobilizing heparin conjugates and examined for the antithrombogenic effects on the cell surface. The heparinized cells were incubated in human whole blood to evaluate their hemocompatibility by measuring blood parameters such as platelet count, coagulation markers, complement markers, and Factor Xa activity. We found that one of the heparin-binding peptides did not show cytotoxicity after the immobilization with heparin conjugates. The degree of binding of the heparin conjugates on the cell surface (analyzed by flow cytometer) depended on the ratio of the active peptide to control peptide. For both human MSCs and hepatocytes in whole-blood experiments, no platelet aggregation was seen in the heparin conjugate-immobilized cell group vs. the controls (non-coated cells or control peptide). Also, the levels of thrombin-antithrombin complex (TAT), C3a, and sC5b-9 were significantly lower than those of the controls, indicating a lower activation of coagulation and complement. Factor Xa analysis indicated that the heparin conjugate was still active on the cell surface at 24 h post-coating. It is possible to immobilize heparin conjugates onto hMSC and human hepatocyte surfaces and thereby protect the cell surfaces from damaging thromboinflammation. Statement of Signigficance We present a promising approach to enhance the biocompatibility of therapeutic cells. Here we used short peptide-conjugated PEG-lipid for cell surface modification and heparin conjugates for the coating of human hepatocytes and MSCs. We screened the short peptides to find higher affinity for heparinization of cell surface and performed hemocompatibility assay of heparinized human hepatocytes and human MSCs in human whole blood. Using heparin-binding peptide with higher affinity, not only coagulation activation but also complement activation was significantly suppressed. Thus, it was possible to protect human hepatocytes and human MSCs from the attack of thromboinflammatory activation, which can contribute to the improvement graft survival.

  • 8.
    Asif, Sana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Jonsson, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden..
    Teramura, Yuji
    Univ Tokyo, Dept Bioengn, Tokyo, Japan..
    Gustafson, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Ekdahl, Kristina N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden..
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Conjugation of human recombinant CD39 to primary human hepatocytes protects against thromboinflammation2015In: Xenotransplantation, ISSN 0908-665X, E-ISSN 1399-3089, Vol. 22, p. S87-S87Article in journal (Other academic)
  • 9.
    Asif, Sana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Jonsson, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden..
    Teramura, Yuji
    Univ Tokyo, Dept Bioengn, Tokyo, Japan..
    Gustafson, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Ekdahl, Kristina N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden..
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Conjugation Of Human Recombinant CD39 To Primary Human Hepatocytes Protects Against Thromboinflammation2015In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 99, no 11, p. S140-S140Article in journal (Other academic)
  • 10.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Olsen, Leif
    Akad Sjukhuset, Dept Pediat Surg, S-75185 Uppsala, Sweden..
    Wester, Tomas
    Karolinska Univ Hosp, Dept Pediat Surg, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Posterior sagittal anorectoplasty results in better bowel function and quality of life in adulthood than pull-through procedures2015In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 50, no 9, p. 1556-1559Article in journal (Refereed)
    Abstract [en]

    Background/purpose: The short-term outcome of posterior sagittal anorectoplasty (PSARP) procedure has been reported to be better than after abdominoperineal or abdominosacroperineal (AP) procedures. This study aimed to investigate the long-term functional outcome and quality of life after PSARP in adulthood and compare with the outcome after AP procedures. Methods: Twenty-four patients operated with PSARP at the Department of Pediatric Surgery, Uppsala, Sweden, from 1984 to 1993 were identified. They were compared with 20 patients that underwent AP pull-through procedures from 1974 to 1983. The patients were sent validated bowel function and quality of life (SF-36) questionnaires. Sixteen PSARP (median age 21, five females) patients and fourteen AP patients (seven abdominosacroperineal and seven abdominoperineal pull-throughs, median age 32, seven females) responded and were included in the study. Results: The median Miller incontinence score was 1 (range 0-13) in the PSARP group and 10 (range 3-16) in the pull-through group (P = 0.0042). The use of underwear protection and oral loperamide was significantly less frequent in the PSARP group (P = 0.0096 and 0.0021 respectively). The SF-36 scores of Vitality, Mental health and Mental Cluster Scale were higher in the PSARP group (P = 0.0291, 0.0500, 0.0421 respectively). Conclusions: PSARP results in superior bowel function and better quality of life in adulthood compared with AP procedures for the repair of anorectal malformations.

  • 11.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wester, Tomas
    Department of Pediatric Surgery, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Outcome in adults with anorectal malformations in relation to modern classification – Which patients do we need to follow beyond childhood?2017In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 52, no 3, p. 463-468Article in journal (Refereed)
    Abstract [en]

    Background/purpose

    Knowledge about the functional outcome in adults with anorectal malformations is essential to organize structured transition to adult care for this patient group. The aim of this study was to investigate the functional outcome and quality of life in adults with anorectal malformations characterized according to the Krickenbeck classification.

    Methods

    Of 256 patients diagnosed with anorectal malformations at our institution in 1961–1993, 203 patients could be traced and were invited to participate in the study. One hundred and thirty-six patients replied (67%) and were compared with one hundred and thirty-six population based sex and age-matched controls. Patients and controls were evaluated with both a validated questionnaire as well as a study-specific questionnaire to assess bowel function. SF-36 was used for quality of life. Outcome in nine incontinence-related parameters, 10 constipation-related, 6 urogenital function-related, and 13 quality of life parameters were assessed in the patients and compared to the outcome of controls as well as to the type of anorectal malformations according to the Krickenbeck classification.

    Results

    The ARM-patients had an inferior outcome (P < 0.05) for all incontinence parameters, 8 of 10 parameters for constipation, 2 of 6 for urogenital function and 7 of 13 quality of life parameters. Patients with rectobulbar and vestibular fistulas had the worst statistical outcome but patients with cloaca and rectoprostatic/bladder-neck fistula had worse outcome in absolute numbers. Forty-four patients (32%) reported incontinence of stool at least once a week and 16 (12%) had a permanent colostomy.

    Conclusions

    The functional outcome and quality of life in adults with anorectal malformations are closely related to the type of malformation. A large proportion of the patients have persistent fecal incontinence, constipation and sexual problems that have a negative influence on their quality of life. Structured multidisciplinary follow-up of adults with anorectal malformations by pediatric and colorectal surgeons, as well as urologists and gynecologists is therefore advocated.

  • 12.
    Danielson, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Sonesson, Ann-Cathrine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Wester, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Submucosal injection of stabilized nonanimal hyaluronic acid with dextranomer: a new treatment option for fecal incontinence2009In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 52, no 6, p. 1101-1106Article in journal (Refereed)
    Abstract [en]

    PURPOSE: NASHA Dx gel has been used extensively for treatments in the field of urology. This study was performed to evaluate NASHA Dx gel as an injectable anal canal implant for the treatment of fecal incontinence. METHODS: Thirty-four patients (5 males, 29 females; median age, 61 years; range, 34 to 80) were injected with 4 x 1 ml of NASHA Dx gel, just above the dentate line in the submucosal layer. The primary end point was change in the number of incontinence episodes and a treatment response was defined as a 50 percent reduction compared with pretreatment. All patients were followed up at 3, 6, and 12 months. RESULTS: The median number of incontinence episodes during four weeks was 22 (range, 2 to 77) before treatment, at 6 months it was 9 (range, 0 to 46), and at 12 months it was 10 (range, 0 to 70, P = 0.004). Fifteen patients (44 percent) were responders at 6 months, compared with 19 (56 percent) at 12 months. No long-term side effects or serious adverse events were reported. CONCLUSIONS: Submucosal injection of NASHA Dx gel is an effective treatment for fecal incontinence. The effect is sustained for at least 12 months. The treatment is associated with low morbidity.

  • 13.
    Danielson, Johan
    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 Surgical Sciences.
    Karlbom, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wester, T
    Department of Pediatric Surgery, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Efficacy and quality of life 2 years after treatment for faecal incontinence with injectable bulking agents2013In: Techniques in Coloproctology, ISSN 1123-6337, E-ISSN 1128-045X, Vol. 17, no 4, p. 389-395Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Stabilized non-animal hyaluronic acid/dextranomer (NASHA® Dx) gel as injectable bulking therapy has been shown to decrease symptoms of faecal incontinence, but the durability of treatment and effects and influence on quality of life (QoL) is not known. The aim of this study was to assess the effects on continence and QoL and to evaluate the relationship between QoL and efficacy up to 2 years after treatment.

    METHODS:

    Thirty-four patients (5 males, mean age 61, range 34-80) were injected with 4 × 1 ml NASHA Dx in the submucosal layer. The patients were followed for 2 years with registration of incontinence episodes, bowel function and QoL questionnaires.

    RESULTS:

    Twenty-six patients reported sustained improvement after 24 months. The median number of incontinence episodes before treatment was 22 and decreased to 10 at 12 months (P = 0.0004) and to 7 at 24 months (P = 0.0026). The corresponding Miller incontinence scores were 14, 11 (P = 0.0078) and 10.5 (P = 0.0003), respectively. There was a clear correlation between the decrease in the number of leak episodes and the increase in the SF-36 Physical Function score but only patients with more than 75 % improvement in the number of incontinence episodes had a significant improvement in QoL at 24 months.

    CONCLUSIONS:

    Anorectal injection of NASHA Dx gel induces improvement of incontinence symptoms for at least 2 years. The treatment has a potential to improve QoL. A 75 % decrease in incontinence episodes may be a more accurate threshold to indicate a successful incontinence treatment than the more commonly used 50 %.

  • 14.
    Dantonello, Tobias M
    et al.
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Lochbühler, Helmut
    Department of Pediatric Surgery, Olgahospital, Klinikum Stuttgart, Germany.
    Schuck, Andreas
    Department of Radiotherapy, University of Muenster, Münster, Germany.
    Kube, Stefanie
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Godzinski, Jan
    Department of Pediatric Surgery, University of Wroclaw, Poland.
    Sköldenberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Ljungman, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Kosztyla, Daniel
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Veit-Friedrich, Iris
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Hallmen, Erika
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Feuchtgruber, Simone
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Wessalowski, Ruediger
    Department of Pediatric Oncology, University of Duesseldorf, Germany.
    Franke, Markus
    Department of Pediatric Surgery, University of Freiburg, Germany.
    Bielack, Stefan S
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Klingebiel, Thomas
    Department of Pediatric Oncology, University of Frankfurt, Germany.
    Koscielniak, Ewa
    Pediatrics 5, Olgahospital, Klinikum Stuttgart, Germany.
    Challenges in the Local Treatment of Large Abdominal Embryonal Rhabdomyosarcoma2014In: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 21, no 11, p. 3579-3586Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Embryonal rhabdomyosarcoma is the most common pediatric soft tissue sarcoma. The best local treatment in large, nonmetastatic primary unresected nongenitourinary embryonal rhabdomyosarcoma of the abdomen (LARME) is however unclear.

    METHODS:

    We analyzed patients with LARME treated in four consecutive CWS trials. All diagnoses were confirmed by reference reviews. Treatment included multiagent chemotherapy and local treatment of the primary tumor with surgery and/or radiotherapy. The impact of primary debulking surgery (PDS) also was studied.

    RESULTS:

    One hundred patients <21 years with a median age of 4 years had LARME. Sixty-one of them had a tumor >10 cm in diameter at diagnosis. PDS was performed in 19 of 100 children. The outcomes of patients with PDS were similar to those of the other patients. In 36 children, the tumor was resected after induction chemotherapy; 60 RME were irradiated. The toxic effects of radiochemotherapy were not significantly increased compared with the nonirradiated patients. With a median follow-up of 10 years, the 5-year EFS and OS were 52 ± 10 and 65 ± 9 %, respectively. Significant risk factors in multivariate analysis were age >10 years; no achievement of complete remission; and inadequate secondary local treatment, defined as incomplete secondary resection or no radiation.

    CONCLUSIONS:

    Children with LARME have a fair prognosis, despite an often huge tumor size and unfavorable primary site, if the tumors can either be resected or irradiated following induction chemotherapy. PDS was only performed in a small subgroup. Radiation performed concomitantly with chemotherapy did not increase the acute toxicity significantly.

  • 15.
    Donoso, Felipe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Engstrand Lilja, Heléne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Risk Factors for Anastomotic Strictures after Esophageal Atresia Repair: Prophylactic Proton Pump Inhibitors Do Not Reduce the Incidence of Strictures2017In: European journal of pediatric surgery, ISSN 0939-7248, E-ISSN 1439-359X, Vol. 27, no 1, p. 50-55Article in journal (Refereed)
    Abstract [en]

    Background Since 2005, infants with esophageal atresia (EA) in our unit are given prophylactic proton pump inhibitors (PPI) after repair until 1 year of age. The aims of this study were to identify risk factors for anastomotic strictures (AS) and to assess the efficacy of postoperative PPI prophylaxis in reducing the incidence of AS compared with symptomatic PPI. Methods Patients who underwent EA repair from 1994 to 2013 in our unit were included in this retrospective observational study approved by the local ethics review board. They were divided into two subgroups; symptomatic PPI-group with EA repair from 1994 to 2004 and prophylactic PPI-group with EA repair from 2005 to 2013. Data were collected from the patient records. Potential risk factors for AS analyzed were gender, long gap EA, birth weight, premature birth (< 37 gestational weeks), anastomotic tension, and anastomotic leakage. Number of dilatations until the age of 1 and 5 years were recorded. To evaluate risk factors for AS and the effect of prophylactic PPI Logistic, Cox and Poisson regression models were used. For descriptive statistics Fisher exact test and Wilcoxon rank sum test were used. Results A total of 128 patients were included. Patient characteristics, surgical method, grading of anastomotic tension, complications, and survival rates did not differ significantly between the symptomatic PPI-group (n = 71) and the prophylactic PPI-group (n = 57). Comparing the symptomatic and prophylactic PPI-group, there was no significant difference in the median age at the first AS (9.3 vs 6 mo), the number of dilatations until 1 year (2 vs 2) and 5 years (5 vs 4), or the incidence of anastomotic stricture (56.5% vs 50.9%). Long gap EA, high birth weight, and anastomotic tension were found to be independent risk factors. Conclusion Surgeons should aim to perform anastomosis under less tension at EA repair. Prophylactic PPI-treatment does not appear to reduce the rate of AS. Randomized controlled trials with larger study populations are needed to further evaluate the efficacy of prophylactic PPI.

  • 16.
    Donoso, Felipe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Kassa, Ann-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Gustafson, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Meurling, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Engstrand Lilja, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Outcome and management in infants with esophageal atresia - a single centre observational study.2016In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 51, no 9, p. 1421-1425Article in journal (Refereed)
    Abstract [en]

    Background/Purpose: A successful outcome in the repair of esophageal atresia (EA) is associated with a high quality pediatric surgical centre, however there are several controversies regarding the optimal management. The aim of this study was to investigate the outcome and management EA in a single pediatric surgical centre.

    Methods: Medical records of infants with repaired EA from 1994 to 2013 were reviewed.

    Results: 129 infants were included. Median follow-up was 5.3 (range 0.1-21) years. Overall survival was 94.6%, incidences of anastomotic leakage 7.0%, recurrent fistula 4.6% and anastomotic stricture 53.5% (36.2% within first year). In long gap EA (n = 13), delayed primary anastomosis was performed in 9 (69.2%), gastric tube in 3 (23.1%) and gastric transposition in one (7.7%) infants. The incidences of anastomotic leakage and stricture in long gap EA were, 23.1% and 69.2%, respectively. Peroperative tracheobronchoscopy and postoperative esophagography were implemented as a routine during the study-period, but chest drains were routinely abandoned.

    Conclusion: The outcome in this study is fully comparable with recent international reports showing a low mortality but a significant morbidity, especially considering anastomotic strictures and LGEA. Multicenter EA registry with long-term follow up may help to establish best management of EA.

  • 17.
    Edler, Gertrud
    et al.
    Umea Univ, Dept Clin Sci, Paediat, Umea, Sweden..
    Axelsson, Inge
    Ostersund Hosp, Unit Res Educ & Dev, Ostersund, Sweden..
    Barker, Gillian M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Lie, Susanne
    Norwegian Board Hlth Supervis, Dept Special Hlth Serv, Oslo, Norway..
    Naumburg, Estelle
    Umea Univ, Dept Clin Sci, Paediat, Umea, Sweden.;Ostersund Hosp, Unit Res Educ & Dev, Ostersund, Sweden..
    Serious complications in male infant circumcisions in Scandinavia indicate that this always be performed as a hospital-based procedure2016In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 105, no 7, p. 842-850Article in journal (Refereed)
    Abstract [en]

    AimMore than 7000 male circumcisions are performed in Scandinavia every year. Circumcision is regulated in different ways in Sweden and Denmark and Norway. This study reviewed and described factors associated with complications of circumcision in infant boys in Scandinavia over the last two decades and discussed how these complications could be avoided. MethodsData on significant complications following circumcision on boys under the age of one in Scandinavia over the last 20 years were collected. Information was retrieved from testimonies of circumcisers, witnesses, medical records and verdicts. A systematic review was performed of fatal cases in the literature. ResultsWe found that 32 cases had been reported to the health authorities in the three countries, and we identified a total of 74 complications in these cases. These included four boys with severe bleeding and circulatory shock, which ended in the death of one boy. Other less serious complications may have occurred in other boys, but not been reported. ConclusionComplications following male circumcision in Scandinavia were relatively rare, but serious complications did occur. Based on the analyses of the severe cases, we argue that circumcision should only be performed at hospitals with 24-hour emergency departments.

  • 18.
    Ekdahl, Kristina N.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden..
    Teramura, Yuji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Univ Tokyo, Dept Bioengn, Tokyo, Japan..
    Hamad, Osama A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Asif, Sana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Duehrkop, Claudia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Fromell, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Gustafson, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Hong, Jaan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Kozarcanin, Huda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Magnusson, Peetra U.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Huber-Lang, Markus
    Univ Ulm, Dept Orthoped Trauma Hand Plast & Reconstruct Sur, Ulm, Germany..
    Garred, Peter
    Univ Copenhagen, Fac Hlth & Med Sci, Mol Med Lab, Rigshosp,Dept Clin Immunol,Sect 7631, Copenhagen, Denmark..
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Dangerous liaisons: complement, coagulation, and kallikrein/kinin cross-talk act as a linchpin in the events leading to thromboinflammation2016In: Immunological Reviews, ISSN 0105-2896, E-ISSN 1600-065X, Vol. 274, no 1, p. 245-269Article, review/survey (Refereed)
    Abstract [en]

    Innate immunity is fundamental to our defense against microorganisms. Physiologically, the intravascular innate immune system acts as a purging system that identifies and removes foreign substances leading to thromboinflammatory responses, tissue remodeling, and repair. It is also a key contributor to the adverse effects observed in many diseases and therapies involving biomaterials and therapeutic cells/organs. The intravascular innate immune system consists of the cascade systems of the blood (the complement, contact, coagulation, and fibrinolytic systems), the blood cells (polymorphonuclear cells, monocytes, platelets), and the endothelial cell lining of the vessels. Activation of the intravascular innate immune system in vivo leads to thromboinflammation that can be activated by several of the system's pathways and that initiates repair after tissue damage and leads to adverse reactions in several disorders and treatment modalities. In this review, we summarize the current knowledge in the field and discuss the obstacles that exist in order to study the cross-talk between the components of the intravascular innate immune system. These include the use of purified in vitro systems, animal models and various types of anticoagulants. In order to avoid some of these obstacles we have developed specialized human whole blood models that allow investigation of the cross-talk between the various cascade systems and the blood cells. We in particular stress that platelets are involved in these interactions and that the lectin pathway of the complement system is an emerging part of innate immunity that interacts with the contact/coagulation system. Understanding the resulting thromboinflammation will allow development of new therapeutic modalities.

  • 19.
    Engstrand Lilja, Helene
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Finkel, Yigael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Wester, Tomas
    Serial transverse enteroplasty (STEP) är en ny kirurgisk teknik för behandling av korta tarmens syndrom2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 24-25, p. 1849-1851Article in journal (Refereed)
  • 20.
    Engstrand Lilja, Helene
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Wester, Tomas
    Outcome in neonates with esophageal atresia treated over the last 20 years2008In: Pediatric surgery international (Print), ISSN 0179-0358, E-ISSN 1437-9813, Vol. 24, no 5, p. 531-536Article in journal (Refereed)
    Abstract [en]

    We evaluated the outcome in infants with esophageal atresia (EA) treated in our department over the last two decades. The medical records of 147 infants treated from 1986 to 2005 were reviewed. Patient characteristics, associated anomalies, surgery and complications were recorded. We divided the material into two time-periods: 1986-1995 and 1996-2005; 125 patients or parents were interviewed regarding gastrointestinal function, respiratory symptoms and education. The incidence of major cardiac defects increased from 23 to 29% and the overall survival increased from 87 to 94%. Using Spitz' classification survival increased from 93.5 to 100% in group I and from 68.4 to 77.8% in group II. In group III, during the second time period, survival was 100% in three patients. The incidence of anastomotic leakage and recurrent fistula did not change over time. The rate of anastomotic strictures increased from 53 to 59% between the two time-periods. A primary anastomosis could be done in 85% of the patients during the second period versus 78% of the patients during the first period. Anti-reflux surgery was done in only 11 and 9%, respectively, during the two time-periods. In patients who were 16-20 years old, 40-50% had gastrointestinal and respiratory symptoms. Ninety percent of the patients attended normal school. The major difference between the periods 1986-1995 and 1996-2005 was an increased survival despite an increased incidence of major cardiac defects. Gastrointestinal and respiratory symptoms were frequent. Long-term follow-up and treatment of complications of esophageal atresia is important for this patient group.

  • 21.
    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
  • 22.
    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.

  • 23.
    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)
  • 24.
    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).

  • 25.
    Georgantzi, Clary
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sköldenberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Jakobson, A.
    Christofferson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Chromogranin A In Neuroblastoma: Correlation To Stage And Prognostic Factors2013In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 60, no S3, p. 228-228Article in journal (Refereed)
  • 26.
    Georgantzi, Kleopatra
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Tsolakis, Apostolos V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Jakobson, Åke
    Department of Womeńs and Childreńs Health, Astrid Lindgren Childreńs Hospital, Karolinska Institute, Stockholm, Sweden.
    Christofferson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Janson, Eva Tiensuu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Differentiated expression of somatostatin receptor subtypes in experimental models and clinical neuroblastoma2011In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 56, no 4, p. 584-589Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Neuroblastoma (NB) is a solid tumor of childhood originating from the adrenal medulla or sympathetic nervous system. Somatostatin (SS) is an important regulator of neural and neuroendocrine function, its actions being mediated through five specific membrane receptors. The aim of this study was to investigate the expression of the different somatostatin receptors (SSTRs) in NB tumor cells that may form targets for future therapeutic development.

    PROCEDURE:

    Tumor specimens from 11 children with stage II-IV disease were collected before and/or after chemotherapy. Experimental tumors derived from five human NB cell lines were grown subcutaneously in nude mice. Expression of SSRTs, the neuroendocrine marker chromogranin A (CgA) and SS was detected by immunohistochemistry using specific antibodies.

    RESULTS:

    SSTR2 was detected in 90%, SSTR5 in 79%, SSTR1 in 74%, SSTR3 in 68% whereas SSTR4 was expressed in 21% of the clinical tumors. The experimental tumors expressed SSTRs in a high but variable frequency. All clinical tumors showed immunoreactivity for CgA but not for SS.

    CONCLUSION:

    The frequent expression of SSTRs indicates that treatment with unlabeled or radiolabeled SS analogs should be further explored in NB.

  • 27.
    Granstrom, Anna Lof
    et al.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Div Pediat Surg, SE-17176 Stockholm, Sweden..
    Danielson, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Husberg, Britt
    Karolinska Inst, Dept CLINTEC, Stockholm, Sweden..
    Nordenskjold, Agneta
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Div Pediat Surg, SE-17176 Stockholm, Sweden..
    Wester, Tomas
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Div Pediat Surg, SE-17176 Stockholm, Sweden..
    Adult outcomes after surgery for Hirschsprung's disease: Evaluation of bowel function and quality of life2015In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 50, no 11, p. 1865-1869Article in journal (Refereed)
    Abstract [en]

    Background and Aims: Hirschsprung's disease (HSCR) is treated surgically. There is a risk for faecal incontinence and constipation postoperatively. The long-term bowel functional outcome in adults and quality of life are sparsely studied. The aim of this study was to assess bowel function and quality of life in patients who had undergone surgery for HSCR during childhood. Methods: All patients treated between 1969 and 1994 at St. Goran's Children's Hospital in Stockholm were invited to participate in the study. After consent, the patients received questionnaires containing general questions, validated questions on bowel function, questions about urinary function, SF-36 health survey (SF-36) and the Gastrointestinal Quality of Life Index (GIQLI). Clinical data were extracted from the case records. Controls matched for sex and age were randomly selected from the National Swedish Population Register. Results: 48 of 60 (80%) invited patients responded to the questionnaires. Nine patients were excluded since the HSCR diagnosis could not be confirmed. The median age of the included patients was 28 (20-43) years. Most patients had undergone Soave's operation (73.4%) and two patients had a stoma at the time of follow-up. The bowel function was impaired in the HSCR group compared to controls, especially problems with flatulence, need to strain at defecation and several defecations for emptying. Patients in the HSCR group also had significantly more problems with faecal incontinence than controls. Quality of life according to SF-36 did not differ significantly between patients and controls, but the GIQLI score showed a significantly worse outcome in the HSCR group compared to the controls. Conclusion: General quality of life in adults treated for HSCR during childhood is comparable to controls. However, they have impaired bowel function and gastrointestinal quality of life.

  • 28.
    Gustafson, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Asif, Sana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Kozarcanin, Huda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Meurling, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ekdahl, Kristina Nilsson
    Linnaeus Univ, Linnaeus Ctr Biomat Chem, Kalmar, Sweden.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Control of IBMIR induced by fresh and cryopreserved hepatocytes by low molecular weight dextran sulfate2017In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 26, no 1, p. 71-81Article in journal (Refereed)
    Abstract [en]

    Rapid destruction of hepatocytes after hepatocyte transplantation has hampered the application of this procedure clinically. The instant blood-mediated inflammatory reaction (IBMIR) is a plausible underlying cause for this cell loss. The present study was designed to evaluate the capacity of low molecular weight dextran sulfate (LMW-DS) to control these initial reactions from the innate immune system. Fresh and cryopreserved hepatocytes were tested in an in vitro whole-blood model using ABO-compatible blood. The ability to elicit IBMIR and the capacity of LMW-DS (100 mu g/ml) to attenuate the degree of activation of the cascade systems were monitored. The effect was also compared to conventional anticoagulant therapy using unfractionated heparin (1 IU/ml). Both fresh and freeze thawed hepatocytes elicited IBMIR to the same extent. LMW-DS reduced the platelet loss and maintained the cell counts at the same degree as unfractionated heparin, but controlled the coagulation and complement systems significantly more efficiently than heparin. LMW-DS also attenuated the IBMIR elicited by freeze thawed cells. Therefore, LMW-DS inhibits the cascade systems and maintains the cell counts in blood triggered by both fresh and cryopreserved hepatocytes in direct contact with ABO-matched blood. LMW-DS at a previously used and clinically applicable concentration (100 mu g/ml) inhibits IBMIR in vitro and is therefore a potential IBMIR inhibitor in hepatocyte transplantation.

  • 29.
    Gustafson, Elisabet K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Elgue, Graciela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Hughes, Robin D.
    Mitry, Ragai R.
    Sanchez, Javier
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Haglund, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Meurling, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Dhawan, Anil
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    The Instant Blood-Mediated Inflammatory Reaction Characterized in Hepatocyte Transplantation2011In: Transplantation, ISSN 0041-1337, E-ISSN 1534-6080, Vol. 91, no 6, p. 632-638Article in journal (Refereed)
    Abstract [en]

    Background. Hepatocyte transplantation (HcTx) has proven to be a safe procedure, although the functional results have been unsatisfactory, probably due to insufficient engraftment or a loss of transplanted mass or function. In this study, we investigate whether hepatocytes in contact with blood induce an inflammatory reaction leading to, similar to what happens in clinical islet transplantation, an instant blood-mediated inflammatory reaction (IBMIR) resulting in an early loss of transplanted cells. Methods. By using an experimental model that mimics the portal vein blood flow, we could study different parameters reflecting the effects on the innate immunity elicited by hepatocytes in contact with ABO-matched human blood. Results. We report that all aspects of the IBMIR such as platelet and granulocyte consumption, coagulation, and complement activation were demonstrated. Addition of various specific inhibitors of coagulation allowed us to clearly delineate the various stages of the hepatocyte-triggered IBMIR and show that the reaction was triggered by tissue factor. Analysis of a case of clinical HcTx showed that hepatocyte-induced IBMIR also occurs in vivo. Both the inflammatory and the coagulation aspects were controlled by low-molecular-weight dextran sulfate. Conclusion. Isolated hepatocytes in contact with blood induce the IBMIR in vitro, and there are indications that these events are also relevant in vivo. According to these findings, HcTx would benefit from controlling a wider range of signals from the innate immune system.

  • 30.
    Hermansson, Olga
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    George, Mary
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wester, Tomas
    Christofferson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Local delivery of bupivacaine in the wound reduces opioid requirements after intraabdominal surgery in children2013In: Pediatric surgery international (Print), ISSN 0179-0358, E-ISSN 1437-9813, Vol. 29, no 5, p. 451-454Article in journal (Refereed)
    Abstract [en]

    Local anaesthetic infusions into the surgical wound have been shown to reduce postoperative pain and the need for opioids in adults. In children, it was found to be safe and efficacious following sternotomy and orthopaedic surgery. The aim of this study was to evaluate the need for opioids postoperatively in children receiving wound catheters delivering either bupivacaine or saline following one of three defined abdominal or bladder procedures. Prospective, randomized, double-blind, placebo controlled study. Thirty-three children, 6 months of age to 13 years of age, undergoing elective surgery for enterostomy closure, open gastrostomy or ureteral reimplantation were randomized to receive bupivacaine or saline wound infusions for 72 h postoperatively. All patients received acetaminophen orally or rectally for every 6 h. Breakthrough pain was treated with morphine bolus doses of 0.05 mg/kg or infusions if more than three morphine doses were required. Pain scores were assessed every 3 h. Outcome measures were morphine dosages, return to full oral intake and length of hospital stay. On the first postoperative day, patients with bupivacaine infusions had significantly less need for morphine (1.3 +/- A 1.3 SD doses) compared to those receiving saline infusions (3.1+/2.5 SD doses, p < 0.05). No difference was seen during postoperative day two or three. There was no significant difference between the groups regarding time to full oral intake and time to discharge. Continuous infusion of bupivacaine in the abdominal wound was effective in reducing postoperative pain in children. It significantly reduced the need for additional opioids and can be considered for postoperative pain management in children.

  • 31.
    Högberg, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Experimental and Clinical Necrotizing Enterocolitis2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Necrotizing enterocolitis (NEC), a severe inflammatory disorder of the gastrointestinal tract with high morbidity and mortality, affects primarily preterm infants. The diagnosis represents a challenging task, and no biomarker has been found to aid early diagnosis with high accuracy. Microdialysis has been widely used to detect metabolites of anaerobic metabolism, enabling a local and early detection of ischemia. This thesis aims to evaluate the possibility of detecting intestinal ischemic stress in experimental and clinical  NEC, by use of rectal intraluminal microdialysis.

    Intraluminal rectal microdialysis was performed on rats subjected to total intestinal ischemia. Metabolites of ischemia were detectable in both ileum and rectum, with raised glycerol concentrations and lactate/pyruvate ratios. Elevated concentrations of glycerol correlated to increasing intestinal histopathological injury.

    Experimental early NEC was induced in newborn rat pups, by hypoxia/re-oxygenation treatment. Development of NEC was confirmed by histopathology. Elevated glycerol concentrations were detected by rectal microdialysis.

    The genetic alterations following experimental NEC in rat pups were studied with microarray. Immunohistochemistry staining was performed for tight junction proteins claudin-1 and claudin-8. Several genes were altered in experimental NEC, mainly genes regulating tight junctions and cell adhesion. Immunohistochemistry revealed reduced expression of claudin-1.

    A prospective study was conducted on preterm infants with a gestational age of less than 28 weeks. The infants were admitted to a neonatal intensive care unit, and observed during a 4-week period. Rectal microdialysis was performed twice a week, and blood was drawn for analysis of I-FABP. A total of 15 infants were included in the study, whereof four infants developed NEC, and 11 served as controls. Rectal glycerol and I-FABP displayed high concentrations, which varied considerably during the observation periods, both in NEC and controls. No differences in either glycerol or I-FABP concentrations were seen in the NEC-group vs. the controls.

    In conclusion, rectal microdialysis can detect metabolites of intestinal ischemia, both in experimental and clinical NEC. Rectal microdialysis is safe and could provide a valuable non-invasive aid to detect hypoxia-induced intestinal damage or ischemic stress in extremely preterm infants. In this study however, it was not possible to predict the development of clinical NEC using microdialysis or I-FABP.

    List of papers
    1. Intestinal ischemia measured by intraluminal microdialysis
    Open this publication in new window or tab >>Intestinal ischemia measured by intraluminal microdialysis
    Show others...
    2012 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 1, p. 59-66Article in journal (Refereed) Published
    Abstract [en]

    Objective.

    To evaluate the possibility of detecting intestinal ischemia by intraluminal microdialysis and comparing the ileum and colon.

    Methods.

    The studies were performed on male Sprague-Dawley rats. In the fi rst part of the study, microdialysis catheters were placed in the sigmoid part of the colon and in the subcutaneous adipose tissue. In the second part of the study, microdialysis catheters were placed in the lumen of the ileum and the colon. The infrarenal aorta was clamped proximal to the cranial mesenteric artery. Microdialysate levels of glucose, lactate, pyruvate and glycerol were measured. Intestinal specimens were removed at the end of the ischemic period for microscopic evaluation.

    Results.

    Intraluminal microdialysis could detect early signs of ischemic injury in the ileum, as well as in the colon, with a marked increase of lactate, lactate/pyruvate ratio and glycerol. The increased levels of intraluminal glycerol showed a positive correlation to prolonged ischemia and to higher degrees of intestinal damage.

    Conclusion.

    Intraluminal measurement of glycerol is a good marker for intestinal ischemia. Intraluminal microdialysis in the colon is easily accessible through the rectum, and ay prove to be a valuable clinical tool for diagnosing intestinal ischemia.

    Keywords
    Intestinal, ischemia, microdialysis, intraluminal
    National Category
    Surgery
    Research subject
    Pediatric Surgery
    Identifiers
    urn:nbn:se:uu:diva-159807 (URN)10.3109/00365513.2011.629307 (DOI)000299283700009 ()22103734 (PubMedID)
    Available from: 2011-12-07 Created: 2011-10-10 Last updated: 2017-12-08Bibliographically approved
    2. Intraluminal intestinal microdialysis detects markers of hypoxia and cell damage in experimental necrotizing enterocolitis
    Open this publication in new window or tab >>Intraluminal intestinal microdialysis detects markers of hypoxia and cell damage in experimental necrotizing enterocolitis
    Show others...
    2012 (English)In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 47, no 9, p. 1646-1651Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND/PURPOSE:

    Necrotizing enterocolitis (NEC) represents one of the gravest complications in premature infants and carries significant morbidity and mortality. There is a great need for improved diagnostic methods to reduce the severity and incidence of NEC. The aim of the study was to investigate if intraluminal microdialysis can detect intestinal ischemia in newborn rats with induced experimental NEC.

    METHODS:

    The studies were performed on 1-day-old Sprague-Dawley rat pups. Experimental NEC was induced using hypoxia/reoxygenation treatment. Microdialysis catheters were rectally inserted and placed in the rectosigmoid part of the colon. Microdialysate levels of glucose, lactate, pyruvate, and glycerol were measured. Intestinal specimens were collected at the end of the experiments for microscopic evaluation.

    RESULTS:

    Intraluminal microdialysis revealed signs of intestinal hypoxia and cellular damage, with a marked increase of lactate and glycerol. Microscopic evaluation confirmed intestinal damage in the NEC group.

    CONCLUSION:

    Intraluminal microdialysis can detect intestinal hypoxic stress and mucosal cell membrane decay in a rat model of NEC. Intestinal intraluminal microdialysis is easily accessible through the rectum and may be a useful noninvasive complement to other methods in the assessment of NEC.

    National Category
    Surgery
    Research subject
    Pediatric Surgery
    Identifiers
    urn:nbn:se:uu:diva-183821 (URN)10.1016/j.jpedsurg.2012.03.086 (DOI)000308810400013 ()22974600 (PubMedID)
    Available from: 2012-11-01 Created: 2012-11-01 Last updated: 2017-12-07Bibliographically approved
    3. Genes regulating tight junctions and cell adhesion are altered in early experimental necrotizing enterocolitis
    Open this publication in new window or tab >>Genes regulating tight junctions and cell adhesion are altered in early experimental necrotizing enterocolitis
    Show others...
    2013 (English)In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 48, no 11, p. 2308-2312Article in journal (Refereed) Published
    Abstract [en]

    Background/purpose:

    Necrotizing enterocolitis (NEC) represents one of the gravest complications in preterm infants and carries significant morbidity and mortality. Increased intestinal permeability may play an important role in the pathogenesis of NEC. In this study we investigated the genes regulating structural proteins such as tight junctions (TJ) and cell adhesion in a neonatal rat model of early NEC, as well as the expression of TJ proteins by immunohistochemistry staining.

    Methods:

    The studies were performed on Sprague-Dawley rat pups. Experimental NEC was induced using hypoxia/reoxygenation treatment on day 1 after birth. Intestinal specimens from the ileum were obtained, mRNA was purified and the transcriptome was analyzed using microarray. Immunohistochemistry staining was performed for TJ proteins.

    Results:

    We found several TJ genes such as claudins 1, 8, 14, 15 and gap junction protein to be affected. Immunohistochemistry staining for TJ protein claudin-1 revealed decreased levels in experimental NEC compared to controls. Alterations in genes involved in the inflammatory response was confirmed, along with several genes regulating proteins used as biomarkers for NEC.

    Conclusion:

    This study indicates that tight junctions and cell adhesion may play a critical role in the pathogenesis of early experimental NEC. Better understanding of the pathogenesis of NEC may lead to novel strategies for the prevention and treatment of NEC.

    National Category
    Surgery Basic Medicine
    Research subject
    Pediatric Surgery; Pathology
    Identifiers
    urn:nbn:se:uu:diva-197750 (URN)10.1016/j.jpedsurg.2013.06.027 (DOI)000327140800022 ()
    Note

    De två sista författarna delar sistaförfattarskapet.

    Available from: 2013-04-03 Created: 2013-04-03 Last updated: 2018-01-11Bibliographically approved
    4. Intestinal intraluminal glycerol and plasma I-FABP levels in preterm infants with necrotizing enterocolitis
    Open this publication in new window or tab >>Intestinal intraluminal glycerol and plasma I-FABP levels in preterm infants with necrotizing enterocolitis
    Show others...
    2016 (English)In: Clinics in Surgery, Vol. 1, no 1085, p. 1-6Article in journal (Refereed) Published
    Abstract [en]

    Background/Purpose: Necrotizing enterocolitis (NEC) is highly associated with prematurity and is characterized by bowel necrosis and multi-organ failure. There is a strong need for improved diagnostic methods to reduce the significant morbidity and mortality associated with NEC. The aim of this single centre prospective study was to investigate the possibility to detect early signs of NEC, by using rectal intraluminal microdialysis and plasma intestinal fatty acid binding protein (I-FABP) in preterm infants admitted to a level III neonatal intensive care unit.

    Methods: The study was performed on extremely preterm infants with a gestational age of less than 28 weeks. During a 4-week period after birth, rectal intraluminal microdialysate levels of glucose, lactate, pyruvate and glycerol were measured, and plasma was collected for I-FABP analysis. Infants not developing NEC served as controls.

     Results: Microdialysis revealed signs of intestinal hypoxic or ischemic damage and cell membrane degradation, with a marked increase of both intraluminal glycerol and plasma I-FABP in infants developing NEC, as well as in infants suffering from other complications. The microdialysate levels of glucose, lactate and pyruvate were too low to be evaluated in this setting. All infants tolerated the microdialysis well without any complications.

    Conclusion: Elevated levels of intraluminal glycerol and plasma I-FABP suggests mucosal cell membrane degradation and hypoxic or ischemic damage in preterm infants developing NEC, as well as in preterm infants suffering from other complications such as volvulus, sepsis or respiratory distress. However, it was not possible to predict development of NEC before clinical diagnosis using these markers. 

    National Category
    Surgery
    Research subject
    Pediatric Surgery
    Identifiers
    urn:nbn:se:uu:diva-197752 (URN)
    Available from: 2013-04-03 Created: 2013-04-03 Last updated: 2017-01-04
  • 32.
    Högberg, Niclas
    et al.
    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.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Meurling, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Stenbäck, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Intestinal ischemia measured by intraluminal microdialysis2012In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 72, no 1, p. 59-66Article in journal (Refereed)
    Abstract [en]

    Objective.

    To evaluate the possibility of detecting intestinal ischemia by intraluminal microdialysis and comparing the ileum and colon.

    Methods.

    The studies were performed on male Sprague-Dawley rats. In the fi rst part of the study, microdialysis catheters were placed in the sigmoid part of the colon and in the subcutaneous adipose tissue. In the second part of the study, microdialysis catheters were placed in the lumen of the ileum and the colon. The infrarenal aorta was clamped proximal to the cranial mesenteric artery. Microdialysate levels of glucose, lactate, pyruvate and glycerol were measured. Intestinal specimens were removed at the end of the ischemic period for microscopic evaluation.

    Results.

    Intraluminal microdialysis could detect early signs of ischemic injury in the ileum, as well as in the colon, with a marked increase of lactate, lactate/pyruvate ratio and glycerol. The increased levels of intraluminal glycerol showed a positive correlation to prolonged ischemia and to higher degrees of intestinal damage.

    Conclusion.

    Intraluminal measurement of glycerol is a good marker for intestinal ischemia. Intraluminal microdialysis in the colon is easily accessible through the rectum, and ay prove to be a valuable clinical tool for diagnosing intestinal ischemia.

  • 33.
    Högberg, Niclas
    et al.
    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, Endocrinology, Diabetes and Metabolism.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Stenbäck, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Engstrand Lilja, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Intraluminal intestinal microdialysis detects markers of hypoxia and cell damage in experimental necrotizing enterocolitis2012In: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 47, no 9, p. 1646-1651Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/PURPOSE:

    Necrotizing enterocolitis (NEC) represents one of the gravest complications in premature infants and carries significant morbidity and mortality. There is a great need for improved diagnostic methods to reduce the severity and incidence of NEC. The aim of the study was to investigate if intraluminal microdialysis can detect intestinal ischemia in newborn rats with induced experimental NEC.

    METHODS:

    The studies were performed on 1-day-old Sprague-Dawley rat pups. Experimental NEC was induced using hypoxia/reoxygenation treatment. Microdialysis catheters were rectally inserted and placed in the rectosigmoid part of the colon. Microdialysate levels of glucose, lactate, pyruvate, and glycerol were measured. Intestinal specimens were collected at the end of the experiments for microscopic evaluation.

    RESULTS:

    Intraluminal microdialysis revealed signs of intestinal hypoxia and cellular damage, with a marked increase of lactate and glycerol. Microscopic evaluation confirmed intestinal damage in the NEC group.

    CONCLUSION:

    Intraluminal microdialysis can detect intestinal hypoxic stress and mucosal cell membrane decay in a rat model of NEC. Intestinal intraluminal microdialysis is easily accessible through the rectum and may be a useful noninvasive complement to other methods in the assessment of NEC.

  • 34.
    Högberg, Niclas
    et al.
    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.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Stenbäck, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Larsson, A