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Outcome and prevention strategies in peritoneal adhesion formation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
2016 (English)Doctoral 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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. , 65 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1217
Keyword [en]
peritoneal adhesion prevention, inflammatory cytokines, experimental adhesion model, adhesive small bowel obstruction, adhesion-related morbidity
National Category
Surgery
Research subject
Pediatric Surgery
Identifiers
URN: urn:nbn:se:uu:diva-282119ISBN: 978-91-554-9557-2 (print)OAI: oai:DiVA.org:uu-282119DiVA: diva2:918690
Public defence
2016-06-03, Rosensalen, Ing 95/96 NBV, Akademiska Barnsjukhuset, Uppsala, 08:15 (Swedish)
Opponent
Supervisors
Available from: 2016-05-12 Created: 2016-04-02 Last updated: 2016-06-01
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, 1480-1484 p.Article 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.

Keyword
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, 284-289 p.Article 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

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