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Surgical and not analgesic technique affects postoperative inflammation following colorectal cancer surgery: a prospective, randomized study
Örebro University, School of Medical Sciences. Department of Anesthesiology and Intensive Care, Örebro University Hospital, Örebro, Sweden.
Department of Anesthesiology and Intensive care, County Council of Östergötland, Linköping, Sweden.
School of Medical Sciences, Örebro University, Örebro, Sweden. (Clinical Epidemiology and Biostatistics)
Cell and Experimental Pathology, Department of Translational Medicine, Lund University, Malmö, Sweden.
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2017 (English)In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 19, no 6, p. O186-O195Article in journal (Refereed) Published
Abstract [en]

AIM: Epidural analgesia reduces the surgical stress response. However, its effect on pro- and anti-inflammatory cytokines in the genesis of inflammation following major abdominal surgery remains unclear. Our main objective was to elucidate whether perioperative epidural analgesia prevents the inflammatory response following colorectal cancer surgery.

METHODS: 96 patients scheduled for open or laparoscopic surgery were randomized to epidural analgesia (group E) or patient controlled intravenous analgesia (group P). Surgery and anaesthesia were standardized in both groups. Plasma cortisol, insulin and serum cytokines (IL-1β,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12p70,IL-13,TNFα,IFNγ,GM-CSF,PGE2 and VEGF) were measured preoperatively (T0), 1-6 hours postoperatively (T1) and 3-5 days postoperatively (T2). Mixed model analysis was used, after logarithmic transformation when appropriate, for analyses of cytokines and stress markers.

RESULTS: There were no significant differences in any serum cytokine concentration between groups P and E at any time point except in IL-10 which was 87% higher in group P (median and range 4.1 (2.3-9.2) pg/ml,) compared to group E (2.6 (1.3-4.7) pg/ml) (p=0.002) at T1. There was no difference in plasma cortisol and insulin between the groups at any time point after surgery. Significant difference in median serum cytokine concentration was found between open and laparoscopic surgery with higher levels of IL-6,IL-8 and IL-10 at T1 in patients undergoing open surgery compared to laparoscopic surgery. No difference in serum cytokine concentration was detected between the groups or between the surgical technique at T2.

CONCLUSIONS: Open surgery, compared to laparoscopic surgery, has greater impact on these inflammatory mediators than epidural analgesia vs. intravenous analgesia. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017. Vol. 19, no 6, p. O186-O195
Keywords [en]
Anaesthesia, epidural, surgery, colorectal cancer, inflammation, cytokines
National Category
Anesthesiology and Intensive Care Surgery
Research subject
Oncology; Surgery; Anaesthesiology
Identifiers
URN: urn:nbn:se:oru:diva-57387DOI: 10.1111/codi.13643ISI: 000402674400003PubMedID: 28258664Scopus ID: 2-s2.0-85018758511OAI: oai:DiVA.org:oru-57387DiVA, id: diva2:1092732
Note

Funding Agency:

Regional Research Committee, Örebro-Uppsala Region, Sweden

Available from: 2017-05-03 Created: 2017-05-03 Last updated: 2022-02-11Bibliographically approved
In thesis
1. Epidural Analgesia for Colorectal Cancer Surgery: Experimental and Clinical studies
Open this publication in new window or tab >>Epidural Analgesia for Colorectal Cancer Surgery: Experimental and Clinical studies
2021 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Epidural analgesia (EA) with local anaesthetics and opioids is used for pain management after colorectal cancer (CRC) surgery. In recent years, a possible beneficial effect of EA on cancer recurrence and survival after surgery has been proposed. The aim of this thesis was to study the effects of EA on short- and long-term postoperative outcomes after CRC surgery with curative intent.

Study I, an in vitro study, investigated the effects of two different local anaesthetics, lidocaine and ropivacaine, on cell viability and cell proliferation in colon cancer cell lines SW480 and SW620. Neither lidocaine nor ropivacaine reduced cell viability or proliferation at systemically, by epidural administration achievable concentrations.

In study II, the effect of EA on the systemic level of different cytokines as a marker of inflammation was studied. Except for a reduced level of the anti-inflammatory cytokine IL-10, no other significant effects of EA on the systemic cytokine levels at two time points postoperatively could be shown, when compared to patients receiving intravenous morphine.

Study III was an epidemiological study, examining the question if EA affects postoperative complications and mortality after surgery using data from the Swedish Colorectal Cancer Registry and the Swedish Perioperative Registry. No association between EA and a reduction in postoperative complications or mortality could be established.

Study IV, a randomised, controlled trial, the effects of EA on diseasefree survival (DFS), postoperative complications and pain after surgery were compared to patient-controlled intravenous analgesia with morphine. Apart from superior pain relief during the first postoperative day, no significant effects of EA on the occurrence of postoperative complications, length of hospital stay or DFS were found.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2021. p. 67
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 237
Keywords
colorectal cancer, epidural analgesia, local anaesthetics, colon cancer cells, inflammation, postoperative complications, pain, recurrence, disease-free survival, mortality
National Category
Surgery
Identifiers
urn:nbn:se:oru:diva-90317 (URN)978-91-7529-384-4 (ISBN)
Public defence
2021-06-03, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (Swedish)
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Supervisors
Available from: 2021-03-09 Created: 2021-03-09 Last updated: 2022-02-11Bibliographically approved

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Siekmann, WiebkeMatthiessen, PeterGupta, Anil

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