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  • 1.
    Forget, Patrice
    et al.
    Anesthesiology and Perioperative Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
    Aguirre, Jose A.
    Anesthesiology, Balgrist University Hospital Zurich, Zurich, Switzerland.
    Bencic, Ivanka
    University Hospital for Tumors, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia.
    Borgeat, Alain
    Anesthesiology, Balgrist University Hospital Zurich, Zurich, Switzerland.
    Cama, Allessandro
    Department of Pharmacy, Unit of General Pathology, Center on Aging Sciences and Translational Medicine (CeSI-MeT), “G. d’Annunzio” University of Chieti-Pescara, Chieti, Italy.
    Condron, Claire
    Department of Surgery, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.
    Eintrei, Christina
    Department of Anesthesiology and Intensive Care, University of Linköping, Linköping, Sweden.
    Eroles, Pilar
    INCLIVA Biomedical Research Institute, Valencia, Spain; Biomedical Research, Network in Breast Cancer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain.
    Gupta, Anil
    Physiology and Pharmacology, Karolinska Institutet, Perioperative Medicine and Intensive Care, Karolinska Hospital, Stockholm, Sweden.
    Hales, Tim G.
    Division of Systems Medicine, School of Medicine, University of Dundee, Dundee, UK.
    Ionescu, Daniela
    Head Department of Anesthesia and Intensive Care, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania, Outcome Research Consortium, Cleveland OH, USA.
    Johnson, Mark
    Department of Anesthesia, Fiona Stanley Hospital, Perth, Western Australia. University College Dublin School of Medicine and Medical Science, Dublin, Ireland.
    Kabata, Pawel
    Department of Surgical Oncology, Medical University of Gdansk, Gdansk, Poland.
    Kirac, Iva
    Surgical Oncology, University Hospital for Tumors, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia.
    Ma, Daqing
    Anesthetics, Pain Medicine & Intensive Care, Department of Surgery and Cancer, Imperial College London, Chelsea & Westminster Hospital, London, UK.
    Mokini, Zhirajr
    San Gerardo University Hospital, Monza, Italy. Clinique Saint Francois, Chateauroux, France.
    Guerrero Orriach, Jose Luis
    Institute of Biomedical Research in Malaga [IBIMA], Department of Cardio-Anaesthesiology, Virgen de la Victoria University Hospital, Malaga, Spain; Department of Pharmacology and Pediatrics, School of Medicine, University of Malaga, Malaga, Spain .
    Retsky, Michael
    Department of Environmental Health, Harvard TH Chan School of Public Health, Boston MA, USA.
    Sandrucci, Sergio
    Visceral Sarcoma Unit, CDSS—University of Turin, Turin, Italy.
    Siekmann, Wiebke
    Örebro University, School of Medical Sciences. Department of Anesthesiology and Intensive Care.
    Stefancic, Ljilja
    Intensive Care Unit, University Hospital for Tumors, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia.
    Votta-Vellis, Gina
    Departments of Anesthesiology and Surgery, College of Medicine, University of Illinois at Chicago, Chicago IL, USA.
    Connolly, Cara
    Mater Misericordiae University Hospital, Dublin, Ireland.
    Buggy, Donal
    Mater University Hospital, School of Medicine, University College Dublin, Dublin, Ireland; Anaesthesiology & Perioperative Medicine, Mater University Hospital, School of Medicine, University College Dublin, Ireland; Outcomes Research Consortium, Cleveland Clinic OH, USA.
    How Anesthetic, Analgesic and Other Non-Surgical Techniques During Cancer Surgery Might Affect Postoperative Oncologic Outcomes: A Summary of Current State of Evidence2019In: Cancers, ISSN 2072-6694, Vol. 11, no 5, article id 592Article, review/survey (Refereed)
    Abstract [en]

    The question of whether anesthetic, analgesic or other perioperative intervention during cancer resection surgery might influence long-term oncologic outcomes has generated much attention over the past 13 years. A wealth of experimental and observational clinical data have been published, but the results of prospective, randomized clinical trials are awaited. The European Union supports a pan-European network of researchers, clinicians and industry partners engaged in this question (COST Action 15204: Euro-Periscope). In this narrative review, members of the Euro-Periscope network briefly summarize the current state of evidence pertaining to the potential effects of the most commonly deployed anesthetic and analgesic techniques and other non-surgical interventions during cancer resection surgery on tumor recurrence or metastasis.

  • 2.
    Siekmann, Wiebke
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Anesthesiology and Intensive Care, Örebro University Hospital, Örebro, Sweden.
    Eintrei, Christina
    Department of Anesthesiology and Intensive care, County Council of Östergötland, Linköping, Sweden.
    Magnuson, Anders
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Sjölander, Anita
    Cell and Experimental Pathology, Department of Translational Medicine, Lund University, Malmö, Sweden.
    Matthiessen, Peter
    Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Myrelid, Pär
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Department of Surgery, County Council of Östergötland, Linköping, Sweden.
    Gupta, Anil
    Örebro University, School of Medical Sciences. Karolinska University Hospital, Stockholm, Sweden.
    Surgical and not analgesic technique affects postoperative inflammation following colorectal cancer surgery: a prospective, randomized study2017In: Colorectal Disease, ISSN 1462-8910, E-ISSN 1463-1318, Vol. 19, no 6, p. O186-O195Article in journal (Refereed)
    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.

  • 3.
    Siekmann, Wiebke
    et al.
    Örebro University, School of Medical Sciences. Anaesthesiology and Intensive Care, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Tina, Elisabet
    Örebro University, School of Medical Sciences. Örebro University Hospital. Clinical Research Laboratory, Örebro University Hospital, Örebro, Sweden.
    Gupta, Anil
    Clinical Research Laboratory, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Physiology and Pharma cology, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden.
    Concentration-dependent cell viability and proliferation in vitro of colon cancer cell lines SW480 and SW620 on exposure to lidocaine or ropivacaine2017In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 61, no 8, p. 1017-1018Article in journal (Other academic)
    Abstract [en]

    Background: Cancer cells change phenotypes and properties when evolving from primary tumor cells to metastatic cells. These changes might affect the response to local anesthetics (LA). The aim of this study was to investigate if lidocaine or ropivacaine have a dose- dependent effect on cell viability and proliferation of a primary and a secondary colon carcinoma cell line in vitro.

    Methods: The colon cancer cell lines SW 480, derived from primary tumor and SW620 from metastatic tumor in the same patient, were exposed to increasing log-concentrations of lidocaine and ropivacaine. Cell viability was measured using CellTiter Blue, and cell proliferation by PKH67, after exposure for up to 72 h.

    Results: Cell viability was not affected after 24 h of exposure. However, the metastatic cell line SW620 showed a significant increase in cell viability at low concentrati ons after 48 and 72 h. Exposure to the higher, but clinically relevant, concentrations of both LA resulted in decreased cell viability in both cell lines. These higher concentrations also showed an inhibitory effect on cell proliferation after 72 h, which was more pronounced for ropivacaine.

    Conclusions: Low concentrations of lidocaine and ropivacaine, as achieved in plasma by epidural infusion of LA, do not have direct antiproliferative effects on these colon cancer cell lines in vitro. Higher concentrations of LA, as during continuous local infiltration into tissues over 72 h, inhibit proliferation of both cancer cell lines. The increase in cell viability seen in SW620 should be investigated and underlying mechanisms further elucidated in future studies.

  • 4.
    Siekmann, Wiebke
    et al.
    Örebro University, School of Medical Sciences. Department of Anesthesiology and Intensive Care.
    Tina, Elisabet
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory,.
    Koskela von Sydow, Anita
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory.
    Gupta, Anil
    Department of Physiology and Pharmacology, Karolinska Institute and Karolinska University Hospital, Stockholm; School of Medical Sciences, Örebro University, Örebro, Sweden.
    Effect of lidocaine and ropivacaine on primary (SW480) and metastatic (SW620) colon cancer cell lines2019In: Oncology Letters, ISSN 1792-1074, E-ISSN 1792-1082, Vol. 18, no 1, p. 395-401Article in journal (Refereed)
    Abstract [en]

    Regional anesthesia may prolong survival following surgery for different types of cancers. The mechanisms behind this are unclear but direct effects on cancer cells by local anesthetics (LA) have been suggested. The aim of this study was to investigate if lidocaine or ropivacaine have a dose-dependent effect on the cell viability and proliferation of a primary and a secondary colon carcinoma cell line in vitro. The colon cancer cell lines SW480 derived from primary tumor and SW620 from a metastatic site in the same patient were exposed to increasing concentrations of lidocaine and ropivacaine (5-1,000 mu M). Cell viability was measured using CellTiter-Blue((R)) and cell proliferation by PKH67 after exposure for up to 72 h. Cell viability was significantly reduced by ropivacaine at the highest concentration (1,000 mu M) after 48 and 72 h in the cell line SW480 and at 72 h in SW620. Exposure to lidocaine did not show any significant reduction in cell viability. Notably, low concentrations of both lidocaine and ropivacaine significantly increased cell viability after 48 and 72 h in SW620. Cell proliferation was significantly reduced by 1,000 mu M lidocaine in SW480 and by 1,000 mu M ropivacaine in SW620. In summary, both lidocaine and ropivacaine showed an anti-proliferative effect in the colon cancer cell lines at high concentrations and after prolonged exposure to LA in vitro. Our findings also indicate that lower concentrations promote cell viability in the metastatic cell line.

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