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      Effects of Anesthesia on Postoperative Recurrence and Metastasis of Malignant Tumors

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          Abstract

          It is difficult to control the recurrence and metastasis of malignant tumors; furthermore, anesthesia is considered one of the main influencing factors. There has been increasing clinical attention on the effects of anesthetic drugs and methods on postoperative tumor growth and metastasis. We reviewed the effects of anesthesia on tumor recurrence and metastasis; specifically, the effects of anesthetic agents, anesthesia methods, and related factors during the perioperative period on the tumor growth and metastasis were analyzed. This study can provide reference standards for rational anesthesia formulations and cancer-related pain analgesia protocols for surgical procedures in patients with malignant tumors. Moreover, it contributes toward an experimental basis for the improvement and development of novel anesthetic agents and methods.

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          Clinical Pharmacokinetics and Pharmacodynamics of Propofol

          Marko Sahinovic, Michel M. R. F. Struys, Anthony Absalom (2018)
          Propofol is an intravenous hypnotic drug that is used for induction and maintenance of sedation and general anaesthesia. It exerts its effects through potentiation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) at the GABAA receptor, and has gained widespread use due to its favourable drug effect profile. The main adverse effects are disturbances in cardiopulmonary physiology. Due to its narrow therapeutic margin, propofol should only be administered by practitioners trained and experienced in providing general anaesthesia. Many pharmacokinetic (PK) and pharmacodynamic (PD) models for propofol exist. Some are used to inform drug dosing guidelines, and some are also implemented in so-called target-controlled infusion devices, to calculate the infusion rates required for user-defined target plasma or effect-site concentrations. Most of the models were designed for use in a specific and well-defined patient category. However, models applicable in a more general population have recently been developed and published. The most recent example is the general purpose propofol model developed by Eleveld and colleagues. Retrospective predictive performance evaluations show that this model performs as well as, or even better than, PK models developed for specific populations, such as adults, children or the obese; however, prospective evaluation of the model is still required. Propofol undergoes extensive PK and PD interactions with both other hypnotic drugs and opioids. PD interactions are the most clinically significant, and, with other hypnotics, tend to be additive, whereas interactions with opioids tend to be highly synergistic. Response surface modelling provides a tool to gain understanding and explore these complex interactions. Visual displays illustrating the effect of these interactions in real time can aid clinicians in optimal drug dosing while minimizing adverse effects. In this review, we provide an overview of the PK and PD of propofol in order to refresh readers’ knowledge of its clinical applications, while discussing the main avenues of research where significant recent advances have been made.
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            Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial

            Daniel Sessler, Lijian Pei, Yuguang Huang … (2019)
            Three perioperative factors impair host defence against recurrence during cancer surgery: the surgical stress response, use of volatile anaesthetic, and opioids for analgesia. All factors are ameliorated by regional anaesthesia-analgesia. We tested the primary hypothesis that breast cancer recurrence after potentially curative surgery is lower with regional anaesthesia-analgesia using paravertebral blocks and the anaesthetic propofol than with general anaesthesia with the volatile anaesthetic sevoflurane and opioid analgesia. A second hypothesis was that regional anaesthesia-analgesia reduces persistent incisional pain.
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              Suppression of natural killer cell activity and promotion of tumor metastasis by ketamine, thiopental, and halothane, but not by propofol: mediating mechanisms and prophylactic measures.

              Nadav Bar, Keren Shakhar, R. Melamed … (2003)
              Postoperative immunosuppression is partly ascribed to anesthesia and has been suggested to compromise patients' resistance to infection and tumor metastasis. We compared the effects of various anesthetics on natural killer (NK) cell activity and on resistance to experimental metastasis, and studied mediating mechanisms and prophylactic measures. Fischer 344 rats served as controls or were anesthetized for 1 h with ketamine, thiopental, halothane, or propofol. Anesthetized rats were either maintained in normothermia or left to spontaneously reach 33 degrees C-35 degrees C. Rats were then injected IV with MADB106 tumor cells, and 24 h later lung tumor retention was assessed, or 3 wk later, lung metastases were counted. Additionally, the number and activity of circulating NK cells were assessed after anesthesia. All anesthetics, except propofol, significantly reduced NK activity and increased MADB106 lung tumor retention or lung metastases. Hypothermia had no significant effects. Ketamine increased metastasis most potently, and this effect was markedly reduced in rats pretreated with a beta-adrenergic antagonist (nadolol) or with chronic small doses of an immunostimulator (polyriboinosinic:polyribocytidylic acid). Overall, the marked variation in the NK-suppressive effects of anesthetics seems to underlie their differential promotion of MADB106 metastasis. Prophylactic measures may include perioperative immunostimulation and the use of beta-blockers. This study in a rat model of pulmonary metastasis demonstrates that some anesthetics, but not others, increase susceptibility to tumor metastasis, apparently by suppressing natural killer cell activity. Ketamine was most deleterious, and its effects were prevented by peripheral blockade of beta-adrenoceptors combined with low levels of immunostimulation.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancer Manag Res
                Journal ID (iso-abbrev): Cancer Manag Res
                Journal ID (publisher-id): cmar
                Journal ID (pmc): cancmanres
                Title: Cancer Management and Research
                Publisher: Dove
                ISSN (Electronic): 1179-1322
                Publication date (Electronic): 24 August 2020
                Publication date Collection: 2020
                Volume: 12
                Pages: 7619-7633
                Affiliations
                [1 ]Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC) , Hefei, Anhui 230001, People’s Republic of China
                [2 ]Department of Anesthesiology, Anhui Provincial Hospital , Hefei 230001, Anhui, People’s Republic of China
                [3 ]Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences , Hefei, Anhui 230031, People’s Republic of China
                [4 ]Department of Molecular Pathology, Hefei Cancer Hospital, Chinese Academy of Sciences , Hefei, Anhui 230031, People’s Republic of China
                Author notes
                Correspondence: Xueran Chen; Ruiting Wang Email xueranchen@cmpt.ac.cn; 13003069919@163.com
                Author information
                http://orcid.org/0000-0002-7690-4749
                Article
                Publisher ID: 265529
                DOI: 10.2147/CMAR.S265529
                PMC ID: 7457832
                PubMed ID: 32922072
                SO-VID: 1af9b84c-70c6-4f62-ac41-55869ad393ee
                Copyright © © 2020 Fan et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 01 June 2020
                Date accepted : 04 August 2020
                Page count
                Figures: 0, Tables: 6, References: 165, Pages: 15
                Categories
                Subject: Review

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: anesthesia,cancer,recurrence,metastasis,prognosis,immunosuppression
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: anesthesia, cancer, recurrence, metastasis, prognosis, immunosuppression

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