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      Effects of propofol-based total intravenous anesthesia on recurrence and overall survival in patients after modified radical mastectomy: a retrospective study

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          Abstract

          Background

          The optimal combination of anesthetic agent and technique may have an influence on long-term outcomes in cancer surgery. In vitro and in vivo studies suggest that propofol independently reduces migration of cancer cells and metastasis. Thus, the authors retrospectively examined the link between propofol-based total intravenous anesthesia (TIVA) and recurrence or overall survival in patients undergoing modified radical mastectomy (MRM).

          Methods

          A retrospective analysis of the electronic database of all patients undergoing MRM for breast cancer between January 2007 and December 2008 was undertaken. Patients received either propofol-based TIVA (propofol group) or sevoflurane-based anesthesia (sevoflurane group). We analyzed prognostic factors of breast cancer and perioperative factors and compared recurrence-free survival and overall survival between propofol and sevoflurane groups.

          Results

          A total of 363 MRMs were carried out during the period of the trial; 325 cases were suitable for analysis (173 cases of propofol group, and 152 cases of sevoflurane group). There were insignificant differences between the groups in age, weight, height, histopathologic results, surgical time, or postoperative treatment (chemotherapy, hormonal therapy, and radiotherapy). The use of opioids during the perioperative period was greater in propofol group than in sevoflurane group. Overall survival was no difference between the two groups. Propofol group showed a lower rate of cancer recurrence (P = 0.037), with an estimated hazard ratio of 0.550 (95% CI 0.311–0.973).

          Conclusions

          This retrospective study provides the possibility that propofol-based TIVA for breast cancer surgery can reduce the risk of recurrence during the initial 5 years after MRM.

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          Most cited references29

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          Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis?

          Regional anesthesia is known to prevent or attenuate the surgical stress response; therefore, inhibiting surgical stress by paravertebral anesthesia might attenuate perioperative factors that enhance tumor growth and spread. The authors hypothesized that breast cancer patients undergoing surgery with paravertebral anesthesia and analgesia combined with general anesthesia have a lower incidence of cancer recurrence or metastases than patients undergoing surgery with general anesthesia and patient-controlled morphine analgesia. In this retrospective study, the authors examined the medical records of 129 consecutive patients undergoing mastectomy and axillary clearance for breast cancer between September 2001 and December 2002. Fifty patients had surgery with paravertebral anesthesia and analgesia combined with general anesthesia, and 79 patients had general anesthesia combined with postoperative morphine analgesia. The follow-up time was 32 +/- 5 months (mean +/- SD). There were no significant differences in patients or surgical details, tumor presentation, or prognostic factors. Recurrence- and metastasis-free survival was 94% (95% confidence interval, 87-100%) and 82% (74-91%) at 24 months and 94% (87-100%) and 77% (68-87%) at 36 months in the paravertebral and general anesthesia patients, respectively (P = 0.012). This retrospective analysis suggests that paravertebral anesthesia and analgesia for breast cancer surgery reduces the risk of recurrence or metastasis during the initial years of follow-up. Prospective trials evaluating the effects of regional analgesia and morphine sparing on cancer recurrence seem warranted.
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            The effects of surgery on tumor growth: a century of investigations.

            A few clinical investigations suggest that while primary breast cancer surgical removal favorably modifies the natural history for some patients, it may also hasten the metastatic development for others. The concepts underlying this disease paradigm, i.e. tumor homeostasis, tumor dormancy and surgery-driven enhancement of metastasis development, have a long history that is reviewed. The review reveals the context in which these concepts were conceived and structured to explain experimental data and shows that they are not so new and far fetched. The idea that surgical cancer resection has both beneficial and adverse effects upon cancer spread and growth that result from the modulation of tumor dormancy by the resection should be considered a potentially fruitful working hypothesis.
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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.

              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
                Korean J Anesthesiol
                Korean J Anesthesiol
                KJAE
                Korean Journal of Anesthesiology
                The Korean Society of Anesthesiologists
                2005-6419
                2005-7563
                April 2016
                30 March 2016
                : 69
                : 2
                : 126-132
                Affiliations
                [1 ]Department of Anesthesiology and Pain Medicine, Center for Breast Cancer, Korea Cancer Center Hospital, Seoul, Korea.
                [2 ]Department of General Surgery, Center for Breast Cancer, Korea Cancer Center Hospital, Seoul, Korea.
                [3 ]Department of Hemato-oncology, Veterans Health Service Medical Center, Seoul, Korea.
                Author notes
                Corresponding author: Ji Heui Lee, M.D., Ph.D. Departments of Anesthesiology and Pain Medicine, Center for Breast Cancer, Korea Cancer Center Hospital, 75, Nowon-ro, Nowon-gu, Seoul 01812, Korea. Tel: 82-2-970-2820, Fax: 82-2-970-2413, jiheui0255@ 123456naver.com
                Author information
                http://orcid.org/0000-0003-3378-588X
                Article
                10.4097/kjae.2016.69.2.126
                4823406
                27066202
                1b98e86e-a6fd-4c57-9717-02e4fea6cf8b
                Copyright © the Korean Society of Anesthesiologists, 2016

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 September 2015
                : 10 December 2015
                : 11 December 2015
                Categories
                Clinical Research Article

                Anesthesiology & Pain management
                breast neoplasms,propofol,recurrence,sevoflurane
                Anesthesiology & Pain management
                breast neoplasms, propofol, recurrence, sevoflurane

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