Skip to main content
Top
Published in: BMC Anesthesiology 1/2018

Open Access 01-12-2018 | Research article

Effects of propofol/remifentanil-based total intravenous anesthesia versus sevoflurane-based inhalational anesthesia on the release of VEGF-C and TGF-β and prognosis after breast cancer surgery: a prospective, randomized and controlled study

Authors: Tao Yan, Guo-Hua Zhang, Bao-Na Wang, Li Sun, Hui Zheng

Published in: BMC Anesthesiology | Issue 1/2018

Login to get access

Abstract

Background

Vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) have been involved in tumor growth and metastasis. Sevoflurane may promote angiogenesis, whereas propofol can present an anti-angiogenic effect. In this study, we compared the effects of propofol/remifentanil-based total intravenous anesthesia (TIVA) and sevoflurane-based inhalational anesthesia on the release of VEGF-C and TGF-β, as well as recurrence- free survival (RFS) rates in the patients undergoing breast cancer surgery.

Methods

Eighty female patients undergoing breast cancer resection were enrolled and randomized to receive either sevoflurane-based inhalational anesthesia (SEV group) or propofol/remifentanil-based TIVA (TIVA group). The serum concentrations of VEGF-C and TGF-β before and 24 h after surgery were measured and RFS rates over a two-year follow-up were analyzed in both groups. The postoperative pain scores assessed using a visual analogue scale (VAS) and the use of perioperative opioids were also evaluated.

Results

Although VAS scores at 2 h and 24 h after surgery were comparable between the two groups, there were more patients receiving postoperative fentanyl in the TIVA group (16[40%]) compared with the SEV group (6[15%], p = 0.023). VEGF-C serum concentrations increased after surgery from 105 (87–193) pg/ml to174 (111–281) pg/ml in the SEV group (P = 0.009), but remained almost unchanged in the TIVA group with 134 (80–205) pg/ml vs.140(92–250) pg/ml(P = 0.402). The preoperative to postoperative change for VEGF-C of the SEV group (50 pg/ml) was significantly higher than that of the TIVA group (12 pg/ml) with a difference of 46 (− 11–113) pg/ml (P = 0.008). There were also no significant differences in the preoperative and postoperative TGF-β concentrations between the two groups. The two-year RFS rates were 78% and 95% in the SEV and TIVA groups (P = 0.221), respectively.

Conclusion

In comparison with sevoflurane-based inhalational anesthesia, propofol/remifentanil -based total intravenous anesthesia can effectively inhibit the release of VEGF-C induced by breast surgery, but didn’t seem to be beneficial in the short-term recurrence rate of breast cancer.

Trial registration

Chictr.org.cn ChiCTR1800017910​. Retrospectively Registered (Date of registration: August 20, 2018).
Literature
1.
go back to reference Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;6:7–30.CrossRef Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;6:7–30.CrossRef
2.
go back to reference Looney M, Doran P, Buggy DJ. Effect of anesthetic technique on serum vascular endothelial growth factor C and transforming growth factor β in women undergoing anesthesia and surgery for breast cancer. Anesthesiology. 2010;113:1118–25.CrossRef Looney M, Doran P, Buggy DJ. Effect of anesthetic technique on serum vascular endothelial growth factor C and transforming growth factor β in women undergoing anesthesia and surgery for breast cancer. Anesthesiology. 2010;113:1118–25.CrossRef
3.
go back to reference Lee JH, Kang SH, Kim Y, Kim HA, Kim BS. Effects of propofol-based total intravenous anesthesia on recurrence and overall survival in patients after modified radical mastectomy: a retrospective study. Korean J Anesthesiol. 2016;69:126–32.CrossRef Lee JH, Kang SH, Kim Y, Kim HA, Kim BS. Effects of propofol-based total intravenous anesthesia on recurrence and overall survival in patients after modified radical mastectomy: a retrospective study. Korean J Anesthesiol. 2016;69:126–32.CrossRef
4.
go back to reference Zhang T, Fan Y, Liu K, Wang Y. Effects of different general anesthetic techniques on immune responses in patients undergoing surgery for tongue cancer. Anaesth Intensive Care. 2014;42:220–7.PubMed Zhang T, Fan Y, Liu K, Wang Y. Effects of different general anesthetic techniques on immune responses in patients undergoing surgery for tongue cancer. Anaesth Intensive Care. 2014;42:220–7.PubMed
5.
go back to reference Tavare AN, Perry NJ, Benzonana LL, Takata M, Ma D. Cancer recurrence after surgery: direct and indirect effects of anesthetic agents. Int J Cancer. 2012;130:1237–50.CrossRef Tavare AN, Perry NJ, Benzonana LL, Takata M, Ma D. Cancer recurrence after surgery: direct and indirect effects of anesthetic agents. Int J Cancer. 2012;130:1237–50.CrossRef
6.
go back to reference Ecimovic P, McHugh B, Murray D, Doran P, Buggy DJ. Effects of sevoflurane on breast cancer cell function in vitro. Anticancer Res. 2013;33:4255–60.PubMed Ecimovic P, McHugh B, Murray D, Doran P, Buggy DJ. Effects of sevoflurane on breast cancer cell function in vitro. Anticancer Res. 2013;33:4255–60.PubMed
7.
go back to reference Ecimovic P, Murray D, Doran P, Buggy DJ. Propofol and bupivacaine in breast cancer cell function in vitro-role of the NET1 gene. Anticancer Res. 2014;34:1321–31.PubMed Ecimovic P, Murray D, Doran P, Buggy DJ. Propofol and bupivacaine in breast cancer cell function in vitro-role of the NET1 gene. Anticancer Res. 2014;34:1321–31.PubMed
8.
go back to reference Kushida A, Inada T, Shingu K. Enhancement of antitumor immunity after propofol treatment in mice. Immunopharmacol Immunotoxicol. 2007;29:477–86.CrossRef Kushida A, Inada T, Shingu K. Enhancement of antitumor immunity after propofol treatment in mice. Immunopharmacol Immunotoxicol. 2007;29:477–86.CrossRef
9.
go back to reference Ren XF, Li WZ, Meng FY, Lin CF. Differential effects of propofol and isoflurane on the activation of T-helper cells in lung cancer patients. Anaestheisa. 2010;65:478–82.CrossRef Ren XF, Li WZ, Meng FY, Lin CF. Differential effects of propofol and isoflurane on the activation of T-helper cells in lung cancer patients. Anaestheisa. 2010;65:478–82.CrossRef
10.
go back to reference Yardeni IZ, Beilin B, Mayburd E, Alcalay Y, Bessler H. Relationship between fentanyl dosage and immune function in the postoperative period. J Opioid Manag. 2008;4:27–33.CrossRef Yardeni IZ, Beilin B, Mayburd E, Alcalay Y, Bessler H. Relationship between fentanyl dosage and immune function in the postoperative period. J Opioid Manag. 2008;4:27–33.CrossRef
11.
go back to reference Lin X, Wang YJ, Li Q, Hou YY, Hong MH, Cao YL, et al. Chronic high dose morphine treatment promotes SH-SY5Y cell apoptosis via c-Jun N-terminal kinase-mediated activation of mitochondria-dependent pathway. FEBS J. 2009;276:2022–36.CrossRef Lin X, Wang YJ, Li Q, Hou YY, Hong MH, Cao YL, et al. Chronic high dose morphine treatment promotes SH-SY5Y cell apoptosis via c-Jun N-terminal kinase-mediated activation of mitochondria-dependent pathway. FEBS J. 2009;276:2022–36.CrossRef
12.
go back to reference Juneja R. Opioids and cancer recurrence. Curr Opin Support Palliat Care. 2014;8:91–101.CrossRef Juneja R. Opioids and cancer recurrence. Curr Opin Support Palliat Care. 2014;8:91–101.CrossRef
13.
go back to reference Page GG, Ben-Eliyahu S, Yirmiya R, Liebeskind JC. Morphine attenuates surgery-induced enhancement of metastatic colonization in rats. Pain. 1993;54:21–8.CrossRef Page GG, Ben-Eliyahu S, Yirmiya R, Liebeskind JC. Morphine attenuates surgery-induced enhancement of metastatic colonization in rats. Pain. 1993;54:21–8.CrossRef
14.
go back to reference Page GG, McDonald JS, Ben-Eliyahu S. Pre-operative versus postoperative administration of morphine: impact on the neuroendocrine, behavioural, and metastatic-enhancing effects of surgery. Br J Anaesth. 1998;81:216–23.CrossRef Page GG, McDonald JS, Ben-Eliyahu S. Pre-operative versus postoperative administration of morphine: impact on the neuroendocrine, behavioural, and metastatic-enhancing effects of surgery. Br J Anaesth. 1998;81:216–23.CrossRef
15.
go back to reference Deegan CA, Murray D, Doran P, Ecimovic P, Moriarty DC, Buggy DJ. Effect of anesthetic technique on oestrogen receptor-negative breast cancer cell function in vitro. Br J Anaesth. 2009;103:685–90.CrossRef Deegan CA, Murray D, Doran P, Ecimovic P, Moriarty DC, Buggy DJ. Effect of anesthetic technique on oestrogen receptor-negative breast cancer cell function in vitro. Br J Anaesth. 2009;103:685–90.CrossRef
16.
go back to reference Gisterek I, Matkowski R, Lacko A, Sedlaczek P, Szewczyk K, Biecek P, et al. Serum VEGF A, C, D in human breast tumors. Pathol Oncol Res. 2010;16:337–44.CrossRef Gisterek I, Matkowski R, Lacko A, Sedlaczek P, Szewczyk K, Biecek P, et al. Serum VEGF A, C, D in human breast tumors. Pathol Oncol Res. 2010;16:337–44.CrossRef
17.
go back to reference Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nature Med. 2001;7:192–8.CrossRef Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, et al. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nature Med. 2001;7:192–8.CrossRef
18.
go back to reference Dumont N, Arteaga CL. Transforming growth factor-beta and breast cancer: tumor promoting effects of transforming growth factor-beta. Breast Cancer Res. 2000;2:125–32.CrossRef Dumont N, Arteaga CL. Transforming growth factor-beta and breast cancer: tumor promoting effects of transforming growth factor-beta. Breast Cancer Res. 2000;2:125–32.CrossRef
19.
go back to reference Yang EV, Kim SJ, Donovan EL, Chen M, Gross AC, Webster Marketon JI, et al. Norepinephrine upregulates VEGF, IL-8, and IL-6 expression in human melanoma tumor cell lines: implications for stress related enhancement of tumor progression. Brain Behav Immun. 2009;23:267–75.CrossRef Yang EV, Kim SJ, Donovan EL, Chen M, Gross AC, Webster Marketon JI, et al. Norepinephrine upregulates VEGF, IL-8, and IL-6 expression in human melanoma tumor cell lines: implications for stress related enhancement of tumor progression. Brain Behav Immun. 2009;23:267–75.CrossRef
20.
go back to reference Loop T, Dovi-Akue D, Frick M, Roesslein M, Egger L, Humar M, et al. Volatile anesthetics induce caspase-dependent, mitochondria mediated apoptosis in human T lymphocytes in vitro. Anesthesiology. 2005;102:1147–57.CrossRef Loop T, Dovi-Akue D, Frick M, Roesslein M, Egger L, Humar M, et al. Volatile anesthetics induce caspase-dependent, mitochondria mediated apoptosis in human T lymphocytes in vitro. Anesthesiology. 2005;102:1147–57.CrossRef
21.
go back to reference Pinto MP, Badtke MM, Dudevoir ML, Harrell JC, Jacobsen BM, Horwitz KB. Vascular endothelial growth factor secreted by activated stroma enhances angiogenesis and hormone-independent growth of estrogen receptor-positive breast cancer. Cancer Res. 2010;70:2655–64.CrossRef Pinto MP, Badtke MM, Dudevoir ML, Harrell JC, Jacobsen BM, Horwitz KB. Vascular endothelial growth factor secreted by activated stroma enhances angiogenesis and hormone-independent growth of estrogen receptor-positive breast cancer. Cancer Res. 2010;70:2655–64.CrossRef
22.
go back to reference Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DI. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology. 2006;105:660–4.CrossRef Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DI. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology. 2006;105:660–4.CrossRef
23.
go back to reference Sacerdote P, Bianchi M, Gaspani L, Manfredi B, Maucione A, Terno G, et al. The effects of tramadol and morphine on immune responses and pain after surgery in cancer patients. Anesth Analg. 2000;90:1411–4.CrossRef Sacerdote P, Bianchi M, Gaspani L, Manfredi B, Maucione A, Terno G, et al. The effects of tramadol and morphine on immune responses and pain after surgery in cancer patients. Anesth Analg. 2000;90:1411–4.CrossRef
24.
go back to reference Gupta K, Kshirsagar S, Chang L, Schwartz R, Law PY, Yee D, et al. Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth. Cancer Res. 2002;62:4491–8.PubMed Gupta K, Kshirsagar S, Chang L, Schwartz R, Law PY, Yee D, et al. Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth. Cancer Res. 2002;62:4491–8.PubMed
25.
go back to reference Bimonte S, Barbieri A, Rea D, Palma G, Luciano A, Cuomo A, et al. Morphine promotes tumor angiogenesis and increases breast cancer progression. Biomed Res Int. 2015;2015:161508.PubMedPubMedCentral Bimonte S, Barbieri A, Rea D, Palma G, Luciano A, Cuomo A, et al. Morphine promotes tumor angiogenesis and increases breast cancer progression. Biomed Res Int. 2015;2015:161508.PubMedPubMedCentral
26.
go back to reference Shavit Y, Ben-Eliyahu S, Zeidel A, Beilin B. Effects of fentanyl on natural killer cell activity and on resistance to tumor metastasis in rats. Dose and timing study. Neuroimmunomodulation. 2004;11:255–60.CrossRef Shavit Y, Ben-Eliyahu S, Zeidel A, Beilin B. Effects of fentanyl on natural killer cell activity and on resistance to tumor metastasis in rats. Dose and timing study. Neuroimmunomodulation. 2004;11:255–60.CrossRef
27.
go back to reference Sacerdote P, Gaspani L, Rossoni G, Panerai AE, Bianchi M. Effect of the opioid remifentanil on cellular immune response in the rat. Int Immunopharmocol. 2001;1:713–9.CrossRef Sacerdote P, Gaspani L, Rossoni G, Panerai AE, Bianchi M. Effect of the opioid remifentanil on cellular immune response in the rat. Int Immunopharmocol. 2001;1:713–9.CrossRef
28.
go back to reference Li AX, Xin WQ, Ma CG. Fentanyl inhibits the invasion and migration of colorectal cancer cells via inhibiting the negative regulation of Ets-1 on BANCR. Biochem Biophys Res Commun. 2015;465:594–600.CrossRef Li AX, Xin WQ, Ma CG. Fentanyl inhibits the invasion and migration of colorectal cancer cells via inhibiting the negative regulation of Ets-1 on BANCR. Biochem Biophys Res Commun. 2015;465:594–600.CrossRef
29.
go back to reference Farooqui M, Li Y, Rogers T, Poonawala T, Griffin RJ, Song CW, et al. COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumor growth, metastasis, and mortality, without compromising analgesia. Br J Cancer. 2007;97:1523–31.CrossRef Farooqui M, Li Y, Rogers T, Poonawala T, Griffin RJ, Song CW, et al. COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumor growth, metastasis, and mortality, without compromising analgesia. Br J Cancer. 2007;97:1523–31.CrossRef
30.
go back to reference Inada T, Kubo K, Shingu K. Promotion of interferon-gamma production by natural killer cells via suppression of murine peritoneal macrophage prostaglandin E2 production using intravenous anesthetic propofol. Int Immunopharmacol. 2010;10:1200–8.CrossRef Inada T, Kubo K, Shingu K. Promotion of interferon-gamma production by natural killer cells via suppression of murine peritoneal macrophage prostaglandin E2 production using intravenous anesthetic propofol. Int Immunopharmacol. 2010;10:1200–8.CrossRef
31.
go back to reference Inada T, Kubo K, Shingu K. Possible link between cyclooxygenase-inhibiting and antitumor properties of propofol. J Anesth. 2011;25:569–75.CrossRef Inada T, Kubo K, Shingu K. Possible link between cyclooxygenase-inhibiting and antitumor properties of propofol. J Anesth. 2011;25:569–75.CrossRef
32.
go back to reference Leahy KM, Ornverg RL, Wang Y, Zweifel BS, Koki AT, Masferrer JL. Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo. Cancer Res. 2002;62:625–31.PubMed Leahy KM, Ornverg RL, Wang Y, Zweifel BS, Koki AT, Masferrer JL. Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo. Cancer Res. 2002;62:625–31.PubMed
33.
go back to reference Forget P, Vandenhende J, Berliere M, Machiels JP, Nussbaum B, Legrand C, et al. Do intraoperative analgesics influence breast cancer recurrence after mastectomy? A retrospective analysis. Anesth Analg. 2010;110:1630–5.CrossRef Forget P, Vandenhende J, Berliere M, Machiels JP, Nussbaum B, Legrand C, et al. Do intraoperative analgesics influence breast cancer recurrence after mastectomy? A retrospective analysis. Anesth Analg. 2010;110:1630–5.CrossRef
34.
go back to reference Echevarría G, Elgueta F, Fierro C, Bugedo D, Faba G, Iñiguez-Cuadra R, .et al. Nitrous oxide (N2O) reduces postoperative opioid-induced hyperalgesia after remifentanil-propofol anesthesia in humans. Br J Anaesth2011; 107: 959–965.CrossRef Echevarría G, Elgueta F, Fierro C, Bugedo D, Faba G, Iñiguez-Cuadra R, .et al. Nitrous oxide (N2O) reduces postoperative opioid-induced hyperalgesia after remifentanil-propofol anesthesia in humans. Br J Anaesth2011; 107: 959–965.CrossRef
35.
go back to reference Ben-Eliyahu S, Page GG, Yirmiya R, Shakhar G. Evidence that stress and surgical interventions promote tumor development by suppressing natural killer cell activity. Int J Cancer. 1999;15:880–8.CrossRef Ben-Eliyahu S, Page GG, Yirmiya R, Shakhar G. Evidence that stress and surgical interventions promote tumor development by suppressing natural killer cell activity. Int J Cancer. 1999;15:880–8.CrossRef
36.
go back to reference Ke JJ, Zhan J, Feng XB, Wu Y, Rao Y, Wang YL. A comparison of the effect of total intravenous anesthesia with propofol and remifentanil and inhalational anesthesia with isoflurane on the release of pro- and anti-inflammatory cytokines in patients undergoing open cholecystectomy. Anaesth Intensive Care. 2008;36:74–8.PubMed Ke JJ, Zhan J, Feng XB, Wu Y, Rao Y, Wang YL. A comparison of the effect of total intravenous anesthesia with propofol and remifentanil and inhalational anesthesia with isoflurane on the release of pro- and anti-inflammatory cytokines in patients undergoing open cholecystectomy. Anaesth Intensive Care. 2008;36:74–8.PubMed
37.
go back to reference Rocca A, Cancello G, Bagnardi V, Sandri MT, Torrisi R, Zorzino L, et al. Perioperative serum VEGF and extracellular domains of EGFR and HER2 in early breast cancer. Anticancer Res. 2009;29:5111–9.PubMed Rocca A, Cancello G, Bagnardi V, Sandri MT, Torrisi R, Zorzino L, et al. Perioperative serum VEGF and extracellular domains of EGFR and HER2 in early breast cancer. Anticancer Res. 2009;29:5111–9.PubMed
38.
go back to reference Cronin-Fenton DP, Heide-Jørgensen U, Ahern TP, Lash TL, Christiansen PM, Ejlertsen B, et al. Opioids and breast cancer recurrence: a Danish population-based cohort study. Cancer. 2015;121:3507–14.CrossRef Cronin-Fenton DP, Heide-Jørgensen U, Ahern TP, Lash TL, Christiansen PM, Ejlertsen B, et al. Opioids and breast cancer recurrence: a Danish population-based cohort study. Cancer. 2015;121:3507–14.CrossRef
Metadata
Title
Effects of propofol/remifentanil-based total intravenous anesthesia versus sevoflurane-based inhalational anesthesia on the release of VEGF-C and TGF-β and prognosis after breast cancer surgery: a prospective, randomized and controlled study
Authors
Tao Yan
Guo-Hua Zhang
Bao-Na Wang
Li Sun
Hui Zheng
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2018
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/s12871-018-0588-3

Other articles of this Issue 1/2018

BMC Anesthesiology 1/2018 Go to the issue