Table of Contents  

Regional anesthesia and analgesia for cancer surgery

Xavier Capdevila, Phillippe Rene Bertrand Macaire, Karine Nouette-Gaulain, Christophe Dadure, Aruna Godwin, Mansour Nadhari
Published in : HAMDAN MEDICAL JOURNAL ; Vol 5, No 2 (2012)
DOI : 10.7707/hmj.v5i2.131


The evolution of cancer cells in clinical metastases depends on antimetastatic immune activity and the ability of the tumour to proliferate and generate new blood vessels (neoangiogenesis). Surgery by itself can depress cellular immunity and functions of cytotoxic T lymphocytes and natural killer (NK) cells. The perioperative stress response releases tumour cells into the circulation and anaesthesia further reduces immune functions, including the functions of neutrophils, macrophages, dendritic cells, T lymphocytes and NK cells. Effective treatment of postoperative pain could play an important role in limiting the metastatic migration following oncology surgery. Opioids used intraoperatively and postoperatively inhibit cellular and humoral immune functions in humans and have natural pro-angiogenic properties. In a retrospective analysis, paravertebral anaesthesia and analgesia for breast cancer surgery reduced the risk of recurrence or metastasis by four during the first years of follow-up. Similarly, following epidural anaesthesia for resection of the prostate, biochemical recurrence of prostate cancer was reduced by 65% and, following colon surgery, the oncological prognosis was enhanced in the first two years. To date there are only retrospective clinical studies available. A prospective, randomized, large-size study focused on cancers with high risk of recurrence is needed to determine if regional anaesthesia and analgesia could have potential for clinically reducing cancer recurrence after oncology surgery.

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Eschwege P, Dumas F, Blanchet P, et al. Haematogenous dissemination of prostatic epithelial cells during radical prostatectomy. Lancet 1995; 346: 1528–30.

Foss OP, Brennhovd IO, Messelt OT, Efskind J, Liverud K. Invasion of tumor cells into the bloodstream caused by palpation or biopsy of the tumor. Surgery 1966; 59: 691–5.

Denis MG, Lipart C, Leborgne J, et al. Detection of disseminated tumor cells in peripheral blood of colorectal cancer patients. Int J Cancer 1997; 74: 540–4.

Holmgren L, O’Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1995; 1: 149–53.

ShakharG, Ben-Eliyahu S. Potential prophylactic measures against postoperative immunosuppression: could they reduce recurrence rates in oncological patients? Ann Surg Oncol 2003; 10: 972–92.

Smyth MJ, Godfrey DI, Trapani JA. A fresh look at tumor immunosurveillance and immunotherapy. Nat Immunol 2001; 2: 293–9.

Fidler IJ. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer 2003; 3:453-8.

Forget P, De Kock M. L'anesthésie, l'analgésie et la modulation sympathique augmentent-elle l'incidence des récidives néoplasiques après chirurgie? Une revue de la littérature centrée sur la modulation de l'activité des lymphocytes natural killer. Ann Fr Anesth Reanim 2009; 28:751-68.

Bar-Yosef S, Melamed R, Page GG, Shakhar G, Shakhar K, Ben- Eliyahu S. Attenuation of the tumor-promoting effect of surgery by spinal blockade in rats. Anesthesiology 2001; 94: 1066–73.

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; 80: 880–8.

Page GG, Blakely WP, Ben-Eliyahu S. Evidence that postoperative pain is a mediator of the tumor-promoting effects of surgery in rats. Pain 2001; 90: 191–9.

Wong IH, Lau WY, Leung T, Yeo W, Johnson PJ. Hematogenous dissemination of hepatocytes and tumor cells after surgical resection of hepatocellular carcinoma: a quantitative analysis. Clin

Cancer Res 1999; 5: 4021–7.

Zetter BR. Angiogenesis and tumor metastasis. Annu Rev Med 1998; 49: 407–24.

O’Reilly MS, Holmgren L, Shing Y, et al. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994; 79: 315–28.

O’Reilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997; 88: 277–85.

Folkman J. Tumor angiogenesis. In: Mendelsohn J, Howley PM, Israel MA, Liotta LA, editors. The Molecular Basis of Cancer. WB Saunders; 1995.

Lutgendorf SK, Cole S, Costanzo E, et al. Stress-related mediators stimulate vascular endothelial growth factor secretion by two ovarian cancer cell lines. Clin Cancer Res 2003; 9: 4514–21.

Antoni MH, Lutgendorf SK, Cole SW, et al. The influence of biobehavioural factors on tumour biology: pathways and mechanisms. Nat Rev Cancer 2006; 6: 240–8.

Sacerdote P, Bianchi M, Gaspani L, et al. The effects of tramadol and morphine on immune responses and pain after surgery in cancer patients. Anesth Analg 2000; 90: 1411–4.

Brand JM, Kirchner H, Poppe C, Schmucker P. The effects of general anesthesia on human peripheral immune cell distributionand cytokine production. Clin Immunol Immunopathol 1997; 83:


Markovic SN, Knight PR, Murasko DM. Inhibition of interferonstimulation of natural killer cell activity in mice anesthetized with halothane or isoflurane. Anesthesiology 1993; 78: 700–6.

Shapiro J, Jersky J, Katzav S, Feldman M, Segal S. Anesthetic drugs accelerate the progression of postoperative metastases of mouse tumors. J Clin Invest 1981; 68: 678–85.

Melamed R, Bar-Yosef S, Shakhar G, et al. 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. Anesth Analg 2003;97:1331-9.

Zhou W, Fontenot HJ, Wang SN, Kennedy RH. Propofol-induced alterations in myocardial beta-adrenoceptor binding and responsiveness. Anesth Analg 1999;89:604-8.

Beilin B, Shavit Y, Hart J, et al. Effects of anesthesia based on large versus small doses of fentanyl on natural killer cell cytotoxicity in the perioperative period. Anesth Analg 1996; 82: 492–7.

Yeager MP, Colacchio TA, Yu CT, et al. Morphine inhibits spontaneous and cytokine-enhanced natural killer cell cytotoxicity in volunteers. Anesthesiology 1995; 83: 500–8.

Gupta K, Kshirsagar S, Chang L, et al. Morphine stimulates angiogenesis by activating proangiogenic and survival-promoting signaling and promotes breast tumor growth. Cancer Res 2002;

: 4491–8.

Shavit Y, Lewis JW, Terman GW, Gale RP, Liebeskind JC. Opioid peptides mediate the suppressive effect of stress on natural killer cell cytotoxicity. Science 1984; 223:188-90.

Gaveriaux-Ruff C, Matthes HW, Peluso J, Kieffer BL. Abolition of morphine-immunosuppression in mice lacking the mu-opioid receptor gene. Proc Natl Acad Sci U S A 1998; 95:6326-30.

Page GG, Ben-Eliyahu S, Yirmiya R, Liebeskind JC. Morphine attenuates surgery-induced enhancement of metastatic colonization in rats. Pain 1993; 54:21-8.

Kehlet H. The stress response to surgery. In: Cousins MJ, Brindenbaugh PO, editors. Neural Blockade in Clinical Anaesthesia and Management of Pain. New York: Lippincott Williams & Wilkins; 1998 .

Buggy DJ, Smith G. Epidural anaesthesia and analgesia: better outcome after major surgery? Growing evidence suggests so. BMJ 1999; 319: 530–1.

Sakaguchi M, Kuroda Y, Hirose M. The antiproliferative effect of lidocaine on human tongue cancer cells with inhibition of the activity of epidermal growth factor receptor. Anesth Analg 2006; 102:1103-7.

Martinsson T. Ropivacaine inhibits serum-induced proliferation of colon adenocarcinoma cells in vitro. J Pharmacol Exp Ther 1999; 288:660-4.

Jose C, Bellance N, Chatelain EH, Benard G, Nouette-Gaulain K, Rossignol R. Antiproliferative activity of levobupivacaine and aminoimidazole carboxamide ribonucleotide on human cancer cells of variable bioenergetic profile. Mitochondrion 2011.In press

Wada H, Seki S, Takahashi T, et al. Combined spinal and general anesthesia attenuates liver metastasis by preserving TH1/TH2 cytokine balance. Anesthesiology 2007;106:499-506

Schlagenhauff B, Ellwanger U, Breuninger H, Stroebel W, Rassner G, Garbe C. Prognostic impact of the type of anaesthesia used during the excision of primary cutaneous melanoma. Melanoma

Res 2000; 10: 165–9.

Exadaktylos AK, Buggy DJ, Moriarty DC, Mascha E, Sessler DI. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology 2006; 4: 660–4.

Biki B, Mascha E, Moriarty DC, Fitzpatrick JM, Sessler DI, Buggy DJ. Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis. Anesthesiology 2008; 109: 180–7.

Tsui BCH, Rashiq S, Schopflocher D, Murtha A, Broemling S, Pillay J, Finucane BT. Epidural anesthesia and cancer recurrence rates after radical prostatectomy. Can J Anesth 2010; 57: 107-112

Wuethrich PY, Hsu Schmitz SF, Kessler TM, Thalmann GN, Studer UE, Stueber F, et al. Potential influence of the anesthetic technique used during open radical prostatectomy on prostate cancer-related outcome: a retrospective study. Anesthesiology 2010; 113:570-6.

Christopherson R, James KE, Tableman M, Marshall P, Johnson FE Long-term survival after colon cancer surgery: a variation associated with choice of anesthesia. Anesth Analg. 2008 ;107:325-32.

Gottschalk A, Ford JG, Regelin CC, You J, Mascha EJ, Sessler DI, et al. Association between epidural analgesia and cancer recurrence after colorectal cancer surgery. Anesthesiology

; 113:27-34.

Gupta A, Bjornsson A, Fredriksson M, Hallbook O, Eintrei C. Reduction in mortality after epidural anaesthesia and analgesia in patients undergoing rectal but not colonic cancer surgery: a retrospective analysis of data from 655 patients in central Sweden. Br J Anaesth 2011; 107:164-70.

Myles PS, Peyton P, Silbert B, Hunt J, Rigg JR, Sessler DI. Perioperative epidural analgesia for major abdominal surgery for cancer and recurrence-free survival: randomised trial. BMJ 2011; 342:d1491.

de Oliveira GS, Jr., Ahmad S, Schink JC, Singh DK, Fitzgerald PC, McCarthy RJ. Intraoperative neuraxial anesthesia but not postoperative neuraxial analgesia is associated with increased relapse-free survival in ovarian cancer patients after primary cytoreductive surgery. Reg Anesth Pain Med 2011; 36:271-7.

Lin L, Liu C, Tan H, Ouyang H, Zhang Y, Zeng W. Anaesthetic technique may affect prognosis for ovarian serous adenocarcinoma: a retrospective analysis. Br J Anaesth 2011; 106:814-22

Ismail H, Ho KM, Narayan K, Kondalsamy-Chennakesavan S. Effect of neuraxial anaesthesia on tumour progression in cervical cancer patients treated with brachytherapy: a retrospective cohort study. Br J Anaesth 2010; 105:145-9.

Montélimard A MF, Nourissat A, Zufferey P, Molliex S. . Can cervical epidural anesthesia improve survival in head and neck cancer surgery? ASA abstract 2010; A017.

Sessler DI. Long-term consequences of anesthetic management. Anesthesiology 2009; 111:1-4.

Arain MR, Buggy DJ. Anaesthesia for cancer patients. Curr Opin Anaesthesiol 2007;20:247-53.

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