Skip to main content

Advertisement

Springer Nature Link
Log in

Potential Prophylactic Measures Against Postoperative Immunosuppression: Could They Reduce Recurrence Rates in Oncological Patients?

  • Original Articles
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background: Removing the primary tumor is indispensable for eliminating the major pool of metastasizing cells, but the surgical procedure itself is suspected of promoting metastases. This adverse effect is attributed to several mechanisms acting in synergy, including mechanical release of tumor cells, enhanced angiogenesis, secretion of growth factors, and immunosuppression. Here we provide new insights into mechanisms of postoperative immunosuppression and assess the assumptions underlying the hypothesis that, by suppressing cell-mediated immunity (CMI), surgery may render the patient vulnerable to metastases that otherwise could have been controlled.

Methods: An extensive review of relevant articles in English identified by using the MEDLINE database and cross-referencing.

Results: Current literature suggests that (1) CMI can control minimal residual disease, especially if surgery is performed early; (2) major surgery transiently but markedly suppresses CMI through multiple mechanisms now better understood; (3) surgical stress promotes experimental metastasis through immunosuppression, but the clinical evidence remains indirect because of ethical limitations.

Conclusions: Minimizing postoperative immunosuppression seems feasible, may limit recurrence, and should be introduced into the broader array of considerations when planning oncological surgeries. In the short run, physicians could try to avoid immunosuppressive anesthetic approaches, inadvertent hypothermia, excessive blood transfusions, and untended postoperative pain. When feasible, minimally invasive surgery should be considered. In the long run, clinical trials should evaluate prophylactic measures, including perioperative immunostimulation and several antagonists to cytokines and hormones specified herein.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Buinauskas P, McDonald GO, Cole WH. Role of operative stress on the resistance of the experimental animal to inoculated cancer cells. Ann Surg 1958;148:642–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fielding LP, Wells BW. Survival after primary and after staged resection for large bowel obstruction caused by cancer. Br J Surg 1974;61:16–8.

    Article  CAS  PubMed  Google Scholar 

  3. Weese JL, Ottery FD, Emoto SE. Do operations facilitate tumor growth? An experimental model in rats. Surgery 1986;100:273–7.

    CAS  PubMed  Google Scholar 

  4. Sietses C, Beelen RH, Meijer S, Cuesta MA. Immunological consequences of laparoscopic surgery, speculations on the cause and clinical implications. Langenbecks Arch Surg 1999;384:250–8.

    Article  CAS  PubMed  Google Scholar 

  5. Lennard TW, Shenton BK, Borzotta A, et al. The influence of surgical operations on components of the human immune system. Br J Surg 1985;72:771–6.

    Article  CAS  PubMed  Google Scholar 

  6. Eggermont AM, Steller EP, Marquet RL, Jeekel J, Sugarbaker PH. Local regional promotion of tumor growth after abdominal surgery is dominant over immunotherapy with interleukin-2 and lymphokine activated killer cells. Cancer Detect Prev 1988;12:421–9.

    CAS  PubMed  Google Scholar 

  7. 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.

    Article  CAS  PubMed  Google Scholar 

  8. Carter JJ, Whelan RL. The immunologic consequences of laparoscopy in oncology. Surg Oncol Clin North Am 2001;10:655–77.

    Article  CAS  Google Scholar 

  9. Weitz J, Herfarth C. Surgical strategies and minimal residual disease detection. Semin Surg Oncol 2001;20:329–33.

    Article  CAS  PubMed  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. Hofer SO, Molema G, Hermens RA, Wanebo HJ, Reichner JS, Hoekstra HJ. The effect of surgical wounding on tumour development. Eur J Surg Oncol 1999;25:231–43.

    Article  CAS  PubMed  Google Scholar 

  12. Pettit SJ, Seymour K, O’Flaherty E, Kirby JA. Immune selection in neoplasia: towards a microevolutionary model of cancer development. Br J Cancer 2000;82:1900–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002;3:991–8.

    Article  CAS  PubMed  Google Scholar 

  14. Morton DL, Ollila DW, Hsueh EC, Essner R, Gupta RK. Cytoreductive surgery and adjuvant immunotherapy: a new management paradigm for metastatic melanoma. CA Cancer J Clin 1999;49:101–16, 65.

    Article  CAS  PubMed  Google Scholar 

  15. Pantel K, Schlimok G, Braun S, et al. Differential expression of proliferation-associated molecules in individual micrometastatic carcinoma cells. J Natl Cancer Inst 1993;85:1419–24.

    Article  CAS  PubMed  Google Scholar 

  16. Algarra I, Gaforio JJ, Garrido A, Mialdea MJ, Perez M, Garrido F. Heterogeneity of MHC-class-I antigens in clones of methylcholanthrene-induced tumors. Implications for local growth and metastasis. Int J Cancer Suppl 1991;6:73–81.

    Article  CAS  PubMed  Google Scholar 

  17. Mansi JL, Gogas H, Bliss JM, Gazet JC, Berger U, Coombes RC. Outcome of primary-breast-cancer patients with micrometastases: a long-term follow-up study. Lancet 1999;354:197–202.

    Article  CAS  PubMed  Google Scholar 

  18. Rosenberg SA. Progress in human tumour immunology and immunotherapy. Nature 2001;411:380–4.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  20. Gumperz JE, Parham P. The enigma of the natural killer cell. Nature 1995;378:245–8.

    Article  CAS  PubMed  Google Scholar 

  21. Street SE, Cretney E, Smyth MJ. Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 2001;97:192–7.

    Article  CAS  PubMed  Google Scholar 

  22. Dithmar SA, Rusciano DA, Armstrong CA, Lynn MJ, Grossniklaus HE. Depletion of NK cell activity results in growth of hepatic micrometastases in a murine ocular melanoma model. Curr Eye Res 1999;19:426–31.

    Article  CAS  PubMed  Google Scholar 

  23. Marton I, Johnson SE, Damjanov I, Currier KS, Sundberg JP, Knowles BB. Expression and immune recognition of SV40 Tag in transgenic mice that develop metastatic osteosarcomas. Transgenic Res 2000;9:115–25.

    Article  CAS  PubMed  Google Scholar 

  24. Yano S, Nishioka Y, Izumi K, et al. Novel metastasis model of human lung cancer in SCID mice depleted of NK cells. Int J Cancer 1996;67:211–7.

    Article  CAS  PubMed  Google Scholar 

  25. Brittenden J, Heys SD, Ross J, Eremin O. Natural killer cells and cancer. Cancer 1996;77:1226–43.

    Article  CAS  PubMed  Google Scholar 

  26. Fujisawa T, Yamaguchi Y. Autologous tumor killing activity as a prognostic factor in primary resected nonsmall cell carcinoma of the lung. Cancer 1997;79:474–81.

    Article  CAS  PubMed  Google Scholar 

  27. Uchida A, Kariya Y, Okamoto N, Sugie K, Fujimoto T, Yagita M. Prediction of postoperative clinical course by autologous tumor-killing activity in lung cancer patients. J Natl Cancer Inst 1990;82:1697–701.

    Article  CAS  PubMed  Google Scholar 

  28. McCoy JL, Rucker R, Petros JA. Cell-mediated immunity to tumor-associated antigens is a better predictor of survival in early stage breast cancer than stage, grade or lymph node status. Breast Cancer Res Treat 2000;60:227–34.

    Article  CAS  PubMed  Google Scholar 

  29. Dranoff G. Immune recognition and tumor protection. Curr Opin Immunol 2002;14:161–4.

    Article  CAS  Google Scholar 

  30. Bingle L, Brown NJ, Lewis CE. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 2002;196:254–65.

    Article  CAS  PubMed  Google Scholar 

  31. Stewart TH, Hollinshead AC, Raman S. Tumour dormancy: initiation, maintenance and termination in animals and humans. Can J Surg 1991;34:321–5.

    CAS  PubMed  Google Scholar 

  32. Penn I. The effect of immunosuppression on pre-existing cancers. Transplantation 1993;55:742–7.

    Article  CAS  PubMed  Google Scholar 

  33. Barrett WL, First MR, Aron BS, Penn I. Clinical course of malignancies in renal transplant recipients. Cancer 1993;72:2186–9.

    Article  CAS  PubMed  Google Scholar 

  34. Detry O, Honore P, Meurisse M, Jacquet N. Cancer in transplant recipients. Transplant Proc 2000;32:127.

    Article  CAS  PubMed  Google Scholar 

  35. Gilboa E. How tumors escape immune destruction and what we can do about it. Cancer Immunol Immunother 1999;48:382–5.

    Article  CAS  PubMed  Google Scholar 

  36. Shankaran V, Ikeda H, Bruce AT, et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 2001;410:1107–11.

    Article  CAS  PubMed  Google Scholar 

  37. Garcia-Lora A, Algarra I, Gaforio JJ, Ruiz-Cabello F, Garrido F. Immunoselection by T lymphocytes generates repeated MHC class I-deficient metastatic tumor variants. Int J Cancer 2001;91:109–19.

    Article  CAS  PubMed  Google Scholar 

  38. Seliger B, Maeurer MJ, Ferrone S. Antigen-processing machinery breakdown and tumor growth. Immunol Today 2000;21:455–64.

    Article  CAS  PubMed  Google Scholar 

  39. Gilboa E, Nair SK, Lyerly HK. Immunotherapy of cancer with dendritic-cell-based vaccines. Cancer Immunol Immunother 1998;46:82–7.

    Article  CAS  PubMed  Google Scholar 

  40. Seliger B, Maeurer MJ, Ferrone S. TAP off–tumors on. Immunol Today 1997;18:292–9.

    CAS  PubMed  Google Scholar 

  41. Hensler T, Hecker H, Heeg K, et al. Distinct mechanisms of immunosuppression as a consequence of major surgery. Infect Immun 1997;65:2283–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Yeager MP, DeLeo JA, Hoopes PJ, Hartov A, Hildebrandt L, Hickey WF. Trauma and inflammation modulate lymphocyte localization in vivo: quantitation of tissue entry and retention using indium-111-labeled lymphocytes. Crit Care Med 2000;28:1477–82.

    Article  CAS  PubMed  Google Scholar 

  43. Toft P, Svendsen P, Tonnesen E, Rasmussen JW, Christensen NJ. Redistribution of lymphocytes after major surgical stress. Acta Anaesthesiol Scand 1993;37:245–9.

    Article  CAS  PubMed  Google Scholar 

  44. Munford RS, Pugin J. Normal responses to injury prevent systemic inflammation and can be immunosuppressive. Am J Respir Crit Care Med 2001;163:316–21.

    Article  CAS  PubMed  Google Scholar 

  45. Nelson CJ, Lysle DT. Severity, time, and beta-adrenergic receptor involvement in surgery-induced immune alterations. J Surg Res 1998;80:115–22.

    Article  CAS  PubMed  Google Scholar 

  46. Targarona EM, Balague C, Knook MM, Trias M. Laparoscopic surgery and surgical infection. Br J Surg 2000;87:536–44.

    Article  CAS  PubMed  Google Scholar 

  47. Xu YX, Ayala A, Chaudry IH. Prolonged immunodepression after trauma and hemorrhagic shock. J Trauma 1998;44:335–41.

    Article  CAS  PubMed  Google Scholar 

  48. Klein HG. Immunomodulatory aspects of transfusion: a once and future risk? Anesthesiology 1999;91:861–5.

    Article  CAS  PubMed  Google Scholar 

  49. Blajchman MA. Transfusion-associated immunomodulation and universal white cell reduction: are we putting the cart before the horse? Transfusion 1999;39:665–70.

    Article  CAS  PubMed  Google Scholar 

  50. Kurz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical-wound infection and shorten hospitalization. N Engl J Med 1996;334:1209–15.

    Article  CAS  PubMed  Google Scholar 

  51. Salman H, Bergman M, Bessler H, Alexandrova S, Beilin B, Djaldetti M. Hypothermia affects the phagocytic activity of rat peritoneal macrophages. Acta Physiol Scand 2000;168:431–6.

    Article  CAS  PubMed  Google Scholar 

  52. Beilin B, Shavit Y, Razumovsky J, Wolloch Y, Zeidel A, Bessler H. Effects of mild perioperative hypothermia on cellular immune responses. Anesthesiology 1998;89:1133–40.

    Article  CAS  PubMed  Google Scholar 

  53. Ben-Eliyahu S, Shakhar G, Rosenne E, Levinson Y, Beilin B. Hypothermia in barbiturate-anesthetized rats suppresses natural killer cell activity and compromises resistance to tumor metastasis: a role for adrenergic mechanisms. Anesthesiology 1999;91:732–40.

    Article  CAS  PubMed  Google Scholar 

  54. Schaffer M, Beiter T, Becker HD, Hunt TK. Neuropeptides: mediators of inflammation and tissue repair? Arch Surg 1998;133:1107–16.

    Article  CAS  PubMed  Google Scholar 

  55. Panerai AE, Sacerdote P. Beta-endorphin in the immune system: a role at last? Immunol Today 1997;18:317–9.

    Article  CAS  PubMed  Google Scholar 

  56. Galley HF, DiMatteo MA, Webster NR. Immunomodulation by anaesthetic, sedative and analgesic agents: does it matter? Intensive Care Med 2000;26:267–74.

    Article  CAS  PubMed  Google Scholar 

  57. 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.

    Article  CAS  PubMed  Google Scholar 

  58. Koltun WA, Bloomer MM, Tilberg AF, et al. Awake epidural anesthesia is associated with improved natural killer cell cytotoxicity and a reduced stress response. Am J Surg 1996;171:68–73.

    Article  CAS  PubMed  Google Scholar 

  59. Hashimoto T, Hashimoto S, Hori Y, Nakagawa H, Hosokawa T. Epidural anaesthesia blocks changes in peripheral lymphocytes subpopulation during gastrectomy for stomach cancer. Acta Anaesthesiol Scand 1995;39:294–8.

    Article  CAS  PubMed  Google Scholar 

  60. Rodgers A, Walker N, Schug S, et al. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials. BMJ 2000;321:1493.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hogevold HE, Lyberg T, Kahler H, Haug E, Reikeras O. Changes in plasma IL-1beta, TNF-alpha and IL-6 after total hip replacement surgery in general or regional anaesthesia. Cytokine 2000;12:1156–9.

    Article  CAS  PubMed  Google Scholar 

  62. Cohen S, Herbert TB. Health psychology: psychological factors and physical disease from the perspective of human psychoneuroimmunology. Annu Rev Psychol 1996;47:113–42.

    Article  CAS  PubMed  Google Scholar 

  63. Moynihan JA, Ader R. Psychoneuroimmunology: animal models of disease. Psychosom Med 1996;58:546–58.

    Article  CAS  PubMed  Google Scholar 

  64. Ishihara Y, Matsunaga K, Iijima H, Fujii T, Oguchi Y, Kagawa J. Time-dependent effects of stressor application on metastasis of tumor cells in the lung and its regulation by an immunomodulator in mice. Psychoneuroendocrinology 1999;24:713–26.

    Article  CAS  PubMed  Google Scholar 

  65. Freire-Garabal M, Nunez MJ, Balboa JL, et al. Effects of alprazolam on cellular immune response to surgical stress in mice. Cancer Lett 1993;73:155–60.

    Article  CAS  PubMed  Google Scholar 

  66. Andersen BL, Farrar WB, Golden-Kreutz D, et al. Stress and immune responses after surgical treatment for regional breast cancer. J Natl Cancer Inst 1998;90:30–6.

    Article  CAS  PubMed  Google Scholar 

  67. Larson MR, Duberstein PR, Talbot NL, Caldwell C, Moynihan JA. A presurgical psychosocial intervention for breast cancer patients: psychological distress and the immune response. J Psychosom Res 2000;48:187–94.

    Article  CAS  PubMed  Google Scholar 

  68. Woiciechowsky C, Schoning B, Lanksch WR, Volk HD, Docke WD. Mechanisms of brain-mediated systemic anti-inflammatory syndrome causing immunodepression. J Mol Med 1999;77:769–80.

    Article  CAS  PubMed  Google Scholar 

  69. Naito Y, Tamai S, Shingu K, et al. Responses of plasma adrenocorticotropic hormone, cortisol, and cytokines during and after upper abdominal surgery. Anesthesiology 1992;77:426–31.

    Article  CAS  PubMed  Google Scholar 

  70. Tashiro T, Yamamori H, Takagi K, et al. Changes in immune function following surgery for esophageal carcinoma. Nutrition 1999;15:760–6.

    Article  CAS  PubMed  Google Scholar 

  71. Shakhar G, Blumenfeld B. Glucocorticoid involvement in suppression of NK activity following surgery in rats. J Neuroimmunol 2003;138:83–91.

    Article  CAS  PubMed  Google Scholar 

  72. Deguchi M, Isobe Y, Matsukawa S, Yamaguchi A, Nakagawara G. Usefulness of metyrapone treatment to suppress cancer metastasis facilitated by surgical stress. Surgery 1998;123:440–9.

    Article  CAS  PubMed  Google Scholar 

  73. Jameson P, Desborough JP, Bryant AE, Hall GM. The effect of cortisol suppression on interleukin-6 and white blood cell responses to surgery. Acta Anaesthesiol Scand 1997;41:304–8.

    Article  CAS  PubMed  Google Scholar 

  74. Yamashita Y, Shimada M, Hamatsu T, et al. Effects of preoperative steroid administration on surgical stress in hepatic resection: prospective randomized trial. Arch Surg 2001;136:328–33.

    Article  CAS  PubMed  Google Scholar 

  75. Schulze S, Andersen J, Overgaard H, et al. Effect of prednisolone on the systemic response and wound healing after colonic surgery. Arch Surg 1997;132:129–35.

    Article  CAS  PubMed  Google Scholar 

  76. Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. The sympathetic nerve—an integrative interface between two supersystems—the brain and the immune system. Pharmacol Rev 2000;52:595–638.

    CAS  PubMed  Google Scholar 

  77. Downing JE, Miyan JA. Neural immunoregulation: emerging roles for nerves in immune homeostasis and disease. Immunol Today 2000;21:281–9.

    Article  CAS  PubMed  Google Scholar 

  78. Landmann R. Beta-adrenergic receptors in human leukocyte subpopulations. Eur J Clin Invest 1992;1:30–6.

    Google Scholar 

  79. Platzer C, Docke W, Volk H, Prosch S. Catecholamines trigger IL-10 release in acute systemic stress reaction by direct stimulation of its promoter/enhancer activity in monocytic cells. J Neuroimmunol 2000;105:31–8.

    Article  CAS  PubMed  Google Scholar 

  80. Rosenne E, Melamed R, Abudarham N, Ben-Eliyahu S. Attenuation of the immunosuppressive and metastasis-promoting effects of surgery by the combined use of beta-adrenergic and prostaglandin antagonists. Brain Behav Immun 2001;15:180.

    Google Scholar 

  81. Woiciechowsky C, Asadullah K, Nestler D, et al. Sympathetic activation triggers systemic interleukin-10 release in immunodepression induced by brain injury. Nat Med 1998;4:808–13.

    Article  CAS  PubMed  Google Scholar 

  82. Nelson CJ, Carrigan KA, Lysle DT. Naltrexone administration attenuates surgery-induced immune alterations in rats. J Surg Res 2000;94:172–7.

    Article  CAS  PubMed  Google Scholar 

  83. Chambrier C, Chassard D, Bienvenu J, et al. Cytokine and hormonal changes after cholecystectomy. Effect of ibuprofen pretreatment. Ann Surg 1996;224:178–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Faist E, Ertel W, Cohnert T, Huber P, Inthorn D, Heberer G. Immunoprotective effects of cyclooxygenase inhibition in patients with major surgical trauma. J Trauma 1990;30:8–17.

    Article  CAS  PubMed  Google Scholar 

  85. Colacchio TA, Yeager MP, Hildebrandt LW. Perioperative immunomodulation in cancer surgery. Am J Surg 1994;167:174–9.

    Article  CAS  PubMed  Google Scholar 

  86. Yakar I, Melamed R, Shakhar G, et al. Prostaglandin e(2) suppresses NK activity in vivo and promotes postoperative tumor metastasis in rats. Ann Surg Oncol 2003;10:469–79.

    Article  PubMed  Google Scholar 

  87. Kimura Y, Yaegashi Y, Sato N. Tumor necrosis factor-alpha production after esophageal cancer surgery: differences in the response to lipopolysaccharide stimulation among whole blood, pleural effusion cells, and bronchoalveolar lavage fluid cells. Surg Today 1999;29:10–5.

    Article  CAS  PubMed  Google Scholar 

  88. Klava A, Windsor AC, Farmery SM, et al. Interleukin-10. A role in the development of postoperative immunosuppression. Arch Surg 1997;132:425–9.

    Article  CAS  PubMed  Google Scholar 

  89. Ogata M, Okamoto K, Kohriyama K, Kawasaki T, Itoh H, Shigematsu A. Role of interleukin-10 on hyporesponsiveness of endotoxin during surgery. Crit Care Med 2000;28:3166–70.

    Article  CAS  PubMed  Google Scholar 

  90. Hensler T, Heidecke CD, Hecker H, et al. Increased susceptibility to postoperative sepsis in patients with impaired monocyte IL-12 production. J Immunol 1998;161:2655–9.

    CAS  PubMed  Google Scholar 

  91. Perez-Diez A, Marincola FM. Immunotherapy against antigenic tumors: a game with a lot of players. Cell Mol Life Sci 2002;59:230–40.

    Article  CAS  PubMed  Google Scholar 

  92. Moudgil GC, Singal DP. Halothane and isoflurane enhance melanoma tumour metastasis in mice. Can J Anaesth 1997;44:90–4.

    Article  CAS  PubMed  Google Scholar 

  93. Melamed R, Bar-Yosef S, Rosenne E, Weisman T, Ben-Eliyahu S. Suppression of NK activity and promotion of tumor metastasis by specific anesthetic agents and by hypothermia: mediating mechanisms and potential prophylactic measures (abstract). Brain Behav Immun 2001;15:169–70.

    Google Scholar 

  94. 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.

    Article  CAS  PubMed  Google Scholar 

  95. 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.

    Article  CAS  PubMed  Google Scholar 

  96. Kaseda S, Aoki T, Hangai N, Shimizu K. Better pulmonary function and prognosis with video-assisted thoracic surgery than with thoracotomy. Ann Thorac Surg 2000;70:1644–6.

    Article  CAS  PubMed  Google Scholar 

  97. Sugi K, Kaneda Y, Esato K. Video-assisted thoracoscopic lobectomy achieves a satisfactory long-term prognosis in patients with clinical stage IA lung cancer. World J Surg 2000;24:27–30; discussion 31.

    Article  CAS  PubMed  Google Scholar 

  98. Tschernko EM, Hofer S, Bieglmayer C, Wisser W, Haider W. Early postoperative stress: video-assisted wedge resection/lobectomy vs conventional axillary thoracotomy. Chest 1996;109:1636–42.

    Article  CAS  PubMed  Google Scholar 

  99. Yim AP, Wan S, Lee TW, Arifi AA. VATS lobectomy reduces cytokine responses compared with conventional surgery. Ann Thorac Surg 2000;70:243–7.

    Article  CAS  PubMed  Google Scholar 

  100. Leaver HA, Craig SR, Yap PL, Walker WS. Lymphocyte responses following open and minimally invasive thoracic surgery. Eur J Clin Invest 2000;30:230–8.

    Article  CAS  PubMed  Google Scholar 

  101. Yamashita JI, Kurusu Y, Fujino N, Saisyoji T, Ogawa M. Detection of circulating tumor cells in patients with non-small cell lung cancer undergoing lobectomy by video-assisted thoracic surgery: a potential hazard for intraoperative hematogenous tumor cell dissemination. J Thorac Cardiovasc Surg 2000;119:899–905.

    Article  CAS  PubMed  Google Scholar 

  102. Abudarham N, Rosenne E, Melamed R, Ben-Eliyahu S. Using immunostimulation with poly-I:C to circumvent promotion of metastasis by surgery. Brain Behav Immun 2001;15:131.

    Google Scholar 

  103. Yamauchi H, Kobayashi E, Yoshida T, et al. Changes in immune-endocrine response after surgery. Cytokine 1998;10:549–54.

    Article  CAS  PubMed  Google Scholar 

  104. Novak-Jankovic V, Paver Eren V, Bovill JG, Ihan A, Osredkar J. Effect of epidural and intravenous clonidine on the neuro-endocrine and immune stress response in patients undergoing lung surgery. Eur J Anaesthesiol 2000;17:50–6.

    Article  CAS  PubMed  Google Scholar 

  105. Dietz A, Heimlich F, Daniel V, Polarz H, Weidauer H, Maier H. Immunomodulating effects of surgical intervention in tumors of the head and neck. Otolaryngol Head Neck Surg 2000;123:132–9.

    Article  CAS  PubMed  Google Scholar 

  106. Oka M, Hirazawa K, Yamamoto K, et al. Induction of Fas-mediated apoptosis on circulating lymphocytes by surgical stress. Ann Surg 1996;223:434–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Sasajima K, Inokuchi K, Onda M, et al. Detection of T cell apoptosis after major operations. Eur J Surg 1999;165:1020–3.

    Article  CAS  PubMed  Google Scholar 

  108. Norman JG, Fink GW. The effects of epidural anesthesia on the neuroendocrine response to major surgical stress: a randomized prospective trial. Am Surg 1997;63:75–80.

    CAS  PubMed  Google Scholar 

  109. Berguer R, Bravo N, Bowyer M, Egan C, Knolmayer T, Ferrick D. Major surgery suppresses maximal production of helper T-cell type 1 cytokines without potentiating the release of helper T-cell type 2 cytokines. Arch Surg 1999;134:540–4.

    Article  CAS  PubMed  Google Scholar 

  110. Walker CB, Bruce DM, Heys SD, Gough DB, Binnie NR, Eremin O. Minimal modulation of lymphocyte and natural killer cell subsets following minimal access surgery. Am J Surg 1999;177:48–54.

    Article  CAS  PubMed  Google Scholar 

  111. Mafune K, Tanaka Y. Influence of multimodality therapy on the cellular immunity of patients with esophageal cancer. Ann Surg Oncol 2000;7:609–16.

    Article  CAS  PubMed  Google Scholar 

  112. Braga M, Gianotti L, Vignali A, Di Carlo V. Immunonutrition in gastric cancer surgical patients. Nutrition 1998;14:831–5.

    Article  CAS  PubMed  Google Scholar 

  113. Tonnesen E, Hohndorf K, Lerbjerg G, Christensen NJ, Huttel MS, Andersen K. Immunological and hormonal responses to lung surgery during one-lung ventilation. Eur J Anaesthesiol 1993;10:189–95.

    CAS  PubMed  Google Scholar 

  114. Lausten SB, Ibrahim TM, El-Sefi T, et al. Systemic and cell-mediated immune response after laparoscopic and open cholecystectomy in patients with chronic liver disease. A randomized, prospective study. Dig Surg 1999;16:471–7.

    Article  CAS  PubMed  Google Scholar 

  115. Katoh J, Tsuchiya K, Osawa H, et al. Cimetidine reduces impairment of cellular immunity after cardiac operations with cardiopulmonary bypass. J Thorac Cardiovasc Surg 1998;116:312–8.

    Article  CAS  PubMed  Google Scholar 

  116. Rothenburger M, Wilhelm M, Hammel D, et al. Immune response in the early postoperative period after implantation of a left-ventricular assist device system. Transplant Proc 2001;33:1955–7.

    Article  CAS  PubMed  Google Scholar 

  117. Wang LS, Lin HY, Chang CJ, Fahn HJ, Huang MH, Lin CF. Effects of en bloc esophagectomy on nutritional and immune status in patients with esophageal carcinoma. J Surg Oncol 1998;67:90–8.

    Article  CAS  PubMed  Google Scholar 

  118. Ogawa K, Hirai M, Katsube T, et al. Suppression of cellular immunity by surgical stress. Surgery 2000;127:329–36.

    Article  CAS  PubMed  Google Scholar 

  119. Cristaldi M, Rovati M, Elli M, et al. Lymphocytic subpopulation changes after open and laparoscopic cholecystectomy: a prospective and comparative study on 38 patients. Surg Laparosc Endosc 1997;7:255–61.

    Article  CAS  PubMed  Google Scholar 

  120. Decker D, Lindemann C, Springer W, Low A, Hirner A, von Ruecker A. Endoscopic vs. conventional hernia repair from an immunologic point of view. Surg Endosc 1999;13:335–9.

    Article  CAS  PubMed  Google Scholar 

  121. Decker D, Schondorf M, Bidlingmaier F, Hirner A, von Ruecker AA. Surgical stress induces a shift in the type-1/type-2 T-helper cell balance, suggesting down-regulation of cell-mediated and up-regulation of antibody-mediated immunity commensurate to the trauma. Surgery 1996;119:316–25.

    Article  CAS  PubMed  Google Scholar 

  122. Page GG, Ben-Eliyahu S, Liebeskind JC. The role of LGL/NK cells in surgery-induced promotion of metastasis and its attenuation by morphine. Brain Behav Immun 1994;8:241–50.

    Article  CAS  PubMed  Google Scholar 

  123. Brivio F, Gilardi R, Bucocev R, et al. Surgery-induced decline in circulating dendritic cells in operable cancer patients: a possible explanation of postoperative immunosuppression. Hepatogastroenterology 2000;47:1337–9.

    CAS  PubMed  Google Scholar 

  124. Kloosterman T, von Blomberg BM, Borgstein P, Cuesta MA, Scheper RJ, Meijer S. Unimpaired immune functions after laparoscopic cholecystectomy. Surgery 1994;115:424–8.

    CAS  PubMed  Google Scholar 

  125. Krohn CD, Reikeras O, Aasen AO. The cytokines IL-1beta and IL-1 receptor antagonist, IL-2 and IL-2 soluble receptor-alpha, IL-6 and IL-6 soluble receptor, TNF-alpha and TNF soluble receptor I, and IL10 in drained and systemic blood after major orthopaedic surgery. Eur J Surg 1999;165:101–9.

    Article  CAS  PubMed  Google Scholar 

  126. Hatada T, Miki C. Nutritional status and postoperative cytokine response in colorectal cancer patients. Cytokine 2000;12:1331–6.

    Article  CAS  PubMed  Google Scholar 

  127. Kono K, Sekikawa T, Matsumoto Y. Influence of surgical stress on monocytes and complications of infection in patients with esophageal cancer—monocyte HLA-DR antigen expression and respiratory burst capacity. J Surg Res 1995;58:275–80.

    Article  CAS  PubMed  Google Scholar 

  128. Sablotzki A, Dehne M, Welters I, et al. Alterations of the cytokine network in patients undergoing cardiopulmonary bypass. Perfusion 1997;12:393–403.

    Article  CAS  PubMed  Google Scholar 

  129. Hisano S, Sakamoto K, Ishiko T, Kamohara H, Ogawa M. IL-6 and soluble IL-6 receptor levels change differently after surgery both in the blood and in the operative field. Cytokine 1997;9:447–52.

    Article  CAS  PubMed  Google Scholar 

  130. Curtis GE, McAtear CA, Formela L, Walsh A, Shenkin A. The effect of nutritional status on the cytokine and acute phase protein responses to elective surgery. Cytokine 1995;7:380–8.

    Article  CAS  PubMed  Google Scholar 

  131. O’Nuallain EM, Puri P, Reen DJ. Early induction of IL-1 receptor antagonist (IL-1Ra) in infants and children undergoing surgery. Clin Exp Immunol 1993;93:218–22.

    Article  Google Scholar 

  132. Kristiansson M, Saraste L, Soop M, Sundqvist KG, Thorne A. Diminished interleukin-6 and C-reactive protein responses to laparoscopic versus open cholecystectomy. Acta Anaesthesiol Scand 1999;43:146–52.

    Article  CAS  PubMed  Google Scholar 

  133. Sakamoto K, Arakawa H, Mita S, et al. Elevation of circulating interleukin 6 after surgery: factors influencing the serum level. Cytokine 1994;6:181–6.

    Article  CAS  PubMed  Google Scholar 

  134. van Deuren M, Twickler TB, de Waal Malefyt MC, et al. Elective orthopedic surgery, a model for the study of cytokine activation and regulation. Cytokine 1998;10:897–903.

    Article  CAS  PubMed  Google Scholar 

  135. Hall GM, Peerbhoy D, Shenkin A, Parker CJ, Salmon P. Hip and knee arthroplasty: a comparison and the endocrine, metabolic and inflammatory responses. Clin Sci 2000;98:71–9.

    Article  CAS  Google Scholar 

  136. Nishiguchi K, Okuda J, Toyoda M, Tanaka K, Tanigawa N. Comparative evaluation of surgical stress of laparoscopic and open surgeries for colorectal carcinoma. Dis Colon Rectum 2001;44:223–30.

    Article  CAS  PubMed  Google Scholar 

  137. Holzheimer RG, Gross J, Schein M. Pro- and anti-inflammatory cytokine-response in abdominal aortic aneurysm repair: a clinical model of ischemia-reperfusion. Shock 1999;11:305–10.

    Article  CAS  PubMed  Google Scholar 

  138. Kudoh A, Katagai H, Takazawa T. Plasma inflammatory cytokine response to surgical trauma in chronic depressed patients. Cytokine 2001;13:104–8.

    Article  CAS  PubMed  Google Scholar 

  139. Kato M, Honda I, Suzuki H, Murakami M, Matsukawa S, Hashimoto Y. Interleukin-10 production during and after upper abdominal surgery. J Clin Anesth 1998;10:184–8.

    Article  CAS  PubMed  Google Scholar 

  140. Welborn MB, Oldenburg HS, Hess PJ, et al. The relationship between visceral ischemia, proinflammatory cytokines, and organ injury in patients undergoing thoracoabdominal aortic aneurysm repair. Crit Care Med 2000;28:3191–7.

    Article  CAS  PubMed  Google Scholar 

  141. Schwenk W, Jacobi C, Mansmann U, Bohm B, Muller JM. Inflammatory response after laparoscopic and conventional colorectal resections—results of a prospective randomized trial. Langenbecks Arch Surg 2000;385:2–9.

    Article  CAS  PubMed  Google Scholar 

  142. Holmberg A, Bergqvist D, Westman B, Siegbahn A. Cytokine and fibrinogen response in patients undergoing open abdominal aortic aneurysm surgery. Eur J Vasc Endovasc Surg 1999;17:294–300.

    Article  CAS  PubMed  Google Scholar 

  143. Kato M, Kurosawa S, Matsuoka H, Murakami M, Imai R, Takahashi M. Plasma soluble interleukin-2 receptor levels during and after upper abdominal surgery. Anaesth Intensive Care 2000;28:650–3.

    Article  CAS  PubMed  Google Scholar 

  144. Khan AL, Larsen F, Heys SD, Eremin O. Peri-operative acute phase response and cytokine release in women with breast cancer: modulation by polyadenylic-polyuridylic acid. Eur J Surg Oncol 1999;25:574–9.

    Article  CAS  PubMed  Google Scholar 

  145. Cruickshank AM, Fraser WD, Burns HJ, Van Damme J, Shenkin A. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci 1990;79:161–5.

    Article  CAS  Google Scholar 

  146. Yuen PM, Mak TW, Yim SF, et al. Metabolic and inflammatory responses after laparoscopic and abdominal hysterectomy. Am J Obstet Gynecol 1998;179:1–5.

    Article  CAS  PubMed  Google Scholar 

  147. Furukawa K, Tashiro T, Yamamori H, et al. Effects of soybean oil emulsion and eicosapentaenoic acid on stress response and immune function after a severely stressful operation. Ann Surg 1999;229:255–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Hubel K, Mansmann G, Schafer H, Oberhauser F, Diehl V, Engert A. Increase of anti-inflammatory cytokines in patients with esophageal cancer after perioperative treatment with G-CSF. Cytokine 2000;12:1797–800.

    Article  CAS  PubMed  Google Scholar 

  149. Misoph M, Babin-Ebell J. Interindividual variations in cytokine levels following cardiopulmonary bypass. Heart Vessels 1997;12:119–27.

    Article  CAS  PubMed  Google Scholar 

  150. McBride WT, Armstrong MA, Gilliland H, McMurray TJ. The balance of pro and anti-inflammatory cytokines in plasma and bronchoalveolar lavage (BAL) at paediatric cardiac surgery. Cytokine 1996;8:724–9.

    Article  CAS  PubMed  Google Scholar 

  151. Kruimel JW, Pesman GJ, Sweep CG, et al. Depression of plasma levels of cytokines and ex-vivo cytokine production in relation to the activity of the pituitary-adrenal axis, in patients undergoing major vascular surgery. Cytokine 1999;11:382–8.

    Article  CAS  PubMed  Google Scholar 

  152. Roth-Isigkeit A, Borstel TV, Seyfarth M, Schmucker P. Perioperative serum levels of tumour-necrosis-factor alpha (TNF-alpha), IL-1 beta, IL-6, IL-10 and soluble IL-2 receptor in patients undergoing cardiac surgery with cardiopulmonary bypass without and with correction for haemodilution. Clin Exp Immunol 1999;118:242–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. O’Nuallain EM, Puri P, Mealy K, Reen DJ. Induction of interleukin-1 receptor antagonist (IL-1ra) following surgery is associated with major trauma. Clin Immunol Immunopathol 1995;76:96–101.

    Article  PubMed  Google Scholar 

  154. Pruitt JH, Welborn MB, Edwards PD, et al. Increased soluble interleukin-1 type II receptor concentrations in postoperative patients and in patients with sepsis syndrome. Blood 1996;87:3282–8.

    CAS  PubMed  Google Scholar 

  155. Crozier TA, Muller JE, Quittkat D, Sydow M, Wuttke W, Kettler D. Effect of anaesthesia on the cytokine responses to abdominal surgery. Br J Anaesth 1994;72:280–5.

    Article  CAS  PubMed  Google Scholar 

  156. Lahat N, Shtiller R, Zlotnick AY, Merin G. Early IL-2/sIL-2R surge following surgery leads to temporary immune refractoriness. Clin Exp Immunol 1993;92:482–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Altomare DF, Caccavo D, Rinaldi M, et al. Postoperative changes in serum interleukin-2 concentrations. Eur J Surg 1997;163:493–9.

    CAS  PubMed  Google Scholar 

  158. Parodi JC, Ferreira LM, Fornari MC, Berardi VE, Diez RA. Neutrophil respiratory burst activity and pro- and anti-inflammatory cytokines in AAA surgery: conventional versus endoluminal treatment. J Endovasc Ther 2001;8:114–24.

    Article  CAS  PubMed  Google Scholar 

  159. Frank SM, Kluger MJ, Kunkel SL. Elevated thermostatic setpoint in postoperative patients. Anesthesiology 2000;93:1426–31.

    Article  CAS  PubMed  Google Scholar 

  160. Oldenburg HS, Burress Welborn M, Pruitt JH, et al. Interleukin-10 appearance following thoraco-abdominal and abdominal aortic aneurysm repair is associated with the duration of visceral ischaemia. Eur J Vasc Endovasc Surg 2000;20:169–72.

    Article  CAS  PubMed  Google Scholar 

  161. Smith RM, Giannoudis PV, Bellamy MC, Perry SL, Dickson RA, Guillou PJ. Interleukin-10 release and monocyte human leukocyte antigen-DR expression during femoral nailing. Clin Orthop 2000;233–40.

    Article  Google Scholar 

  162. Shirakawa T, Tokunaga A, Onda M. Release of immunosuppressive substances after gastric resection is more prolonged than after mastectomy in humans. Int Surg 1998;83:210–4.

    CAS  PubMed  Google Scholar 

  163. Barton DP, Blanchard DK, Michelini-Norris B, et al. Serum soluble interleukin-2 receptor alpha levels in patients with gynecologic cancers: early effect of surgery. Am J Reprod Immunol 1993;30:202–6.

    Article  CAS  PubMed  Google Scholar 

  164. Sietses C, Wiezer MJ, Eijsbouts QA, et al. A prospective randomized study of the systemic immune response after laparoscopic and conventional Nissen fundoplication. Surgery 1999;126:5–9.

    Article  CAS  PubMed  Google Scholar 

  165. Redmond HP, Watson RW, Houghton T, Condron C, Watson RG, Bouchier-Hayes D. Immune function in patients undergoing open vs laparoscopic cholecystectomy. Arch Surg 1994;129:1240–6.

    Article  CAS  PubMed  Google Scholar 

  166. Wallace AM, Sattar N, McMillan DC. The co-ordinated cytokine/hormone response to acute injury incorporates leptin. Cytokine 2000;12:1042–5.

    Article  CAS  PubMed  Google Scholar 

  167. Mizutani Y, Terachi T, Okada Y, Yoshida O. Effect of surgical stress on immune function in patients with urologic cancer. Int J Urol 1996;3:426–34.

    Article  CAS  PubMed  Google Scholar 

  168. Booker PD, Taylor C, Saba G. Perioperative changes in alpha 1-acid glycoprotein concentrations in infants undergoing major surgery. Br J Anaesth 1996;76:365–8.

    Article  CAS  PubMed  Google Scholar 

  169. Naito Y, Fukata J, Tamai S, et al. Biphasic changes in hypothalamo-pituitary-adrenal function during the early recovery period after major abdominal surgery. J Clin Endocrinol Metab 1991;73:111–7.

    Article  CAS  PubMed  Google Scholar 

  170. Donald RA, Perry EG, Wittert GA, et al. The plasma ACTH, AVP, CRH and catecholamine responses to conventional and laparoscopic cholecystectomy. Clin Endocrinol 1993;38:609–15.

    Article  CAS  Google Scholar 

  171. Aono H, Takeda A, Tarver SD, Goto H. Stress responses in three different anesthetic techniques for carbon dioxide laparoscopic cholecystectomy. J Clin Anesth 1998;10:546–50.

    Article  CAS  PubMed  Google Scholar 

  172. Karayiannakis AJ, Makri GG, Mantzioka A, Karousos D, Karatzas G. Systemic stress response after laparoscopic or open cholecystectomy: a randomized trial. Br J Surg 1997;84:467–71.

    CAS  PubMed  Google Scholar 

  173. Ozawa A, Konishi F, Nagai H, Okada M, Kanazawa K. Cytokine and hormonal responses in laparoscopic-assisted colectomy and conventional open colectomy. Surg Today 2000;30:107–11.

    Article  CAS  PubMed  Google Scholar 

  174. Tonnesen H, Rosenberg J, Nielsen HJ, et al. Effect of preoperative abstinence on poor postoperative outcome in alcohol misusers: randomised controlled trial. BMJ 1999;318:1311–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Le Blanc-Louvry I, Coquerel A, Koning E, Maillot C, Ducrotte P. Operative stress response is reduced after laparoscopic compared to open cholecystectomy: the relationship with postoperative pain and ileus. Dig Dis Sci 2000;45:1703–13.

    Article  CAS  PubMed  Google Scholar 

  176. Guieu R, Dufour H, Devaux C, et al. The hormonal response to stress is not modified by the dramatic decrease in prolactin plasma concentration during surgery for microprolactinoma. J Neurol Neurosurg Psychiatry 1998;65:502–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Dubois M, Pickar D, Cohen M, Gadde P, Macnamara TE, Bunney WE. Effects of fentanyl on the response of plasma beta-endorphin immunoreactivity to surgery. Anesthesiology 1982;57:468–72.

    Article  CAS  PubMed  Google Scholar 

  178. Elimam A, Tjader I, Norgren S, et al. Total parenteral nutrition after surgery rapidly increases serum leptin levels. Eur J Endocrinol 2001;144:123–8.

    Article  CAS  PubMed  Google Scholar 

  179. Motamed S, Klubien K, Edwardes M, Mazza L, Carli F. Metabolic changes during recovery in normothermic versus hypothermic patients undergoing surgery and receiving general anesthesia and epidural local anesthetic agents. Anesthesiology 1998;88:1211–8.

    Article  CAS  PubMed  Google Scholar 

  180. Chernow B, Alexander HR, Smallridge RC, et al. Hormonal responses to graded surgical stress. Arch Intern Med 1987;147:1273–8.

    Article  CAS  PubMed  Google Scholar 

  181. Pickar D, Cohen MR, Dubois M. The relationship of plasma cortisol and beta-endorphin immunoreactivity to surgical stress and postoperative analgesic requirement. Gen Hosp Psychiatry 1983;5:93–8.

    Article  CAS  PubMed  Google Scholar 

  182. DeKeyser FG, Leker RR, Weidenfeld J. Activation of the adrenocortical axis by surgical stress: involvement of central norepinephrine and interleukin-1. Neuroimmunomodulation 2000;7:182–8.

    Article  CAS  PubMed  Google Scholar 

  183. Bessler M, Whelan RL, Halverson A, Treat MR, Nowygrod R. Is immune function better preserved after laparoscopic versus open colon resection? Surg Endosc 1994;8:881–3.

    Article  CAS  PubMed  Google Scholar 

  184. Berkenbosch F, Vermes I, Tilders FJ. The beta-adrenoceptor-blocking drug propranolol prevents secretion of immunoreactive beta-endorphin and alpha-melanocyte-stimulating hormone in response to certain stress stimuli. Endocrinology 1984;115:1051–9.

    Article  CAS  PubMed  Google Scholar 

  185. Brinkmann A, Seeling W, Wolf CF, et al. Ibuprofen does not impair renal function in patients undergoing infrarenal aortic surgery with epidural anaesthesia. Intensive Care Med 1998;24:322–8.

    Article  CAS  PubMed  Google Scholar 

  186. Vogeser M, Felbinger TW, Kilger E, Roll W, Fraunberger P, Jacob K. Corticosteroid-binding globulin and free cortisol in the early postoperative period after cardiac surgery. Clin Biochem 1999;32:213–6.

    Article  CAS  PubMed  Google Scholar 

  187. Tinnikov AA, Legan MV, Sheveluk NA, Cvetovskaya GA, Naumenko SE, Sidelnikov SG. Corticosteroid and immune responses to cardiac surgery. Steroids 1996;61:411–5.

    Article  CAS  PubMed  Google Scholar 

  188. Dalin AM, Magnusson U, Haggendal J, Nyberg L. The effect of thiopentone-sodium anesthesia and surgery, relocation, grouping, and hydrocortisone treatment on the blood levels of cortisol, corticosteroid-binding globulin, and catecholamines in pigs. J Anim Sci 1993;71:1902–9.

    Article  CAS  PubMed  Google Scholar 

  189. Tashiro T, Yamamori H, Takagi K, Morishima Y, Nakajima N. Effect of severity of stress on whole-body protein kinetics in surgical patients receiving parenteral nutrition. Nutrition 1996;12:763–5.

    Article  CAS  PubMed  Google Scholar 

  190. Bacher H, Mischinger HJ, Cerwenka H, et al. Liver ischemia, catecholamines and preoperative condition influencing postoperative tachycardia in liver surgery. Life Sci 2000;66:11–8.

    Article  CAS  PubMed  Google Scholar 

  191. Troullos E, Hargreaves KM, Dionne RA. Ibuprofen elevates immunoreactive beta-endorphin levels in humans during surgical stress. Clin Pharmacol Ther 1997;62:74–81.

    Article  CAS  PubMed  Google Scholar 

  192. Baxevanis CN, Papilas K, Dedoussis GV, Pavlis T, Papamichail M. Abnormal cytokine serum levels correlate with impaired cellular immune responses after surgery. Clin Immunol Immunopathol 1994;71:82–8.

    Article  CAS  PubMed  Google Scholar 

  193. Vitoratos N, Hassiakos D, Louridas C, Limuris G, Zourlas PA. Prostaglandin F1a and prostaglandin E2 plasma levels after transvaginal cervical cerclage. Clin Exp Obstet Gynecol 1996;23:21–5.

    CAS  PubMed  Google Scholar 

  194. Quintiliani L, Pescini A, Di Girolamo M, et al. Relationship of blood transfusion, post-operative infections and immunoreactivity in patients undergoing surgery for gastrointestinal cancer. Haematologica 1997;82:318–23.

    CAS  PubMed  Google Scholar 

  195. Parsson HN, Lord RS, Scott K, Zemack G. Maintaining carotid flow by shunting during carotid endarterectomy diminishes the inflammatory response mediating ischaemic brain injury. Eur J Vasc Endovasc Surg 2000;19:124–30.

    Article  CAS  PubMed  Google Scholar 

  196. Lai OF, Chow PK, Tan S, et al. Changes in prostaglandin and nitric oxide levels in the hyperdynamic circulation following liver resection. J Gastroenterol Hepatol 2000;15:895–901.

    Article  CAS  PubMed  Google Scholar 

  197. Riese J, Schoolmann S, Beyer A, Denzel C, Hohenberger W, Haupt W. Production of IL-6 and MCP-1 by the human peritoneum in vivo during major abdominal surgery. Shock 2000;14:91–4.

    Article  CAS  PubMed  Google Scholar 

  198. Pirenne J, Ribbens C, Medot M, et al. Adverse effect of abdominal operations on production of interferon-gamma. Eur J Surg 1995;161:77–83.

    CAS  PubMed  Google Scholar 

  199. Lemaire LC, van der Poll T, van Lanschot JJ, et al. Minimally invasive surgery induces endotoxin-tolerance in the absence of detectable endotoxemia. J Clin Immunol 1998;18:414–20.

    Article  CAS  PubMed  Google Scholar 

  200. Kawasaki T, Ogata M, Kawasaki C, Tomihisa T, Okamoto K, Shigematsu A. Surgical stress induces endotoxin hyporesponsiveness and an early decrease of monocyte mCD14 and HLA-DR expression during surgery. Anesth Analg 2001;92:1322–6.

    Article  CAS  PubMed  Google Scholar 

  201. Brune IB, Wilke W, Hensler T, Holzmann B, Siewert JR. Downregulation of T helper type 1 immune response and altered pro-inflammatory and anti-inflammatory T cell cytokine balance following conventional but not laparoscopic surgery. Am J Surg 1999;177:55–60.

    Article  CAS  PubMed  Google Scholar 

  202. Griffith JP, Everitt NJ, Lancaster F, et al. Influence of laparoscopic and conventional cholecystectomy upon cell-mediated immunity. Br J Surg 1995;82:677–80.

    Article  CAS  PubMed  Google Scholar 

  203. 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.

    Article  CAS  PubMed  Google Scholar 

  204. Lee SW, Southall JC, Gleason NR, Huang EH, Bessler M, Whelan RL. Lymphocyte proliferation in mice after a full laparotomy is the same whether performed in a sealed carbon dioxide chamber or in room air. Surg Endosc 2000;14:235–8.

    Article  CAS  PubMed  Google Scholar 

  205. Pollock RE, Lotzova E, Stanford SD. Mechanism of surgical stress impairment of human perioperative natural killer cell cytotoxicity. Arch Surg 1991;126:338–42.

    Article  CAS  PubMed  Google Scholar 

  206. Khan AL, Richardson S, Drew J, et al. Polyadenylic-polyuridylic acid enhances the natural cell-mediated cytotoxicity in patients with breast cancer undergoing mastectomy. Surgery 1995;118:531–8.

    Article  CAS  PubMed  Google Scholar 

  207. Tonnesen E, Huttel MS, Christensen NJ. Natural killer cell activity in patients undergoing minor gynaecological surgery. Eur J Anaesthesiol 1987;4:119–25.

    Google Scholar 

  208. Sandoval BA, Robinson AV, Sulaiman TT, Shenk RR, Stellato TA. Open versus laparoscopic surgery: a comparison of natural antitumoral cellular immunity in a small animal model. Am Surg 1996;62:625–31.

    CAS  PubMed  Google Scholar 

  209. Zoller M, Heumann U, Betzler M, Stimmel H, Matzku S. Depression of nonadaptive immunity after surgical stress: influence on metastatic spread. Invasion Metastasis 1989;9:46–68.

    CAS  PubMed  Google Scholar 

  210. Toft P, Dagnaes-Hansen F, Tonnesen E, Basse PM. The effect of surgical stress and endotoxin-induced sepsis on the NK-cell activity, distribution and pulmonary clearance of YAC-1 and melanoma cells. APMIS 1999;107:359–64.

    Article  CAS  PubMed  Google Scholar 

  211. Da Costa ML, Redmond HP, Finnegan N, Flynn M, Bouchier-Hayes D. Laparotomy and laparoscopy differentially accelerate experimental flank tumour growth. Br J Surg 1998;85:1439–42.

    Article  CAS  PubMed  Google Scholar 

  212. Sietses C, Wiezer MJ, Eijsbouts QA, et al. The influence of laparoscopic surgery on postoperative polymorphonuclear leukocyte function. Surg Endosc 2000;14:812–6.

    Article  CAS  PubMed  Google Scholar 

  213. Redmond HP, Hofmann K, Shou J, Leon P, Kelly CJ, Daly JM. Effects of laparotomy on systemic macrophage function. Surgery 1992;111:647–55.

    CAS  PubMed  Google Scholar 

  214. Freire-Garabal M, Nunez MJ, Balboa JL, Gonzalez-Bahillo J, Belmonte A. Effects of midazolam on the activity of phagocytosis in mice submitted to surgical stress. Pharmacol Biochem Behav 1993;46:605–8.

    Article  CAS  PubMed  Google Scholar 

  215. Sietses C, Havenith CE, Eijsbouts QA, van Leeuwen PA, Meijer S, Beelen RH, Cuesta MA. Laparoscopic surgery preserves monocyte-mediated tumor cell killing in contrast to the conventional approach. Surg Endosc 2000;14:456–60.

    Article  CAS  PubMed  Google Scholar 

  216. Wakefield CH, Carey PD, Foulds S, Monson JR, Guillou PJ. Changes in major histocompatibility complex class II expression in monocytes and T cells of patients developing infection after surgery. Br J Surg 1993;80:205–9.

    Article  CAS  PubMed  Google Scholar 

  217. Delogu G, Moretti S, Antonucci A, et al. Apoptosis and surgical trauma: dysregulated expression of death and survival factors on peripheral lymphocytes. Arch Surg 2000;135:1141–7.

    Article  CAS  PubMed  Google Scholar 

  218. Hjortso NC, Andersen T, Frosig F, Neumann P, Rogon E, Kehlet H. Failure of epidural analgesia to modify postoperative depression of delayed hypersensitivity. Acta Anaesthesiol Scand 1984;28:128–31.

    Article  CAS  PubMed  Google Scholar 

  219. Hammer JH, Nielsen HJ, Moesgaard F, Kehlet H. Duration of postoperative immunosuppression assessed by repeated delayed type hypersensitivity skin tests. Eur Surg Res 1992;24:133–7.

    Article  CAS  PubMed  Google Scholar 

  220. Markewitz A, Faist E, Lang S, Hultner L, Weinhold C, Reichart B. An imbalance in T-helper cell subsets alters immune response after cardiac surgery. Eur J Cardiothorac Surg 1996;10:61–7.

    Article  CAS  PubMed  Google Scholar 

  221. Gitzelmann CA, Mendoza-Sagaon M, Talamini MA, Ahmad SA, Pegoli W Jr, Paidas CN. Cell-mediated immune response is better preserved by laparoscopy than laparotomy. Surgery 2000;127:65–71.

    Article  CAS  PubMed  Google Scholar 

  222. Allendorf JD, Bessler M, Whelan RL, et al. Postoperative immune function varies inversely with the degree of surgical trauma in a murine model. Surg Endosc 1997;11:427–30.

    Article  CAS  PubMed  Google Scholar 

  223. Little D, Regan M, Keane RM, Bouchier-Hayes D. Perioperative immune modulation. Surgery 1993;114:87–91.

    CAS  PubMed  Google Scholar 

  224. Garcia-Lechuz JM, Navarro M, Morandeira MJ, et al. Immunorestorative effect of thymostimulin on surgery immunodepression: experimental model. Eur Surg Res 1993;25:74–82.

    Article  CAS  PubMed  Google Scholar 

  225. Radosevic-Stasic B, Cuk M, Mrakovcic-Sutic I, et al. Immunosuppressive properties of halothane anesthesia and/or surgical stress in experimental conditions. Int J Neurosci 1990;51:235–6.

    Article  CAS  PubMed  Google Scholar 

  226. Jacobi CA, Ordemann J, Zieren HU, et al. Increased systemic inflammation after laparotomy vs laparoscopy in an animal model of peritonitis. Arch Surg 1998;133:258–62.

    Article  CAS  PubMed  Google Scholar 

  227. Balague C, Targarona EM, Pujol M, Filella X, Espert JJ, Trias M. Peritoneal response to a septic challenge. Comparison between open laparotomy, pneumoperitoneum laparoscopy, and wall lift laparoscopy. Surg Endosc 1999;13:792–6.

    Article  CAS  PubMed  Google Scholar 

  228. Chekan EG, Nataraj C, Clary EM, et al. Intraperitoneal immunity and pneumoperitoneum. Surg Endosc 1999;13:1135–8.

    Article  CAS  PubMed  Google Scholar 

  229. Hattori T, Hamai Y, Takiyama W, Hirai T, Ikeda T. Enhancing effect of thoracotomy on tumor growth in rats with special reference to the duration and timing of the operation. Gann 1980;71:280–4.

    CAS  PubMed  Google Scholar 

  230. Hirai T, Yoshimoto A, Iwata T, Yamashita Y, Kuwahara M, Toge T. Enhancing effect of thoraco-laparotomy on liver metastasis and the role played by active oxygens in its mechanism. Surg Today 1997;27:1040–5.

    Article  CAS  PubMed  Google Scholar 

  231. Da Costa ML, Redmond P, Bouchier-Hayes DJ. The effect of laparotomy and laparoscopy on the establishment of spontaneous tumor metastases. Surgery 1998;124:516–25.

    Article  CAS  PubMed  Google Scholar 

  232. Kuntz C, Wunsch A, Rosch R, Autschbach F, Windeler J, Herfarth C. Short- and long-term results after laparoscopic vs conventional colon resection in a tumor-bearing small animal model. Surg Endosc 2000;14:561–7.

    Article  CAS  PubMed  Google Scholar 

  233. Shiromizu A, Suematsu T, Yamaguchi K, Shiraishi N, Adachi Y, Kitano S. Effect of laparotomy and laparoscopy on the establishment of lung metastasis in a murine model. Surgery 2000;128:799–805.

    Article  CAS  PubMed  Google Scholar 

  234. Bouvy ND, Marquet RL, Jeekel H, Bonjer HJ. Impact of gas(less) laparoscopy and laparotomy on peritoneal tumor growth and abdominal wall metastases. Ann Surg 1996;224:694–701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  235. Bouvy ND, Marquet RL, Jeekel J, Bonjer HJ. Laparoscopic surgery is associated with less tumour growth stimulation than conventional surgery: an experimental study. Br J Surg 1997;84:358–61.

    CAS  PubMed  Google Scholar 

  236. Mutter D, Hajri A, Tassetti V, Solis-Caxaj C, Aprahamian M, Marescaux J. Increased tumor growth and spread after laparoscopy vs laparotomy: influence of tumor manipulation in a rat model. Surg Endosc 1999;13:365–70.

    Article  CAS  PubMed  Google Scholar 

  237. Allendorf JD, Bessler M, Horvath KD, Marvin MR, Laird DA, Whelan RL. Increased tumor establishment and growth after open vs laparoscopic bowel resection in mice. Surg Endosc 1998;12:1035–8.

    Article  CAS  PubMed  Google Scholar 

  238. Allendorf JD, Bessler M, Horvath KD, Marvin MR, Laird DA, Whelan RL. Increased tumor establishment and growth after open vs laparoscopic surgery in mice may be related to differences in postoperative T-cell function. Surg Endosc 1999;13:233–5.

    Article  CAS  PubMed  Google Scholar 

  239. Lundy J, Lovett EJ, Hamilton S, Conran P. Halothane, surgery, immunosuppression and artificial pulmonary metastases. Cancer 1978;41:827–30.

    Article  CAS  PubMed  Google Scholar 

  240. Tanemura H, Sakata K, Kunieda T, Saji S, Yamamoto S, Takekoshi T. Influences of operative stress on cell-mediated immunity and on tumor metastasis and their prevention by nonspecific immunotherapy: experimental studies in rats. J Surg Oncol 1982;21:189–95.

    Article  CAS  PubMed  Google Scholar 

  241. Rushfeldt C, Sveinbjornsson B, Seljelid R, Smedsrod B. Early events of hepatic metastasis formation in mice: role of Kupffer and NK-cells in natural and interferon-gamma-stimulated defense. J Surg Res 1999;82:209–15.

    Article  CAS  PubMed  Google Scholar 

  242. Weese JL, Emoto SE, Sondel PM. Reduced incidence of hepatic metastases by perioperative treatment with recombinant human interleukin-2. Dis Colon Rectum 1987;30:503–7.

    Article  CAS  PubMed  Google Scholar 

  243. Weese JL, Gilbertson EM, Syrjala SE, Starling JR. Prevention of rat colon cancer metastases by perioperative immunostimulation. Surgery 1984;96:420–6.

    CAS  PubMed  Google Scholar 

  244. Weese JL, Gilbertson EM, Syrjala SE, Whitney PD, Starling JR. Reduced incidence of rat colon cancer metastases by perioperative immunostimulation with maleic anhydride-divinyl ether-2 (MVE-2). Dis Colon Rectum 1985;28:217–21.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  246. Oka M, Hazama S, Suzuki M, et al. Depression of cytotoxicity of nonparenchymal cells in the liver after surgery. Surgery 1994;116:877–82.

    CAS  PubMed  Google Scholar 

  247. Eggermont AM, Steller EP, Sugarbaker PH. Laparotomy enhances intraperitoneal tumor growth and abrogates the antitumor effects of interleukin-2 and lymphokine-activated killer cells. Surgery 1987;102:71–8.

    CAS  PubMed  Google Scholar 

  248. Gorelik E, Segal S, Feldman M. Host’s immune state and kinetics of local tumor growth control—progression of postoperative lung metastasis. Recent Results Cancer Res 1980;75:20–8.

    Article  CAS  PubMed  Google Scholar 

  249. Pollock RE, Babcock GF, Romsdahl MM, Nishioka K. Surgical stress-mediated suppression of murine natural killer cell cytotoxicity. Cancer Res 1984;44:3888–91.

    CAS  PubMed  Google Scholar 

  250. Dorrance HR, Oien K, O’Dwyer PJ. Effects of laparoscopy on intraperitoneal tumor growth and distant metastases in an animal model. Surgery 1999;126:35–40.

    Article  CAS  PubMed  Google Scholar 

  251. Saba TM, Antikatzides TG. Decreased resistance to intravenous tumour-cell challenge during reticuloendothelial depression following surgery. Br J Cancer 1976;34:381–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  252. Lewis MR, Cole WH. Experimental increase of lung metastases after operative trauma (amputation of limb with tumour). Arch Surg 1958;77:621.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neuroimmunology Research Unit, Department of Psychology, Tel Aviv University, Tel Aviv, Israel

    Guy Shakhar PhD & Shamgar Ben-Eliyahu PhD

  2. Department of Psychology, Tel Aviv University, Ramat Aviv, Tel Aviv, 69978, Israel

    Shamgar Ben-Eliyahu PhD

Authors
  1. Guy Shakhar PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shamgar Ben-Eliyahu PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shamgar Ben-Eliyahu PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shakhar, G., Ben-Eliyahu, S. Potential Prophylactic Measures Against Postoperative Immunosuppression: Could They Reduce Recurrence Rates in Oncological Patients?. Ann Surg Oncol 10, 972–992 (2003). https://doi.org/10.1245/ASO.2003.02.007

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/ASO.2003.02.007

Key Words

Search

Navigation