title: Combined spinal and general anesthesia attenuates liver metastasis by preserving TH1/TH2 cytokine balance.
abstract: BACKGROUND
  Many studies have shown that regional anesthesia improves postoperative outcome and particularly lessens infection by attenuating perioperative immunosuppression related to the stress response to surgery and general anesthesia. However, it remains to be determined whether regional anesthesia improves oncologic outcome after surgery.
  
  
  METHODS
  C57BL/6 mice were subjected to laparotomy during sevoflurane general anesthesia alone or combined with spinal block achieved with bupivacaine (5 microg) and morphine (1.25 microg). Control groups were anesthetized only or were untreated. Liver was removed 5 h after surgery to assess antitumor killer cell activity and production of interferon gamma and interleukin 4 by liver mononuclear cells, or mice were inoculated intravenously with liver-metastatic EL4 cells and hepatic metastases were counted 12 days later.
  
  
  RESULTS
  Laparotomy during sevoflurane anesthesia significantly increased the number (+/- SD) of liver metastases from 15.5 +/- 8.7 (control) and 19.4 +/- 5.4 (sevoflurane alone) to 33.7 +/- 8.9. Sevoflurane anesthesia plus spinal block significantly reduced this increase to 19.8 +/- 9. The in vitro killer activity of liver mononuclear cells against EL4 cells decreased from 32.7% (control) and 29.4% (sevoflurane alone) to 18.5% after sevoflurane plus laparotomy, and the addition of spinal block increased activity to 26.6%. The interferon-gamma/interleukin-4 ratio decreased from 89.3 (control) and 95.7 (anesthesia alone) to 15.7 after sevoflurane plus laparotomy, and the addition of spinal block increased the ratio to 46.5.
  
  
  CONCLUSIONS
  The addition of spinal block to sevoflurane general anesthesia accompanying surgery attenuates the suppression of tumoricidal function of liver mononuclear cells, presumably by preserving the T helper 1/T helper 2 (Th1/Th2) balance, and thereby reduces the promotion of tumor metastasis.
authors.affiliation: Department of Anesthesiology, National Defense Medical College, Namiki, Tokorozawa, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Wada
authors.forename: Shuhji
authors.initials: S
authors.lastname: Seki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takahashi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Kawarabayashi
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Higuchi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Habu
authors.forename: Shinya
authors.initials: S
authors.lastname: Sugahara
authors.forename: Tomiei
authors.initials: T
authors.lastname: Kazama
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000768:Anesthesia, General / Q000379:methods; D000775:Anesthesia, Spinal / Q000379:methods; D019162:Anesthetics, Combined / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000187:drug effects; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control* / Q000556:secondary; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D009407:Nerve Block / Q000379:methods; D000077149:Sevoflurane; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D000701:Analgesics, Opioid; D019162:Anesthetics, Combined; D018685:Anesthetics, Inhalation; D000779:Anesthetics, Local; D016207:Cytokines; D008738:Methyl Ethers; D015847:Interleukin-4; D000077149:Sevoflurane; D009020:Morphine; D007371:Interferon-gamma; D002045:Bupivacaine