title: Clinical monitoring of innate cellular immunity of monocytes/macrophages by tumor necrosis factor alpha productivity in whole blood stimulated by lipopolysaccharide in patients with pancreatic cancer.
abstract: OBJECTIVE
  The aim of this study was to evaluate the tumor necrosis factor alpha (TNF-alpha) releasing capacity in whole blood stimulated by lipopolysaccharide (LPS) in patients with pancreatic cancer during the perioperative period, and before and after chemotherapy.
  
  
  METHODS
  The current study involved a total of 39 patients with pancreatic cancer (PC), who were further divided into a PC-Op group (n = 16, underwent pancreatectomy) and a PC-chemo group (n = 23, received chemotherapy). The control groups consisted of patients with hepatocellular carcinoma (n = 27, HCC group) and with benign diseases (n = 15, control group). Serial changes in TNF-alpha in whole blood stimulated by LPS were compared in various clinical settings.
  
  
  RESULTS
  Preoperative TNF-alpha levels in the PC-Op group were significantly lower than those in the HCC and control groups (P = 0.034). The TNF-alpha variable surgical index (s-index) was defined as the ratio of the preoperative TNF-alpha level to postoperative level in the PC-Op and HCC groups. Although the TNF-alpha s-index in the PC-Op group was significantly decreased on postoperative day 1 and recovered on postoperative day 3 (P < 0.002), there were no significant changes in the TNF-alpha s-index in the HCC group. The TNF-alpha variable chemotherapeutic index (c-index) was defined as the ratio of the TNF-alpha level before to that after chemotherapy in the PC-chemo group. The TNF-alpha c-index in all 7 patients was reduced to less than 0.3 until leukopenia appeared. Patients who had an increase in TNF-alpha production (TNF-alpha c-index >1.0) on day 3 or 7 after chemotherapy had significantly better cumulative survival than those with no increase (P < 0.033).
  
  
  CONCLUSIONS
  TNF-alpha production stimulated by LPS in the whole blood of patients with pancreatic cancer was low. Surgical stress and depressed immunocompetence might induce such profound decreases. A method of assessing the capability of leukocytes, particularly macrophages, to produce TNF-alpha could be useful for prognostis and for monitoring immunocompetence in patients with pancreatic cancer who have undergone chemotherapy.
authors.affiliation: Departments of Surgery, Kansai Medical University, Osaka, Japan.
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Terakawa
authors.forename: Sohei
authors.initials: S
authors.lastname: Satoi
authors.forename: Soichiro
authors.initials: S
authors.lastname: Takai
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yanagimoto
authors.forename: Kanji
authors.initials: K
authors.lastname: Takahashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Komiyama
authors.forename: Kwon
authors.initials: K
authors.lastname: A-Hon
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kamiyama
authors.forename: Hakuo
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000276:immunology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007111:Immunity, Cellular; D008070:Lipopolysaccharides; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000601:surgery*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D003841:Deoxycytidine; D005472:Fluorouracil; D000093542:Gemcitabine