Effects of a protease inhibitor on reduction of surgical stress in esophagectomy.
OBJECTIVE
To evaluate the efficacy of gabexate mesilate (GM) in reducing surgical stress after esophagectomy.


METHODS
In a prospective, randomized, clinical study, 11 patients with squamous cell carcinoma of the esophagus were randomly assigned to two groups: 5 patients were continuously administered gabexate mesilate 1.5 mg/kg per hour from the beginning of anesthesia until the third postoperative day (preop GM group); and 6 patients were administered gabexate mesilate 1.5 mg/kg per hour continuously from the end of surgery and for the same postoperative period (postop GM group). Blood samples were taken from all patients before surgery, immediately after it, and 3 days after surgery. Serum interleukin-6 (IL-6) level, tumor necrosis factor-alpha (TNF-alpha) production, and Mac-1 antigen expression of peripheral blood monocytes were measured. Clinical courses of patients in the two groups were compared.


RESULTS
Time courses of serum IL-6 levels in the preop GM group were significantly lower than those in the postop GM group. Ex vivo TNF-alpha production by lipopolysaccharide (LPS) stimulated monocyte was much higher than that by monocyte without LPS stimulation. Gabexate mesilate showed a little inhibition of TNF-alpha production by monocyte without LPS stimulation. On the other hand, gabexate mesilate significantly inhibited TNF-alpha production by LPS stimulated monocyte. Mac-1 antigen expression by monocyte immediately after operation in the preop GM group was significantly lower than that in the postop GM group. Duration of systemic inflammatory response syndrome was significantly shorter in the preop GM group than in the postop GM group.


CONCLUSIONS
Reduction of systemic inflammatory response syndrome duration after esophagectomy by the continuous administration of gabexate mesilate started before operation may be through the suppression of TNF-alpha production capacity and Mac-1 expression on monocytes immediately after operation, and to suppression of increase in serum IL-6 level.
Ono
S
S
First Department of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan.
Aosasa
S
S
Mochizuki
H
H
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000601:surgery*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000601:surgery*; D016629:Esophagectomy; D005260:Female; D016670:Gabexate / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D016177:Macrophage-1 Antigen / Q000097:blood; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000276:immunology / Q000517:prevention & control*; D011292:Premedication; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology / Q000517:prevention & control*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D016177:Macrophage-1 Antigen; D015842:Serine Proteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016670:Gabexate