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-α (TNF-α) 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-α production by lipopolysaccharide (LPS) stimulated monocyte was much higher than that by monocyte without LPS stimulation. Gabexate mesilate showed a little inhibition of TNF-α production by monocyte without LPS stimulation. On the other hand, gabexate mesilate significantly inhibited TNF-α 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-α production capacity and Mac-1 expression on monocytes immediately after operation, and to suppression of increase in serum IL-6 level.