Post-operative levamisole may compromise early healing of experimental intestinal anastomoses

Abstract

Summary There exists growing interest in immediate post-operative local adjuvant therapy after resection of intestinal malignancies. It is therefore necessary to assess its potential effect on the healing of intestinal anastomoses. Five groups (n = 20) of rats underwent resection and anastomosis of both ileum and colon: a control group and four experimental groups receiving intraperitoneal 5-fluorouracil (5-FU), 5-FU plus leucovorin, 5-FU plus levamisole or levamisole alone, on the day of surgery and the next 2 days. Animals were killed 3 or 7 days after operation. Another three groups (n = 6) of animals were used to compare anastomotic collagen synthetic capacity in control rats or rats receiving 5-FU or 5-FU plus levamisole. On the third post-operative day, the average anastomotic bursting pressure in the 5-FU/levamisole group was reduced by 36% as compared with the control group, both in ileum (P = 0.02) and in colon (P = 0.01). Values in the other groups were similar to those in the control group. Anastomotic breaking strength was significantly (P<0.025) lowered in the ileum from the levamisole group at both days 3 and 7. Anastomotic collagen synthetic capacity was strongly reduced in the 5-FU and 5-FU/levamisole groups. However, there was no significant difference between the control group and the four experimental groups with regard to anastomotic hydroxyproline concentration and content, either 3 or 7 days after operation. Thus, limited use of levamisole, alone or in combination with intraperitoneal 5-FU, may compromise intestinal healing.

Combined preoperative irradiation and direct postoperative 5-fluorouracil without negative effects on early anastomotic healing in the rat colon

“…The bursting site was noted. The breaking strength of the segment, as a measure of the resistance to longitudinal forces, was measured immedi ately after determination of the bursting pressure [27], The segment was placed in a tensiometer that provided a constantly increasing distraction, The peak force (in g) necessary to induce total disruption of the segment was taken as the breaking strength. The breaking site was noted.…”

The effects of 5-fluorouracil and interferon-α on early healing of experimental intestinal anastomoses

“…Cytostatic drugs are by nature anti-proliferative and may therefore be expected to interfere with wound healing. Indeed, 5-FU administered daily from the day of operation onwards until sacrifice after 7 days severely impairs anastomotic healing in the rat intestine (Graf et al, 1992;de Waard et al, 1995b). In earlier experiments, we tried to mitigate this negative effect by concomitant administration of either interleukin 2 or granulocytemacrophage colony-stimulating factor, but 5-FU impaired repair was not essentially altered by either cytokine.…”

“…The validity of this procedure has been confirmed in a pilot experiment. Anastomotic breaking strength was compared in two groups of rats, either measured directly or after the procedure used for measuring the bursting pressure, and found to be similar in both groups (de Waard et al, 1995b). The anastomotic segment was then cleaned from the surrounding tissue and a 5 mm segment with the suture line in the middle was collected.…”

“…If administration of 5-FU remains limited to the day of operation and the first two post-operative days anastomotic strength is not significantly affected (de Waard et al, 1993). In a recent experiment we have examined the effects of 5-FU plus levamisole or leucovorin on anastomotic healing (de Waard et al, 1995b). Here, we describe our experiments into the effects of a 3 day post-operative course of interferon-a and interferon-a plus 5-FU on early healing of intestinal anastomoses in the rat.…”

Safety of total gastrectomy without nasogastric and nutritional intubation

“…During the first postoperative days, wound strength is considered to solely depend on the suture-holding capacity of the existing collagen fibrils (27). From 3 h to 4 days after the operation, the absolute and the relative collagen synthesis steadily increases (26,28), providing evidence that an anastomosis strength increases from the beginning of wound healing, and the risk of anastomotic leakage decreases. The role of intubation in the healing of anastomosis is controversial, as a previous study demonstrated that an indwelling catheter traversing the anastomosis slows down the healing process in that segment (29).…”