GastrointestinalEffect of IGF-I on Healing of Colonic Anastomoses in Rats Under 5-FU Treatment
Introduction
Leaking colonic anastomoses are a major problem in colorectal surgery. They are responsible for numerous complications and as many as one-third of the postoperative deaths associated with colonic operations [1, 2, 3]. Clinically observed failure of anastomotic healing has been observed to increase hospital stay 2-fold and perioperative mortality 3-fold [4, 5, 6].
Moreover, it is well known that after colon resection for colonic cancer, the immediate postoperative intraperitoneal administration of 5-fluorouracil (5-FU) destroys the cancer cells that have been disseminated during operation and inhibits the micrometastases, which can later lead to recurrence [7, 8, 9, 10, 11]. However, previous experimental studies carried out in our laboratory, as well as those of other investigators, have shown that the immediate postoperative intraperitoneal administration of 5-FU has an adverse effect on the healing of colonic anastomoses [12, 13, 14, 15, 16, 17, 18].
The effects of growth hormone and growth factors on healing of bowel anastomoses are currently being evaluated in an attempt to identify agents that promote and improve the anastomotic healing progress. Insulin-like growth factor I (IGF-I) is a peptide hormone structurally related to insulin which has pleotrophic effects on cell growth and metabolism. This growth factor is synthesized by hepatocytes in response to growth hormone and has been shown to stimulate amino acid uptake, amino acid incorporation into liver and muscle proteins, and to decrease muscle protein degradation [19, 20].
The aim of this experimental study was to investigate whether the administration of IGF-I can protect the colonic healing from the adverse effects of immediate postoperative intraperitoneal administration of 5-FU, when injected intraperitoneally after colon resection.
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Materials and Methods
Eighty male Wistar rats, weighing between 200 and 300 g, were used. Animals were housed individually and had unrestricted access to the standard laboratory diet and water pre- and postoperatively. The rats were weighed on the day of operation and when the animals were killed, and changes in weight were noted. Surgery was performed through a 3-cm midline incision under intraperitoneal thiopental anesthesia (40 mg/kg body weight). After resection of a 1-cm segment of the middle transverse colon,
Results
Mean body weight changed significantly in all groups (P < 0.05), except in the IGF-I +5-FU group (P = 0.181). The mean postoperative decrease of body weight was significantly higher in 5-FU group compared with the control group (P = 0.010, Fig. 1), the IGF-I (P < 0.001) and the IGF-I +5-FU group (P = 0.009). Also, the mean postoperative increase of body weight was significantly higher the IGF-I group compared with the control (P = 0.003) and the IGF-I +5-FU group (P = 0.006). There was no
Discussion
Dehiscence is much more common in colonic anastomoses compared with those in the small bowel [24]. Even though there have been significant advances in surgical techniques, leakage of the colonic anastomoses continues to be a significant cause of postoperative morbidity and mortality in patients undergoing colonic surgery [3, 5, 6]. The reported incidence of anastomotic leakage ranges from as low as 4% to as high as 30% [3, 4, 5, 6]. A variety of growth factors have been shown to enhance wound
References (35)
- et al.
Effect of chronic corticosteroids and vitamin A on the healing of intestinal anastomosis
Am J Surg
(1992) - et al.
Keratinocyte growth factor as a mitogen for primary culture of rat hepatocytes
Biochem Biophys Res Commun
(1993) - et al.
Contribution of circulating IGF-I to wound repair in GH-treated rats
Growth Horm IGF Res
(2002) - et al.
Prospective study of hand-sutured anastomosis after colorectal resection
Br J Surg
(1996) - et al.
Anastomotic leakage after anterior resection of the rectum
Eur J Surg
(1994) - et al.
The failed intraperitoneal colon anastomosis after colon resection
Tech Coloproctol
(2004) - et al.
Anastomotic integrity after operations for large bowel cancer: A multicenter study
BMJ
(1980) - et al.
A multivariate analysis of factors contributing to leakage of intestinal anastomoses
J Am Coll Surg
(1997) - et al.
Low anterior resection without protective colostomy
Tech Coloproctol
(2002) - et al.
Adjuvant intraperitoneal 5-flouorouracil and intravenous leucovorin after colorectal cancer surgeryA randomized phase II placebo-controlled study
Int J Colorectal Dis
(1994)