The administration of NSAIDs after gastrointestinal surgery is also very controversial (Mastboom et al. 1991b; Gorissen et al. 2012; Bhangu et al. 2014; Collaborative 2014). The non‐selective cyclo‐oxygenase inhibitors seem to increase the risk of leakage after colorectal surgery (Gorissen et al. 2012). Two meta‐analyses in human patients reported opposite results (Bhangu et al. 2014; Collaborative 2014). However, both of those studies have focused on colorectal surgery, which is not performed frequently in small animal surgery. In one of the studies, animal experiments were reviewed and showed that NSAID administration in the post‐post‐operative period increased the risk of leakage (Bhangu et al. 2014). The NSAIDs affect production of VEGF and angiogenesis. They also interfere with collagen formation and cross‐linking (Inan et al. 2006; Gorissen et al. 2012). After administration of NSAIDs, hydroxyproline concentration was significantly reduced after resection and anastomosis of the ileum. This effect was mostly present three days after surgery. Seven days after surgery, the concentration of hydroxyproline had risen again (Mastboom et al. 1991b). In a study on rats, NSAIDs increased the morbidity and mortality rates without necessarily leading to an increased risk of leakage (Mastboom et al. 1991b).
The chemotherapy drugs because of their immunosuppressant effect can negatively affect the healing of the gastrointestinal tract (Thornton and Barbul 1997).
1.3.9 Disease
There is very little evidence that diabetes interferes with gastrointestinal healing. In a rat model of diabetes, collagen synthesis was not affected. However, the bursting pressure of the intestinal anastomosis was reduced on day 3 after surgery, but this effect did not persist past day 7 (Verhofstad and Hendriks 1994; Thornton and Barbul 1997). Icterus has been shown to interfere with tissue healing (Bayer and Ellis 1976; Muftuoglu et al. 2005).
1.3.10 Large Intestine
The colon is considered by most surgeons as a rather “unforgiving” structure when it is incised and repaired, largely because of its unique healing qualities, and when leakage occurs, the results are often devastating to the animal (Williams 2012). An understanding of colonic healing is important, and incorporation of all the principles of repair are critical to reduce life‐threatening anastomotic dehiscence. Healing of the colon undergoes similar phases of wound healing to those found in the skin and other tissue layers but with a number of important differences (Agren et al. 2006). During the inflammatory phase, a fibrin clot forms over the site and, although this clot has minimal strength, it is important to achieve an early “seal,” and it is vital that it remains to act as a scaffold for fibroblast migration during the early repair phase. For the first three to four days, nearly all support for the colonic repair comes from the suture or staple line. Angiogenesis and migration of fibroblasts occurs and eventually replaces the fibrin clot scaffold during days 3 and 4. It is during this stage of repair that breakdown is most likely to occur (Williams 2012).
Although a fragile mucosal bridge also occurs within the first three to four days, depending on the size of the defect, substantive wound strength occurs only when local recruited smooth muscle cells and fibroblasts from the colonic submucosa and muscularis bridge the incision and begin producing collagen. Appropriate‐sized tissue bites are particularly important when repairing the colon because a zone of active collagen lysis occurs in a 1–3 mm zone immediately adjacent to the incised colon edge. The activity of matrix metalloproteases that cause collagen degradation peaks during the debridement phase through day 3 (Agren et al. 2006). Provided there is ample vascular supply after this time, collagen synthesis is accelerated, coupled with a rapid gain in wound strength. Aggressive tissue handling and excess contamination of the colonic wound can greatly increase the debridement activity at the sutured wound edge and this increases the risk of early tissue disruption, leading to dehiscence and leakage (Williams 2012). Return of strength at the healing site reaches about 75% of normal strength at four months after surgery, which is considerably slower than in the small intestine (Thornton and Barbul 1997). Surgeons can influence uncomplicated colonic healing by ensuring adequate tissue perfusion, eliminating any tension on the repair, accurately apposing colonic edges without inducing excess trauma, containing contamination, and avoiding increased intraluminal pressures by eliminating any distal obstruction (Holt and Brockman 2003; Williams 2012). Omental pedicle wraps have been advocated to reinforce the gastrointestinal repairs and support the local healing environment. Omentum may stimulate and augment angiogenesis and may also help maintain the vital fibrin clot and seal during the early phases of wound healing. The benefit of omental wraps in colonic surgery have not been proven in recent human clinical studies of colonic resection and anastomosis. However, most surgeons still recommend covering colonic repairs with omentum (Hao et al. 2008).
References
1 Agren, M.S. et al. (2006). Action of matrix metalloproteinases at restricted sites in colon anastomosis repair: an immunohistochemical and biochemical stud`. Surgery 140 (1): 72–82.
2 Ahrendt, G.M. et al. (1996). Intra‐abdominal sepsis impairs colonic reparative collagen synthesis. Am. J. Surg. 171 (1): 102–107; discussion 107–108.
3 Apostolidis, S.A. et al. (2000). Prevention of blood‐transfusion‐induced impairment of anastomotic healing by leucocyte depletion in rats. Eur. J. Surg. 166 (7): 562–567.
4 Bayer, I. and Ellis, H. (1976). Jaundice and wound healing: an experimental study. Br. J. Surg. 63 (5): 392–396.
5 Bhangu, A. et al. (2014). Postoperative nonsteroidal anti‐inflammatory drugs and risk of anastomotic leak: meta‐analysis of clinical and experimental studies. World J. Surg. 38 (9): 2247–2257.
6 Bobkiewicz, A. et al. (2017). Gastrointestinal tract anastomoses with the biofragmentable anastomosis ring: is it still a valid technique for bowel anastomosis? Analysis of 203 cases and review of the literature. Int. J. Color. Dis. 32 (1): 107–111.
7 Chu, C.C. and Williams, D.F. (1984). Effects of physical configuration and chemical structure of suture materials on bacterial adhesion. A possible link to wound infection. Am. J. Surg. 147 (2): 197–204.
8 Chung, R.S. (1987). Blood flow in colonic anastomoses. Effect of stapling and suturing. Ann. Surg. 206 (3): 335–339.
9 Collaborative, S.T. (2014). Impact of postoperative non‐steroidal anti‐inflammatory drugs on adverse events after gastrointestinal surgery. Br. J. Surg. 101 (11): 1413–1423.
10 Corman, M.L. et al. (1989). Comparison of the valtrac biofragmentable anastomosis ring with conventional suture and stapled anastomosis in colon surgery. Results of a prospective, randomized clinical trial. Dis. Colon Rectum 32 (3): 183–187.
11 Duell, J.R. et al. (2016). Frequency of dehiscence in hand‐sutured and stapled intestinal anastomoses in dogs. Vet. Surg. 45 (1): 100–103.
12 Ellison, G.W. et al. (1982). End‐to‐end approximating intestinal anastomosis in the dog – a comparative fluorescein dye, angiographic and histopathologic evaluation. J. Am. Anim. Hosp. Assoc. 18 (5): 729–736.
13 Gorissen, K.J. et al. (2012). Risk of anastomotic leakage with non‐steroidal anti‐inflammatory drugs in colorectal surgery. Br. J. Surg. 99 (5): 721–727.
14 Hansen, L.A. and Smeak, D.D. (2015). In vitro comparison of leakage pressure and leakage location for various staple line offset configurations in functional end‐to‐end stapled small intestinal anastomoses of canine tissues. Am. J. Vet. Res. 76 (7): 644–648.
15 Hao, X.Y. et al. (2008). Omentoplasty in the prevention of anastomotic leakage after colorectal resection: a meta‐analysis. Int. J. Color. Dis. 23 (12): 1159–1165.
16 Hawley, P.R. (1970). Collagenase activity and colonic anastomotic breakdown. Br. J. Surg. 57 (5): 388.
17 Holt, D.E. and Brockman, D. (2003). Large intestine. In: Textbook of Small Animal Surgery (ed. D. Slatter), 665–682. Philadelphia: Saunders.
18 Inan, A. et al. (2006). Effects of diclofenac sodium on bursting pressures of anastomoses and hydroxyproline contents of perianastomotic tissues