Gastrointestinal Surgical Techniques in Small Animals. Группа авторов
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The neutrophils predominate during the first 24 hours but then macrophages become predominant past 48 hours following the initial injury. The macrophages play an important role in healing of the gastrointestinal tract by controlling local infection with phagocytosis, production of oxygen radicals, and nitric oxide. They also participate in debridement with phagocytosis and production of collagenase and elastase. The macrophages also regulate matrix synthesis and cell recruitment and activation. They release several growth factors (PDGF, transforming growth factor (TGFβ), fibroblast growth factor (FGF), IGF) and cytokines (TNFα, IL‐1) important for tissue healing. The macrophages recruit lymphocytes that liberate interleukin (IL‐6) and interferon (IFN) and promote angiogenesis with production of VEGF (Vasculogenic Endothelial Growth Factor). Finally, the capillary permeability is increased resulting in inflammation and edema on the edges of the incision that can persist for two weeks. Care should be taken initially when the sutures are placed to not induce tissue strangulation and necrosis. A fibrin seal develops over the serosa very quickly to provide a leakage protection of the surgical site (Pascoe and Peterson 1989; Thornton and Barbul 1997; Thompson et al. 2006).
Overlapping with the inflammatory phase is the debridement phase, with removal of injured tissue by macrophages. The debridement phase should not exceed 1–2 mm from the edges of the incision. During this process, collagen is resorbed by collagenase and synthesized by smooth muscle and fibroblast. The smooth muscles are the major contributor in collagen production within the gastrointestinal tract. The collagen degrade by the collagenase activity weakens the strength of the anastomosis. In the colon, the collagenase activity is increased over the entire length of the colon while in the small intestine, it is increased only at the site of the anastomosis (Hawley 1970; Jiborn et al. 1978a). The risk of dehiscence is high between 3 and 10 days after surgery. Usually, after 4 to 5 days, collagen synthesis is superior to lysis and the anastomosis regains strength. This collagenase activity can be increased by the amount of trauma induced by tissue manipulation at the time of surgery or the presence of a foreign body, and by the degree of contamination. The amount of collagen synthesized is affected by hypotension, hypovolemia, shock, and certain medications.
The granulation tissue appears at the beginning of the proliferative phase of intestinal healing. Fibroblast is the major cell type present past day 4 after surgery. The fibroblasts migrate under the control of PDGF, TGFβ and FGF. Fibroblast and smooth muscle lay down collagen fibers and new capillaries appear in the field.
After one to two weeks following the anastomosis, the epithelial layer is fully restored. The epithelialization of the anastomosis reduces the formation of excessive fibrosis tissue secondary to inflammation. The excessive fibrosis could lead to stricture formation. During the maturation phase, the collagen fibers are reorganized and the anastomosis is becoming thinner.
In summary, an intestinal anastomosis loses bursting strength during the first 3 to 5 days to finally regain 50–70% of the initial bursting strength in 2 to 3 weeks (Jiborn et al. 1978a, 1978b; Thompson et al. 2006; Munireddy et al. 2010).
1.3 Factors Affecting Gastrointestinal Tract Healing
1.3.1 Ischemia and Tissue Perfusion
Ischemia interferes with healing of any tissue and especially the gastrointestinal tract. The oxygen delivery to the peripheral tissue depends on the anatomy of the capillaries, vasomotor control, and oxygen saturation. The tissue perfusion depends on the amount of soft tissue trauma and especially trauma to the blood supply of the loop of intestine. The placement of tight sutures interferes with tissue perfusion and may increase the risk of dehiscence, especially in the colon and esophagus (Shikata et al. 1982; Chung 1987; Jonsson and Hogstrom 1992; Thornton and Barbul 1997). Hypovolemia and hypotension are critical factors that divert blood flow to essential organs, and oxygen delivery is also very important for collagen synthesis. A partial pressure of oxygen of at least 40 mmHg is required for collagen synthesis. During a hypovolemic event, the gastrointestinal tract downregulates its own blood flow. Anemia does not interfere with healing as long as the patient has a good cardiac output to compensate (Thompson et al. 2006).
1.3.2 Suture Intrinsic Tension
Incising oral and visceral tissues stimulate an initial vasoconstriction, followed by secondary vasodilation and increased vascular permeability mediated largely by kinins, ultimately causing edema and swelling of tissue edges. This should be kept in mind when tensioning suture lines or stitches because ischemic necrosis may develop as the suture strangulates the swelling tissue. In general, sutures in viscera of the digestive tract should be tensioned such that the incision edges are held firmly together without crushing or cutting through the needle purchase. When inverting suture patterns are used, the suture line is firmly tensioned such that the incised edges are fully inverted and minimal suture is exposed on the surface of the organ (Thornton and Barbul 1997).
1.3.3 Surgical Technique
A simple apposition of the submucosa of the gastrointestinal tract is desired to achieve primary healing because it is associated with the least amount of fibrous tissue and better function. An apposition of the submucosa is important for the rapid healing of the mucosa and preventing migration of microorganisms within the surgical site. An eversion or inversion of the mucosa has been shown to interfere with primary healing (Jiborn et al. 1978a, 1978c; Jansen et al. 1981; Ellison et al. 1982; Jonsson et al. 1985; Pascoe and Peterson 1989; Thornton and Barbul 1997). Stapled anastomoses are becoming commonplace in veterinary surgery (Hansen and Smeak 2015; Duell et al. 2016; Snowdon et al. 2016). Staples do not promote better healing of the gastrointestinal tract when sepsis or ischemia are present (Thornton and Barbul 1997). Sutureless anastomoses have been performed with devices working by compressing two inverted ring of bowel (Maney et al. 1988; Corman et al. 1989; Ryan et al. 2006; Bobkiewicz et al. 2017).
1.3.4 Nutrition
The nutritional support of the patient is paramount for the healing of the gastrointestinal tract. Malnourished patients are at increased risk for dehiscence. The addition of a feeding tube is very important to support the anorectic patient in the post‐operative period as the enterocytes are getting their nutrients mostly from the intestinal content traveling in the lumen. Vitamin A, C, and B6 are required for collagen synthesis. Iron and copper are also important for the cross‐linking of protein and tissue healing. The enteral nutrition is beneficial for the integrity of the gastrointestinal tract and prevent bacterial translocation (Thornton and Barbul 1997; Marks 2013).
1.3.5 Blood Transfusion
A blood transfusion has been associated with an increased risk of leakage after gastrointestinal surgery. It has been postulated that blood transfusion is affecting the inflammatory phase and the migration of macrophages (Apostolidis et al. 2000; Munireddy et al. 2010).
1.3.6 Local Infection
A local infection increases protease activity, which delays epithelialization because protease resorbs growth factors required for healing. A braided suture should be avoided even if they received an antimicrobial treatment as bacteria adhere to them more than to monofilament (Chu and Williams 1984; Masini et al. 2011). Polydioxanone seems to have the lowest affinity for bacteria (Chu and Williams 1984).
1.3.7 Intraperitoneal Infection
A septic peritonitis interferes with healing of an intestinal anastomosis because it reduces collagen content at the level of the anastomosis. The combination of bacterial and neutrophil collagenases increases the collagen fibers breakdown. The collagen synthesis and deposition are reduced by the peritonitis (Ahrendt et al. 1996; Munireddy et al. 2010). The septic exudate present in the anastomosis prevents synthesis and deposition of collagen and angiogenesis (Thornton and Barbul 1997).
1.3.8 Medications
In an experiment in rats, it was shown that the administration of methylprednisolone did not affect the mechanical strength of colonic anastomosis (Mastboom