The healing of colonic anastomoses after early intraperitoneal chemotherapy: an experimental study in rats

Early postoperative intraperitoneal administration of 5-fluorouracil (5-Fu) is a logical adjuvant treatment of patients with resectable colonic cancers. It is easier and less invasive than the intraportal administration of the drug. However, before applying the procedure to humans it must be demonstrated than it does not disturb the healing of recent colonic anastomoses. Colonic sutures were performed in 78 male Wistar rats. The animals then either served as controls or received intraperitoneal 5-Fu during 5 days starting on the first, third, or seventh postoperative day. No statistical difference was observed between treated and control groups when observing the incidence of anastomotic spontaneous disruptures, anastomotic healing strength, or the weight of the animals. It is concluded that early intraperitoneal 5-Fu administration does not impair the healing of recent colonic anastomoses in rats.     

The effect of tissue adhesive, octyl-cyanoacrylate, on the healing of experimental high-risk and normal colonic anastomoses

BACKGROUND: Tissue adhesives may be advantageous over sutures in colonic anastomoses because they do not result in potentially dangerous tight tissue approximation. METHODS: Ninety male Wistar-albino rats were used in the study. Excluding the 10 animals that constituted the control, the rest of the animals were divided in two groups: normal (N) and high-risk (HR). Only resection and anastomosis were done on half of the animals in each group. Octyl-cyanoacrylate was applied on the anastomosis of the other half of the groups. Anastomotic assessment was done at the third and seventh postoperative days. Gross anastomotic healing, mechanical strength, hydroxyproline deposition, and histopathological healing indices were used for the assessment. RESULTS: There was no difference in the third day and the seventh day groups regarding the gross healing parameters and hydroxyproline concentration. Similarly there was no difference between the third day groups in terms of mechanical healing (P = 0.669). However, the mechanical strength of the anastomosis assessed the seventh postoperative day was lower in groups in which octyl-cyanoacrylate was applied (P <0.001). Furthermore, inflammatory reaction, presence of necrosis, peritonitis, and exudate was pronounced in groups in which octyl-cyanoacrylate was applied. CONCLUSIONS: Application of octyl-cyanoacrylate to both normal and high-risk colonic anastomosis does not provide any benefit over conventional suturing at the early phase of the healing. However, octyl-cyanoacrylate seems to be detrimental at the late phase of the healing probably due to the ongoing intense inflammatory reaction.     

Effect of the combination of fibrin glue and growth hormone on incomplete intestinal anastomoses in a rat model of intra-abdominal sepsis

BACKGROUND: The presence of established intra-abdominal sepsis has been considered a contraindication to primary anastomoses. Our hypothesis was that fibrin glue (FG), growth hormone (rhGH), and combination of them synergistically improve intestinal primary anastomotic healing in a rat model of intestinal fistulae with peritonitis. MATERIALS AND METHODS: Male Wistar rats, induced intestinal fistulae with peritonitis after 24 h, were performed an enterectomy and intestinal anastomoses. Group A, rats (n = 60) had a complete anastomoses (end-to-end single layer anastomoses using 12 inverted interrupted 6-0 sutures) without peritonitis, group B, rats (n = 60) had a complete anastomoses after 24 h of peritonitis, group C rats had an incomplete anastomoses (four inverted interrupted sutures), groups D, E, F rats (n = 60) received FG, rhGH, or both of them, respectively. rhGH was given daily for 5 days. Anastomoses indicated the anastomotic bursting pressure (ABP), tensile strength, and hydroxyproline content, were determined. RESULTS: On POD 1, ABP of group C and group D was significantly lower than that of other groups (P < 0.01); On POD 3, ABP could not be determined because of intestinal dehiscence in groups C and E, ABP was significantly higher in groups D and F than that of groups A and B (P < 0.01); the ABP increased after 5 days of operation in groups A, B, and F. At the same time, that of group D decreased (P < 0.01). On POD 5, the tensile strength was significantly higher in groups A, D, and F than that in groups C, and E. On POD 5, hydroxyproline content was higher in groups D and F compared to that in group C (P < 0.05). CONCLUSIONS: These data suggested that FG improve intestinal primary anastomotic healing within post-operative 5 days in a rat model of intestinal fistulae with peritonitis. RhGH alone fails to improve intestinal anastomotic healing, and the combination of FG and rhGH have no synergistic effect to improves intestinal anastomotic healing.     

Influence of methylprednisolone on the healing of intestinal anastomoses in rats

Although steroids are generally thought to impair intestinal anastomotic healing, this effect has never been proven unequivocally in either clinical or experimental studies. We have investigated the influence of methylprednisolone (2.5 or 10.0 mg kg-1 day-1) given from 2 days before operation onwards, on 3-day-old and 7-day-old ileal and colonic anastomoses in rats. Anastomotic abscesses occurred more frequently in the ileum, but not in the colon, after steroid medication. However, methylprednisolone did not lower anastomotic bursting pressures in either of the bowel segments. Comparison of the hydroxyproline content of the anastomotic segment yielded no significant difference between control and methylprednisolone groups in either small or large bowel. Thus, healing of experimental colonic anastomoses remains unaffected by short-term administration of this corticosteroid.     

The Effect of Purified Micronized Flavonoid Fraction on the Healing of Anastomoses in the Colon in Rats

Purpose Anastomotic leakage of colonic and rectal anastomoses is a major complication after large intestine surgery. Many factors influence the healing of colon anastomoses. Flavonoids have been recognized for centuries as physiologically active constituents that are used to treat human diseases. We studied the effects of a clinically used, micronized, purified flavonoid fraction on the healing of colonic anastomosis in rats. Methods Male Sprague–Dawley rats were used. The flavonoid group of rats received 100 mg/kg per day of Daflon for 14 days until surgery. Thereafter, a resection and anastomosis were performed. The bursting pressure of the anastomoses and the hydroxyproline levels of the perianastomotic tissue were determined to evaluate the healing on the third and seventh days of surgery for both flavonoid and control groups. Results The bursting pressure of the flavonoid group was higher on the seventh day. The hydroxyproline levels of the flavonoid group were significantly higher than in the control group on both the third and seventh days after surgery. Conclusions Although the micronized purified flavonoid fraction has some inhibitory properties on the healing of the anastomosis, its net effect was to obtain a better anastomotic healing of the colon in rats.     

Hypovolaemia and healing in colonic anastomoses

Colonic anastomotic leakage is more common following emergency resections than after elective operations. Transient hypovolaemia, which is more likely to occur during emergency surgery, has been shown to impair collagen metabolism in abdominal and skin wounds but its effect on colonic anastomotic healing has not been previously examined. Acute intra-operative loss of 10 per cent circulating blood volume in rats significantly impaired collagen concentration in both ileocolic (P less than 0.02) and colocolic (P less than 0.05) anastomoses measured on the third postoperative day. This degree of blood loss did not significantly affect early anastomotic strength. Hypovolaemia leads to tissue hypoxia, and this in turn may lead to impaired anastomotic healing. Measurement of tissue oxygen tension may predict poor healing by identifying inadequate intestinal perfusion. Colonic pTO2 measured in rabbits was significantly lower than in small bowel (37 +/- 18 mmHg versus 42 +/- 18 mmHg; P less than 0.001), and fell significantly in colon following 10 per cent blood loss (P less than 0.001). We conclude that adequate intra-operative fluid replacement during colonic resection and anastomosis is a prerequisite for successful healing.     

Creating the Uncreatable

ABSTRACT

Introduction: Metoclopramide is often used in the treatment of postoperative nausea and vomiting, but a literature review failed to find reports on the influence of this drug on the healing of bowel anastomoses in the setting of abdominal sepsis. The aim of this study was to evaluate the effects of metoclopramide on the healing of left colonic anastomoses in rats with induced abdominal sepsis. Materials and Methods: Forty rats were divided into two groups of 20 animals each to receive either metoclopramide (experimental group: E) or saline (control group: C). Each group was further divided into subgroups of 10 animals each to be killed on the third (E3 and C3) or seventh postoperative day (E7 and C7). A segmental resection of the left colon was performed, followed by end-to-end anastomosis. Sepsis was induced by cecal ligation and puncture. On the day of reoperation, the total number of adhesions was assessed and the anastomosed bowel segment was removed for tensile strength testing, histopathological analysis, measurement of hydroxyproline levels, and histomorphometric evaluation of collagen. Results: Intraoperative findings, number of intra-abdominal adhesions in the anastomosed area, and tensile strength before anastomosis rupture were similar among all subgroups at all assessments. On the third postoperative day, the anastomoses of animals treated with metoclopramide showed significantly lower hydroxyproline levels (p = 0.01) when compared with controls. Collagen content was similar among all subgroups. Conclusions: Metoclopramide does not have deleterious effects on the healing of bowel anastomoses in rats subjected to experimental abdominal sepsis.     

Sirolimus and intraoperative hyperthermic peritoneal chemoperfusion with mitomycin-C do not impair healing of bowel anastomoses.

Surgeons will increasingly have to address the development of gastrointestinal disease in transplant patients or deal with extended bowel resection and bowel anastomosis in advanced cancer patients. Immunosuppressants as well as intraoperative hyperthermic peritoneal chemoperfusion (IHPC) may alter intestinal anastomotic healing. We evaluated the effects of the immunosuppressant sirolimus and of IHPC on healing and stability of bowel anastomoses in pigs. Twenty-four pigs were divided into four groups (SIR: sirolimus was administered orally; IHPC: animals received IHPC with mitomycin-C; COMP: combination of sirolimus and IHPC was administered; CON: sham-treated control group). Animals underwent hand-sutured small bowel and left colon anastomoses and were killed on postoperative day 4. Anastomoses were evaluated by morphometric analysis and immunohistochemistry (IHC) and by measuring the bursting pressure (BP). In all experimental groups (SIR, IHPC, COMP), anastomotic BPs remained unaltered and were not statistically different compared with control (CON). In addition, ileum villous height and colonic crypt depth analysis revealed no significant difference in mucosal thickness, and IHC showed no difference among groups in proliferation, as assessed by the number of KI-67- and bromodeoxyuridine-labeled cells. Immunosuppression with sirolimus as well as IHPC with mitomycin-C do not alter healing of intestinal anastomosis in pigs.     

Blood transfusion impairs the healing of experimental intestinal anastomoses.

Blood transfusions are reported to impair the cell-mediated immune response. Because both T lymphocyte and macrophage function are important for wound repair, the authors investigated the effect of blood transfusions on anastomotic repair. Lewis rats underwent resection of both ileum and colon, followed by the construction of either an everted or an inverted end-to-end anastomosis. Immediately after operation, they received either 3 mL saline intravenously, or 3 mL heparinized blood from Lewis or Brown Norway donors. The animals were killed 3 or 7 days after operation, and anastomotic strength was assessed by measuring the bursting pressure. Anastomotic abscesses and generalized peritonitis were not found in the control group. Blood transfusions, particularly allogeneic, significantly increased the incidence of these septic complications. Three days after operation, anastomotic strength was significantly reduced in both Lewis and Brown Norway transfused groups. For instance, average bursting pressures (+/- standard deviation [SD]) of inverted ileal anastomoses were 79 +/- 13 mmHg in the control group and 46 +/- 14 and 21 +/- 12 mmHg in the Lewis and Brown Norway transfused groups, respectively. Seven days after operation, the rupture site was found significantly more often within the anastomotic line in the animals that had received blood transfusions. The authors conclude that blood transfusions impair the healing of experimental intestinal anastomoses and increase susceptibility to intra-abdominal sepsis.     

Mycophenolate mofetil impairs healing of left-sided colon anastomoses

INTRODUCTION: Inadequate healing and consequent leakage from bowel anastomoses are a significant cause of postoperative morbidity and mortality. Immunosuppressive drugs are known to disturb healing processes and to impair the mechanical stability of bowel anastomosis. Mycophenolate mofetil (MMF) is an immunosuppressive agent that selectively inhibits the proliferation of T and B lymphocytes and has been shown to be effective in preventing allograft rejection after organ transplantation. Adverse effects are few; however, nothing is known in regard to possible adverse effects of MMF administration on the healing of bowel anastomosis. The aim of the present study was to evaluate the effect of systemic MMF administration on the healing of colon anastomoses in rats. METHODS: Rats underwent laparotomy, division of the left colon, and sigmoidostomy. MMF (25 mg/kg) or vehicle was administered intraperitoneally in two groups (n=21 per group) 3 days before surgery and then once daily until euthanization (7 animals per group; 2, 4, and 6 days after surgery). Bursting pressure measurements, histologic evaluation, morphometric analysis, mucin and collagen staining, and BrdU immunohistochemistry of the anastomotic site were performed. Furthermore, matrix protein expression at the anastomotic site was determined by collagen I and fibronectin Western blots. RESULTS: Administration of MMF significantly decreased anastomotic bursting pressure postoperatively. Accordingly, histology, mucin staining, and BrdU immunohistochemistry and measurements of the colonic crypt depth showed more extended inflammation, a significantly lower proliferation rate, and a significantly thinned mucosal layer in the MMF-treated groups when compared to control animals, whereas matrix synthesis at the anastomotic site was not different. CONCLUSIONS: The administration of the immunosuppressive agent MMF significantly impairs healing and mechanical stability of colon anastomosis in rats during the early postoperative period. MMF act to disturb host reparative processes mainly by impairment of reparative colonic epithelium proliferation and less by a disturbance of matrix synthesis.     

Granulocyte Macrophage-Colony Stimulating Factor Improves Impaired Anastomotic Wound Healing in Rats Treated with Intraperitoneal Mitomycin-C

Purpose Intraperitoneal chemotherapy (IPCT) delivers higher local concentrations of cytotoxic drugs than intravenous (IV) chemotherapy, but it can adversely affect the healing of intestinal anastomoses if given in the early postoperative period. Intestinal anastomotic leakage is a serious surgical complication. Experimental and clinical studies have shown that the local administration of granulocyte macrophage-colony stimulating factor (GM-CSF) improves would healing. Therefore, we evaluated the effects of locally applied GM-CSF on anastomotic wound healing in rats treated with intraperitoneal mitomycin-C immediately after surgery.Methods We performed colon anastomoses in albino rats, which were then divided into three treatment groups. Group A was a control group that received no treatment, Group B was given intraperitoneal mitomycin-C postoperatively, and Group C was given intraperitoneal mitomycin-C with a local injection of GM-CSF postoperatively. We measured bursting pressures and hydroxyproline content, and histologically examined the resected anastomoses on postoperative day (POD) 3.Results Anastomotic healing was impaired after intraperitoneal mitomycin-C, but this was overcome by the injection of GM-CSF into the perianastomotic area.Conclusion Local GM-CSF administration counteracts the detrimental effects of intraperitoneal mitomycin-C treatment on intestinal anastomoses in rats.     

Opposite effects of interleukin-2 on normal and transfusion-suppressed healing of experimental intestinal anastomoses.

OBJECTIVE: This study was done to investigate whether administration of interleukin-2 (IL-2) can abrogate the negative effects of blood transfusions on anastomotic healing. SUMMARY BACKGROUND DATA: Recently, the authors showed that blood transfusion severely impairs anastomotic repair and significantly increases the susceptibility to intra-abdominal septic complications in rats. It has been reported that blood transfusions suppress IL-2 production and that IL-2 may stimulate wound healing. METHODS: Lewis rats underwent resection and anastomosis of both the ileum and colon. Subsequently, they received either 3 mL of saline (control and IL-2 groups) or 3 mL of blood from brown Norway donors (transfusion and transfusion/IL-2 groups) intravenously. From the operation onward, the animals in the IL-2 and transfusion/IL-2 groups received daily injections of 5.4 x 10(5) IU of IL-2 in dextrose solution subcutaneously; the rats in the other groups received only the dextrose solution. The animals were killed 3 or 7 days after the operation and examined for septic complications and anastomotic repair. RESULTS: Transfusion led to an enhanced incidence of anastomotic abscesses, which was almost completely abrogated after IL-2 administration. The anastomotic strength was consistently and significantly reduced after transfusion. Seven days after surgery, the anastomotic strength was completely restored by IL-2 treatment. For instance, the average bursting pressure (+/- the standard deviation) of the ileal anastomoses in the control, transfusion, and transfusion/IL-2 groups were 86 +/- 15, 32 +/- 8,* and 63 +/- 10 mmHg* [symbol: see text] on day 3 and 293 +/- 36, 227 +/- 16,* and 299 +/- 19 mmHg on day 7, respectively (where * = significant vs. control group and [symbol: see text] = significant vs. transfusion group). In addition, IL-2 administration elevated the anastomotic hydroxyproline content, which was significantly decreased by transfusion alone, to the level found in the control group. The administration of IL-2 to control animals resulted unexpectedly in a significant reduction in anastomotic strength. CONCLUSIONS: Exogenous IL-2 reverses the negative effects of blood transfusions on anastomotic repair, but it impairs healing under normal conditions.     

Predicting anastomotic disruption after emergent small bowel surgery

BACKGROUND/AIMS: Small bowel anastomoses performed in the emergent setting have a high risk of leakage. Attention to technical detail is imperative but does not guarantee success in these situations. We sought out factors that could play a role in the process of anastomotic dehiscence under these conditions. METHODS: 70 patients underwent 74 emergency small bowel anastomoses over a 21-month period in our institution during this prospective study. Patients with anastomotic disruption formed the case group and those without, the control group. Several preoperative, intraoperative and postoperative variables identified at the outset of the study were analyzed for possible associations with anastomotic dehiscence. RESULTS: Suture line disruption occurred in 26 of 74 anastomoses (35%). The duration of symptoms before presentation did not differ significantly between groups. Hypoalbuminemia (p = 0.004), hyponatremia at presentation (p = 0.012), and intraoperative hypotension (p = 0.042) were found to be significantly associated with disruption. Neither the nature of the primary pathology in the bowel nor the anastomotic level had a significant bearing on anastomotic leakage. CONCLUSION: Risk factors for leakage of emergent small bowel anastomoses include hypoalbuminemia, hyponatremia at presentation, and intraoperative hypotension. Under these circumstances, the creation of a temporary stoma or exteriorization may be a wiser option than primary anastomosis.     

Sutureless small bowel anastomoses: experimental study in pigs.

OBJECTIVE: To evaluate a new technique for experimental anastomosis with fibrin glue, and to compare the results with those of stapled and one-layer sutured anastomosis. DESIGN: Open laboratory study. SETTING: Teaching hospital, Sweden. ANIMALS: Ten Swedish domestic pigs. INTERVENTIONS: Each pig had three anastomoses made in the small bowel, one by each technique. The pigs were killed on the 4th postoperative day. MAIN OUTCOME MEASURES: Blood flow, collagen concentration, anastomotic index, breaking strength, thickness of bowel wall, and histological appearance. RESULTS: Two pigs died postoperatively, leaving 8 for analysis. The blood flow at each anastomotic site studied by the microsphere technique was similar irrespective of the type of anastomosis (p = 0.3), as was anastomotic collagen concentration (p = 0.09). The anastomotic index, however, was significantly higher in the stapled than in the glued or sutured ones (p = 0.03). The glued anastomosis was the weakest, being only one fifth the strength of the stapled and one third the strength of the sutured anastomosis. There was no sign of rejection of the glue (of human origin) on histological examination. Glued and stapled anastomoses showed signs of mild inflammation, which did not reach the intensity of that around the sutured anastomoses. CONCLUSION: It is possible to make a sutureless anastomosis that does not leak with a modified stapler using fibrin glue instead of staples, but the anastomosis has considerably lower breaking strength than either stapled or sutured anastomoses.     

Selective cyclo-oxygenase 2 inhibition affects ileal but not colonic anastomotic healing in the early postoperative period

BACKGROUND: Selective cyclo-oxygenase 2 (COX-2) inhibitors are increasingly prescribed in the perioperative period. Recent recognition of a possible role for COX-2 in wound healing has raised concerns about the safety of their use in surgical practice. Therefore, the influence of celecoxib, a selective COX-2 inhibitor, on early anastomotic healing was investigated. METHODS: Celecoxib, in doses of 15, 50 or 200 mg per kg per day, was given daily from the day before operation onwards to male Wistar rats that received both ileal and colonic anastomoses. Anastomotic strength was assessed by measuring the breaking strength and bursting pressure on the third day after operation. A second group received a dose of 50 mg per kg per day and a colonic anastomosis only, and healing was assessed on the third and fifth day after surgery. RESULTS: Expression of COX-2 protein was upregulated in the anastomotic area. Administration of celecoxib, at all doses tested, resulted in a significantly higher ileal dehiscence rate than in control rats (P = 0.002). In contrast, colonic anastomoses healed normally within the same animals. The latter was confirmed in rats with colonic anastomoses only. CONCLUSION: In this model, administration of the COX-2 inhibitor celecoxib affected ileal but not colonic anastomotic healing in the early postoperative period.     

Omentoplasty reinforcement of esophagogastric anastomoses in rats.

BACKGROUND AND OBJECTIVES: Esophagogastric anastomotic leaks complicate 5-20% of esophagectomies for esophageal cancer, and they are responsible for approximately one-third of perioperative deaths. Omentoplasty reinforcement has been recommended for esophagogastric anastomoses, but there is little evidence to support this practice. An animal experiment was done to test the hypothesis that omentoplasty reinforcement of esophagogastric anastomoses would have a beneficial effect on healing. METHODS: Twenty-eight rats had single layer esophagogastric anastomoses constructed using interrupted 7-0 polypropylene sutures. In the experimental group (14 rats) the anastomoses were covered with omentum. This was not done in the control group (14 rats). Rats were killed 1 week after surgery and their anastomoses were excised, mounted in a tensiometer, and distracted at 10 mm/min to measure breaking strength. After that, anastomotic tissue was subjected to hydroxyproline analysis (an indicator of wound collagen). RESULTS: There were no anastomotic leaks. Esophagogastric anastomotic breaking strength was 3.45+/-0.63 N in the omentoplasty rats and 3.86+/-0.85 N in the control rats (p=0.24, not significant). Esophagogastric anastomotic tissue hydroxyproline concentration was 388.7+/-33 nmol/mg in the omentoplasty rats and 463.9+/-56 nmol/mg in the control rats (p=0.001). CONCLUSIONS: Omentoplasty reinforcement of esophagogastric anastomoses did not have any beneficial effect on anastomotic healing in this animal experiment.     

Suture-Free Small Bowel Anastomoses Using Collagen Fleece Covered with Fibrin Glue in Pigs

Background: Several studies investigating anastomotic healing could objectify that the regularly used suture material leads to an impairment of wound healing due to ischemia at the anastomotic line. This study was initiated to test a hypothesis that a reduction of suture material leading to suture-free glued intestinal anastomoses is feasible and enables an improved wound healing. Materials and Methods: Three different types of anastomoses were carried out at the small bowel of 16 pigs. Standard hand-sewn anastomoses, anastomoses with loose-fitting skin staples, and suture-free glued anastomoses using a fibrin covered collagen fleece. When the animals were killed, both gross inspection of the parietes, bursting pressure and tissue for histological study became the basis for evaluation. Analyses were also made regarding the collagen I/III ratio and the expression of MMP 1 and 13. Results: Four leakages at the stapled, one at the sutured, and one at the glued anastomoses occurred. All other anastomoses healed without complications. The bursting pressure did not differ significantly between the groups. The macroscopic inspection and the microscopic examination both showed an improved healing pattern for the material reduced techniques without onset of a deep ulcer at the anastomotic line as seen at the conventional sutured anastomoses. These findings were supported by the immunohistochemical studies. Conclusions: These observations suggest that a suture-free bowel anastomoses using collagen fleece covered with fibrin glue is technically feasible. Obviously, a reduction of foreign body material at the anastomotic line avoids unnecessary ischemia and thus supports a physiological improved wound healing process.     

Antithrombin III prevents deleterious effects of remote ischemia-reperfusion injury on healing of colonic anastomoses

BACKGROUND: Antithrombin III is known as the most important natural inhibitor of thrombin activity and has been shown to attenuate local harmful effects of ischemia-reperfusion injury in many organs. In recent animal studies, delaying effect of remote organ ischemia-reperfusion injury on healing of intestinal anastomoses has been demonstrated. In this study, we investigated whether antithrombin III reduces deleterious systemic effects of ischemia-reperfusion injury on healing of colonic anastomoses in rats. METHODS: Anastomosis of the left colon was performed in 24 rats that were divided into three groups: sham operated control (group I, n = 8), 30 minutes of intestinal ischemia-reperfusion by superior mesenteric artery occlusion (group II, n = 8), antithrombin III treated group (250 U/kg before and after the ischemia-reperfusion, group III, n = 8). On postoperative day 6, all animals were sacrificed, and bursting pressure and tissue hydroxyproline content of the anastomoses were assessed and compared. RESULTS: On postoperative day 6 the mean bursting pressures were 149.6 +/- 4.8, 69.8 +/- 13.5, and 121.8 +/- 8.7 mm Hg for groups I, II, and III, respectively (P = 0.000). Mean tissue hydroxyproline concentration values were 389.5 +/- 29.6, 263.1 +/- 10.0, and 376.0 +/- 33.8 microg/mg for groups I, II, III respectively (P = 0.005). CONCLUSIONS: This study showed that, antithrombin III treatment significantly prevented the delaying effect of remote organ ischemia-reperfusion injury on anastomotic healing in the colon. Further clinical studies are needed to clarify whether antithrombin may be a useful therapeutic agent to increase the safety of the anastomosis during particular operations where remote organ ischemia-reperfusion injury takes place.     

Effect of pyloric drainage on the healing of esophagogastric anastomoses in rats.

BACKGROUND AND OBJECTIVES: Esophagogastric anastomotic leaks complicate 5% to 20% of esophagectomies for esophageal cancer and are responsible for approximately one-third of perioperative deaths. Poor gastric emptying is a predisposing factor for anastomotic leakage. An animal experiment was used to test the hypothesis that a pyloric drainage procedure (pyloromyotomy) would have a positive effect on esophagogastric anastomotic healing. METHODS: In 40 rats single-layer esophagogastric anastomoses were constructed with interrupted 7-0 polypropylene sutures. A pyloromyotomy was done in the experimental group (20 rats) but not in the control group (20 rats). Rats were sacrificed on the 7th postoperative day and their anastomoses were excised, mounted in a tensiometer, and distracted at 10 mm/min to measure breaking strength. After that, the hydroxyproline concentration (an indicator of wound collagen) of the anastomotic tissue was measured. RESULTS: There were no anastomotic leaks. The mean (and standard deviation) breaking strength of the esophagogastric anastomosis was 3.96 (1.14) N in the pyloromyotomy rats and 4.11 (0.75) N in the control rats (p = 0.64). The mean (and SD) hydroxyproline concentration in esophagogastric anastomotic tissue was 368.6 (31.5) nmol/mg in the pyloromyotomy rats and 376.6 (31.3) nmol/mg in the control rats (p = 0.77). CONCLUSION: Pyloric drainage (pyloromyotomy) did not have any effect on esophagogastric anastomotic wound healing in this rat model.     

Influence of local hyperthermia on the healing of small intestinal anastomoses in the rat

Peritoneal hyperthermia may have a role in limiting serosal metastatic disease. When applied to the peritoneal cavity immediately after surgery, it is important to know the optimum temperature, and to investigate the subsequent healing of intestinal anastomoses. To study the first problem, local hyperthermia was applied to the intestinal loop of rats for 30 min. Treatment at 46.0 degrees C or 45.0 degrees C resulted in 100 per cent and 90 per cent mortality respectively, but 100 per cent survival was obtained at 44.0 degrees C. To study the second problem rats with intestinal anastomoses were studied in three groups: group A, local hyperthermia (44.0 degrees C x 30 min) applied to the intestinal loop containing the anastomosis; group B, local hyperthermia (44.0 degrees C x 30 min) applied using saline supplemented with mytomycin C (10 mg/l); group C (controls) no thermal treatment was applied. Anastomotic healing was assessed by breaking strength and histological examination. On the third day after operation, the breaking strength of anastomoses decreased to the lowest values in each group, but no statistically significant differences were noted. On the seventh and 14th day, increased resistance to breaking developed in all three groups and was greatest in the thermally treated groups. Histological findings supported these results. Local hyperthermia up to 44.0 degrees C x 30 min had no adverse effects on the healing of intestinal anastomoses.