Experimental model for the study of perianastomotic recurrence in colorectal cancer.

OBJECTIVE: To determine if an experimental model is valid for the study of perianastomotic recurrence in colorectal cancer, comparing it with previous experimental models. METHODS: Experimental study with 40 male Sprague-Dawley rats, assigned to one of the study groups: control group (n = 20), with manipulation of large descending bowel, and colonic anastomosis group (n = 20), with colonic section and colocolic anastomosis. After pharmacological carcinogenesis with 1-2 dimethylhydrazine at a weekly dose of 25 mg/kg for 18 weeks, colonic tumours were studied at the 20th postoperative week. RESULTS: Number of tumours, colic tumoral area and percentage of colic tumoral area were greater in the colonic anastomosis group. In this group with colonic anastomosis all determinations were higher at the perianastomotic large bowel. CONCLUSIONS: We think this experimental model may be the best model to study perianastomotic recurrence in large bowel cancer. The high incidence of induced colic tumours and their location at the perianastomotic area offer a good field to determine response to experimental manipulations on colorrectal cancer.     

Effect of rofecoxib on colon chemical carcinogenesis at colonic anastomotic area in the rat.

AIM: To investigate the effect of the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib on the incidence of perianastomotic colonic tumors in a model of chemical carcinogenesis in the rat. EXPERIMENTAL DESIGN: Experimental study with 45 male Sprague-Dawley rats randomly assigned to one of three groups: control (n = 15) with colocolic anastomosis and chemical carcinogenesis with 1-2 dimethylhydrazine (1-2 DMH); rofecoxib 0.0027% (n = 15) with colonic anastomosis, chemical carcinogenesis and the addition of dietary rofecoxib at doses of 27 parts per million (ppm), and rofecoxib 0.0058% (n = 15) with colonic anastomosis, chemical carcinogenesis and the addition of dietary rofecoxib at doses of 58 ppm. Carcinogenic induction was performed with 1-2 DMH at a weekly dose of 25 mg/kg of weight for 18 weeks, and colonic tumors induced were analyzed in postoperative week 20. The main parameter evaluated was the percentage of colonic neoplastic tissue, which relates tumor surface area to the colon's surface area. RESULTS: Rofecoxib at doses of 2.5 mg/kg or 0.0058 ppm significantly reduced chemical colon carcinogenesis in rats, both in the perianastomotic area and the rest of the colon (p < 0.01). In the extra-anastomotic area, rofecoxib at doses of 2.5 mg/kg has significantly greater inhibitory effect than rofecoxib in doses of 1.2 mg/kg or 0.0027 ppm (p < 0.005). CONCLUSIONS: Rofecoxib causes a reduction in chemical colon carcinogenesis in rats. This effect is sustained in the perianastomotic area, and the investigation of its role in operated colorectal cancer with risk of locoregional recurrence may therefore be of interest.     

Cyclooxygenase-2 inhibition in colon experimental carcinogenesis.

BACKGROUND: An overexpression of cyclooxygenase-2 (COX-2) has been seen in colon tumors; therefore, COX-2 specific inhibitors may be used as preventive agents. The aim of this study was to investigate the effect of both selective and non-selective COX-2 inhibitors on the incidence of colonic tumors in a model of chemical carcinogenesis in the rat. DESIGN: Experimental study with 65 male Sprague-Dawley rats randomly assigned to one of four groups: (a) control (n = 20), with chemical carcinogenesis using 1-2 dimethylhydrazine (1-2 DMH); (b) acetylsalicylic acid (ASA) (n = 15), with chemical carcinogenesis and the addition of ASA at 30 mg/kg; (c) low-dose rofecoxib (n = 15), with chemical carcinogenesis and the addition of rofecoxib at a dose of 1.2 mg/kg; (d) high-dose rofecoxib (n = 15), with carcinogenesis and the addition of rofecoxib at 3 mg/kg. Carcinogenic induction was performed with 1-2 DMH at a weekly dose of 25 mg/kg for 18 weeks. The main parameter evaluated was percentage of neoplastic colonic tissue, which relates tumor surface area to colon surface area. RESULTS: Rofecoxib at a dose of 3 mg/kg significantly reduced chemical colon carcinogenesis in rats (p < 0.01). Rofecoxib in lower doses had the same effect on adenomas (p < 0.05) with no effect on adenocarcinomas. Rofecoxib reduced COX-2 expression in tumoral tissue from adenomas and adenocarcinomas (p < 0.01). CONCLUSIONS: Rofecoxib prevents chemical colon carcinogenesis in the rat, with a reduction of tumoral colonic percentage in adenocarcinomas and tumoral COX-2 expression.     

Perianastomotic colonic tumors after inclusion of titanium or Lactomer in the anastomotic suture line. An experimental study in rats.

OBJECTIVE: The aim of the study was to find out if there are differences in the incidence of colonic tumors at the anastomosis after the inclusion of titanium or the absorbable material Lactomer in the anastomotic suture line. METHODS: Experimental study with 30 male Sprague-Dawley rats, assigned to 1 of 3 study groups: control (colonic anastomosis with interrupted suture); inclusion of titanium (8 mg) in the anastomotic suture line; and inclusion of Lactomer (8 mg) in the anastomotic line. After pharmacological carcinogenesis with 1-2 dimethylhydrazine, perianastomotic tumors were studied in the 20th postoperative week. RESULTS: The inclusion of titanium in the anastomotic line led to more tumors, a larger anastomotic tumoral area and a larger percentage of tumoral area than Lactomer (p < 0.05). The inclusion of Lactomer may have a protective effect against the induction of cancer in the anastomotic area. CONCLUSIONS: Titanium, a material used in mechanical instruments for digestive tract anastomoses, is not an innocuous material. Its presence in the anastomotic line can promote colonic carcinogenesis after induction. The use of mechanical staplers for colonic anastomoses should be relegated to difficult anastomoses that cannot be sewn manually.     

Effect of defunctionalization on colon carcinogenesis in the rat.

OBJECTIVE: to examine the effect of fecal absence on experimental colon carcinogenesis in both male and female rats. MATERIAL AND METHODS: a total of 138 10-week-old Sprague-Dawley, male and female rats were divided into five groups: A) 20 rats, no treatment; B) 26 rats, colonic defunctionalization; C) 30 rats, 18 weekly doses of dimethylhydrazine (DMH), 21 mg/kg body weight each, from the beginning of the study; D) 20 rats, ethylen-diamine-tetraacetic acid for 18 weeks; and E) 42 rats, same surgical procedure as rats in group B plus DMH injections at the same doses as rats in group C. Animals were sacrificed after 25-27 weeks. Number of tumors, their location, and pathological findings were all compared between groups. RESULTS: no tumors developed in the dimethylhydrazine-free groups. No differences were obtained either in number of tumors or tumors per rat for group C as compared to group E. Fecal absence was associated with smaller-sized tumors (p = 0.007), greater numbers of non-mucinous tumors (p = 0.00009), better differentiation (p = 0.0054), and lesser penetration into the wall (p = 0.015) for group E as compared to group C. In the dimethylhydrazine group, fecal absence altered the number of tumors developing in males as compared to female rats (p = 0.025). Moreover, this fecal absence showed no inhibitory effect on right colonic tumors (p = 0.0065). CONCLUSIONS: fecal absence alters the DMH-carcinogenic pattern in the defunctionalized colon when using an experimental model in both male and female rats.     

Influence of rofecoxib on experimental colonic carcinogenesis in rats.

AIM: To investigate the effect of a selective cyclooxigenase-2 (COX-2) inhibitor, rofecoxib, in the prevalence of experimental colon tumors in rats. EXPERIMENTAL DESIGN: Experimental study with 35 male Sprague-Dawley rats, divided into four groups: a) control group without experimental manipulation (n = 5); b) pharmacological carcinogenesis with 1-2 dimethylhydrazine dihydrocloride (n = 10); c) pharmacological carcinogenesis and addition of acetylsalicylic acid (AAS) (n = 10); and d) carcinogenesis and addition of rofecoxib (n = 10). Carcinogenesis was induced with 1-2 dimethylhydrazine at a weekly dose of 25 mg/kg for 18 weeks. Colon tumors were isolated at 20 weeks. Antiinflammatory agents were given at a dose of AAS 30 mg/kg and rofecoxib at 3 mg/kg. RESULTS: The percentage of colonic tumors was significantly reduced in the rofecoxib group. This result was found for all tumors and for the malignant lesions, adenocarcinomas. CONCLUSIONS: Rofecoxib, a selective COX-2 inhibitor, reduced the percentage of drug-induced neoplastic glandular tissue in rats.     

Repetitive mucosal trauma promotes colon cancer in experimental rat model.

OBJECTIVE: To investigate the effect of repetitive mucosal trauma, anastomosis and intestinal content on experimental colonic carcinogenesis as there is the possibility than non-specific colon lesions can promote cancer. MATERIAL AND METHOD: We performed to sixty female Sprague-Dawley rats a 4 cm colon loop defunctionalization with double colostomy (traumatic site). Intestinal continuity was restored with an end-to-end colo-colic silk anastomosis. The surviving 47 rats were divided in 3 groups: Group A: 27 rats treated with DMH. Group B: 10 rats treated with EDTA and Group C: Control of 10 rats. Animals were sacrificed 31-32 weeks after surgery for macro and micropathological studies. RESULTS: In group A appeared 60 tumours: 44 in the functional colon, 20 of them in the anastomotic site; 8 in the non traumatised defunctionalized segment and 18 in the traumatised segment (p < 0.05). CONCLUSIONS: a) Continuous microtraumas on colonic mucosa in rats are cancer promotional factors; b) silk suture in anastomosis promotes cancer.     

Experimental Colonic Obstruction Increases Collagen Degradation by Matrix Metalloproteinases in the Bowel Wall

PURPOSE: Emergency resections for colonic obstruction are accompanied with increased risk of anastomotic dehiscence. Elevated local degradation of submucosal collagens by matrix metalloproteinases may predispose to anastomotic leakage. This study was designed to study the effect of colon obstruction and surgical trauma on matrix metalloproteinase activities and correlate these results to collagen concentration in the colon wall. METHODS: Colonic obstruction was induced in male, Sprague-Dawley rats (n = 58) by applying a constricting silicone ring around the left colon 3 cm above the peritoneal reflection. After four days of obstruction, 2-mm wide colonic segments were resected approximately 3 mm proximal and 3 mm distal to the stenosis for biochemical analyses. Colonic segments at corresponding locations were obtained from sham-operated rats (n = 5) without obstruction but with silicone ring placed adjacent to colon and from normal, nontraumatized rats (n = 10). Matrix metalloproteinase activity was determined by liberation of fragmented collagens from homogenized colonic tissue incubated ex vivo. Matrix metalloproteinase-2 specifically was analyzed by gelatin zymography. RESULTS: Endogenous collagenolysis by matrix metalloproteinases increased (P < 0.001) in colon as a consequence of obstruction (4.1-fold) and trauma (1.7-fold) compared with normal colon. In the proximity of the colon stenosis, total matrix metalloproteinase activity and matrix metalloproteinase-2 were significantly (P < 0.05) higher above than below the obstruction. Total activity was 22.9 (13.1-32.9) units/mg collagen proximal and 16.6 (12.7-18.4) units/mg collagen distal to the stenosis. Collagen concentration correlated inversely (r = -0.76; P < 0.001) with total matrix metalloproteinase activity. CONCLUSION: Colonic obstruction and trauma up-regulated matrix metalloproteinases and decreased collagen concentration in colonic wall.     

Inhibitory effect of calcium on carcinogenesis at the site of colonic anastomosis

PURPOSE: A study was made to assess the effect of oral calcium supplementation on colorectal carcinogenesis at the colocolic suture line and in the rest of the colon following administration of a carcinogen. METHODS: Fifty-nine rats were randomly divided into two groups: control (given a standard diet for rats and mice containing 0.8 percent calcium) and treatment (given the same diet as before but with 2 percent calcium). Carcinogenesis was induced by 26 weekly injections of 1,2-dimethylhydrazine. All animals were subjected to an end-to-end colonic anastomosis at the beginning of the experiment using five stitches of steel wire. RESULTS: The control group developed significantly more tumors per animal at both the anastomosis ( P < 0.001) and in the rest of the colon ( P <0.001). In addition, the percentage of rats with tumors was significantly higher in the control group at both the anastomosis (chi-squared=12; df=1,P <0.001) and in the rest of the colon (chisquared=7.12; df=1,P <0.01). The mean surface of tumors was likewise greater in the control group at the anastomosis ( P <0.001) and throughout the rest of the colon ( P <0.001). Finally, there were significantly more small-bowel tumors (excluding the duodenum) in the control group ( P <0.05). CONCLUSIONS: It is concluded that calcium supplementation decreases the tumor yield at the site of end-to-end colonic anastomosis and in the rest of the colon and small bowel (excluding the duodenum).     

Efficacy of the povidine-iodine irrigation in healing of colonic anastomosis in rats

BACKGROUND: Anastomotic leakage is a major cause of mortality in colorectal surgery. Several methods have been evaluated in order to prevent anastomotic leakage, and was postulate that povidone-iodine irrigation of colon before anastomosis can improve anastomotic healing, prevent adhesion formation, and may be beneficial in patients undergoing gastrointestinal surgery. AIM: To evaluates the efficacy of this agent in healing of colonic anastomosis in rats. MATERIAL AND METHODS: Twenty Wistar rats were divided into two groups: Group A (n = 10), cleaning of anastomotic borders with saline solution, and group B (n = 10), cleaning of anastomotic borders with 5% povidone-iodine. The animals were submitted to laparotomy, section of colon and treatment according previously described. After anastomosis, the animals were observed, and killed in 7th postoperative day. Blood samples were collected to serum albumin measurement and anastomosis observed macroscopically in relation to presence of fistula, adhesion and dilatation. A 6 cm colonic segment with the anastomosis at the center was excised bursting pressure was determined. RESULT: There was no fistula in any animal in both groups, and there was no difference in relation to obstruction, presence of adhesion or bursting pressure when compared group A and B. CONCLUSION: The use of povidone-iodine was not able to improve anastomotic healing in rats.     

Intraoperative bowel irrigation improves anastomotic collagen metabolism in the left-sided colonic obstruction but not covering colostomy

This study investigated the effects of intraoperative colonic irrigation and proximal diverting end colostomy after segmental bowel resection in experimental left-colonic obstruction on anastomotic healing. Simple obstruction of descending colon was performed in male Sprague-Dawley rats. After 24 h we performed segmental colonic resection and anastomosis in the control group (n = 15); resection, anastomosis, and covering colostomy in the colostomy group (n = 14); resection and anastomosis after antegrade colonic lavage through cecum by using isotonic saline solution in the irrigation group (n = 13). In rats that were killed 7 days later anastomotic dehiscence and bursting pressure and tissue hydroxyproline concentration at the anastomosis were measured. No significant differences were observed between groups in terms of anastomotic dehiscence, bursting site, or pressure. The hydroxyproline concentration was significantly higher in the irrigation group than the control group (P = 0.025) and the colostomy group (P = 0.029), but no difference was noted between the control group and the colostomy group. These findings suggest that intraoperative antegrade colonic irrigation in the acute left-sided colonic obstruction positively affects collagen metabolism at the anastomotic site; if the anastomosis is performed without bowel cleansing, covering colostomy does not improve collagen metabolism. Accepted: 30 September 1998     

Early effects of fibrin sealant on colonic anastomosis in rats: an experimental and case-control study

Background Leakage from colonic anastomoses leads to mortality and morbidity. Fibrin adhesives can be used to increase the strength of the anastomosis. In this study, we evaluated the early effects of fibrin sealant and hyaluronic acid-carboxymethylcellulose on colonic anastomosis in rats. Methods Anastomoses were made in the descending colon of 38 female Wistar-Albino rats, in three groups: control group (n=12), group 1 treated with hyaluronic acid-carboxymethylcellulose (n=16), and group 2 treated with fibrin sealant (n=10). After 72 hours, adhesion scores, bursting pressure, rupture strength and histopathologic healing scores were evaluated. Results Due to postoperative mortality, we evaluated 10, 10 and 9 rats in the control group and in groups 1 and 2, respectively. Of these, we excluded 4, 5 and 4 rats that had macroperforations at autopsy. In the remaining rats, bursting pressure (123.2±14.8 mmHg) and rupture strength (400±16 mg) in the fibrin sealant group were significantly greater than in the two other groups (Control: 68.0±10.6 p=0.006 and 325±52 p=0.009; Group 1: 74.0±9.8 p=0.03, 330±27 p=0.016). However, we did not observe any significant difference between adhesion scores (2.5±0.6, 2.0±0.7, 2.0±0.7, p=0.343). Conclusions In this experimental study, fibrin sealant increased bursting pressure and rupture strength of colonic anastomoses while hyaluronic acid-carboxymethylcellulose had no effetcs in rats, but both of them showed no effect on adhesion scores. In order to use fibrin sealant to decrease the rate of early leakages from colonic anastomoses, further studies have to be performed.     

Goblet cell hyperplasia is a feature of the adaptive response to jejunoileal bypass in rats

The role of goblet cells in the adaptive response of the intestine to jejunoileal bypass was studied in rats submitted to an 85% end-to-side jejunoileal bypass or sham bypass. At 36 weeks the length and wet weight of the duodenum and large bowel was 13-48% greater in animals with jejunoileal bypass. Measurements of villous height and crypt depth confirmed mucosal hyperplasia in the residual functioning small bowel and the distal colon. Histochemical studies in both groups of rats showed an overall predominance of sulphomucins throughout the intestinal tract, but jejunoileal bypass caused a disproportionate increase in the number of sialomucin containing goblet cells in functioning segments of small bowel and distal colon. An abundance of sialomucin cells at the site of anastomosis after jejunoileal bypass may have been a protective response to local mechanical trauma. Goblet cell hyperplasia is a feature of compensatory growth of the intestinal tract after surgical shortening. The changes in colonic mucin seen after jejunoileal bypass resemble those observed in ulcerative colitis and mucosal dysplasia.     

Ultrastructural view of colon anastomosis under propolis effect by transmission electron microscopy

AIM： To evaluate the effect of propolis administration on the healing of colon anastomosis with light and transmission electron microscopes. METHODS： Forty-eight Wistar-AIbino female rats were divided into two groups and had colon resection and anastomosis. In group Ⅰ, rats were fed with standard rat chow pre- and postoperatively. The rats in group Ⅱ were fed with standard rat chow and began receiving oral supplementation of propolis 100 mg/kg per day beginning 7 d before the operation and continued until they were sacrificed. Rats were sacrificed 1, 3, 7 and 14 d after operation, and anastomotic bursting pressures measured. After the resection of anastomotic segments, histopathological examination was performed with light and transmission electron microscopes by two blinded histologists and photographed. RESULTS： The colonic bursting pressures of the propolis group were statistically significantly better than the control group. UItrastructural histopathological analysis of the colon anastomosis revealed that propotis accelerated the phases of the healing process and stimulated mature granulation tissue formation and collagen synthesis of fibroblasts. CONCLUSION： Bursting pressure measurements and ultra structural histopathological evaluation showed that administration of propolis accelerated the healing of colon anastomosis following surgical excision.     

Effect of leptin on healing of colonic anastomoses in rats

BACKGROUND/AIMS: Anastomotic leaks are continuing to be the source of major morbidity in colorectal surgery. Previous studies have shown that leptin acts as a growth factor for several cell types. The aim of this study was to evaluate the effect of leptin on healing of colonic anastomoses in rats. METHODOLOGY: Forty-eight rats were divided into 5 groups. Group I (n=8) sham; group II (n=10) control; right colonic anastomosis, group III (n=10); following right colonic anastomosis, treated with leptin twice-daily 1 mg/kg intraperitoneally, group IV (n=10); before right colonic anastomosis, 45 min of colonic ischemia has been created, group V (n=10); following 45 min of colonic ischemia and right colonic anastomosis, leptin was given twice-daily 1 mg/kg intraperitoneally. On the 7th postoperative day relaparotomy was performed. Bursting pressure (BP), tissue hydroxyproline concentrations (THPC), and histopathologic properties of anastomoses; vascular tissue proliferation (VTP), collagen tissue proliferation (CTP), polymorphonuclear leukocyte infiltration (PMNLI), mononuclear leukocyte infiltration (MNLI) were analyzed and results were compared statistically. RESULTS: BP and THPC were found to be significantly higher in group III and group V in comparison with group II and group IV respectively (P<0.05). Histopathologically, leptin significantly increased VTP, CTP, MNLI (P<0.001), and significantly decreased PMNLI (p<0.05) on non-ischemic and ischemic colonic anastomoses. CONCLUSIONS: Leptin can be used safely in colorectal surgery since it accelerates the healing of colonic anastomoses.     

吻合口支架降低结肠术后吻合口漏发生率的动物研究

目的通过比较放置吻合口支架与单纯手工缝合对大鼠结肠吻合口漏的影响,探索吻合口支架对降低结肠术后吻合口漏发生率的应用价值。 方法以32只雄性SD大鼠为研究对象,随机分为2组,每组16只,行大鼠结肠端端吻合术,实验组行间断缝合的同时放置支架,即支架组;对照组单纯行间断缝合,即手工缝合组。比较两组腹腔粘连程度、吻合口漏、总生存率的差异。 结果相对于手工缝合组,支架组吻合腹腔粘连程度评分较低（5.94±1.69 vs. 9.19±2.52,t=4.181;P=0.008）;支架组吻合口漏发生率明显低于手工缝合组（12.5% vs. 56.25%,χ²=6.788;P=0.023）;支架组总生存率高于手工缝合组（87.5% vs. 43.75%,χ²=5.850;P=0.016）。 结论相对于手工缝合,吻合口支架可以减少大鼠术后腹腔粘连程度,降低吻合口漏发生率,具有潜在临床应用价值。     

Role of the antiangiogenetic drug paclitaxel on healing of intestinal anastomosis: an experimental study

Background The aim of intraperitoneal administration of antineoplastic agents is the prevention of the implantation of tumoral cells after surgical intervention or the treatment of peritoneal carcinomatosis. The efficiency of intraperitoneal administration of paclitaxel, which is also an antiangiogenetic agent, has been investigated recently. The aim of this experimental study was to evaluate, taking into consideration its antiangiogenetic properties, the effects of intraperitoneal paclitaxel on healing of end to end colonic anastomosis. Methods 42 rats were allocated to 2 main groups (n = 21 for each group) to be evaluated on postperative day 3 (group A) and postoperative day 7 (group B). Each of the two main groups was divided into 3 subgroups (7 rats each). These subgroups were determined as control and two treatment groups administered paclitaxel in a dose of 2.5 mg/kg and 3.5 mg/kg intraperitoneally. Anastomosed segments of colon were harvested on postoperative day 3 or 7 and evaluated to determine bursting pressure of anastomoses, hydroxyproline levels and neovascularization with CD–31. Results In both groups, there were no significant differences between control and paclitaxel–treated groups with respect to bursting pressure. The level of hydroxyproline showed a significant decrease in all paclitaxel–treated groups compared with control groups (p = 0.001). Neovascularization was found to be decreased significantly on day 3 in the doses of paclitaxel 2.5 mg/kg (6.4 ± 1.63) and 3.5 mg/kg (5.89 ± 1.01) compared with control (8.02 ± 0.88) (p = 0.029 and p = 0.005, respectively). There were no significant differences in neovascularization in either groups on postoperative day 7. Conclusion We suggest that intraperitoneal administration of paclitaxel during surgical procedure decreases the hydroxyproline content and neovessel formation that are necessary for healing of intestinal anastomosis.     

The influence of omentectomy on the inflammatory phase of anastomotic healing.

BACKGROUND/AIMS: Proper wound healing of the alimentary tract is essential for the prevention of the significant mortality and morbidity associated with complications. The effects of omentectomy on the inflammatory phase of anastomotic healing in rats were examined. METHODOLOGY: Sixty male Wistar-Albino rats that weighed about 200-220 g were used in this study. Animals were divided into three groups as colon anastomosis, colon anastomosis + partial omentectomy and colon anastomosis + total omentectomy. On the third postoperative day, all animals were sacrificed under anesthesia. Bursting pressure of anastomosis amounts and types of cells in the anastomosis, and nitric oxide, malondialdehyde, superoxide dismutase levels in the anastomosis and serum was examined. RESULTS: Bursting pressure values were 102.60 +/- 13.41 mm Hg, 105 +/- 10.80 mm Hg and 102.50 +/- 11.12 mm Hg in the colon anastomosis, colon anastomosis + partial omentectomy and colon anastomosis + total omentectomy groups, respectively (P > 0.05). A significant increase in macrophage count was found in the colon anastomosis + total omentectomy group when compared with the colon anastomosis group (P = 0.02). According to the comparisons with percentages, there was a significant difference in lymphocyte counts between colon anastomosis and colon anastomosis + total omentectomy groups (P = 0.04). The blood level of superoxide dismutase was higher in the colon anastomosis + total omentectomy group than the other two groups, and in the colon anastomosis + partial omentectomy group than the colon anastomoses group (P = 0.0001). There was a significant increase in the blood level of nitric oxide when comparing the colon anastomosis + total omentectomy group with colon anastomosis group (P = 0.02). The tissue level of malondialdehyde was higher in the colon anastomosis + total omentectomy group than the other two groups (P < 0.0001). CONCLUSIONS: Omentectomy may influence the outcome of the inflammatory phase of wound healing in rats. But systemic compensatory regulation of body can tolerate these detrimental effects and wound healing continues in its regular manner.     

Effect of mucosal immunomodulation with fed cholera toxin on healing of experimental colonic anastomosis

PURPOSE: The aim of this study was to investigate in rats whether preoperative orogastric administration of low doses of cholera toxin would influence the mechanical strength of experimental colonic anastomosis on the basis of the gut mucosal immunomodulation effect of this antigen. METHODS: The cholera toxin group (n = 14) was fed 10 g of cholera toxin in phosphate-buffered saline three times before surgery at 10-day intervals, whereas the controls (n = 14) received phosphate-buffered saline only. Twenty-four hours after the last dose of cholera toxin (or placebo in control group), the animals underwent left colonic transection and anastomosis. Seven days after colonic transection-anastomosis, the bursting pressure of the anastomotic segment was recorded in situ. Perianastomotic and extra-anastomotic tissue samples were obtained for measurements of tissue transforming growth factor-beta, interleukin-6, and interferon-gamma levels with enzyme-linked immunosorbent assay. RESULTS: Cholera toxin administration resulted in a significantly higher bursting pressure than in the control group (165.78 ± 12.37 vs. 138.4 ± 7.87 mmHg; P < 0.001). Compared with the control group, the heightened mechanical strength of colonic anastomosis provided by cholera toxin was associated with significant increases in the perianastomotic tissue levels of transforming growth factor-beta (199.34 ± 24.85 vs. 70.66 ± 10.63 pg/ml; P < 0.001) and interleukin-6 (439.31 ± 95.14 vs. 289.57 ± 96.59 pg/ml; P = 0.001), whereas interferon-gamma was significantly lower (174.04 ± 44.82 vs. 219.00 ± 31.35 pg/ml; P < 0.05). This cytokine pattern induced by cholera toxin in the wound milieu was also found to be similar in the extra-anastomotic colon. CONCLUSION: The mechanical strength of uncomplicated experimental colonic anastomosis increased significantly with gut mucosal immunomodulation with repeated low preoperative doses of cholera toxin. This enhanced healing had significant positive correlation with the colonic tissue level of transforming growth factor-beta and inverse correlation with interferon-gamma. If the relevant dose regimen is identified and its safety is assured in humans, gut mucosal immunomodulation might provide an efficient, safe, and inexpensive tool to improve surgical outcome in colorectal surgery, particularly in high-risk situations.     

Subtotal colectomyvs. intraoperative colonic irrigation in the management of obstructed left colon carcinoma

PURPOSE: Whether primary anastomosis should be performed after segmental resection with intraoperative colonic irrigation or subtotal colectomy is not yet established in the surgical treatment of obstructive left colon carcinoma. In this prospective, nonrandomized study, we present the results of 66 patients undergoing one-stage surgery for obstructed left colon carcinoma. PATIENTS AND METHODS: We compared two techniques, subtotal colectomy (35 patients) and intraoperative colonic irrigation with segmental resection and immediate anastomosis (31 patients). RESULTS: The mortality rate was similar in both groups, 8.5 percent in the subtotal colectomy group and 3.2 percent in the intraoperative colonic irrigation group. The surgical complication rate was significantly higher in the intraoperative colonic irrigation group (41.9 percent) than in the subtotal colectomy group (14.2 percent;P<0.05). Mean operating time was significantly lower in the subtotal colectomy group than in the intraoperative colonic irrigation group (P<0.05). Both groups had a similar mean duration of hospital stay. Ten patients who underwent subtotal colectomy (31.2 percent) presented with diarrhea in the immediate postoperative period, which disappeared spontaneously or with antidiarrheal medication; a disabling diarrhea persisted in two patients only (6.2 percent). CONCLUSION: We believe that subtotal colectomy is the treatment of choice for obstructed left-sided colonic carcinoma. Segmental resection with intraoperative colonic irrigation is more appropriate than subtotal colectomy only in patients with carcinomas of the rectosigmoid junction or with previous anal incontinence to avoid the appearance of postoperative diarrhea.