Effects of preoperative fractionated irradiation on left colonic anastomoses in the rat

PURPOSE: Radiotherapy is frequently used as a (neo)adjuvant to surgery in colorectal cancer patients, and because such therapy could influence the integrity of the anastomosis, we decided to investigate the effect of preoperative irradiation on colonic anastomosis. METHODS: Seventy-two male Wistar rats, weighing 200 to 348 g, were divided into three groups: a control group (I) underwent left colon resection and primary anastomosis (n=20); a sham irradiated group (II, n=20); a study group (III) that received fractionated irradiation to the whole pelvis (anterior-posterior pelvic field), for a total dose of 22 Gy, 5.5 Gy per fraction, on four consecutive days with linear accelerator (n=32). Four days after irradiation, both Groups II and III underwent the same operation as performed in Group I. Within each group, one-half of the animals were anesthetized on the third postoperative day and one-half on the seventh postoperative day. Abdominal wound-healing, anastomotic complications, and anastomotic bursting pressure measurements were recorded. Following these measurements, the anastomotic segment was resected for hydroxyproline content and myeloperoxidase activity. RESULTS: Irradiated animals had more pronounced weight loss during therapy. There were no differences with abdominal wound-healing, intraperitoneal adhesions, and anastomotic complications between groups. At days 3 and 7, mean bursting pressures of the anastomosis were determined at 36.5 and 208 mmHg in Group I, 34.5 and 228 mmHg in Group II, and 25 and 150 mmHg in Group III, respectively (P<0.01 Group IIIvs. both Groups I and II on days 3 and 7). The burst occurred at the anastomosis in all animals tested on the third postoperative day and one in Group I (10 percent), none in Group II, and six in Group III (37.5 percent) on the seventh postoperative day. In addition, hydroxyproline content and myeloperoxidase activity was significantly lower in Group III. CONCLUSION: Although preoperative fractionated irradiation significantly decreased the anastomotic bursting pressure and more burst occurred in the anastomotic line on postoperative day 7, the clinical outcome was similar among the groups.Presented at the 37th World Congress of Surgery of the ISS/SIC, Acapulco, Mexico, August 24 to 30, 1997.     

Improvement of Colonic Healing by Preoperative Rectal Irrigation With Short-Chain Fatty Acids in Rats Given Radiotherapy

BACKGROUND We investigated the effect of preoperative rectal irrigation with short-chain fatty acids on irradiated colonic anastomosis in rats.METHODS Sixty male Wistar rats were divided into four groups. Group I (control group, n = 15) underwent left colon resection and primary anastomosis. Group II (Short-chain fatty acids pretreatment group, n = 15) had short-chain fatty acids rectal irrigation for five days preoperatively. Group III (preoperative radiotherapy group, n = 15) underwent irradiation to the whole pelvis eight and four days before the operation, for a total dose of 20 Gy. Group IV (preoperative radiotherapy group + short-chain fatty acids pretreatment group, n = 15) had rectal irrigation with short-chain fatty acids for five days after the second irradiation. Within each group, animals were anesthetized to assess the clinical, mechanical, histologic, and biochemical parameters of anastomotic healing on either the third or seventh postoperative days.RESULTS The mean bursting pressure was significantly low in Group III on Day 3 and was significantly high in Group IV on Day 7 (P = 0.001, P = 0.021). The burst occurred at the anastomoses in all animals tested on the third postoperative day, and outside of the anastomoses in all animals tested on the seventh postoperative day. The histologic parameters of anastomotic healing, such as epithelial regeneration and formation of granulation tissue, were significantly improved by use of preoperative rectal irrigation with short-chain fatty acids on Day 7. The amount of total and salt-soluble collagen concentrations significantly increased in Group IV compared with the control group on Day 3 (P = 0.008, P = 0.004).CONCLUSION Some mechanical and histologic aspects of colonic anastomotic healing can be adversely affected by preoperative radiotherapy, but rectal irrigation with short-chain fatty acids may improve anastomotic healing.Supported by The Turkish Surgical Society, as funded by a grant from the Sanofi Pharma.     

Effect of Iloprost on Impaired Anastomotic Healing Caused by 5-Fluorouracil plus Leucovorin

Purpose This experimental study was designed to investigate whether iloprost can reverse impaired colonic healing caused by immediate postoperative intraperitoneal administration of 5-fluorouracil plus leucovorin. Methods Eighty Wistar rats were randomized into four groups. After resection of a 1-cm segment of transverse colon, an end-to-end sutured anastomosis was generated. Rats received saline solution (Group 1), 5-fluorouracil plus leucovorin (Group 2), iloprost (Group 3), and 5-fluorouracil plus leucovorin plus iloprost (Group 4) intraperitoneally from the day of operation and once daily until killing. Each group was further randomized into two subgroups. Subjects were killed on the fifth (Subgroup a) and eighth (Subgroup b) postoperative days. After killing, anastomoses were examined macroscopically and graded histologically. Rats were measured for anastomotic bursting pressures and tissue hydroxyproline levels. Results The leakage rate of the anastomoses was significantly higher in the 5-fluorouracil plus leucovorin group compared with the other groups (P = 0.049). Bursting pressure was significantly lower in 2a subgroup (5-fluorouracil plus leucovorin, postoperative Day 5) than in 4a (5-fluorouracil plus leucovorin plus iloprost, postoperative Day 5; P < 0.001). Adhesion formation was significantly higher in all b subgroups compared with the Control b subgroup. Neoangiogenesis was significantly higher in iloprost and iloprost plus 5-fluorouracil plus leucovorin subgroups compared with the 5-fluorouracil plus leucovorin subgroups. Hydroxyproline levels, collagen deposition, fibroblasts, and white cell count were significantly higher in the iloprost plus 5-fluorouracil plus leucovorin b subgroup (postoperative Day 8) compared with the 5-fluorouracil plus leucovorin b subgroup (postoperative Day 8). Conclusions The immediate postoperative, intraperitoneal administration of iloprost counteracts and reverses the negative effects of 5-fluorouracil plus leucovorin chemotherapy and protects colonic healing in rats. The authors declare that they have no conflict of interest with the manufacturer of iloprost (ILOMEDIN?, Schering Berlin, Germany).     

Beneficial effect of iloprost® on impaired colonic anastomotic healing induced by intraperitoneal 5-fluorouracil infusion

PURPOSE: 5-Fluorouracil is the most effective chemotherapeutic agent in the management of patients with systemic colorectal cancer. Studies in recent years discussed the gradually increasing benefits of 5-fluorouracil within adjuvant chemotherapy protocols after complete surgical resections. However, many studies also have demonstrated that 5-fluorouracil impairs wound-healing on colonic anastomoses. METHODS: In our experimental study, we examined the influence of intraperitoneal 5-fluorouracil on healing of colonic anastomoses and, also, attempted to discover whether Iloprost® (PGI₂ analog, a potent vasodilator with confirmed cytoprotectivity and inhibitor of thrombocyte aggregation) counteracts impaired wound-healing induced by 5-fluorouracil. A total of 80 Wistar-Albino male rats were separated into four groups. From the day of the operation, Group A received intraperitoneal saline solution, Group B received 20 mg/kg 5-fluorouracil intraperitoneally, Group C received 20 mg/kg 5-fluorouracil plus 2 µg/kg Iloprost® intraperitoneally, and Group D received 2 µg/kg Iloprost® intraperitoneally. Each group was divided into two subgroups, and both subgroups were killed on the third and seventh postoperative days, respectively. The subjects were measured for anastomose bursting pressures and tissue hydroxyproline levels, and wound-healing was evaluated histopathologically. Statistical evaluations among each group were made with Student'st-test and Pearson's chi-squared tests. RESULTS: Iloprost® had an accelerating effect on normal colonic anastomose wound-healing histopathologically, had no significant difference on bursting pressures and hydroxyproline levels, and significantly improved the impaired healing effect of 5-fluorouracil. CONCLUSIONS: Our study showed a positive effect of Iloprost® on the healing of colon anastomosis and, more importantly, if wound-healing is impaired by a chemotherapeutic agent, Iloprost® counteracts and reverses the effect.     

Effects of Combined Pulse Electromagnetic Field Stimulation Plus Glutamine on the Healing of Colonic Anastomosis in Rats

Purpose An experimental study was designed to investigate the effect of combined pulse electromagnetic field (PEMF) stimulation plus glutamine administration on colonic anastomosis. Methods Anastomosis of the left colon was performed in 28 rats, which were divided into four groups; Group 1: normal resection anastomosis plus oral 50 mg/kg/day glutamine; Group 2: normal resection anastomosis plus PEMF stimulation plus oral 50 mg/kg/day glutamine; Group 3: normal resection anastomosis plus PEMF stimulation; Group 4: normal resection anastomosis. On the seventh postoperative day, the animals were killed and the bursting pressure and tissue hydroxyproline concentration of the anastomosis were analyzed and compared. Results The mean anastomotic bursting pressure in Group 2 was significantly higher than in Groups 1 and 4. On the other hand, the mean anastomotic bursting pressure in Group 1 was significantly higher than in Group 4. The collagen deposition and the fibroblast infiltration were significantly increased on the seventh day in Group 3 compared the other groups. On the other hand, Groups 1 and 2 had higher scores for collagen deposition and fibroblast infiltration than Group 4. Conclusions In conclusion, burst pressures, hydroxyproline, and histologic features (fibroblast infiltration and collagen deposition) were improved in the PEMF group, and both PEMF and glutamine-enriched nutrition provide a significant gain in the strength of colonic anastomoses in rats.     

Effect of fibrin glue on irradiated colonic anastomoses

INTRODUCTION: The present study was planned to research the effects of fibrin glue on irradiated colonic anastomoses. METHOD: The effect of fibrin glue on irradiated colonic anastomoses was investigated in four identical groups of rats. In Group I (control group) colonic anastomoses were performed without radiotherapy; in Group II, colonic anastomoses were performed five days after radiotherapy; in Group III, fibrin glue was applied to anastomotic line without radiotherapy; in Group IV, fibrin glue was applied to anastomotic line with radiotherapy. The healing of left colonic anastomoses was evaluated through the bursting pressure of the anastomotic segment and the hydroxyproline contents of the anastomosis. RESULTS: Measurements done on the fourth postoperative day revealed that anastomotic healing was impaired in rats that underwent radiotherapy ( P <0.001); fibrin glue had no effect on anastomotic healing in groups with or without radiotherapy. CONCLUSION: In the early phases of anastomotic healing, fibrin glue cannot help remove unwanted effects of preoperative radiotherapy.     

Effects of recombinant human growth hormone and nandrolone phenylpropionate on the healing of ischemie colon anastomosis in rats

Purpose Recombinant human growth hormone and nandrolone phenylpropionate are two different anabolic agents. This study was designed to investigate the effects of these anabolic agents on the healing of ischemie colon anastomosis in rats. METHODS: Seventy adult male Wistar rats were divided into five groups (n = 14). Group I was the sham laparotomy group. In the other groups, surgical procedures consisting of transsection and anastomosis were made at a distance 3 cm from the peritoneal reflection. Group II was the nonischemic control group. Ischemie colon model was produced in the remaining groups. Group III was the untreated control group. Groups IV and V received recombinant human growth hormone and nandrolone phenylpropionate, respectively. Bursting pressure and hydroxyproline levels were measured on the third and seventh postoperative days to evaluate anastomotic healing. RESULTS: Recombinant human growth hormone increased both collagen deposition and bursting pressure significantly at postoperative Days 3 and 7 compared with the sham and untreated control groups (P < 0.005). When compared with the untreated control, nandrolone phenylpropionate significantly increased collagen deposition at postoperative Days 3 and 7 (P < 0.005) and bursting pressure only at postoperative Day 3 (P < 0.005). CONCLUSIONS: Recombinant human growth hormone has more favorable therapeutic effects on the healing of ischemie colonie anastomoses than nandrolone phenylpropionate. Recombinant human growth hormone also improves healing of nonischemic colonie anastomosis.     

The effects of the immunomodulators on the colonic anastomosis in an experimental model of intraperitoneal sepsis

BACKGROUND/AIMS: The present study examined the effects of G-CSF and Levamisole used as immunomodulators on the colonic anastomosis healing in the presence of an intraabdominal infection. METHODOLOGY: 40 male Spraque-Dawley rats were randomly allocated to 4 groups each consisting of 10 animals. Standard colonic anastomosis, peritonitis and colonic anastomosis, peritonitis and colonic anastomosis and G-CSF, peritonitis and colonic anastomosis and Levamisole were applied to groups I, II, III and IV, respectively. The cecum of the rats in groups II, III and IV was ligated and perforated to create an intraabdominal sepsis model. G-CSF 50 microg/kg/day were given subcutaneously to group III and Levamisole 5 mg/kg/day were given perorally to group IV in the postoperative period until sacrifice. The rats were sacrificed on the fourth postoperative day. Bursting pressure and hydroxyproline level measurements of the anastomosis were evaluated. RESULTS: Bursting pressures of all groups were lower than the control group (p<0.001). The mean bursting pressure of group III was significantly higher than group II (p<0.05). The mean level of hydroxyproline in group III was significantly higher than group II (p<0.05) however; overall, it was lower in all groups than the control (p<0.05). CONCLUSIONS: This study demonstrated that intraabdominal sepsis adversely affects healing of colonic anastomosis, and healing of the anastomosis becomes better and the mortality rate decreases by the use of G-CSF.     

Effect of early preoperative 5-fluorouracil on the integrity of colonic anastomoses in rats

AIM： To determine the effect of chemotherapy on wound healing by giving early preoperative 5-fluorouracil （5-FU） to rats with colonic anastomoses.METHODS： Sixty Albino-Wistar male rats （median weight, 235 g） were used in this study. The rots were fed with standard laboratory food and given tap water ad libitum. The animals were divided into three groups： Group 1： Control group （chemotherapy was not administered）, Group 2： Intraperitoneally （IP） administered 5-FU group （chemotherapy was administered IP to animals at a dose of 20 mg/kg daily during the 5 d preceeding surgery）, Group 3： Intravenously （IV） administered 5-FU group. Chemotherapy was administered v/a the penil vein, using the same dosing scheme and duration as the second group. After a 3-d rest to minimize the side effects of chemotherapy, both groups underwent surgery. One centimeter of colon was resected 2 cm proximally from the peritoneal reflection, then sutured intermittently and subsequently end-to-end anastomosed. In each group, half the animals were given anaesthesia on the 3rd postoperative （PO） day and the other half on the 7th PO day, for in vivo analytic procedures. The abdominal incisions in the rats were dissected, all the new and old anastomotic segments were clearly seen and bursting pressures of each anastomotic segment, tissue hydroxyproline levels and DNA content were determined to assess the histologic tissue repair process. RESULTS： When the IV group was compared with the IP group, bursting pressures of the anastomotic segments on the 3rd and 7th PO days, were found to be significantly decreased, hydroxyproline levels at the anastomotic segment on the 7th PO day were significantly decreased （P 〈 0.01）. CONCLUSION： In this study, we conclude that early preoperative 5-FU, administered IV, negatively affects wound healing. However, IP administered 5-FU does not negatively affect wound healing.     

The effect of tegafur and uracil combination on colonic anastomotic strength: an experimental study on rats

BACKGROUND/AIMS: Some patients are candidates for neo-adjuvant use of Tegafur, a prodrug of 5-fluorouracil, and Uracil combination (UFT). The purpose of this study is to assess the effect of preoperative UFT use on the strength of colonic anastomosis. METHODOLOGY: Forty Wistar albino rats were randomly divided into a control (group 1, n=10) and three study (Group 2, 3 and 4, 10 animals in each group) groups. Animals in control and study groups were given saline or UFT which included 50 mg/kg of Tegafur via an oral-gastric tube for 28 days. A segmental colonic resection and end-to-end anastomosis was performed on all animals 1, 1, 7 and 14 days after the treatments had ended in groups 1, 2, 3 and 4, respectively. On postoperative day 7 the animals were killed and bursting pressure and breaking strength were measured. RESULTS: Three animals in the treatment groups died during the preoperative period, and one in the control group died after surgery. The animals in groups 2 and 3 had lesser bursting pressures than the control group (p<0.001), but no statistical difference was observed in bursting pressures of the control group and group 4 (p>0.05). The breaking strengths of each group were statistically different from the other groups (p<0.001 for each comparison). CONCLUSIONS: UFT use during the preoperative period affected the anastomosis strength in this animal experiment. Current study suggests that an operation should not be performed during the 14 days after UFT use has ended.     

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.     

Prevention of Deleterious Effects of Reperfusion Injury Using One-Week High-Dose Allopurinol

Allopurinol has been widely used to reduce the severity of the reperfusion injury. However, conflicting data have been reported regarding the dosage, the duration of the timing, and the administrative regimen of the drug. The aim of this study was, therefore, to evaluate the effects of short versus long periods of allopurinol pretreatment on the anastomotic healing of intestines, directly after being subjected to ischemia–reperfusion (IR) stress. Furthermore, the effects of an allopurinol pretreatment on the survival rate following IR stress, was also assessed. One hundred thirty-seven male Wistar rats with a median weight of 235 (range, 180–275) g used in the study. In group I (control group, N = 20) superior mesenteric artery (SMA) and collateral vessels were isolated but not occluded. In group II, the profound IR group (PIR, N = 42), the SMA was occluded immediately distal to the aorta with collateral interruption using an atraumatic arterial clip for 30 min. In group III [two days of allopurinol (ALL) pretreatment group, 2ALL, N = 38], allopurinol (100 mg/kg body wt) was given intraperitoneally on a daily basis for two days prior to the experiment. In group IV (seven days of allopurinol pretreatment group, 7ALL, N = 37), the same pretreatment and the allopurinol schedule was performed for seven days before surgery. All animals underwent 3 cm of ileal resection and primary anastomosis, 10 cm proximal to ileocecal valve. Within each group, animals were anesthetized either on the third or seventh postoperative days. Abdominal wound healing, intraabdominal adhesions, anastomotic complications, anastomotic bursting pressure measurements, and bursting site were recorded as were the histopathologic evaluation. No rats in group I, 20 rats in group II, 18 rats in group III, and 7 rats in group IV died (P = 0.0003). Anastomotic dehiscence was found in one of 20 group I, in 11 of 22 in group II, in 9 of 20 in group III, and in 3 of 30 in group IV (P = 0.0003). On the third and seventh days, the median bursting pressures of the anastomosis were determined: 42 and 235 mm Hg in group I, 17 and 105 mm in Hg in group II, 22 and 183 mm Hg in group III, and 36 and 214 mm Hg in group IV (P < 0.0001). The burst occurred at the anastomoses in all animals tested on the third postoperative day, one in group I, six in group II, four in group III and one in group IV on the seventh postoperative day (P < 0.01). All deleterious effects of reperfusion injury on intestinal anastomosis healing, including survival rates and the histopathological parameters, were significantly prevented by seven days, but not two days, of high-dose allopurinol pretreatment.     

Growth hormone increases the bursting strength of colonic anastomoses

The effect of growth hormone on the bursting strength of left colonic anastomoses was investigated experimentally. Seventy-two 3 month-old female rats were randomized into two groups receiving daily injection of either saline (controls) or 2.0 mg biosynthetic human growth hormone per kg body weight per day. All injections were started 7 days before a left colonic resection and anastomosis, and continued until sacrifice at the 2nd, 4th or 6th post-operative day. The bursting strength of the anastomoses was tested in anaesthetized, living rats. The bursting pressure and the bursting wall tension of the growth hormone treated animals were increased two-fold on the second post-operative day (2p<0.005) and three-fold on the fourth post-operative day (2p<0.05), compared with controls. There was no difference in the bursting pressure or the bursting wall tension on the sixth postoperative day. The mass of the resected segment was incresed by the pre-operative growth hormone treatment, whereas the hydroxyproline content was unchanged. In conclusion, treatment with biosynthetic human growth hormone increases the strength of colonic anastomoses in the early phases of healing.     

Histological evaluation of colonic anastomotic healing in the rat following preoperative 5-fluorouracil, fractionated irradiation, and combined treatment

There is a growing interest in neoadjuvant chemo- and radiotherapy as a treatment modality for colorectal cancer which could affect mechanical and biochemical parameters of anastomotic healing. This study investigated the effect of such protocols on colonic anastomotic healing by evaluating the histopathological parameters. One hundred and sixty male Wistar rats were divided into six groups: a control group (I, n=20), a saline group (II, n=30) which received 1 ml NaC1 intraperitoneally, a sham-irradiated group (III, n=20), a 5-fluorouracil (5-FU) group (IV, n=30), which received 5-FU (20 mg/kg) intraperitoneally for 5 consecutive days, an irradiated group (V, n=40) which received fractionated irradiation to the whole pelvis to a totaldose of 22 Gy, 5.5 Gy per fraction on 4 consecutive days, and a concomitant 5-FU + irradiation group (VI, n=20) which received 5-FU as in group IV and irradiated as in group V. All groups underwent left colonic resection with primary anastomosis, and the last fraction of irradiation and the last injection were given 4 and 3 days before the operation, respectively. Within each group one half of the animals were killed on the third postoperative day and the other half on the seventh postoperative. day. After the resection of the anastomotic segments, histopathological examination was evaluated. Apposition of the wound edges of the mucosa and the muscularis were not affected by the therapy. The level of granulocytes was high, inflammatory exudate and necrosis persisted, granulation tissue formation was delayed, and the levels of macrophages and fibroblasts were low. We conclude that colonic anastomotic healing can be affected by the administration of preoperative chemotherapy, irradiation, and chemoirradiation. Accepted: 17 July 1998     

The healing of colon anastomosis covered with fibrin glue after early postoperative intraperitoneal chemotherapy

Background After colon resection for colonic cancer, the administration of antineoplastic agents may prolong survival by killing residual cancer calls and preventing metastasis, but may also slow anastomotic healing. This study was designed to determine the effects of 5-fluorouracil (5-FU) and leucovorin (LEV), injected intraperitoneally, on the healing of colonic anastomoses with or without fibrin glue (FG) covering. Methods Sixty rats were randomized to one of four groups. After resection of a transverse colon segment, an end-to-end sutured anastomosis was performed. Rats in the 5-FU+LEV and the 5- FU+LEV+FG groups received 5-FU+LEV intraperitoneally. The colonic anastomoses of the rats in the FG group and in the 5-FU+LEV+FG group were covered with fibrin glue. All rats were killed on postoperative day 8. Bursting pressure measurements were recorded and the anastomoses were examined macroscopically and histologically. Results The leakage rate of the anastomoses was significantly different among groups. Specifically, the leakage rate was significantly higher in the 5-FU+LEV group (40%) than in the FG and in the 5-FU+LEV+FG groups where there were no leakages (p=0.017). The mean adhesion formation score was significantly higher in rats of the 5-FU+LEV group, compared to the control (p=0.023), the FG (p=0.006) and the 5-FU+LEV+FG (p=0.006) groups. Bursting pressures were significantly lower in the 5-FU+LEV group than in the other groups (p<0.001). Also, bursting pressures were significantly lower in the control group compared to the FG and 5-FU+LEV+FG groups (p<0.001). Rats in the 5-FU+LEV+FG group had significantly greater neoangiogenesis and fibroblast activity than those in the 5-FU+LEV group (p=0.025). Conclusion The early intraperitoneal postoperative administration of 5-fluorouracil plus leucovorin impaired colonic wound healing. However, the application of fibrin glue prevented the deleterious effect of chemotherapy.     

Effect of prostaglandin E1 and steroid on healing colonic anastomoses

PURPOSE: The effect of prostaglandin E₁ (PGE₁) and corticosteroids alone and in combination were studied in the healing rat colon to determine whether PGE₁ could not only improve healing but reverse the negative effect of steroids on colonic wound healing. METHODS: Colonic anastomoses were performed in 144 male Sprague-Dawley rats divided into four groups. The control group (I) received no further treatment. The steroid group (II) received cortisone acetate (5 mg/kg/day) beginning six days preoperatively and continuing until sacrifice. The PGE₁ group (III) received 2 μg of PGE₁ intra-aortically at surgery and for three days postoperatively. The combination PGE₁/steroid group (IV) received both drugs in the same doses as those in Groups II and III. Animals were sacrificed on postoperative days 6, 10, and 14. Wound healing was evaluated by hydroxyproline content, bursting pressures, and histology. RESULTS: The hydroxyproline assay at day 10 revealed that steroid-treated rats have significantly lower levels than any other group. The PGE₁ group (III) had the highest level of significance in comparison to the steroid group (II) (P=0.001). The addition of PGE₁ to steroid (Group IV) appeared to abolish the negative effect of the steroid as measured by hydroxyproline content on day 10 (P=0.038). When measuring bursting pressures, the PGE₁ group (III) had significantly higher pressures than any other group at day 10. However, no amelioration of the steroid effect on bursting pressures was seen. Histologic evaluation of the anastomosis did not reveal any significant differences among the four groups. CONCLUSIONS: PGE₁ reverses the negative effect of the steroid on hydroxyproline levels at day 10. Furthermore, using bursting pressure as a parameter of wound healing, administration of PGE₁ results in significantly improved anastomotic healing at day 10.     

Postoperative peridural analgesia increases the strength of colonic contractions without impairing anastomotic healing in rats

BACKGROUND AND AIMS: Peridural analgesia (PDA) is a common treatment in postoperative management after abdominal surgery to shorten postoperative ileus and to permit early postoperative nutrition. There are conflicting opinions on the effect of early peristalsis on healing of colonic anastomoses. PATIENTS AND METHODS: A short segment of the distal colon was resected in 32 Wistar rats. Two strain gauge transducers were placed on the serosa proximal to the anastomosis to measure the strength and periodicity of bowel contractions. A peridural catheter was placed between lumbar vertebra 7 and the sacral crest. The animals received 4, 16, 20, and 24 h after operation an injection of either 0.03 ml ropivacaine 0.75%/kg body weight or the same amount of sodium chloride (controls). After 3 and 10 days the colonic anastomoses were resected to measure the bursting pressure. The anastomoses were prepared for histopathological examination and determination of relative collagen content. RESULTS: Postoperative PDA led to an increasing amplitude of phasic and tonic contractions while the frequency of contractions was not significantly affected. None of the groups presented with any anastomotic complications. The bursting pressure after 3 and 10 days was similar in the two groups. The relative amount of collagen I in the anastomotic area was significantly higher after treatment with peridural ropivacaine. CONCLUSION: Postoperative PDA with ropivacaine increases the strength of colonic contractions. The increase in phasic contractions suggests a better propulsive bowel function. The significantly higher amount of collagen I in the anastomosis of animals in the PDA group supports the idea that healing of colonic anastomoses is improved rather than diminished by PDA.     

Does Becaplermin (Platelet-Derived Growth Factor-BB) Reverse Detrimental Effects of Ischemia on Colonic Anastomosis?

PURPOSE: The aim of this study was to evaluate the effects of becaplermin on normal and ischemic colon anastomoses. METHODS: Forty adult male Wistar-Albino rats were divided into four equal groups of ten. All rats underwent standard left colon resection and end-to-end anastomosis. The groups were as follows: Group 1, normal anastomosis alone; Group 2, ischemic anastomosis alone; Group 3, normal anastomosis and becaplermin therapy; and Group 4, ischemic anastomosis and becaplermin therapy. All animals were killed on postoperative Day 4. Intra-abdominal adhesions were scored, and anastomotic healing was evaluated with both in situ bursting pressure and hydroxyproline levels. RESULTS: According to bursting pressure results, there was a significant difference between Group 2 and Group 4 (P < 0.05), but there was no statistically significant difference between Group 1 and Group 3 (P > 0.05). Hydroxyproline values revealed no statistically significant difference among any of the groups (P > 0.05). With regard to intra-abdominal adhesion scores, Group 3 had significantly lower values than Group 2 and Group 4 (P < 0.05). No statistically significant difference was observed between the other groups. CONCLUSIONS: Detrimental effects of ischemia on colonic anastomotic healing were reversed with becaplermin therapy. However, there was no such benefit on nonischemic anastomoses. Intra-abdominal application of this gel did not lead to an increase in intra-abdominal adhesion formation.     

Is mechanical bowel preparation necessary before primary colonic anastomosis?

The necessity of preoperative or intraoperative mechanical bowel preparation of the colon, before primary anastomosis, has been recently challenged in clinical elective and emergency situations. PURPOSE: This experimental study in dogs investigated the safety of segmental resection and primary anastomosis in the unprepared or loaded colon. METHODS: Two segments of the descended colon were resected and anastomosed in each animal. Group I (12 anastomoses) received preoperative mechanical bowel preparation; the colon was not prepared in Group II (16 anastomoses); in Group III (12 anastomoses), a preliminary distal colonic obstruction was produced, and during the subsequent resection the colon was loaded. Postoperatively, animals were observed clinically, and anastomoses were assessed at autopsy on the ninth day. RESULTS: All animals recovered uneventfully. At autopsy there was no evidence of anastomotic leakage. CONCLUSIONS: In light of recent clinical reports and this experimental study, the ritual of mechanical bowel preparation should be further scrutinized.     

Effects of amniotic membrane on the healing of primary colonic anastomoses in the cecal ligation and puncture model of secondary peritonitis in rats

Purpose  We aimed to investigate the effects of amniotic membrane on primary colonic anastomoses in a rat peritonitis model. Materials and methods  Fifty female Sprague Dawley rats were used in the study. Bacterial peritonitis was induced in all rats by performing a cecal ligation and puncture. Ten rats served as controls for the bursting pressure measurement, while the other 40 animals were divided into two groups (the anastomosis group (P) or the amniotic membrane group (PA)), and all of them underwent colonic anastomosis. The latter group had amniotic membrane covering their anastomoses. Half of the PA and P groups were sacrificed on the third postoperative day (PA3, P3), and the other half on the seventh postoperative day (PA7, P7). Results  The bursting pressures were significantly higher in groups PA3 and PA7 compared with P3 (p < 0.01) and P7 (p < 0.05), respectively. Inflammatory cell infiltration and adhesion scores were significantly lower in groups PA3 and PA7 compared with groups P3 (p < 0.001, p < 0.01, respectively) and P7 (p < 0.001, p < 0.05, respectively). Neoangiogenesis, fibroblast activity, collagen deposition, and hydroxyproline concentrations were significantly higher in groups with amniotic membrane than in groups without amniotic membrane (p < 0.05, for all comparisons). Conclusion  This study showed that the covering of colonic anastomoses with amniotic membrane significantly prevented the delaying effect of intraperitoneal sepsis and provided a safer and stronger anastomosis than suture and that this was the case for both the early and late phases of anastomotic healing in the colon.