Healing of colon anastomoses covered with fibrin glue after immediate postoperative intraperitoneal administration of 5-fluorouracil

PURPOSE The aim of this experimental study was to investigate whether covering the colonic anastomoses with fibrin glue can protect the colonic healing from the adverse effects of 5-fluorouracil (5-FU), when it is injected intraperitoneally immediately after colon resection. METHODS Sixty-four rats were randomized to one of four groups. After resection of a 1-cm segment of the transverse colon, an end-to-end sutured anastomosis was performed. Rats of the control group and the fibrin glue group were injected with 6 ml of solution 0.9 percent NaCl intraperitoneally. Rats in the 5-FU and the 5-FU + fibrin glue groups received 5-FU intraperitoneally. The colonic anastomoses of the rats in the fibrin glue group and in the 5-FU + fibrin glue group were covered with fibrin glue. All rats were killed on the 8th postoperative day and the anastomoses were examined macroscopically. The bursting pressure measurements were recorded and the anastomoses were graded histologically.RESULTS The leakage rate of the anastomoses was significantly higher in the rats of the 5-FU group than in those of the fibrin glue group and those of the 5-FU + fibrin glue group (37.5 percent vs. 0 percent, P = 0.020). The adhesion formation score was significantly higher in rats of the 5-FU group than in the other groups. Bursting pressures were also significantly lower in the 5-FUgroup than in the other groups (P < 0.001). Rats in the 5-FU + fibrin glue group developed significantly more marked neoagiogenesis than rats in the other groups. Rats in the 5-FU + fibrin glue group also presented significantly more fibroblast activity than those in the 5-FU group. (P = 0.004)CONCLUSIONS The immediate postoperative, intraperitoneal administration of 5-FU inhibited wound healing. However, when the colonic anastomoses were covered with fibrin glue, the injection of 5-FU had no adverse effects on the healing of the anastomoses.     

The integrity of colonic anastomoses following the intraperitoneal administration of oxaliplatin

Introduction  

The purpose of this experimental study was to determine the effect of oxaliplatin on the integrity of colonic anastomoses which were under oxaliplatin administration.     

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.     

A prospective,controlled study of prophylactic drainage after colonic anastomoses

A prospective randomized, controlled trial was designed to study the influence of accorrugated latex drain on anastomotic integrity, wound infection, and respiratory complications after elective colonic resections above the pelvic peritoneum. Sixty patients entered the trial; 28 were drained and 32 undrained. Three patients in the undrained group died soon after surgery of causes unrelated to their colon anastomoses. There were no other differences in the incidence of postoperative complications in the two groups. When an anastomosis leaked, neither feces nor pus emerged via the drain. It is concluded that while the drains did not increase the incidence of postoperative complications, neither did they accomplish the purpose for which they were inserted. If, in addition, the economic cost of drainage is considered, it would seem that there is no advantage in inserting prophylactic drains after colonic anastomoses and their routine use needs to be reconsidered.     

Phospholipids reduce the intraperitoneal adhesion of colonic tumor cells in rats and adhesion on extracellular matrix in vitro

Objective To evaluate the influence of intraperitoneal treatment with phospholipids on the formation of peritoneal carcinosis after inoculation of colonic tumor cells in rats.Summary background data The presence of tumor cells in the peritoneal cavity serves as a prognostic marker for postoperative survival after resection of gastrointestinal cancer. Intraperitoneal tumor cell attachment is a pivotal step in developing peritoneal carcinosis. Intraabdominal application of phospholipids resulted in a significant decrease of adhesion formation, especially at sites of peritoneal lesions.Methods 2×10⁶ colonic tumor cells (DHD/K12/TRb) were injected intraperitonely in female BD-IX rats. A total of 90 rats were divided into three groups with treatments of phospholipids at 75 mg/kg or 150 mg/kg bodyweight or sodium chloride at 0.9% in the control group. The treatment groups were subdivided into animals with defined peritoneal lesions and animals without lesions. After 30 days, the extent of peritoneal carcinosis was determined by measuring the tumor volume, the area of tumor attachment and the Peritoneal Cancer Index. Over a 90-day observation period, the survival rate was analyzed. In vitro, we examined the reduction of tumor cell adhesion on extracellular matrix components after treatment with phospholipids. Microtiter plates were coated with laminin, fibronectin or collagen IV for adhesion experiments.Results In our study, we found a significant reduction of peritoneal dissemination with respect to all evaluation methods after treatment with phospholipids at 150 mg/kg in animals without peritoneal lesions. This could not be achieved using the lower concentration of phospholipids (75 mg/kg). In vitro, the maximum reductions of tumor cell adhesion by phospholipids compared with the control values for laminin and fibronectin were 46% and 37%, respectively, whereas for collagen IV the reduction was only 24% (p<0.0001).Conclusions A new method of prevention of intraperitoneal tumor cell adhesion, possibly leading to a reduced incidence of peritoneal carcinosis after surgery of gastrointestinal tumors, is introduced.     

The Effect of Capecitabine on the Healing of Colonic Anastomoses in Rats

Purpose Capecitabine is a fluoropyrimidine carbamate with antineoplasmatic activity, recommended for the treatment of colorectal cancer. This study was designed to assess the effectiveness of the perioperative administration of capecitabine on the healing process of colonic anastomosis. Methods Sixty Wistar rats were used, which were randomized in 2 groups of 30 each. The study group was subjected to colonic anastomosis and treated with therapeutic doses of capecitabine (359 mg/kg, or 2/3 of the mean toxic dose) by mouth one week before anastomosis and throughout the study. The control group received only placebo medication. Both groups were further divided into three subgroups, each of ten animals. In both study and control groups, ten animals were killed in each session on postoperative Days 3, 7, and 14. Results We found no negative impact on the healing of colonic anastomosis on capecitabine administration. The rate of anastomotic leakage and septic complications were not found to be significantly different between the study and control groups. The median bursting pressure was found to be significantly higher in the study subgroup killed on the third day (68 vs. 46 mmHg of the control group). Conclusions Perioperative administration of capecitabine does not have a negative impact on colonic anastomosis in rats. Presented at the International Congress on Colorectal Cancer, Chalkidiki, Greece, May 28 to 31, 2004. Presented at the Congress of Northern Greece Surgical Association, Alexandroupoli, Greece, October 14 to 15, 2005. Supported by the Procurement of Capecitabine, F. Hoffman La-Roche, Basle, Switzerland. Reprints are not available.     

Healing of colonic anastomoses: Comparative experimental study of glued,manually sutured,and stapled anastomoses

In 10 pigs a nonsutured, glued colonic anastomosis was constructed with a modified stapling device without staples and compared with an EEA-stapled anastomosis and a one-layer-sutured anastomosis concerning radiologic appearance, breaking strength, circulation, and collagen concentration.¹⁴¹Ce-labeled microspheres were used for measurements of the anastomotic blood flow before the animals were sacrificed on the 4th postoperative day. The breaking strength was recorded and an anastomotic index calculated. No leakage was found. The anastomotic width did not differ between the groups, but the interindividual variation was more prominent in the sutured group. The handsewn and stapled anastomoses were stronger than the glued anastomosis (P=0.0009 and 0.0054, respectively). There was an increase in the anastomotic circulation in all of the anastomoses, but no differences were seen between groups. The collagen concentration was independent of the technique used.     

The Effect of Insulin-Like Growth Factor I on Healing of Colonic Anastomoses in Cortisone-Treated Rats

Purpose This study was designed to investigate whether intraperitoneally injected insulin-like growth factor I is able to protect colonic healing from the adverse effects of hydrocortisone therapy. Methods Eighty female Wistar rats were randomized into four groups (20 rats each). After resection of a segment of transverse colon, an end-to-end anastomosis was performed. Hydrocortisone (5 mg/kg body weight) was injected intramuscularly in rats of cortisone (Group B) and insulin-like growth factor I + cortisone (Group D) groups once daily for seven days before and after the operation. Insulin-like growth factor I (2 mg/kg body weight) was intraperitoneally injected in rats of the insulin-like growth factor I (Group C) and the insulin-like growth factor I + Cortisone (Group D) groups immediately after operation and on the second, fourth, and sixth postoperative days. Rats were killed on the seventh postoperative day. Anastomoses were graded macroscopically and histologically, and bursting pressures and anastomotic hydroxyproline levels were recorded. Statistical analyses were performed by using Fisher's exact test for the comparison of proportions and ANOVA for the comparison of means among groups with subsequent post-hoc analysis using Bonferroni correction. Results Leakage rate was significantly higher in the cortisone (Group B) group. Bursting pressures were significantly lower in the cortisone group, whereas they were significantly higher in the insulin-like growth factor I and insulin-like growth factor I + cortisone groups (Group C and D). Histology revealed a significant decrease of inflammatory cell infiltration, neoangiogenesis, and fibroblast activity in the cortisone group compared with the control group, whereas these parameters were significantly higher in the insulin-like growth factor I and insulin-like growth factor I + cortisone groups. Hydroxyproline levels were significantly higher in the insulin-like growth factor I and insulin-like growth factor I + cortisone groups. Conclusions Hydrocortisone inhibits the healing of colonic anastomoses. However, insulin-like growth factor I given intraperitoneally mediates the deleterious effects of cortisone and protects colonic healing in rats.     

Effects of the use of fibrin glue around the colonic anastomosis of the rat

Abstract. Background: This study was aimed at examining whether the addition of fibrin glue to a sutured colonic anastomosis improves its healing or not. Methods: We studied the effect of adding fibrin glue on a sutured colonic anastomosis. Thirty-six Wistar rats were randomized into two groups of 18 rats each. A sutured anastomosis was performed in all rats. Fibrin glue was applied around the anastomosis of the rats of group B. Rats were sacrificed on the eighth postoperative day. Results: The rate of anastomotic leakage was found not to be significantly different between the two groups. The mean bursting pressure of the colonic anastomoses was significantly higher in group B (fibrin-treated) than in group A. Conclusion: Fibrin glue application around a sutured anastomosis provides a safer anastomosis which is stronger than the sutured one.     

Comparison of electromagnetic field stimulation on the healing of small and large intestinal anastomoses

PURPOSE: Magnetic fields have been shown to affect biologic processes. Accordingly, an experimental study was designed to investigate the effect of electromagnetic field stimulation on intestinal healing and to compare small and large intestinal anastomoses. METHODS: An ileal or a colonic anastomosis was constructed in rats. Beginning the day after surgery, randomly assigned groups were exposed to sinusoidal electromagnetic field stimulation of 10.76-mT intensity and 50-Hz frequency, with 2-hour-on/10-hour-off cycles. After seven days, intestinal anastomoses were assessed for hydroxyproline content and breaking strength. Statistical comparison between each experimental and control group yielded significance (P<0.05) in all cases. RESULTS: Hydroxyproline content increased significantly in ileum from 1.650±0.11 (mean ± standard error of the mean) to 2.036±0.11µg/mg (P=0.0249) and in colon from 1.526±0.11 to 1.922±0.11µg/mg (P=0.0135). Breaking strength also increased significantly in ileum from 0.213±0.01 to 0.255±0.01 MPa (P=0.001) and in colon from 0.227±0.01 to 0.270±0.01 MPa (P=0.006). CONCLUSIONS: Electromagnetic field stimulation provided a significant gain in anastomotic healing in both small and large intestine. There were no apparent differences detected between the healing of small and large intestinal anastomoses except for slight differences in the time sequences of events and magnitude. The study demonstrated a significant increase in both biochemical and mechanical parameters. Additional investigations are needed to determine optimal conditions and promote selective biologic responses.     

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.     

Tempol prevents harmful effects of remote ischemia reperfusion injury on healing of experimental colonic anastomoses

Background and aims Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) is a water-soluble analogue of the spin label TEMPO. As an antioxidative agent, it is a member of nitroxides, which detoxifies superoxide and possibly other toxic radicals in vivo. In this study, we aimed to investigate whether tempol prevents harmful systemic effects of superior mesenteric ischemia-reperfusion on left colonic anastomosis in rats. Materials and methods Anastomosis of the left colon was performed in 30 rats that were divided into three groups each having ten animals: sham-operated control (group I), 60 min of intestinal ischemia-reperfusion by superior mesenteric artery occlusion (group II), and tempol-treated group (30 mg/kg before and after the ischemia-reperfusion (group III). On postoperative day 5, all animals were killed and anastomotic bursting pressures were measured in vivo. Tissue samples were obtained for further investigation of anastomotic hydroxyproline content, perianastomotic malondialdehyde, and glutathione levels. Results There was a statistically significant increase in the quantity of myeloperoxidase activity and malondialdehyde levels in group II, along with a decrease in glutathione levels, anastomotic hydroxyproline content, and bursting pressure values when compared to controls. However, all of the investigated parameters were normalized in tempol-treated animals (group III). Conclusion We conclude that tempol significantly prevents harmful systemic effects of reperfusion injury on colonic anastomoses in a rat model of superior mesenteric artery occlusion.     

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.     

Physiologic characteristics of straight and colonic J-pouch anastomoses after rectal excision for cancer

PURPOSE: The colonic J-pouch anastomosis has been advocated to obviate urgent and frequent defecations following a sphincter-saving rectal excision. Physiologic characteristics of the colonic J-pouch were compared with those of the traditional straight anastomosis and related to clinical function. METHOD: Patients with total mesorectal excision for carcinoma were randomized to either a straight (n=23) or a colonic pouch anastomosis (n=23). The patients were examined before and at one year after surgery (n=42), which included laboratory studies, and a questionnaire regarding anorectal function was completed. RESULTS: Preoperative compliance of the rectum was restored after surgery in the pouch group, 2.9 (2.2–3.4) ml/cm H ₂ O, but there was a significant decrease after surgery in the straight anastomosis group, 1.9 (1.1–2.3) P <0.001 (median (interquartile range)). Sphincter pressures in both groups were similar. In a multiple regression analysis, high compliance was associated with favorable clinical function, and hypermotility of the anal canal was associated with adverse clinical function. CONCLUSIONS: Colonic pouch-anal anastomosis restores neorectal compliance, which is important for good function after low anterior resection. Presence of an unstable internal sphincter is a negative factor for clinical function in both straight and pouch anastomoses.Supported by the Research Funds of the University Hospital in Linköping and the County of Östergötland.     

Nitric oxide synthase inhibition results in immediate postoperative recovery of gastric, small intestinal and colonic motility in awake rats

Background Nitric oxide (NO) is known to inhibit gastrointestinal motility. However, no detailed analysis of gastric, small intestinal and colonic motor effects, including effects on contraction frequency, has, as yet, been reported after NO inhibition in awake rats. We therefore investigated the effects of NO synthase inhibition on gastric, small intestinal and colonic motility in awake rats under baseline conditions and in a postoperative ileus model.Methods In Sprague–Dawley rats, strain gauge transducers were sutured either to the gastric corpus, the small intestine or the colon. After 3 days, l-NMMA (NO synthase inhibitor), d-NMMA or vehicle was given i.v., while the motility was recorded continuously. In addition, postoperative gastric, small intestinal or colonic motility was investigated after l-NMMA or vehicle treatment prior to abdominal surgery. The motility index, the contraction amplitude, the area under the contraction amplitude and the contraction frequency were analysed.Results l-NMMA decreased gastric motility to 60±8% for about 15 min, but continuously increased small intestinal motility to 221±22% and colonic motility to 125±7% compared to baseline (baseline=100%; p<0.01 for all comparisons). l-NMMA increased the contraction frequency throughout the gastrointestinal tract (stomach, 13±2%; small intestine, 8±1%; colon, 16±5%; p<0.01 vs. baseline for all comparisons). l-NMMA injection prior to surgery did not prohibit intraoperative inhibition of gastrointestinal motility, but did result in immediate recovery of gastric, small intestinal and colonic motility postoperatively (l-NMMA vs. vehicle, 0–60 min postoperatively; stomach, 90±9% vs. 53±3%; small intestine, 101±5% vs. 57±3%; colon, 134±6% vs. 60±5%; p<0.01 for all comparisons; no significant difference between preoperative baseline motility and l-NMMA treated rats postoperatively).Conclusions Under baseline conditions, endogenous NO inhibits small intestinal and colonic motility and gastric, small intestinal and colonic contraction frequency in awake rats. In the early postoperative period, endogenous NO is a major inhibitory component that seems to constitute the common final pathway of mediators and the neural pathways inhibiting gastrointestinal motility in rats.     

Influence of alcohol on morbidity after colonic surgery

Postoperative morbidity after colorectal surgery was retrospectively investigated, comparing 32 alcoholics (≥60 gm of alcohol a day) to 32 controls (<25 gm of alcohol a day). The material originated from 260 male patients and the two groups were paired with respect to operative procedure, diagnosis, age-complicating cardiopulmonary diseases, weight, and smoking habits. Postoperative morbidity was higher (P<.01) in the alcohol group (59 percent with major complications, 75 percent with major and minor complications) compared with the control group (19 percent with major, 33 percent with major and minor). The alcoholics also stayed longer in the hospital (26 daysvs. 17 days) (P>.01). This apparent increased surgical risk in alcoholics is reevaluated in prospective investigations.     

Incidence of leukopenia after intraperitoneal vs combined intravenous/intraperitoneal chemotherapy in pseudomyxoma peritonei

AIM: To investigate the clinical impact of post-hyperthermic intraperitoneal chemotherapy(HIPEC) leukopenia, intraperitoneal and combined intravenous/intraperitoneal drug administrations were compared.METHODS: Two patient cohorts were retrospectively analyzed regarding the incidence of postoperative leukopenia. The first cohort(n = 32) received Mitomycin C(MMC)-based HIPEC intraperitoneally(35 mg/m2 for 90 min) and the second cohort(n = 10) received a bidirectional therapy consisting of oxaliplatin(OX)(300 mg/m2 for 30 min) intraperitoneally and 5-fluorouracil(5-FU) 400 mg/m2 plus folinic acid 20 mg/m2 intravenously. The following data were collected retrospectively: Age, sex, length of operation, length of hospital stay, amount of resection including extent of peritonectomy, peritoneal cancer index, CC(completeness of cytoreduction)-status and leukocyte-count before cytoreductive surgery(CRS) and HIPEC, on days 3, 7 and 14 after CRS and HIPEC. HIPEC leukopenia was defined as 4000 cells/m3. RESULTS: Leukopenia occurred statistically more often in the MMC than in the OX/5-FU-group(10/32 vs 0/10; P = 0.042). Leukopenia set-on was on day 7 after CRS and MMC-HIPEC and lasted for two to three days. Three patients(33%) required medical treatment. Patients affected by leukopenia were predominantly female(7/10 patients) and older than 50 years(8/10 patients). Thelength of hospital stay tended to be higher in the MMCgroup without reaching statistical significance(22.5± 11 vs 16.5 ± 3.5 d). Length of operation(08:54 ± 01:44 vs 09:48 ± 02:28 h) were comparable between patients with and without postoperative leukopenia. Prior history of systemic chemotherapy did not trigger postHIPEC leukopenia. Occurrence of leucopenia did not trigger surgical site infections, intraabdominal abscess formations, hospital-acquired pneumonia or anastomotic insufficiencies. CONCLUSION: Surgeons must be aware that there is a higher incidence of postoperative leukopenia in MMCbased HIPEC protocols primarily affecting females and older patients.     

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.     

Effects of amniotic membrane on the healing of normal and high-risk colonic anastomoses in rats

Bacground  This study was aimed at examining whether or not the addition of amniotic membrane to a sutured colonic anastomosis improves its healing. Material and methods  Ninety female Sprague Dawley rats were used in the study. Ten served as controls for bursting pressure measurement, while the other 80 animals were divided into four groups: Anastomosis group (NA), high-risk anastomosis group (HRA), anastomosis plus amniotic membrane group (NA-AM), and high-risk anastomosis plus amniotic membrane group (HRA-AM). The last two groups had amniotic membrane covering their anastomoses. Anastomotic evaluation was carried out on the third (NA3, HRA3, NA-AM3, and HRA-AM3, respectively) and seventh (NA7, HRA7, NA-AM7, and HRA-AM7, respectively) postoperative days. The main outcome measures were gross anastomotic healing, adhesion formation, mechanical strength, hydroxyproine content, and parameters of histopathological healing. Results  Anastomotic dehiscence rate was 66.7%, 40%, 20%, and 10% in group HRA7, HRA3, NA7, and NA3, respectively. However, there was no significant difference between groups regarding the dehiscence rate. The adhesion scores were significantly higher in groups NA3 and HRA3 compared with groups NA-AM3 and HRA-AM3, respectively (p < 0.05, p < 0.001). Bursting pressure was significantly higher in groups with amniotic membrane compared without amniotic membrane (p < 0.05, for all comparison). Inflammatory cell infiltration was significantly lower in groups with amniotic membrane compared with groups without amniotic membrane (p < 0.05, for all both comparisons). Neoangiogenesis was significantly higher in the NA-AM3 and HRA-AM3 groups compared with the NA3 (p < 0.01) and HRA3 (p < 0.05) groups, respectively. Fibroblast activity was significantly higher in groups NA-AM3 and NA-AM7 compared with groups NA3 (p < 0.05) and NA7 (p < 0.05), respectively. Collagen deposition and hydroxyproline concentrations were significantly higher in groups with amniotic membrane compared with groups without amniotic membrane (p < 0.05, for all both comparisons). Conclusion  The covering of both normal and high-risk colonic anastomoses with amniotic membrane provides a beneficial effect over conventional suturing of healing. This study was presented as an oral presentation in the 18th World Congress of the International Association of Surgeons, Gastroenterologists, and Oncologists.