Healing Of Colonic Anastomoses Research Articles

The Effects of Intraperitoneal Sildenafil Administration on Healing of Left Colonic Anastomoses and Intra-Abdominal Adhesion Formation in the Presence of Intra-Abdominal Infection

The objective of this pilot study was to establish an animal model for intra-abdominal infection and to examine the effect of sildenafil on anastomotic healing of the left colon and intra-abdominal adhesion formation. Fourteen Winstar rats underwent colonic transsection and primary anastomosis after performing intra-abdominal infection. Rats were divided into two groups: Group 1 (n = 7): intra-abdominal infection, resection, and anastomoses; Group 2 (n = 7): intra-abdominal infection, resection, anastomoses, and sildenafil. Anastomotic bursting pressures, hydroxyproline levels, histopathologic grading, and abdominal adhesions were accessed on the postoperative Day 7. Anastomotic healing was found to be improved in terms of a bursting pressure (P = 0.02). Histopathological examination revealed an increase in angiogenesis (P = 0.007). Moreover, intra-abdominal adhesions were significantly less in rats given sildenafil (P = 0.03). Sildenafil may improve anastomotic healing of the left colon and diminishes peritoneal adhesion formation in the presense of abdominal infection.

Does sildenafil reverse the adverse effects of ischemia on ischemic colon anastomosis: Yes, ‘no’

Introduction Sildenafil may lead an improvement in anastomotic healing of ischemic left colon anastomosis. Methods Thirty-six male Wistar albino rats were randomized into four experimental groups ( n = 9 in each group). In group 1, a well-perfused left colonic segment was transected, and free ends were anatomosed. In groups 2, 3 and 4 animals underwent a standardized surgical procedure to induce ischemic left colon anastomosis. Group 2 animals received only tap water. In groups 3 and 4 animals received 10 mg/kg/body-weight and 20 mg/kg/body-weight sildenafil, single dose a day during 4 days, respectively. Rats were sacrificed on day 4 following operation. Anastomotic integrity, intra-peritoneal adhesion scores, anastomotic bursting pressures and tissue hydroxyproline levels were recorded. Histopathological examination of the anastomosis was also performed. Results There was no statistically significant difference among groups with respect to anastomotic integrity ( p = 0.142) but ischemia decreased the anastomotic bursting pressure. The mean bursting pressure values were 78.8 ± 24.1, 43.3 ± 26, 55.1 ± 32.4, and 43.3 ± 20.4 in groups 1, 2, 3, and 4, respectively. Group 1 had the highest values whereas; there was no statistically significant difference between groups 1 and 3. There was no statistically significant difference among groups 2, 3, and 4 with respect to tissue hydroxyproline levels, adhesion scores and the Chiu scores. The highest inflammatory cell presence in the granulation tissue was detected in group 2, whereas the lowest was detected in group 4 ( p = 0.0001). The highest fibroblast infiltration in the granulation tissue was detected in group 1 ( p = 0.045). Discussion Our results showed that 10 mg/kg sildenafil decreased the adverse effects of ischemia on the healing of ischemic left colon anastomosis. Additional investigations are needed to confirm the effects of phosphodiesterase-5 inhibitors in ischemic colon anastomosis models.

Influence of Preoperative Feeding on the Healing of Colonic Anastomoses in Malnourished Rats

Malnutrition influences healing of gastrointestinal anastomoses. The authors hypothesize that colonic anastomotic healing is decreased by malnutrition and might be improved by preoperative feeding. Eighty adult male Wistar rats were divided into 4 groups: (1) control rats 1 (C1), fed regular chow ad libitum for 21 days; (2) malnourished pair-fed rats (M), fed 50% of the food ingested by the control rats for 21 days; (3) preoperative nutrition rats (PRE), fed 50% of the average of the controls for 21 days and then fed preoperative nutrition with regular chow ad libitum for 1 week before the operation; and (4) control rats 2 (C2), fed regular chow ad libitum for 28 days. On days 21 (C1 and M) and 28 (PRE and C2), rats underwent 2 colonic transections and, subsequently, 2 end-to-end anastomoses. Rats were killed on postoperative day 5. The anastomoses were resected for tensile strength and histological analysis. PRE rats showed increased maximal tensile strength vs the M group (0.09+/-0.01 vs 0.15+/-0.01; P<.05) and similar values of maximal tensile strength as the controls (0.15+/-0.01 vs 0.15+/-0.02; P=.91). Collagen type I was higher in controls vs the PRE group (6.13+/-0.39 vs 4.90+/-1.53; P<.05); nevertheless, the PRE group showed higher collagen type I than M rats (4.90+/-0.36 vs 3.83+/-0.35; P<.05). Preoperative feeding for 7 days increases the maximal tensile strength, as well as the percentage area of mature collagen, approaching similar values as the control group.

Effect of honey on intestinal morphology, intraabdominal adhesions and anastomotic healing

In the present study, attempts have been made to determine the effects of honey on intestinal morphology, postoperative adhesions, and the healing of colonic anastomoses in the rats after colonic resection and anastomosis. Thirty-six rats were randomly divided into three groups each including 12 animals. Colonic resection and anastomosis were performed on all animals. Rats were fed with standard rat chow in group I, standard rat chow plus 10 g/kg/day honey in group II and artificial honey including the same caloric amount with honey in group III. Adhesion scores, bursting pressures and histopathological examinations were evaluated. Colonic bursting pressures of honey group were significantly better than control and artificial honey groups. Histological analysis of anastomotic site showed that submucosa and muscularis propria were nearly filled with granulation tissue and regular fibrin matrix in honey group. There was statistically significant difference between the adhesion scores of honey vs artificial honey and control groups. The scores of histological changes of ileum in honey group were significantly different from other groups. These results indicate a protective role of honey against intraabdominal adhesions and anastomotic dehiscence.

Adipose-derived mesenchymal stem cells in biosutures do not improve healing of experimental colonic anastomoses

The feasibility of producing 'biosutures' coated with adipose-derived mesenchymal stem cells (ASCs) was assessed and their effect on colonic anastomoses evaluated. Sutures were cultured with ASCs isolated from BDIX rats before analysis by light and scanning electron microscopy. Anastomoses were performed in 40 BDIX rats using either biosutures or conventional sutures. Histopathological features, adhesion formation and anastomotic strength were evaluated. Sutures were coated with ASCs within 24 h. Anastomoses made with biosutures had a lower adhesion index only during the first week (P = 0.006 at 7 days), but not subsequently. There were no significant differences in anastomotic healing with the two types of suture. ASC biosutures have no effect on anastomotic healing in rats.

Healing of colonic anastomoses after immediate postoperative intraperitoneal administration of oxaliplatin

The aim of this experimental study was to investigate the effect of intraperitoneal administration of oxaliplatin on the healing of colonic anastomoses when injected immediately after colon resection. Thirty male Wistar rats were used. During the operation, the rats were randomized to two groups of 15 rats each. Immediately after colonic anastomoses were performed, the rats were injected intraperitoneally with either 3 ml of 0.9% NaCl solution or oxaliplatin (2.4 mg/kg body weight) depending on their group. All rats were killed on the eighth postoperative day. The anastomoses were examined macroscopically. The anastomotic bursting pressures were recorded, the anastomoses graded histologically, and the hydroxyproline tissue contents determined. Anastomotic leakage was noted in four rats (26.7%) of the oxaliplatin group, whereas no anastomotic dehiscence was detected among rats of the control group (p = 0.016). The adhesion formation at the anastomotic sites and the inflammatory cell infiltration were significantly higher in the oxaliplatin group than in the control group (p = 0.001). The bursting pressures (p = 0.001), the hydroxyproline tissue content (p = 0.001), the neoangiogenesis (p = 0.033), the fibroblast activity (p = 0.001), and the collagen deposition (p = 0.001) were significantly lower in the oxaliplatin group in comparison to the control group. The immediate postoperative intraperitoneal administration of oxaliplatin seems to impair healing of colonic anastomoses in rats.

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

An experimental study was designed to investigate the effect of combined pulse electromagnetic field (PEMF) stimulation plus glutamine administration on colonic anastomosis. 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. 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. 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.

Effects of Intraperitoneal Sildenafil Administration on Healing of Left Colonic Anastomoses and Intra-Abdominal Adhesion Formation in the Presence of Intra-Abdominal Infection

Purpose The objective of this pilot study was to establish an animal model for intra-abdominal infection and to examine the effect of sildenafil on anastomotic healing of the left colon and intra-abdominal adhesion formation.

Insulin-like growth factor I improves aspects of mycophenolate mofetil-impaired anastomotic healing in an experimental model

Patients taking immunosuppressants after transplantation may require intestinal surgery. Mycophenolate mofetil (MMF) has been found to impair the healing of colonic anastomoses in rats. This study examined whether insulin-like growth factor (IGF) I prevents MMF impairment of anastomotic healing. Sixty-three rats were divided into three groups (MMF, MMF/IGF and control). Animals underwent a sigmoid colon anastomosis with a 6/0 suture, and were killed on days 2, 4 and 6 after surgery. Investigations included bursting pressure measurement, morphometric analysis, and assessment of mucosal proliferation by 5-bromo-2'-deoxyuridine and Ki67 immunohistochemistry of the anastomoses. The leak rate was three of 21, one of 20 and two of 20 in the MMF, MMF/IGF-I and control groups respectively. Anastomotic bursting pressures were significantly lower in the MMF group than in the control group on days 2 and 4, but there was no significant difference by day 6. Values in the MMF/IGF-I and control groups were similar. Colonic crypt depth was significantly reduced in MMF-treated animals on days 2 and 4, but this impairment was attenuated by IGF-I on day 4. Similarly, IGF-I reduced the negative impact of MMF on mucosal proliferation on days 2 and 6. Exogenous IGF-I improves some aspects of MMF-impaired anastomotic healing.

Effect of thalidomide on the healing of colonic anastomosis, in rats

Thalidomide, because of its anti-inflammatory properties, as re-emerged as an option for the treatment of Crohn's disease refractory to standard therapy. We studied the effect of thalidomide on the healing of colonic anastomosis. Sixty male rats (Rattus norvegicus), were divided into 3 groups of 20 animals each, respectively receiving 0.5 or 1.0 mg/kg thalidomide by the oral route for 7 days, or saline solution (control). All animals were submitted to continuous end-to-end anastomosis with 6-0 Prolene sutures. After sacrifice the anastomoses were analyzed macroscopically and submitted to determination of hydroxyproline, to histology and to immunohistochemistry for metalloproteinase 1, metalloproteinase 1 inhibitor and vascular endothelial growth factor (VEGF). Statistical analysis of the data showed no significant difference in macroscopic aspect or hydroxyproline determination (p= 0.5403). In the immunohistochemical analysis, the following p values were obtained: p = 0.5817 for VEGF, p = 0.1854 for metalloproteinase 1, and p = 0.0023 for metalloproteinase 1 inhibitor, with this last value being considered statistically significant. We conclude that thalidomide influenced collagen maturation. There was a stronger action of metalloproteinases, possibly indicating a negative tendency for the healing process.

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

To evaluate the effect of propolis administration on the healing of colon anastomosis with light and transmission electron microscopes. Forty-eight Wistar-Albino 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. The colonic bursting pressures of the propolis group were statistically significantly better than the control group. Ultrastructural histopathological analysis of the colon anastomosis revealed that propolis accelerated the phases of the healing process and stimulated mature granulation tissue formation and collagen synthesis of fibroblasts. Bursting pressure measurements and ultra structural histopathological evaluation showed that administration of propolis accelerated the healing of colon anastomosis following surgical excision.

Effects of preoperative pelvic irradiation on colonic anastomosis healing: an experimental study in rats

Colorectal anastomosis is a constant worry-issue among surgeons because of high rates of complications, specially the dehiscence. The preoperative irradiation on cancer surgeries might interfere in the healing process, leading to an unfavorable outcome. In the present study, two groups of rats were irradiated previously to a colorectal anastomosis surgery, with intervals of 4 and 8 weeks between the procedures. Seven days after the surgery, healing process was evaluated for dehiscence presence and histologic inflammatory characteristics. Also, levels of hydroxyproline, metalloproteinases and vascular endothelial growth factor were measured. Our results showed a higher incidence of dehiscences on the animals submitted to irradiation, compared to controls, with a reduced inflammatory activity in the healing tissue. Comparing both irradiated groups, those irradiated 8 weeks before surgery showed higher levels of hydroxyproline and metalloproteinases, indicating higher efficiency of the healing process. In conclusion, preoperative irradiation interferes with intestinal anastomosis healing and a larger time interval between both procedures is safer in terms of the healing quality.

The Effects of Duration of CO2 Pneumoperitoneum on Colonic Anastomosis

The aim of this study is to evaluate the effects of duration of carbon dioxide (CO2) pneumoperitoneum on experimental colonic anastomosis. Forty-eight male Sprague–Dawley rats were used. The rats were divided into three groups. The rats in group 1 (n = 16) underwent laparotomy and colonic anastomosis without pneumoperitoneum. The rats in group 2 (n = 16) and group 3 (n = 16) were subjected to 2 and 4 hours of 12 mm Hg pneumoperitoneum, respectively, before laparotomy and colonic anastomosis. Half of the rats were sacrified on the third postoperative day; and the other half, on the seventh postoperative day. A colonic segment including anastomosis site was resected for histopathologic and biochemical evaluation. On day 3, hydroxyproline levels of the three groups were similar. The edema score of group 2 was significantly higher than that of group 1, and the necrosis score was higher in group 2 than in group 3. The scores of the other histopathologic parameters were similar. On day 7, group 3 showed significantly higher hydroxyproline levels than group 1, and group 1 showed a higher necrosis score than group 3. In conclusion, CO2 pneumoperitoneum of 12 mm Hg for 2 and 4 hours did not result in impaired healing of experimental colonic anastomosis.

The Effects of Irinotecan on the Healing of Colonic Anastomoses in Rats

Aim: The aim of this experimental study was to investigate the effects of intraperitoneally injected irinotecan on the healing of colonic anastomoses after colon resection. Methods: Thirty male Wistar rats were used. The rats were randomized into two groups of 15 rats each. Immediately after colonic anastomoses were performed, the rats were injected intraperitoneally with either 3 ml of 0.9% NaCl solution or ir- inotecan (3 mg/kg body weight) depending on their group. All rats were sacrificed on the eighth postoperative day. The anastomoses were examined macroscopically and histologically. The anastomotic bursting pressures were recorded. Results: Anastomotic dehiscence was noted in 3 rats of the irinotecan group. All anastomoses of the control group re- mained intact until sacrifice. The adhesion formation at the anastomotic sites and the average inflammatory cell infiltra- tion scores were significantly higher in the irinotecan group compared to the control group. The bursting pressures, the hydroxyproline tissue content, the fibroblast activity and the collagen deposition were significantly lower in the irinotecan group. Neoangiogenesis did not differ significantly between the groups. Conclusion: Irinotecan, when injected intraperitoneally, affects the healing of colonic anastomoses in rats.

Effects of Cholerella sp. microalgae extract on colonic anastomosis in rats with protein–energy malnutrition

Algae, which are used as supplementary nutrients in various countries, are products rich in protein, vitamins and minerals. The aim of this study was to investigate the effects of algae extracts on the healing of colonic anastomosis in malnourished rats. Seventy-two rats were randomized to three groups. Group 1 was fed with standard diet for 15 days, before and after the colonic anastomosis. Groups 2 and 3 were fed with a malnutrition diet for 15 days prior to colonic anastomosis and then with the basic diet for 15 days there after. Group 3 also received an extract of algae derived from Cholerella sp. via oral gavage postoperatively, in addition to the basic diet. Rats were killed on the 3rd, 7th and 15th postoperative day. Blood samples were collected to evaluate prealbumin, transferring and albumin levels. Anastomotic bursting pressures (BPs), histopathology and tissue hydroxyproline levels were evaluated after killing. In group 3, the prealbumin level on the 3rd postoperative day and transferrin and albumin levels on the 7th and 15th postoperative days were significantly increased compared with the other groups (P < 0.05). Tissue hydroxyproline levels and anastomotic BPs of group 3 were significantly higher than in group 2 on the 3rd, 7th and 15th postoperative days (P < 0.05). Histopathological examination of the anastomosis revealed significantly better healing patterns for group 3 than for groups 1 and 2 (P < 0.05). Extract derived from Cholerella sp. microalgae has favourable effects on healing of experimental colon anastomoses.

The Effects of Irinotecan on the Healing of Colonic Anastomoses in Rats

The Effects of Irinotecan on the Healing of Colonic Anastomoses in Rats

Histological evaluation of colonic anastomotic healing, during perioperative Capecitabine administration. Experimental study in rats.

Neoadjuvant chemotherapy is a highly promising treatment modality for colorectal cancer. One of the basic side effects of this method is the possible impact on anastomotic healing. Capecitabine is a tumor selective pro-drug of 5-fluorouracil, indicated for the therapy of colorectal cancer. The aim of this study is to estimate the effect of perioperative Capecitabine administration on the colonic anastomotic healing process, by evaluating histopathological findings. We studied the effect of Capecitabine on hand sutured colonic anastomosis in rats. Sixty Wistar rats were randomized in two groups. In the study group (n=30) Capecitabine was given p.o. in therapeutic dose of 359 mg/kg, (2/3 of the mean toxic dose), 1 week prior the anastomosis and throughout the study. In the control group (n=30) placebo medication was administrated. Both groups were further subdivided into 3 groups, each consisting of 10 animals. Rats of each group were sacrificed on the 3rd, 7th and 14th postoperative day, in both study and control groups. No negative impact on the healing process of colonic anastomosis was found. Histological findings indicated a more effective healing during the early postoperative days, with lesser necrosis effects on the anastomotic line for the study group, in comparison with the control group. The median bursting pressure was found to be significantly higher in the subdivision of the study group sacrificed on the 3rd day, in comparison to respective control subdivision. Perioperative administration of Capecitabine, as neoadjuvant chemotherapy, does not impair the healing of colonic anastomosis in rats.

The Effect of Remote Ischemic Preconditioning on Healing of Colonic Anastomoses

We aimed to investigate the potential protective effect of remote ischemic preconditioning (IPC) on delayed colonic anastomotic healing induced by remote ischemia and reperfusion (I/R) injury. Forty male Wistar rats were randomly assigned into four groups, each consisting of 10 rats: the control group (C), the remote I/R group [I/R, 40 min of superior mesenteric artery (SMA) occlusion], the preconditioned I/R group (IPC, two cycles of 5 min temporary occlusion of SMA before an ischemic insult of 40 min), and the preconditioned group (PC, two cycles of 5 min temporary occlusion of SMA). Colonic anastomosis was performed immediately after the ischemic insult. Anastomotic healing was assessed on postoperative day 7 by determining anastomotic bursting pressure (ABP), tissue hydroxyproline content, histopathological examination, malondialdehyde (MDA), and nitric oxide levels. Remote I/R injury resulted with significant impairment in anastomotic healing in terms of mean ABP (P = 0.004), hydroxyproline content (P = 0.002), histopathological healing score (P = 0.001), nitric oxide level (P = 0.010), and MDA levels (P = 0.0001) when compared with the control group, but remote IPC did not improve all above mentioned parameters (P = NS for all), except MDA level (P = 0.011) when compared with I/R group. PC alone impaired the ABP (P = 0.0001), but it did not significantly change the other parameters measured (P = NS). The results of this study showed that remote IPC did not prevent I/R-induced delaying in colonic anastomotic healing.

Effect of IGF-I on Healing of Colonic Anastomoses in Rats Under 5-FU Treatment

The aim of this experimental study was to investigate whether insulin-like growth factor I (IGF-I) can protect the colonic healing from the adverse effects of intraperitoneal administration of 5-fluorouracil (5-FU). Eighty male Wistar rats were randomized into four groups of 20 rats each. Immediately after anastomoses were performed, rats in the control group were injected with 1 mL/100 gr of intraperitoneal saline solution, which was repeated daily until killed. Rats in the 5-FU and IGF-I +5-FU groups received 5-FU in a dose of 20 mg/kg body weight intraperitoneally, from the day of operation until killed. Rats in the IGF-I and IGF-I +5-FU groups received IGF-I in a dose of 2 mg/kg body weight intraperitoneally, immediately after the colonic anastomosis was performed and on 2nd, 4th, and 6th postoperative day. Rats were sacrificed on the 7th postoperative day. The dehiscence rate in the 5-FU group was 30% and it was significantly higher compared with the control and the IGF-I group (P = 0.020 for both comparisons). However, in the IGF-I +5-FU group, the dehiscence rate decreased to 10%. The administration of IGF-I resulted in a significant rise of bursting pressure in the IGF-I +5-FU group compared with the 5-FU group (P < 0.001). There was no statistical difference in bursting pressure between the IGF-I +5-FU and control groups (P = 1.000). The hydroxyproline levels were higher in the IGF-I and the IGF-I +5-FU groups as a result of the stimulating act of IGF-I. IGF-I, when given intraperitoneally, seems to mediate some of the adverse effects of 5-FU on the colonic healing in rats.

Icodextrin and Seprafilm® Do Not Interfere with Colonic Anastomosis in Rats

Background: Physical barriers and instilled solutions have been studied to prevent intra-abdominal adhesions. However, undesirable side effects of these substances on the healing of intestinal anastomoses may limit their use. This study was designed to compare the effects of antiadhesives on the healing of colonic anastomosis in rats. Methods: Sixty female Sprague-Dawley rats were divided into 3 groups of 20. The animals received isotonic saline and 7.5% icodextrin, intraperitoneally after standard left colonic anastomosis. In group 3, Seprafilm® was wrapped around the anastomosis and also laid over the abdominal viscera. Half of the animals from each group were killed on postoperative day (POD) 4 and the remaining half on POD 21. Adhesion scoring, bursting pressure and tissue hydroxyproline measurements and histopathological assessment were performed. Results: Mean hydroxyproline levels were significantly higher in groups receiving icodextrin and Seprafilm compared with the control group, whereas mean bursting pressures were significantly higher in the group that received icodextrin (p < 0.05). Intraperitoneal administration of icodextrin resulted in significant reduction of adhesion formation on POD 21 (p < 0.05). Conclusions: Seprafilm does not prevent formation of adhesions as much as icodextrin does, but its effect on the healing of colonic anastomoses is similar.