Healing Process Of Colonic Anastomosis Research Articles

Intraperitoneal BromAc® Does Not Interfere with the Healing of Colon Anastomosis

A combination of bromelain and acetylcysteine, BromAc®, is an efficient intraperitoneal mucolytic for thick mucus secreted in pseudomyxoma peritonei (PMP). Patients with PMP quite often undergo colon anastomosis. Hence, we investigated the effect of the intraperitoneal delivery of BromAc® on colon-anastomosis healing in a rat model. Sixteen Wistar rats were divided into two groups (N = 8). The controls received intraperitoneal saline after anastomosis, whilst the other group received BromAc®. They were monitored for body-weight and general health parameters. Half the rats in each group (N = 4) were culled at 4 or 13 days post-surgery for assessment. The healing process of the tissues was assessed by burst pressure and collagen density with histology to assess the integrity of the internal organs. The results indicated that there was a similar pattern of weight fluctuation during the experiment, although the rats treated with the BromAc® showed slightly greater weight loss during the first 4 days. Although the burst pressure was similar in both groups, the BromAc® group at day 13 showed a slightly higher burst pressure, which was complemented by a higher collagen density (albeit not statistically significant). The histology of the internal organs was comparable to those of the controls. This study indicates that the intraperitoneal delivery of BromAc® in a rat model does not interfere with the healing process of colonic anastomosis.

Functional mucous layer and healing of proximal colonic anastomoses in an experimental model.

Anastomotic leakage (AL) is the most dreaded complication after colorectal surgery, causing high morbidity and mortality. Mucus is a first line of defence against external factors in the gastrointestinal tract. In this study, the structural mucus protein Muc2 was depleted in genetically engineered mice and the effect on healing of colonic anastomoses studied in an experimental model. Mice of different Muc2 genotypes were used in a proximal colonic AL model. Tissues were scored histologically for inflammation, bacterial translocation was determined by quantitative PCR of bacterial 16S ribosomal DNA, and epithelial cell damage was determined by assessing serum levels of intestinal fatty acid-binding protein. Of 22 Muc2-deficient (Muc2-/- ) mice, 20 developed AL, compared with seven of 22 control animals (P < 0·001). Control mice showed normal healing, whereas Muc2-/- mice had more inflammation with less collagen deposition and neoangiogenesis. A tendency towards higher bacterial translocation was seen in mesenteric lymph nodes and spleen in Muc2-/- mice. Intestinal fatty acid-binding protein levels were significantly higher in Muc2-/- mice compared with controls (P = 0·011). A functional mucous layer facilitates the healing of colonic anastomoses. Clinical relevance Colorectal anastomotic leakage remains the most dreaded complication after colorectal surgery. It is known that the aetiology of anastomotic leakage is multifactorial, and a role is suggested for the interaction between intraluminal content and mucosa. In this murine model of proximal colonic anastomotic leakage, the authors investigated the mucous layer at the intestinal mucosa, as the first line of defence, and found that a normal, functioning mucous layer is essential in the healing process of colonic anastomoses. Further research on anastomotic healing should focus on positively influencing the mucous layer to promote better postoperative recovery.

Evaluating the effect of infliximab on the healing of left colonic anastomosis in the presence of intra-abdominal sepsis

Background and study aimsInfliximab (IFX) is a chimeric anti-TNF-α body which is effectively used in the treatment of inflammatory bowel diseases and a variety of autoimmune diseases. The effect of IFX on the healing of intestinal anastomosis has been evaluated in several studies, however with conflicting results. Furthermore, the effect of IFX on colonic anastomosis in sepsis has not been evaluated to date. In this study, we aimed to investigate whether IFX has an adverse effect on the healing process of colonic anastomosis either under normal or septic condition. Material and methodThe efficiency of IFX was assessed with respect to anastomotic bursting pressure (ABP), tissue hydroxyproline levels (THL) and histopathological examination of left colonic anastomosis in 40 male rats. The rats were randomly allocated into four groups of 10 rats each as control (C), septic control (SC), control IFX (C-IFX) and septic IFX (S-IFX). ResultsThe anastomotic bursting pressure was measured at 182±19.1, 158±15.4, 161±26.8 and 100±10.3mm/Hg, in C, SC, C-IFX and S-IFX; respectively. IFX administration did not influence the anastomotic strength under normal condition whereas in sepsis significantly induced the reduction of APB. The mean THL was almost similar in both control groups (p=0.87), whilst IFX reduced the level of TH in sepsis comparing with control groups (p=0.01). IFX significantly impaired immune response in sepsis resulting in poor anastomotic healing in S-IFX group. ConclusionOur study demonstrated that IFX had no detrimental effect on the healing of colonic anastomosis under normal condition whilst significantly impaired the healing process in sepsis.

Cyanoacrylate application on colonic anastomosis: is it safe or not?

IntroductionMajor complications of colonic anastomosis include fistula, bleeding, and anastomotic stricture, and the most common one is anastomotic leakage. Many organic or inorganic tissue adhesives are being used such as fibrin glue or cyanoacrylate to strengthen or protect colonic anastomosis. Up to now, a great number of studies have been carried out to investigate the effects of these biomaterials.AimTo determine the effect of cyanoacrylate application on anastomosis safety.Material and methodsIn this experimental study, rats were divided into two groups; a control group and an experimental group. Full-thickness incisions were done on the left colon of the rats, and then end-to-end anastomosis was performed by using 5/0 silk separated sutures. In the experimental group we applied cyanoacrylate over the sutures. The samples were taken on the 7th day.ResultsIn the control group the average tissue hydroxyproline levels and the average bursting pressures were significantly higher than in the experimental group.ConclusionsThe purpose of all the experimental studies is to prevent and reduce anastomotic complications. Despite all the studies that have been done, colonic anastomosis complications continue to be a problem. As a result, we suggest that cyanoacrylate has a negative effect on the healing process of colonic anastomosis.

Influence of arterial hypertension on colonic healing in rats

Evaluation of colonic healing in spontaneously hypertensive rats. Fifty male, young and inbred rats were used. Twenty-five Wistar Kyoto rats (WKY) as control and twenty-five spontaneously hypertensive rats (SHR) as an experimental group. Colotomy and bowel suture at 2.5 cm from the peritoneal reflection were performed. All animals were allocated randomly into sub-groups for review at the third, seventh and fourteenth days after surgery. We evaluated the concentration of angiotensin II, the burst pressure, epithelialization, the organization of the tunics of the bowel wall, inflammatory response and collagen deposition. The burst pressure, epithelialization, organization of the tunics and collagen deposition was not significant between groups. The inflammatory reaction was more intense in the control group on the third postoperative day (p=0.023) as the experimental group on the remaining time. Systemic arterial hypertension in rats did not influence significantly the healing process of colonic anastomoses.

The effect of bevacizumab on colon anastomotic healing in rats

The aim of the study was to investigate the effect of angiogenesis inhibition by bevacizumab, a monoclonal anti-vascular endothelial growth factor (VEGF) antibody, on the healing process of colonic anastomoses in rats, assessing some specific involved factors. This new agent is used mainly in metastatic colorectal cancer. The angiogenesis plays an important role in both wound healing and metastatic invasion and spread of malignant cells. There has not been any evidence assessing the optimal time for its safe use in operated patients. Forty Wistar rats were randomly allocated into four equal groups. A colonic anastomosis was performed in all rats. Half of them received intraoperatively a single dose of bevacizumab 5 mg/body weight and the rest received placebo. The animals were sacrificed on the 7th (Avastin 7th, placebo 7th) and 14th (Avastin 14th, placebo 14th) postoperative day. The anastomosis was resected and sent for histological study and for tissue biochemical assays (VEGF, endothelin-1 (ET-1), C-reactive protein (CRP), pro-oxidant-antioxidant balance (PAB), carbonylated proteins, hydroxyproline) using specific enzyme-linked immunosorbent assay kits. For statistical analysis, the Mann-Whitney U test was used (of statistical significance when P < 0.05). No complication or anastomotic dehiscence was observed. Histology did not reveal statistically significant differences between groups concerning degree of inflammation, fibroblasts, collagen, and fibrosis. Likewise, hydroxyproline levels did not differ. However, some statistically significant differences were found in VEGF, CRP and carbonyl proteins (Avastin 7th vs placebo 7th, placebo 14th vs placebo 7th), ET-1, and PAB (Avastin 14th vs Avastin 7th), which did not finally affect the collagen synthesis marker hydroxyproline, nor did the anastomotic strength. Bevacizumab, when administered intraoperatively, has no significant effect on colon anastomotic healing in rats despite a transient mild ischemia.

The effect of sealing with a fixed combination of collagen matrix-bound coagulation factors on the healing of colonic anastomoses in experimental high-risk mice models

Experimental and clinical studies on the sealing of colorectal anastomoses in order to reduce the rate of leakage have previously been performed with divergent results. However, comparatively few studies have been performed on anastomotic healing using a fibrin glue-coated patch. The aim of this experimental basic scientific study in mice was to investigate the effect of fibrin glue-coated collagen patches on the healing process of colonic anastomoses in situations of adverse healing process (technical deficiency and peritonitis). Colonic anastomoses were carried out in 206 mice and randomized into six groups (I: complete anastomoses, II: sealed complete anastomoses, III: incomplete anastomoses, IV: sealed incomplete anastomoses, V: complete anastomoses in the presence of bacterial peritonitis, VI: sealed complete anastomoses in the presence of bacterial peritonitis). Tissues from the anastomoses were removed and used for functional, histochemical, molecular, and biochemical investigations. The evaluation of postoperative course data revealed the beneficial effect of additional sealing with a fixed combination of collagen matrix-bound coagulation factors I and IIa (Tachosil(®), Nycomed Austria, Linz) in high-risk experimental anastomotic healing. Sealing incomplete anastomoses resulted in significantly lower lethality and leakage rates, as well as significantly higher bursting pressure values and histopathologic scores. Collagen 1 and 3 expressions and hydroxyproline concentrations are greatly increased with additional sealing in all high-risk anastomoses. In our current model, we demonstrate that additionally sealing high-risk experimental colonic anastomoses provides a positive effect on the healing process. The effect on the molecular level in particular seems to be essential and requires further experimental studies to evaluate the mechanism.

Simvastatin Improves Wound Strength after Intestinal Anastomosis in the Rat

BackgroundSimvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor commonly known as a cholesterol-lowering drug with additional pleiotropic effects. Also, it is demonstrated that it prevents postoperative peritoneal adhesions in rat. This study was designed to assess its effects on the healing process of colonic anastomosis. MethodsThirty-two male Wistar albino rats were randomized into two groups and subjected to colonic anastomosis. The study group was treated with simvastatin and the control group received only tap water instead. The rats were killed 3 and 7 days postoperatively. Wound complications, intra-abdominal abscesses, and anastomotic leaks and stenosis were recorded. Four types of assessment were performed: bursting pressure, hydroxyproline content, histopathology, and biochemical analysis. ResultsCompared to the control group, simvastatin-treated rats displayed a higher bursting pressure (p < 0.001) and anastomotic hydroxyproline content (p < 0.05). Simvastatin treatment leads to a significant decrease in malondealdehyde levels (p < 0.05) and increase in paraoxonase activity (p < 0.001) at both time points. Histopathological analysis revealed that simvastatin administration leads to a better anastomotic healing in terms of reepithelialization, decreased granuloma formation, reduced ischemic necrosis, and inflammatory infiltration to muscle layer. ConclusionClinically relevant doses of simvastatin do not have a negative impact on colonic anastomosis but improve intestinal wound healing 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.

Effects of Unfractionated Heparin and Low-Molecular-Weight Heparin on Colonic Anastomoses in the Presence of Experimental Peritonitis

Background: We aimed at investigating the effects of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) on the healing process of colonic anastomoses in the presence of peritonitis which is known to adversely affect the healing process. Study Design: Three groups of Wistar albino rats (n = 15 in each group) with experimental fecal peritonitis were studied. A 1-cm colonic segment was resected, and an end-to-end anastomosis was performed. The control group (group 1) was given no treatment; group 2 animals received 50 IU/kg s.c. UFH twice a day, and group 3 rats received LMWH at a dose of 1.5 mg/kg daily for 7 days postoperatively. Relaparotomy was done on day 7 in the surviving rats. The rats were sacrificed by resection of the colonic segment. The anastomosis bursting pressures were measured and the tissue samples from anastomosis lines were histopathologically examined. Results: The bursting pressures were significantly higher in UFH and LMWH groups as compared with the controls (p = 0.021 and p < 0.001, respectively), while there was no statistically significant difference between UFH and LMWH groups. Positive bacterial culture results were more common in controls (90%) than in the other two groups (p = 0.029 and p = 0.002, respectively). Also the polymorphonuclear leukocyte counts were higher (p = 0.005) and the fibrin formation more common (p = 0.007) in the controls. On the other hand, the number of fibroblasts was higher (p = 0.002) and collagen formation and revascularization more frequent (p = 0.001 and p = 0.001, respectively) in the UFH and LMWH groups. Conclusion: UFH and LMWH may have positive effects on the healing process of colonic anastomoses in the presence of peritonitis.

Efeito do extrato hidroalcoólico de Aroeira (Schinus terebinthifolius Raddi) na cicatrização de anastomoses colônicas: estudo experimental em ratos

The healing is a complex biological event that involves inflammation, chemotaxis, cells proliferation, differentiation and remodeling. In Brazilian popular medicine, the "Aroeira" is used to treat different situations The anastomotic healing is always a preoccupation among surgeons. The fail in intestinal anastomosis leads to fistulas and dehiscences. To evaluate the effect of the hydroalcoholic extract of Schinus terebinthifolius Raddi (Brazilian pepper tree) in the healing of colonic anastomosis. Forty Wistar rats were randomly divided in two groups (Aroeira and control), each one with 20 animals, according to the treatment received after the anastomosis (Aroeira extract or saline solution 0,9%) and each group was divided in two subgroups (C3 and C7 and A3 and A7,) according to the euthanasia day (at 3rd and at 7th). The macroscopic, microscopic and bursting pressure measurements were performed. To evaluate the groups, the non-parametric test of Mann-Whitney was applied. In the macroscopic aspects, there was no significant difference between the Aroeira and the control group, both at the 3rd and the 7th days. When compared the subgroups of microscopic analysis at the 3rd day, the difference between the Aroeira and the control group was significant in the variables congestion (p = 0.005), polymorphonuclears (p = 0.034), mononuclears (p = 0.023), fibroblastic proliferation (p = 0.023) and at the healing stage (p = 0.001). At the 7th day analysis, the difference between the Aroeira and the control group was significant in all the variables of microscopic analysis. No significant differences were found in the bursting pressure. It was observed a favorable effect of Aroeira, at microscopic level, in the healing process of colonic anastomosis.

Análise histológica da cicatrização da anastomose colônica, em ratos, sob ação de enema de Aroeira-do-sertão (Myracrodruon urundeuva fr. all.) a 10%

Evaluate, from a histologic view point, the action of the aqueous extract of aroeira-do-sertão on the healing of colonic anastomosis, in Wistar rats. There were used 48 Wistar rats, males, with average weight of 320g, distributed in two groups, with 24 animals, each. All animals were subjected to a complete transverse section of the descending colon, followed by colonic anastomosis. The rats on group A received daily post-operative enemas of carboxymethylcellulose (CMC) based vehicle. The animals on group B received post-operative enemas of 10% aqueous extract of aroeira-do-sertão in CMC based vehicle, until the date of euthanasia. On days 3, 7, 14 and 21 of the experiment, six rats in each group were subjected to removal of a colonic segment, including the anastomosis, destined to histological evaluation and qualitative analysis of inflammatory and healing cell response. The morphologic analysis reveals a significant difference between groups, on day 7 (ñ < 0.05), when the group studied showed lower score than the control group. The collagen deposition on the aroeira group was lower, on days 3, 7 and 14 (ñ < 0.05), compared to the control group. The aqueous extract of aroeira-do-sertão has anti-inflammatory action. It also has inhibitory effect on collagen deposition during the phases of inflammation and fibroplasia of the healing process of colonic anastomoses, in Wistar rats, but in advanced phases (day 21) the healing process is similar to that in the animals of the control group.

Effect of photodynamic therapy on normal fibroblasts and colon anastomotic healing in mice

Photodynamic therapy as an adjuvant modality to surgical resection of colon cancer is feasible provided that it does not affect healing of the anastomosis. The aim of this study was to evaluate the effects of photodynamic therapy on the viability of normal fibroblasts and on the healing process of colonic anastomosis in mice. Both in vitro and in vivo methods were employed. For in vitro study, 2 × 10 5 human fibroblasts were incubated in triplicate with 5-aminolevulinic acid (2.5 μg/well) for 48 hours. Cells then underwent photoradiation at light doses of 50, 100, and 200 joules/cm 2 using a nonlaser light source. Viability was assessed by methylene blue dye exclusion. For in vivo studies, 60 mice were randomized into study and control groups and underwent laparotomy involving colonic anastomosis. The anastomosis underwent photodynamic therapy using 5-aminolevulinic acid (60 mg/kg) as a photosensitizer and a nonlaser light (40 joules/cm 2). On postoperative days 1, 4, 7, 14, and 21, six mice were killed and subjected to bursting pressure and histologic examinations. Results of in vitro study showed pretreatment cell viability to be 96% to 99% in both groups. Photodynamic therapy caused no significant change in fibroblast viability at all light doses. Results of in vivo studies showed that the mean bursting pressure of both groups dropped to a low peak on day 4. Subsequently there was a gradual increase in bursting pressure along the examined time points ( P <0.001). There was no difference in bursting pressure between the two groups for all time points examined. It was concluded that photodynamic therapy has no effect on viability of normal human fibroblasts and no adverse effects on healing of colonic anastomosis.