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Abstract
Intra-abdominal adhesion formation and reformation after surgery are still an unavoidable event in spite of modern surgical techniques and are a cause of significant morbidity, resulting in infertility, pain and intestinal obstruction. To date there is no satisfactory treatment or prophylaxis to deal with these adhesions properly.
Because wound healing and adhesion formation have similar pathways, modulation of the release factors could be expected to affect adhesion formation.
Abdominal surgery frequently includes the construction of a bowel anastomosis which carries the risk of symptomatic anastomotic leakage with subsequent increasing mortality rate up to 20% .
Various methods have been tried to reduce postoperative adhesions including mechanical separators and barriers, fibrinolytic agents, anti-coagulants, and anti-inflammatory drugs.
Postoperative adhesions are the largest single cause of intestinal obstruction and account for between 30 and 41 percent of all cases of obstruction requiring further surgery .For small-bowel obstruction , this proportion is even higher, with 65 to 75 percent of cases caused by postoperative adhesions.
Common stimuli of adhesion formation are peritoneal trauma, ischemia, and foreign bodies. Ideally, a good surgical technique prevents the initiation of an adhesiogenic inflammatory reaction by limiting tissue damage whenever possible.
Limiting the introduction of foreign materials, achieving meticulous haemostasis, minimizing tissue manipulation, and preventing tissue desiccation all can contribute to lessening peritoneal injury.
Preclinical studies of ionically crosslinked hyaluronic acid as 0.5% ferric hyaluronate gel were highly effective in reducing adhesion formation in animal models. It was evident that hyaluronate enhanced the fibrinolytic response of the human peritoneal mesothelial cells and hence played an important role in adhesion prevention.
Morbidity and mortality rates as a result of leakage of anastomoses are still high despite advances in operative techniques and suture material and the basic research on the mechanisms of intestinal healing and its disturbances remains necessary.
Indeed, Honey was proved to be effective as anti-adhesion agent in experimental animals. It was observed clinically that healing in open wounds is faster with honey rendering wounds suitable for suture.
The physical properties of honey play a part in its effectiveness as a wound dressing. Because of its viscosity, honey provides a protective barrier which prevents cross-infection.
Honey has a direct anti-inflammatory effect, not a secondary effect resulting from the antibacterial action removing inflammation-causing bacteria. Also, it increases the rate of healing by stimulation of angiogenesis, granulation, and epithelialization.
It was found that honey stimulated white blood cells or macrophages to produce pro-inflammatory cytokines, interlukin-1, interlukin-6 and tumour necrosis factor alpha known to be involved in wound healing and inflammatory process.
Previous work suggested that caffeic acid esters, in honey, are potent inhibitors of human colon tumor cell growth and may possess antitumour activity against colon carcinogenesis.
The results of that study indicated that caffeic acid esters present in honey, inhibit colonic preneoplastic lesions, which are relevant to colon carcinogenesis
Aim of the work
The aim of the present study is to investigate the effect of 0.5% Ferric Hyaluronate: INTERGEL versus HONEY in adhesion prevention and colonic anastomotic healing in rats.
Materials & Methods
In the present study,75 male Sprague-Dawley rats, were used. Rats, subjected to the study were obtained from the documented animal house of the faculty of veterinary medicine, Suez-Canal university, Egypt.
All rats were observed for several days to ascertain health before operations and were divided into 3 groups for study: [25 rats for each], the intergel, honey and control groups.
Surgical procedure in the three groups was performed as end-to-end single layer extramucosal anastomotic construction technique with eight interrupted sutures using 6/0 prolene.
All rats were observed in the postoperative period and data was collected day by day and saved as soft–wear files for later evaluation and after the scheduled two- weeks post-operative period, all survived rats were reopened for second-look laparotomy through a left-sided curvilinear laparotomy incision to detect the following parameters a-adhesion, b-Manometric study and c-histopathological study.
Result
Mortality rate :
The whole number of rats died during the present study was 10 of 75 rats=13.3%.In the control group, the mortality rate was 5of 25 rats =20%,while in the intergel group the number of rats died was 3of 25 rats= 12% and in honey group 2 rats of 25=8%. This distribution is significant.
Adhesion Evaluation:
The total adhesion scoring for the control untreated animals was higher than that of the intergel-treated animals and the honey-treated animals showed the least scoring values with statistically significant distribution.
Manometric study:
The mean values of both bursting pressure and anastomotic strength were higher in case of honey group in comparison of the other two groups’ values with statistically significant distribution.
Histopathological Study:
We observed that the multilayered structure of the colonic wall was preserved completely in the honey group. The mean histopathological score in the control group was less than the intergel group and both were less than that of the mean histopathological score in the honey group with statistically significant distribution.
Discussion
Mortality rate :
As well established, therapeutic success in the management of intra-abdominal infection translates into mortality and despite all the efforts made in the areas of intensive care and surgery, severe peritonitis remains a feared surgical condition that is associated with a high mortality rate.
Anastomotic leakage is a major cause of mortality in colorectal surgery and some variables associated with a high-risk level for anastomotic leakage have been identified and one of the most important risk factor is the level of the anastomoses It was reported recently that despite improved surgical techniques, anastomotic leakage is still a serious complication in colorectal surgery, resulting in increased morbidity and mortality.
Honey has a direct anti-inflammatory effect, not a secondary effect resulting from the antibacterial action removing inflammation-causing bacteria. Also, it increases the rate of healing by stimulation of angiogenesis, granulation, and epithelialization
Adhesion Evaluation:
from the statistical data, it was apparent that all the scale system of extent of adhesion formation was represented in our study but with an obvious, great significant distribution in the three groups of study. The localized adhesion formation was noticed to be much increased in the honey, then in the intergel and lastly in the control group.
While the extensive type of adhesions was greater in the control group in comparison to the other two, and the honey group rats were showed to be the least as regard to the extensive type of adhesion formation. But the moderate scale of extent of adhesion formation was nearly the same in the three groups. from the statistical point of view, these figures are significant when taken as a whole.
Highly significant values were noticed between intergel and honey –treated rats in one hand versus untreated control in the other hand. In case of intergel, this figure is considered to be logic as it was generally accepted to effectively prevent postsurgical abdominal adhesions and patients treated with Intergel solution had significantly less adhesions compared to controls.
Manometric study
In the control rats, the observed data in the present study showed that the mean values of bursting pressure and anastomotic strength with the standard deviation were lower than those of the intergel and honey-treated rats
These distributions are statistically significant and our results agreed that of previously published data of the same interest. Indeed, Intergel was seen to enhance colonic anastomotic healing in our study but to a lesser level than honey did.
This observation could be of logic opinion and molecular bases as honey acts at the level of monocytes by enhancing their activity to release proinflammatory mediators necessary for early steps of wound healing Thus the effects observed in this study may partly explain the observed effects of honey on wound repair.
Honey gives a fast rate of tissue regeneration, a direct nutrient effect on regenerating tissue because it contains a wide range of amino acids, vitamins and trace elements in addition to large quantities of readily assimilable sugars In addition, the high osmolarity of honey causes an outflow of lymph which serves to provide nutrition for regenerating tissue which otherwise can only grow around points of angiogenesis Another point by which honey surpasses the intergel for the healing power is its antibacterial activity.
A direct anti-bacterial action of intergel was suggested to be ruled out as there was no difference in the presence of bacteria in the abdominal cavity between the HA-treated rats and the control As Honey and Intergel were both used intraperitoneally in our experiments, one should expect that these agents are free from any potentiated action on the proposed intraperitoneal malignant diseases.
HA appear to be overexpressed at sites of tumor attachment and is present in large amounts in the mesothelial lining of the peritoneum In the other extreme hand, honey has been used for the treatment of necrotic malignant ulcers and revealed moderate antitumour and pronounced antimetastatic effects and above all, honey caused tumour cell lysis when used as per and post-operative installation solution in mouse models
The antiproliferative activity of honey toward different cancer cell lines showed potent power with a selective activity toward colon carcinoma cell line as well inhibition of cell growth through apoptosis induction and growth inhibition