Suppression of fibroblast proliferation by activated macrophages: Involvement of H2O2 and a non-prostaglandin E product of the cyclooxygenase pathway

Metzger, Zvi; Hoffeld, J. Terrell; Oppenheim, Joost J.

doi:10.1016/0008-8749(86)90048-1

Cited by 16 publications

(17 citation statements)

References 24 publications

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“…Resective surgery involving the esophagus is burdened with high morbidity and mortality. Anastomotic dehiscence and pulmonary infection are the main causes of postoperative complications, [1][2][3][4][5]20 Among the different factors that have been related to anastomotic dehiscence 12 and although not completely proved, it is thought that contamination of the suture line by bacterial flora can favor infection and microabscess 17,18 and therefore local ischemia and risk of dehiscence. Tetteroo et al 21 showed how selective decontamination reduced the incidence of postoperative graminfections in patients with oesophageal resections.…”

Section: Discussionmentioning

confidence: 99%

“…The influence of the oropharyngeal flora on the anastomosis is mediated by the endotoxines and exotoxines liberated by bacteria. These toxines impair the proliferative activity of fibroblasts and alter the microcirculation that then causes necrosis, infection and intramural microabscess 17,18 . All of these phenomena favor anastomotic dehiscence.…”

Section: Introductionmentioning

confidence: 99%

“…These toxines impair the proliferative activity of fibroblasts and alter the microcirculation that then causes necrosis, infection and intramural microabscess. 17,18 All of these phenomena favor anastomotic dehiscence.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of enteral decontamination in the prevention of anastomotic dehiscence and pulmonary infection in esophagogastric surgery

et al. 2008

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Our aim in this study is to evaluate the efficacy of decontamination of the high digestive tract in reducing the incidence of anastomotic dehiscence, pulmonary infection and mortality after resective gastro-esophageal surgery. A prospective randomized and double-blinded study was conducted in patients undergoing total gastrectomy for gastric cancer and esophagectomy for esophageal cancer. Two groups were studied: group A patients were given erythromycin + gentamicine + nistatine sulfate orally; group B patients were given placebo. Mortality, incidence of anastomotic dehiscence and incidence of pulmonary infection were the end points evaluated. One hundred and nine consecutive patients were randomized. Eighteen (16.5%) were excluded. From the 91 patients who were evaluated, 42 (46.2%) received an esophagectomy and 49 (53.8%) had a total gastrectomy. Esophagectomies showed: a 0% rate of anastomotic dehiscence in group A and 12.5% in group B, P = 0.176; a pulmonary infection rate of 22.2% in group A and 29.1% in group B, P = 0.443; and mortality rate was 0% in group A and 12.5% in group B, P = 0.176. After gastrectomy, anastomotic dehiscence rate was 4.5% in group A and 0% in group B, P = 0.449; pulmonary infection rate was 4.5% in group A and 11.1% in group B, P = 0.387 and mortality was 9% in group A and 0% in group B, P = 0.196. Decontamination protocol does not help in decreasing the incidence of anastomotic dehiscence, pulmonary infection and mortality in the present study. Nevertheless, there seems to be a tendency to low pulmonary infection after gastrectomy and esophagectomy and to improve the incidence of anastomotic dehiscence after esophagectomy. Further studies are needed to re-evaluate these findings.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy of enteral decontamination in the prevention of anastomotic dehiscence and pulmonary infection in esophagogastric surgery

et al. 2008

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“…We propose that an additional factor may also be of major importance. The presence of bacteria which produce endo-or exotoxin may interfere with healing of the anastomosis in that they cause macrophage-mediated down regulation of fibroblast proliferation, as could be shown in vitro (2,10). In addition, bacterial invasion and proliferation in necrotic tissue at the suture line may, in the absence of local defense mechanisms, cause direct infection, with intramural abscess formation resulting in anastomotic leakage.…”

Section: Materuils and Methodsmentioning

confidence: 99%

Bacteria: a major pathogenic factor for anastomotic insufficiency

Schardey

Kamps

Rau

et al. 1994

Antimicrob Agents Chemother

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The aim of this study was to determine the influence of bacteria on the development of anastomotic insufficiency following gastrectomy in the rat. Fifty-seven male Wistar rats were randomly assigned to three groups and subjected to gastrectomy. Group I (n = 20) was orally inoculated with 109 Pseudomonas aeroginosa organisms on postoperative day 1. Group II (n = 20) served as the control group. Group III (n = 17) was decontaminated with 320 mg of tobramycin, 400 mg of polymyxin B, and 500 mg of vancomycin per liter of fluid administered from preoperative day 7 to postoperative day 10. Swabs from the oropharynx and rectum were cultured and analyzed daily for gram-positive and gram-negative bacteria. Surviving animals were sacrificed on postoperative day 10. All animals were autopsied immediately following death. Anastomotic insufficiency was defined as a histologically proven transmural defect at the suture line. Along with an effective reduction of pathogenic bacteria colonizing the oropharynx, the rate of anastomotic insufficiency could be reduced significantly, to 6% in decontaminated animals compared with 80% in controls (P < 0.001 by Fisher's exact test). Inoculation of group I animals with P. aeruginosa led to an increase of anastomotic insufficiency up to 95% and a significant increase in mortality (P < 0.05). We conclude that bacteria play a major role in the pathogenesis of anastomotic insufficiency following gastrectomy in the rat.Anastomotic insufficiency is one of the major causes of morbidity and mortality following total gastrectomy. The pathogenesis of esophago-intestinal anastomotic insufficiency, however, is not completely understood. Impaired blood supply or local microcirculatory disturbances leading to necrosis (13), as well as foreign bodies (6, 7), have been thought to be the cause of anastomotic insufficiency for more than 100 years. Anastomotic insufficiency, however, is a septic disease. Exogenous or endogenous potentially pathogenic microorganisms colonizing the digestive tract may play a causative role in the pathogenesis in addition to microcirculatory disturbances. This idea led us to examine the influence of bacterial colonization on the incidence of anastomotic insufficiency.By topical application of nonresorbable bactericidal antibiotics (16, 18), the colonizing microflora of the oropharynx and upper gastrointestinal tract can be easily manipulated. We therefore used deliberate colonization and topical decontamination with tobramycin, polymyxin and vancomycin to test the following hypotheses in an experimental study: (i) anastomotic insufficiency occurs as a result of bacterial infection, and (ii) anastomotic insufficiency can be prevented by preventing bacterial colonization. MATERUILS AND METHODSFifty-seven male Wistar rats were randomly assigned to three groups. In group I (bacterial inoculation), all animals received one oral dose of 109 Pseudomonas aeruginosa organisms on the first postoperative day. P. aeruginosa was chosen because it is commonly causes nosocomial infections i...

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“…After 6-72 h of CP administration, granulocyte, lymphocyte, and macrophage concentrations appear to increase [14]. Activated murine peritoneal macrophages, obtained by in vivo exposure to CP, act as a promoter of fibroblast proliferation [29]. Basic et al [30] found that intrapleural injection of CP caused a three-to fivefold increase in the number of nucleated cells in the pleural cavity which persisted for at least 14 days.…”

Section: Discussionmentioning

confidence: 99%

Seroma Prevention by Using <i>Corynebacterium parvum</i> in a Rat Mastectomy Model

et al. 2001

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Seroma formation is the most common complication after mastectomy and continues to be an important problem during the early postoperative period. Several surgical and medical methods have been developed to try to overcome this problem; however, so far none have been used successfully in the routine clinical practice. The aim of this study is to evaluate the effects of Corynebacterium parvum (CP) as a sclerosing agent in both prevention and treatment of seromas after mastectomy and axillary dissection in an animal model. Sixty female Sprague-Dawley rats underwent mastectomy and axillary dissection under general anaesthesia. Following surgery, the rats were treated in 1 of 3 ways. In the prevention group, 1 cm³ (0.35 mg) CP solution was injected beneath the skin flap just before closure of the incision after mastectomy. In the treatment group, animals in which a seroma was formed, the fluid was aspirated, and 1 cm³ CP solution was injected beneath the flap. In the control group, animals in which seromas formed, aspiration only was performed. The frequency of seroma formation decreased when CP solution was injected immediately after the operation (p < 0.01). In addition, seroma formation was effectively treated by CP injection when compared with the control group (p < 0.05). CP was effective as a prophylactic agent in the prevention group and as a therapeutic agent in the treatment group in this experimental model. CP injection may be useful for the management of this problem in a clinical setting.

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Suppression of fibroblast proliferation by activated macrophages: Involvement of H2O2 and a non-prostaglandin E product of the cyclooxygenase pathway

Cited by 16 publications

References 24 publications

Efficacy of enteral decontamination in the prevention of anastomotic dehiscence and pulmonary infection in esophagogastric surgery

Efficacy of enteral decontamination in the prevention of anastomotic dehiscence and pulmonary infection in esophagogastric surgery

Bacteria: a major pathogenic factor for anastomotic insufficiency

Seroma Prevention by Using <i>Corynebacterium parvum</i> in a Rat Mastectomy Model

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