Reduction of adhesions after uterine myomectomy by Seprafilm membrane (HAL-F): a blinded, prospective, randomized, multicenter clinical study. Seprafilm Adhesion Study Group

OBJECTIVE: To assess the safety and efficacy of Seprafilm (HAL-F), Bioresorbable Membrane, (Genzyme Corporation, Cambridge, MA) in reducing the incidence, severity, extent, and area of uterine adhesions after myomectomy. DESIGN: Prospective, randomized, blinded, multicenter study. Adhesion reduction was assessed by an independent, blinded, gynecologic surgeon who reviewed videotapes of each patient's second-look laparoscopy. SETTING: Nineteen institutions across the United States. PATIENT(s): One hundred twenty-seven women undergoing uterine myomectomy with at least one posterior uterine incision > or = 1 cm in length. INTERVENTION(s): Patients were randomized to treatment with Seprafilm or to no treatment at the completion of the myomectomy. MAIN OUTCOME MEASURE(s): The incidence, severity, extent, and area of uterine adhesions at second-look laparoscopy. RESULT(s): The incidence, measured as the mean number of sites adherent to the uterine surface, was significantly less in treated patients (4.98 +/- 0.52 [mean +/- SEM] sites) than in no treatment patients (7.88 +/- 0.48 sites) as were the mean uterine adhesion severity scores (1.94 +/- 0.14 versus 2.43 +/- 0.10; treatment versus no treatment, respectively), mean extent scores (1.23 +/- 0.12 versus 1.68 +/- 0.10), and mean area of adhesions (13.2 +/- 1.67 versus 18.7 +/- 1.66 cm2). No adverse events occurred that were judged to be related to the use of Seprafilm. CONCLUSION(s): In this multicenter study, treatment of patients after myomectomy with Seprafilm significantly reduced the incidence, severity, extent, and area of postoperative uterine adhesions. Additionally, Seprafilm treatment was not associated with an increase in postoperative complications.     

Effects of hyaluronic acid/carboxymethylcellulose gel on bowel anastomoses in the New Zealand white rabbit

Intra-abdominal adhesions form in more than 90% of patients undergoing major abdominal surgery and can lead to significant complications. Application of a bioresorbable gel consisting of chemically modified hyaluronic acid (HA) and carboxymethylcellulose (CMC) has shown promise as a means of preventing intra-abdominal adhesions, but there have been concerns that the presence of the gel might interfere with the integrity and healing of bowel anastomoses. We tested the effects of HA/CMC gel on adhesion formation and anastomotic healing in 60 New Zealand white rabbits after transection and complete (100%) or incomplete (90%) anastomosis of the ileum. Half of the animals underwent application of HA/CMC gel and half served as control subjects. Animals were killed at 4, 7, or 14 days after surgery. Anastomotic adhesions were scored in a blinded fashion. Integrity of the anastomosis was tested by measuring bursting pressure at the anastomotic site and in an adjacent section of intact bowel. With complete anastomosis, HA/CMC gel significantly reduced adhesion formation at 7 and 14 days after surgery (P<0.05), but gel application did not inhibit adhesion formation when the anastomosis was incomplete. Anastomosed segments of bowel burst at a lower pressure than intact bowel 4 days after surgery, but bursting pressures were normal at 7 and 14 days. Burst pressures of anastomoses receiving an application of HA/CMC gel were nearly identical to control anastomoses at all three time points. HA/CMC gel did not interfere with the normal healing process of bowel anastomoses. Furthermore, HA/CMC gel decreased adhesion formation after complete anastomoses, yet it did not affect adhesion formation in the presence of anastomotic disruption.     

Adhesion formation is reduced after laparoscopic surgery

BACKGROUND: Adhesion formation after abdominal operations causes significant morbidity. METHODS: Adhesion formation in pigs was compared after placement of prosthetic mesh during celiotomy (group 1), laparoscopy with large incision (group 2), and laparoscopy (group 3). After peritoneum was excised, polypropylene mesh was fixed to the abdominal wall, then to the opposite abdominal wall in the preperitoneal space followed by peritoneal closure. Adhesion area, grade, and vascularity were measured. RESULTS: More adhesions (p < 0.02) covered intraperitoneal mesh (7.57 +/- 1.89 cm2) than covered reperitonealized mesh (2.16 +/- 1.13 cm2), and adhesion grade was significantly greater (p < 0.02). Adhesion areas were significantly greater in groups 1 and 2 than in group 3 (p = 0.001 and 0.03, respectively). Adhesion grade was significantly greater in groups 1 and 2 than in group 3 (p = 0.02 and p = 0.04, respectively). Groups 1 and 2 had more vascular adhesions than group 3 (p < 0.01 and p = 0.02, respectively) CONCLUSIONS: A foreign body within the peritoneum stimulates more numerous and denser adhesions. Tissue trauma distant from the site of adhesions increases their formation. A major advantage of laparoscopic surgery is decreased adhesion formation.     

Effects of interleukin-6 and its neutralizing antibodies on peritoneal adhesion formation and wound healing

This study investigates the effects of preoperative IV administration of IL-6 and anti IL-6 on peritoneal adhesion formation and wound healing. Thirty-six male Sprague-Dawley rats (350-400 mg) were divided into three groups: control (group 1); IL-6 (group 2); and anti IL-6 (group 3). Under sterile conditions, all rats underwent a midline laparotomy. Ten cm2 of cecal serosa was abraded, the cecum further irritated with 0.1 ml of 70 per cent alcohol, and the incision closed in layers. At 3 weeks, peritoneal adhesions were graded using a score of 0 (none) to 3 (extensive, dense). Skin samples from incisional sites were examined tensiometrically (true stress and true strain), biochemically (collagen content), and histologically. Adhesion formation score was significantly increased in IL-6 group (2.78 +/- 0.44, Mean +/- SD) and decreased in anti IL-6 group (1.40 +/- 0.52) compared to control (2.00 +/- 0.50). (P < 0.03 by Kruskal Wallis test). There was no significant difference in true stress, true strain, and collagen content between the two treatment groups and controls at the 0.05 level by ANOVA. Histological analysis showed higher number of inflammatory cells and fibroblasts in IL-6 treated groups. We conclude that IL-6 plays a major role in peritoneal adhesion formation. Selective immunosuppression, using IL-6 neutralizing antibodies preoperatively, leads to a reduction of such adhesion formation without a significant effect on wound healing.     

Effectiveness of collagen-gentamicin implant for treatment of "dirty" abdominal wounds

The purpose of this work was to compare the efficacy and safety of the collagen-gentamicin sponge with conventional treatment (wound open, maintaining a close observation, and cleaning it daily with antiseptics) for the prophylaxis of infection in "dirty" abdominal wounds. Seventy-three patients with dirty abdominal wounds caused by gastrointestinal tract surgery were studied. The patients were randomized in two groups: group A, open wounds, treated with local cleansing, metronidazole 20 to 40 mg/kg/day IV and gentamicin 5 mg/kg/day IV for 7 days. Group B, primary closure with collagen-gentamicin implant plus metronidazole 20 to 40 mg/kg/day IV for 7 days. Surgical wound infections were significantly reduced by the collagen-gentamicin implant. Polymicrobial infections were observed in group A, whereas the infections were caused only by a single organism in group B. In conclusion, the collagen-gentamicin implant is effective and well tolerated in the treatment of "dirty" surgical abdominal wounds because it significantly reduces the wound infection rate (p < 0.01) and shortens healing time (p < 0.001) and the period of disability.     

Decrease in contents of pancreatic carboxyl ester lipase, phospholipase A2, and lingual lipase in rats with streptozotocin-induced diabetes

Fibrin glue has been used as a protective seal in normal and high-risk anastomoses to prevent leakage. The influence of fibrin adhesive on the healing colonic anastomosis in a control and high-risk model was tested. Resection and anastomosis of the left colon was performed in rats. In group Ia an end-to-end anastomosis was constructed with 12 7-O polypropylene sutures; in group Ib the anastomosis was sealed with fibrin adhesive. In group II an incomplete anastomosis was constructed with only 4 sutures at 90 degrees, therefore potentially leaking. In group IIb additional sealing with fibrin glue was performed. On Days 2, 4, and 7 body weight, adhesion formation, anastomotic bursting pressure, and collagen concentration were measured. The results showed increased adhesion formation after fibrin sealing. The anastomotic bursting pressure of incomplete anastomoses showed a significant increase after sealing on Day 2 only; on Day 4 and 7 no differences were found. Sealing of control anastomoses caused lower bursting pressures on Day 4. Collagen concentration is significantly reduced after fibrin sealing of normal anastomoses. We conclude that fibrin sealing of control anastomoses inhibits wound healing. Incomplete anastomoses are temporarily protected by fibrin glue sealing. Finally, fibrin sealing of the colon wound does not prevent adhesion formation.     

Experimental studies on the effect of lidocaine on wound healing

Local anesthetics have several effects on wound healing. In experimental studies, procaine at high concentrations has been proved to retard healing in surgical wounds by diminishing the synthesis of mucopolysaccharides and hence probably collagen. Other studies have shown that lidocaine and bupivacaine inhibit collagen synthesis in fibroblast tissue cultures in rats. This study was designed to evaluate the effect of lidocaine on wound healing. An experimental, prospective, comparative, crossover and double-blind study was designed. Forty male guinea pigs, weighing 300 to 600 g, were randomly assigned to two groups. In control group A (20 animals), skin and subcutaneous tissue in a clean wound were incised and infiltrated with regular saline solution; in group B 20 animals were infiltrated with 1% lidocaine. All animals were sacrificed on day 8 and evaluated for breaking strength, number of collagen fibers by morphometry, and histologic examination of collagenization, edema, vascularity, and presence of acute and chronic inflammatory cells. The histopathologic appearance of tissues infiltrated with lidocaine did not vary consistently in relation to collagenization, edema, or acute and chronic inflammatory processes. The mean breaking strength between both groups was not statistically significant (p = 0.120). Important statistical differences were observed in vascularity (p < 0.003) and morphometric results (p < 0.001), where collagen was found in small amounts in the lidocaine group. The results of this study suggest that local infiltration of lidocaine produces significant histopathologic changes, but it does not substantially alter wound healing as there were no differences in the breaking strength of the wounds.     

Effect of fibrin sealant on the integrity of colonic anastomoses in rats with faecal peritonitis

OBJECTIVE: To assess the influence of fibrin adhesive on the healing of colonic anastomoses in rats with and without faecal peritonitis. DESIGN: Controlled study. SETTING: Laboratory for experimental surgery, Erasmus University Rotterdam, The Netherlands. MATERIAL: 120 male Wag/Rij rats. INTERVENTIONS: All rats had a single layer end-to-end anastomosis fashioned with 7/0 polypropylene. Faecal peritonitis was then induced in half of the rats by placement of 200 mg powdered autoclaved rat faeces in the peritoneal cavity near the anastomosis. Rats were allocated to one of four groups (n = 30 in each): 1--control; 2--additional sealing with fibrin glue; 3--peritonitis alone; and 4--peritonitis with fibrin glue. MAIN OUTCOME MEASURES: Body weight, adhesion formation, anastomotic bursting pressure and collagen concentration around the anastomosis on days 2, 4, and 7 in 10 rats from each group. RESULTS: 11 rats died of peritonitis before the experiment was completed. Peritonitis caused increased formation of adhesions and abscesses, with or without fibrin sealant. Bursting pressure at the anastomosis was significantly reduced in peritonitis compared with controls on days 4 and 7, and this was not prevented by fibrin. Sealing of anastomoses resulted in lower bursting pressures on day 4 in control animals. Collagen concentration was significantly reduced in peritonitis with or without fibrin sealant on days 4 and 7, and after fibrin sealing of control anastomoses. CONCLUSION: Faecal peritonitis reduced mechanical strength and collagen concentration of colonic anastomoses, and this was not prevented by additional sealing of the anastomosis with fibrin sealant.     

Tissue markers as predictors of postoperative adhesions

BACKGROUND: Postoperative adhesion formation has been associated with a decreased capacity to degrade intra-abdominally deposited fibrin. Adhesions, once lysed, have a high propensity for reformation. This study tested the hypothesis that patients with a high propensity for adhesion formation as well as adhesion tissue had a reduced fibrinolytic capacity. METHODS: Peritoneal biopsies were taken during abdominal surgery from 21 patients who had previously undergone operation; previously formed adhesion tissue was sampled from ten of these patients. Adhesion formation was scored. The fibrinolytic capacity of peritoneum was determined in tissue extracts. RESULTS: At the time of opening of the abdominal cavity, levels of plasminogen activator inhibitor (PAI) type 1 (P = 0.009) and tissue-type plasminogen activator (tPA)/PAI complex (P = 0.008) were increased in peritoneal samples from patients with severe adhesions compared with those in samples from patients with less severe adhesions. Adhesion tissue similarly had reduced fibrinolytic capacity as judged by a decrease in tPA activity (P = 0.005) and an increase in PAI-1 level (P = 0.01), reflected in an increased level of tPA/PAI complex (P = 0.008) compared with unaffected peritoneum. CONCLUSION: These observations demonstrate reduced fibrinolytic capacity in peritoneal tissue in patients with a greater propensity for development of adhesions and likewise in adhesion tissue. This suggests that components of the fibrinolytic system may be used as markers of an increased risk of adhesion development.     

Talc pleurodesis: talc slurry versus thoracoscopic talc insufflation in a porcine model

BACKGROUND: Pleurodesis using both talc slurry and thoracoscopic talc insufflation has been shown to be clinically effective. This study compares these two modalities of pleural talc instillation in an animal model. METHODS: Eleven immature pigs underwent general endotracheal anesthesia. On one side, a slurry of 5 g sterile United States Pharmacopeia talc in 50 mL of saline solution was instilled through a thoracostomy tube. On the other side, the lung was deflated and 5 g of dry talc was insufflated under thoracoscopic visualization. The animals were sacrificed 30 days later, and the quality of pleural adhesions was graded from 0 to 2 (0 = absent; 1 = light; 2 = dense) in each of six regions of each hemithorax. The distribution of adhesions on each side was graded from 0 to 6, according to the number of areas that contained adhesions. RESULTS: One animal died of anesthetic complications. Among the survivors, adhesions produced by both methods were dense and diffuse in 8 of 10 animals, and light and diffuse in 1 animal. One animal had light or absent adhesions on the talc slurry side, and dense and diffuse adhesions on the thoracoscopic talc insufflation side. There was no difference between the techniques for density of adhesion scores (talc slurry, 9.9 +/- 2.2; thoracoscopic talc insufflation, 10.0 +/- 2.5) or distribution of adhesion scores (talc slurry, 5.5 +/- 1.0; thoracoscopic talc insufflation, 5.8 +/- 0.4) (p > 0.1). CONCLUSIONS: Effective pleurodesis in a porcine model can be obtained with either talc slurry or thoracoscopic talc insufflation.     

The role of neutrophils in peritoneal adhesion formation

The most common cause of intraperitoneal adhesions is previous abdominal surgery. Postoperative adhesion formation results from a fibroproliferative inflammatory reaction that begins with an influx of polymorphonuclear leukocytes (PMNs) into the peritoneal cavity. Adherence of the PMNs to the endothelial cells (EC) is necessary for PMN migration into the tissue in response to a stimulus. Several receptor-counterreceptor pairs of ligands such as CD11/CD18 on the PMN and ICAM-1 (CD54) on EC have been identified. Monoclonal antibody against CD11/CD18 (R15.7) inhibits PMN adherence and migration and consequently protects against PMN-induced tissue injuries. We therefore studied the effect of preventing PMN-EC adherence, using anti-CD18 monoclonal antibody, on postoperative adhesion formation in rabbits. Group 1 was a control receiving physiologic saline, and group 2 received anti-CD18 antibody (R15.7, 2 mg/kg). The treatment was administered iv at the end of surgery and repeated on the first and second postoperative days. Peritoneal adhesions were induced at laparotomy by repairing two peritoneal defects, by oversewing the defect (model 1), and by resuturing the removed parietal peritoneum in its place as an ischemic graft (model 2). Adhesions were evaluated blindly at 10 days after operation by measuring the percentage of the suture line covered with adhesions (model 1) or by a scoring system (model 2). All control animals developed intraperitoneal adhesions and the percentage of the suture line covered with adhesions was 25 +/- 5.9% (mean +/- SEM) and the mean score in model 2 was 0.9 +/- 0.2. Anti-CD18 antibody, R15.7, increased the degree of postoperative adhesion formation in both models, but the results were significant only in model 2. Also, anti-CD18 antibody significantly decreased peritoneal neutrophils from 11.1 x 10(7) +/- 1.8 x 10(7) to 2.2 x 10(7) +/- 0.4 x 10(7) (P < 0.001) on the first postoperative day. It is concluded that inhibition of PMN-EC adherence does influence the postoperative adhesion formation. These results might suggest that PMNs have a role in modulating postoperative adhesion formation.     

Interaction between succinylcholine and ranitidine in rats

The primary objective of this study was to compare the effectiveness of expanded polytetrafluoroethylene (e-PTFE) and polypropylene (PPM) in a rabbit abdominal wall defect model using a double-layer repair technique. Fifty-four New Zealand white rabbits had full thickness resection of a 5 x 5-cm segment of the mid portion of at the abdominal wall. The defect was repaired with two 6 x 6-cm layers of prosthesis in an underlay/overlay fashion incorporating a 1-cm edge of abdominal wall and grouped accordingly. Group I: inner and outer layer of PPM; Group II: inner layer e-PTFE, outer layer PPM; Group III: inner and outer layer e-PTFE. Animals from each group were sacrificed at 3, 6, and 12 months. The abdominal wall was assessed for herniations and bowel adhesions to the inner layer of the prosthesis. Adhesions were graded according to an adhesion scoring system (grade 0-3). No herniations were observed. Intestinal adhesions to PPM were quite dense at 3 months with a mean adhesion score of 2.5; at 12 months, adhesions were more dense and extensive, having a mean score of 3. Adhesions to e-PTFE were thin and filmy with a mean score of 0.4 at 3 months and 0.6 at 12 months (P < 0.001, 95% CI for each time period). Histologically, PPM fibers were consistently surrounded by dense fibrous connective tissue; foreign body giant cells were present. A thin connective tissue capsule covered the inner e-PTFE layer; its pores were progressively infiltrated by fibroblasts. The double-layer technique prevented hernias in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resource utilization in the emergency department: the duty of stewardship

OBJECTIVE: Our purpose was to determine whether there is a difference in adhesion formation after pelvic and paraaortic lymphadenectomy with transperitoneal laparoscopy compared with both extraperitoneal laparotomy and transperitoneal laparotomy in a porcine model. STUDY DESIGN: Ninety female hogs underwent pelvic and paraaortic lymphadenectomy: 40 with transperitoneal laparoscopy, 40 with extraperitoneal laparotomy, and 10 with transperitoneal laparotomy. Three weeks after the initial surgery, a laparotomy was performed to assess adhesion formation. RESULTS: The transperitoneal laparotomy group had significantly higher adhesion formation, with a 100% (10 of 10) adhesion rate. In the transperitoneal laparoscopy group, 12 of 40 hogs (30%) had adhesions develop versus 8 of 38 (21%) in the extraperitoneal laparotomy group (p = not significant). Also no differences were found in the transperitoneal laparoscopy and extraperitoneal laparotomy groups when comparing adhesion thickness or the total surface area of adhesions. More anterior abdominal wall adhesions were noted in the extraperitoneal laparotomy group (5 of 38) than in the transperitoneal laparoscopy group (0 of 40, p = 0.02). CONCLUSIONS: Pelvic and paraaortic lymphadenectomy performed with transperitoneal laparoscopy does not increase adhesion formation when compared with extraperitoneal laparotomy in a porcine model. The transperitoneal laparoscopy (and extraperitoneal laparotomy) approach also induces significantly fewer adhesions than transperitoneal laparotomy.     

Laser Doppler imaging and capillary microscopy in ischemic ulcers

The local distribution of laser Doppler flux (mainly thermoregulatory perfusion) and capillary density (nutritive circulation) within 25 ischemic leg ulcers and their adjacent skin were investigated. For this purpose the technique of laser Doppler imaging and capillary microscopy were applied. In each ulcer a non granulation tissue area (NGTA), a granulation tissue area (GTA) and in adjacent skin a skin area (SA) were defined. In these areas the average laser Doppler area flux (arbitrary units, AU) and the number of capillaries/mm2 were determined for each patient. The mean+/-S.D. of laser Doppler area fluxes were: NGTA 1.30+/-1.93, GTA 2.13+/-1.53 and SA 1.21+/-0.77 AU, respectively. The differences between GTA and NGTA or SA was statistically significant (p < 0.001, each) The mean+/-S.D. of capillary densities were as follows: NGTA: 0.56+/-2.06, GTA 6.76+/-8.39 and SA 16.80+/-7.38 capillaries/mm2, respectively. The following differences were statistically significant: NGTA versus GTA (p < 0.01) and SA versus NGTA or GTA (p < 0.001, each). In conclusion following characteristics of the three areas can be described: In NGTA low laser Doppler area flux is combined with very low capillary density (ulcer area without healing). In GTA the highest laser Doppler area flux of all three areas and an intermediate capillary density (wound healing) is found. In SA an intermediate laser Doppler area flux is associated with the highest capillary density of all three areas with the healing process nearly completed and no granulation tissue.     

Adhesions: pathogenesis and prevention-panel discussion and summary

This article summarizes the discussions of the faculty and chairpersons on four major topics on postsurgical adhesions examined at the symposium, "Adhesions: Pathogenesis and Prevention". These topics are: 1) clinical significance; 2) pathogenesis; 3) research status and directions; and 4) recommendations for reduction or prevention. Abdominal postsurgical adhesions develop following trauma to the mesothelium, which is damaged often by surgical handling and instrument contact, foreign materials such as sutures and glove dusting powder, desiccation, and overheating. Postoperative adhesions occur after most surgical procedures and can result in serious complications, including intestinal obstruction, infertility, and pain. A long-term and unpredictable problem, postoperative adhesions impact the surgical workload and hospital resources, resulting in considerable health care expenditures. Although understanding of the pathogenesis of adhesions has improved recently, the molecular mechanisms involved continue to be delineated. Adhesions result from the normal peritoneal wound healing response and develop in the first five to seven days after injury. Adhesion formation and adhesion-free re-epithelialization are alternative pathways, both of which begin with coagulation which initiates a cascade of events resulting in the buildup of fibrin gel matrix. If not removed, the fibrin gel matrix serves as the progenitor to adhesions by forming a band or bridge when two peritoneal surfaces coated with it are apposed. The band or bridge becomes the basis for the organization of an adhesion. Protective fibrinolytic enzyme systems of the peritoneum, such as the plasmin system, can remove the fibrin gel matrix. However, surgery dramatically diminishes fibrinolytic activity. The pivotal events determining whether the pathway taken is adhesion formation or re-epithelialization are therefore the apposition of two damaged surfaces and the extent of fibrinolysis. Research in postsurgical adhesion formation and prevention abounds in a variety of avenues of investigation, including: 1) identification on a molecular level of the components involved in adhesiogenesis and their interactions; 2) clarification of the role of fibrin and fibrinolysis in adhesion formation; 3) standardization of design in preclinical and clinical studies of adhesion formation and prevention; 4) delineation of the relationship between adhesion formation and adhesive complications; and 5) elucidation of efficient, site-specific methods of prophylactic drug delivery. Currently, it seems logical to focus preventive research on development of barriers, fibrinolytic drugs, and selected agents such as phospholipids. The major strategies for adhesion prevention or reduction are adjusting surgical practice and applying adjuvants. Surgeons should adjust their major practices by: 1) becoming aware of the potential adhesive complications of a procedure; 2) minimizing the invasiveness of surgery; and 3) minimizing surgical trauma, ischemia, exposure to intestinal contents, introduction of foreign material into the body, and the use of talc- or starch-containing gloves. Available adjuvants include a newly developed by hyaluronic acid-phosphate-buffered saline solution applied intraoperatively to protect peritoneal surfaces from indirect surgical trauma and three mechanical barriers. One of these, a bioresorbable membrane consisting of hyaluronic acid and carboxymethylcellulose, has demonstrated efficacy and safety in both general and gynecological surgery. The other two barriers, one made of expanded polytetrafluoroethylene and one developed from oxidized regenerated cellulose, are indicated only for use in gynecological surgery.     

Effects of early postoperative 5-fluorouracil and ageing on the healing capacity of experimental intestinal anastomoses

BACKGROUND: Results from a previous study suggested that advanced age does not affect early repair of experimental intestinal anastomoses. The present study aimed to establish whether anastomotic healing is impaired more easily in old animals by immediate postoperative chemotherapy. METHODS: Young adult (2-3 months) and old (27-30 months) rats underwent resection and anastomosis of both ileum and colon. Within each age group, subgroups received intraperitoneal saline or 5-fluorouracil in a dose of 15 or 20 mg per kg per day from the day of operation onwards. After 7 days, anastomotic healing was assessed by wound strength and collagen deposition in the wound area. RESULTS: No differences were found between young and old control groups. The higher dose of fluorouracil induced severe loss of strength with concomitant reduction of wound collagen, which was similar in both age groups (ileum: from 52(13) to 24(8) volume per cent in young animals and from 56(10) to 20(9) volume per cent in old animals; colon: from 58(10) to 37(18) volume per cent in young animals and from 65(5) to 30(17) volume per cent in old animals). The lower dose of fluorouracil induced a significantly greater loss of strength, measured as the bursting pressure, in the old animals (150(49) versus 201(59) mmHg in colon of young rats). CONCLUSION: In this model early anastomotic repair in older animals proceeds normally under optimal conditions, but it is more easily disturbed in the presence of fluorouracil.     

Bursting pressure in anastomotic healing in experimentally induced colitis in rats

BACKGROUND: Experimental studies on healing of colonic anastomosis have been thoroughly investigated. However, clinical parameters of the healing process of anastomosis in the inflamed colon has not yet been reported. METHODS: In the present study, healing of anastomosis in trinitrobenzene-sulfonic acid-induced colitis in rats was assessed by measuring the bursting pressure and bursting wall tension. RESULTS: On postoperative day 4, bursting pressure and bursting wall tension were significantly lower (P < 0.001) in rats with colitis with or without anastomosis and normal colon with anastomosis, compared with normal colon without anastomosis. On postoperative day 7, bursting pressure and bursting wall tension of normal colon with anastomosis approached that of normal colon without anastomosis. However, bursting pressure and bursting wall tension of rats with colitis with or without anastomosis remained significantly lower (P < 0.001) than the latter. Furthermore, unlike rats without colitis in which perforation occurred mostly at the anastomotic line, the bursting site in colitic rats was predominantly away from the anastomotic line. CONCLUSIONS: These results suggest that in surgery for inflammatory bowel disease, it is the adjoining inflamed bowel wall that is vulnerable to be perforated in response to increasing intraluminal pressure rather than the anastomosis that is braced by the sutures.     

The leaching of nickel from new and used metal spectacle frames

Hyperthermia is a promising method for increasing the efficacy of radiation therapy of colorectal cancer. To study the histological aspects of healing of an anastomosis in the colon, after combined preoperative (sham) irradiation and (sham) hyperthermia treatment, 48 male Wistar rats were divided randomly into four groups. In each animal, a segment of the colon was treated successively by (sham) irradiation (single dose of 25 Gy X rays) and/or (sham) hyperthermia (44 degrees C, 30 min). After 5 days, a resection of the colon was performed by construction of an anastomosis: The distal limb consisted of (sham-) irradiated and/or (sham-) hyperthermia-treated bowel. Rats were killed 3 or 7 days after the surgical procedure. Evaluation of healing of the anastomosis was made by: (1) histological analysis of sections stained with hematoxylin and eosin, (2) semiquantitative measurement of collagen in the area of the anastomosis and (3) semiquantitative analysis of the number of macrophages by immunocytochemistry. Healing of the anastomoses in animals receiving irradiation or hyperthermia alone and in control animals was relatively uneventful. There were no differences between groups in formation of collagen or infiltration by macrophages in the area of the anastomosis. Animals treated with both radiation and hyperthermia showed marked necrosis, infiltration by polymorphonuclear leukocytes and rupture of the anastomosis. It is concluded that preoperative irradiation with a single dose of 25 Gy in combination with local hyperthermia at 44 degrees C for 30 min leads to disturbed repair of anastomoses.     

Reversed-flow affinity elution applied to the purification of carboxypeptidase Y

BACKGROUND: Despite curative resection for colorectal cancer, many patients develop recurrence at the primary site or distant organs. These patients are candidates for (neo)-adjuvant chemotherapy. Very little is known about the effect of preoperative 5-fluorouracil (FU) on the healing of colonic anastomoses. The aim of this study was to assess this in a rat model. METHODS: Eighty male Wistar rats, weighing 160-215 g, were divided into three groups; (1) a control group underwent left colon resection and primary anastomosis (n = 20); (2) a sham group received 1 ml saline intraperitoneally (n = 30); (3) a study group received 5-FU intraperitoneally (20 mg kg-1). Both saline and 5-FU injections were given intraperitoneally for 5 days before operation. RESULTS: There was no difference in the rate of wound complications, intraperitoneal adhesions and anastomotic complications among the groups. Three and seven days after operation, mean bursting pressure of the anastomosis was 36.5 and 198 mmHg in group 1, 34 and 200 mmHg in group 2, and 39 and 190 mmHg in group 3 respectively (P not significant). Although the myeloperoxidase and hydroxyproline content were significantly lower after 5-FU therapy (P < 0.01, compared with others), the clinical outcome was similar. CONCLUSION: Preoperative 5-FU consecutive days before operation had no effect on the healing of colonic anastomoses.     

Model of implantation of tumor cells simulating recurrence in colonic anastomosis in mice

PURPOSE: Local recurrence after colorectal cancer surgery is usually perianastomotic. An experiment was designed to investigate whether free intraluminal cells can penetrate through a colonic anastomosis and thereby cause local recurrence. METHODS: BALB/c and C57/BL mice underwent ascending colotomy followed by watertight anastomosis. Thereafter, CT-26 murine colon carcinoma cells were injected into the cecal lumen 2 cm proximal to the anastomosis of syngeneic BALB/c mice, whereas B-16 murine melanoma cells were injected in the same fashion into C57/BL mice. Control animals without anastomosis received similar injections. Animals were killed 24 hours, 72 hours, and 30 days after surgery and were checked for tumorigenesis. RESULTS: Results of peritoneal fluid cytology were negative after 24 hours, whereas after 72 hours cancer cells were identified in the peritoneal fluid of 80 percent of mice with colotomy and anastomosis compared with 20 percent of control mice. Thirty days after surgery, 11.1 percent of the control BALB/c mice developed pericecal tumor growth, similar to the overall rate of murine melanoma in C57/BL. In mice with anastomoses, perianastomotic tumor growth was observed in 47.5 percent of BALB/c mice (P < 0.001) and was correlated with the number of injected cells. Tumor growth reached approximately 75 percent tumor take with high cell densities, whereas in C57/BL mice no difference was found between the experimental and control groups. CONCLUSIONS: The findings suggest that free intraluminal cancer cells of colonic origin may penetrate through watertight anastomoses and implant on the anastomotic or peritoneal surface and initiate tumor growth. This anastomotic penetration is cell-mass dependent. The reported experimental model is simple, reproducible, and advantageous for studies of colonic anastomosis.