Optimization of photopolymerized bioerodible hydrogel properties for adhesion prevention

The aim of this study was to optimize the properties of a lubricious bioerodible hydrogel barrier for the prevention of postoperative adhesions. Water-soluble macromers based on block copolymers of poly(ethylene glycol) (PEG) and poly(lactic acid) or poly(glycolic acid) with terminal acrylate groups were used, and these macromers were gelled in vivo by exposure to long wavelength ultraviolet light. The precursor was photopolymerized from buffered saline solution while in contact with the tissues. This resulted in the conformal coating of the tissue with an adherent hydrogel film, while forming a nonadhesive barrier at the free surface, on the treated wound site. The hydrogels were evaluated in two animal models of postsurgical adhesions, first in a rat cecum abrasion model and then in a rabbit uterine horn ischemia model. In the rat cecum model, six of seven animals treated with a hydrogel, with glycolide in the precursor as the comonomer, showed no adhesions; untreated animals and animals treated with precursor, but not gelled with light, showed consistent dense adhesions. In the rabbit uterine horn ischemia model, using hydrogels with lactide in the precursor as the comonomer, and PEG of molecular weight from 6,000 to 18,500 Da, adhesions were dramatically reduced, with occurrence in none of seven animals treated with a gel containing PEG 10,000. By contrast, the seven animals in the control group demonstrated a mean of 35% involvement of the horn length in dense, fibrous adhesions. These materials, photopolymerized in vivo in direct contact with the tissues, appear to form an adherent hydrogel barrier that is highly effective in reducing postoperative adhesions in the models used.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

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.     

Native CSF spectrophotometry--contribution to the differential diagnosis of closed cranial injuries

The development of postoperative peritoneal adhesions was studied in rats and rabbits, the frequency of adhesions in the experimental model used being very high. In the development of an adhesion, fibrin seems to be an important contributor to the bridge between different tissues. Dextran, which modifies the fibrin network and makes it more susceptible to lysis, was used as a possible prophylactic agent, but we found no difference between treated and control groups. It is concluded that the stimulus for fibrin formation in the peritoneal adhesions using this atraumatic model was too strong to be overcome by the normal fibrinolytic system. The anti-inflammatory reaction of hyaluronic acid did not diminish the frequency or degree of adhesions.     

Postoperative adhesion prevention with low-dose aspirin: effect through the selective inhibition of thromboxane production

The aim of the present study was to evaluate the efficacy of low-dose versus high-dose aspirin in the prevention of postoperative adhesion formation. Forty New Zealand White rabbits were randomized into three groups: low-dose aspirin (1.7 mg/kg per day for 5 days starting on the day of surgery), high-dose aspirin (28.0 mg/kg per day), and controls. The rabbits underwent a standardized surgical injury on the ovary, uterine horn and abdominal wall on one side at laparotomy. On postoperative day 21, a second-look laparotomy was performed for the evaluation of postoperative adhesions. In five animals in each group, peritoneal fluid samples were collected at initial surgery, then through an additional 2 cm incision performed on postoperative day 3, and at second-look laparotomy. The peritoneal concentrations of thromboxane B2 and 6-keto-prostaglandin F1alpha (the stable hydrolysis product of prostacyclin) were measured by radioimmunoassay. At second-look laparotomy, the adhesion formation rate was 46% in the low-dose aspirin group, 77% in the high-dose group, and 100% in the control group. The adhesion score in the low-dose group was significantly lower (P < 0.01) than in the high-dose and control groups. Peritoneal thromboxane decreased significantly during treatment in both low-dose and high-dose aspirin groups, whereas prostacyclin decreased only in the high-dose group. Postoperative adhesion reduction observed in this study with low-dose aspirin treatment could be due to the selective inhibition of thromboxane over prostacyclin production.     

Robotically assisted laparoscopic microsurgical uterine horn anastomosis

OBJECTIVE: To evaluate the feasibility, safety, and sterility issues with regard to the use of a robotic device to perform uterine horn anastomosis in a live porcine model. DESIGN: Prospective animal study. SETTING: Landrace-Yorkshire pigs in a conventional laboratory setting. INTERVENTION(S): Six female pigs underwent laparoscopic bipolar electrocoagulation of the distal uterine horns. Two weeks later, the uterine horns were reanastomosed laparoscopically with use of a robotic system for microsuturing. Necropsy was performed 4 weeks later to assess postoperative adhesions and anastomosis patency. MAIN OUTCOME MEASURE(S): Tubal patency; secondary measures were operative time, complications, and surgeon fatigue. RESULT(S): The mean (+/-SD) total operative time per animal was 170+/-34 minutes including setting up and dismantling the robotic arms. The robot functioned well with only minor technical problems. All pigs survived both surgeries with no perioperative complications related to the use of the robot. Patency was confirmed after completing each anastomosis (12 anastomoses; 100% patency). Four weeks later, necropsy showed that eight anastomoses were still patent (67%). Only one pig had bilateral occlusion. Surgeon's fatigue was mild for each animal study. CONCLUSION(S): Robotic technology can be used safely in creating laparoscopic microsurgical anastomoses. The robot functioned properly in a sterile operating room environment. Adequate patency rates were achieved during the acute phase and at 4-week follow-up. Robotic technology has the potential to make laparoscopic microsuturing easier.     

In vivo model to study the biocompatibility of peritoneal dialysis solutions

This study was designed to analyze the complex morphologic and functional effects of dialysis solutions on peritoneum in a rat model on chronic peritoneal dialysis. Peritoneal catheters were inserted into 10 male, Wistar rats and the animals were dialyzed twice daily for 4 weeks with 4.25% Dianeal. During the study we observed two opposite effects: healing of the peritoneum after catheter implantation--decreased cell count in dialysate, decreased permeability of the peritoneum to glucose and total protein, increased volume of drained dialysate; and damage to the membrane due to its exposure to peritoneal dialysis solution--increased hyaluronic acid levels in dialysate, a tendency of the peritoneum to thicken when compared to non-dialyzed animals. Our rat model of CAPD may be used for quantitative and qualitative assessment of the effects of peritoneal dialysis solution on the peritoneum during chronic dialysis.     

The effect of training and duration of surgery on adhesion formation in the rabbit model

In order to evaluate the effect of training upon postoperative adhesions, standard bipolar and mechanical, nonopposing injuries were performed in the uterine horns and side walls of 52 mature female rabbits using a conventional three-puncture laparoscopy, by an endoscopic surgeon with limited experience. An additional injury, either bipolar or mechanical or both, was performed in the retro-uterine space. With experience, the duration of surgery decreased progressively from 12 +/- 2 to 8 +/- 1 min in the first and last 10 animals respectively. The amount of perioperative bleeding was not affected by experience. With experience the postoperative adhesions decreased in extent (P = 0.0001), tenacity (P = 0.004), type (P = 0.002) and inflammation (P = 0.003) and for total score (P = 0.0002). These changes were correlated with the briefer duration of surgery but not with the amount of perioperative bleeding. The strong correlations of adhesion scores in the pouch of Douglas, and around both uterine horns confirmed the importance of the inter-animal variability in making adhesions. By logistic regression, the adhesions in the pouch of Douglas were explained simultaneously by the adhesions on the uterine horns (P = 0.0004, thus correcting for inter-animal variability) by the amount of bleeding (P = 0.01) and the duration of surgery (P = 0.05). No major differences were found in adhesions following a mechanical or a bipolar injury or following such a lesion in the pouch of Douglas or at the uterine horns. In conclusion, experience, expressed by the duration of surgery and to a lesser extent perioperative bleeding, is a major co-factor in postoperative adhesions, suggesting that duration of surgery should be strictly standardized in endoscopic adhesion studies. The important inter-animal variability can be circumvented by using a standard control lesion, making each animal its own control.     

Postoperative adhesion formation and reproductive outcome using Interceed after ovarian surgery: a randomized trial in the rabbit model

The efficacy of an oxidized regenerated cellulose barrier (Interceed) in reducing postoperative adhesion formation and improving reproductive outcome after ovarian surgery was evaluated in a prospective randomized trial. Twenty-nine New Zealand White female rabbits were submitted to a mid-line laparotomy and a standardized surgical incision was made on both ovaries. At random, one ovary was entirely wrapped in a sheet of Interceed, whereas the contralateral ovary was left uncovered. Four weeks following surgery, the rabbits were mated with a male of proven fertility. Two weeks later, a second-look laparotomy was performed by a blinded observer who evaluated the incidence and score of adhesions, the number of corpora lutea in each ovary, the number of embryos in the ipsilateral uterine horn and also calculated the nidation index for each side. Adhesions were observed in 66% of Interceed-covered and in 97% of control ovaries (P < 0.0001). The adhesion score on the Interceed side was significantly lower than on the control side. The nidation index for the Interceed side was significantly higher than for the control side. The authors conclude that, in the rabbit model, Interceed significantly reduces the incidence and score of postoperative ovarian adhesions and significantly improves reproductive outcome.     

Peritoneal healing after fibrin glue application: a comparative study in a rat model

The influence of fibrin glue on adhesion formation and peritoneal healing is evaluated in a prospective, randomized, controlled study. In all, 20 Wistar rats underwent microsurgical suturing of two silicone sheets, one covered with a fibrin glue barrier, to the anterior peritoneum. Each animal thus served as its own control. After 10 days, adhesions and peritoneal healing were evaluated by a blinded observer through a second-look laparotomy. Adhesions were scored using a modification of the classification of Diamond. Tissue around the silicone sheet was examined histologically and by scanning electron microscopy to evaluate the inflammatory reaction and peritoneal healing (ingrowth of blood vessels and quality of peritoneal cells). Adhesion scores for treated and control sides were (mean +/- SD) 2.89 +/- 4.68 and 6.79 +/- 9.09 (P = 0.181) respectively, and the percentage of the sheet covered by peritoneum was 26.25 +/- 31.50 and 29.21 +/- 40.21 (P = 0.226) respectively. Using the paired Wilcoxon rank test, the P values for the ingrowth of blood vessels and peritoneal healing evaluated by histology and scanning electron microscopy were 0.842, 0.692 and 0.695 respectively. We conclude that although the mean adhesion score was reduced by > 50% by fibrin glue, there is no statistically significant difference concerning adhesion formation or peritoneal healing with the use of fibrin glue.     

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.     

The gynecologic contribution to intestinal obstruction in females

This study was done to identify the cause of intestinal obstruction with particular emphasis on the gynecologic and perioperative related causes. All medical records from females with the discharge diagnosis "intestinal obstruction" from 1988 to 1991 at Columbia Presbyterian Medical Center were requested. The patient series consisted of the first 100 completed charts received. Forty-eight percent of those patients with intestinal obstruction had experienced a previous gynecologic or obstetric event that could account for the obstruction. Primarily, the gynecologist managed more than 20 percent of all female patients with intestinal obstruction. The most common causative factors contributing to intestinal obstruction were postoperative adhesions (59 percent) and tumor (17 percent). Fifty-six percent of the patients with intestinal obstruction associated with postoperative adhesions had a history of previous gynecologic and obstetric operation. Hysterectomy was the most common previously performed operation. In this series, cesarean section was less likely and myomectomy was more likely to cause subsequent intestinal obstruction than expected. Of 59 female patients with postoperative adhesions associated with intestinal obstruction, 31 had the original operative reports available for analysis. Eleven of these patients were taken to the operating room for management of the obstruction. In the nine patients who had surgical peritoneal closure in the original operation, the adhesions causing the obstruction were always to the site of reperitonealization. In the two patients in whom the peritoneum was left open, the adhesions causing obstruction were remote from the site of spontaneous reperitonealization. In an unselected patient series of intestinal obstruction, a history of previous gynecologic pathology is a significant factor contributing to the total number of instances of intestinal obstruction in females. Also, surgical peritoneal closure may result in an increase in the incidence of intestinal obstruction.     

The effect of mesothelium damage on peritoneal transport functions: in vitro studies

Bidirectional transport across rabbit parietal peritoneum of urea, uric acid, gentamycin and albumin were examined in control conditions and after mechanical or chemical mesothelium damage. The transport mean values, exprerssed as transport coefficients, of intact peritoneum amounted 1.37; 1.18; 4.30; 0.20 [10(-4) cm s-1] respectively. The destruction of mesothelial barrier increased, in similar range, both absorption and excretion component of the transport of urea, uric acid and albumin but not gentamycin. In the latter case, mesothelium injury enhanced peritoneal excretion by 86% and absorption by 162%. An asymmetry in gentamycin transport was observed which can be unfavourable for peritoneal dialysis patients.     

Gastric cancer with metastases to the distant peritoneum: a 20-year surgical experience

BACKGROUND/AIMS: The efficacy of palliative gastrectomy in gastric cancer with peritoneal metastases remains uncertain. The aim of the present study was to evaluate the benefits of gastrectomy on the postoperative course of patients with gastric cancer and simultaneous metastases to the distant peritoneum. METHODOLOGY: A total of 122 patients who had gastric cancer and metastases to the distant peritoneum were studied with respect to survival. RESULTS: The extent of peritoneal metastases did not significantly affect the prognosis. Moreover, multivariate analysis indicated that surgery without gastrectomy was the only significant prognostic factor (relative risk, 2.587). CONCLUSIONS: Our results suggest that the decision to perform gastrectomy does not depend on the extent of peritoneal metastasis in gastric cancer. Furthermore, palliative gastrectomy, if feasible, seems to have a beneficial effect on the postoperative course and is indicated for patients regardless of metastasis to the peritoneum, if the primary tumor is surgically resectable and there is no evidence of liver metastasis.     

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.     

Prevention and therapy of intra-abdominal adhesions. A survey of 1,200 clinics in Germany

A survey of 1200 hospitals in Germany was undertaken to estimate the current standards of prevention and treatment of postoperative peritoneal adhesions. The 751 (62.2%) evaluated questionnaires showed a representative distribution according to postal zones and annual laparotomies. The rate of coeliotomies for adhesional bowel obstruction is 2.6%. Starch-powdered gloves are used in 54.2% and washed before operating in 69.3%. Dry swabs and towels are used in 60.7 and 22.5%, respectively. Most of the surgeons suture the peritoneum. Adhesions are divided in patients with respective symptoms but without intestinal obstruction by 32.6% and during laparotomies for non-adhesion-related diseases by 20.4%. Long intestinal tubes and plication procedures are applied by 43.9 and 33.7%, respectively. Medication is administered for routine prophylaxis of adhesion by 6%, for prevention of recurrencies by 17.2%. Although it has been revealed that adjuvant measures for prevention of adhesions are needed, as of today, no regimen has proofed its efficacy and gotten accepted for clinical usage.     

A comparative study of the effects of thrombin and electrodesiccation used for haemostasis on inflammation and adhesion formation

Electrodesiccation or chemical agents, such as thrombin and fibrin sealant, may be used to control oozing in the peritoneal cavity. Electrodesiccation is time consuming and associated with adjacent thermal damage. Adhesion formation remains a concern with the use of thrombin and fibrin sealant. In this study, adhesion formation and various histological parameters of inflammation were evaluated following haemostasis with electromicrodesiccation or thrombin in the rabbit model (n = 36). Following laparotomy, the right uterine horn was subjected to a measured injury producing sufficient oozing. After the injury was effected, the animals were randomized to haemostasis with electromicrodesiccation (n = 18) or thrombin (n = 18). In the first phase of the study, the histological parameters of acute injury and haemostasis with either modality were evaluated in two animals in each group. In the second phase, one, two and 10 animals, in each group, were submitted to second-look laparotomy on post-operative days 2, 7, and 15, respectively and the type and extent of adhesions were quantified. Histological parameters of inflammation as well as the type and extent of adhesions were comparable between the two groups. We conclude that local application of thrombin is not associated with a statistically greater degree of post-operative adhesions when compared to electromicrodesiccation.     

Randomized trial of periportal peritoneal bupivacaine for pain relief after laparoscopic cholecystectomy

The aim of this study was to determine whether injection of a long-acting local anaesthetic, in relation to the port sites at the level of the parietal peritoneum, would reduce postoperative pain following laparoscopic cholecystectomy. Patients were entered into a randomized, prospective, double-blind study comparing the effects of a standard technique, in which bupivacaine (total of 20 ml, 0.5 per cent) was injected into the subcutaneous periportal tissue around the four port sites, and a technique in which bupivacaine (total of 20 ml, 0.25 per cent) was injected into the subcutaneous periportal tissue as above with the addition of periportal parietal peritoneal injection of bupivacaine (total of 20 ml, 0.25 per cent). Two scores for pain, with the patient at rest, and on movement, were assessed 6 and 18 h after surgery using a visual analogue pain scale. Median pain score was significantly higher in patients who received standard technique (n = 40) than in those given peritoneal injection (n = 40) at both 6 (rest = 3.0 versus 1.0, movement = 5.0 versus 2.9) and 18 h (rest = 1.9 versus 0, movement = 3.2 versus 1.2). Both opiate and oral analgesic requirements were reduced in patients administered peritoneal injection, although this was not statistically significant. The addition of periportal injection of bupivacaine at the level of the parietal peritoneum, performed under direct vision, reduces pain after laparoscopic cholecystectomy.     

L-selectin (CD62L) blockade does not impair peritoneal neutrophil emigration or subcutaneous host defense to bacteria in rabbits

Neutrophil (PMN) recruitment into systemic inflammatory sites in vivo is thought to be initiated by selectin-mediated endothelial adherence. We explored the role of L-selectin (CD62L) in leukocyte emigration following instillation of bacteria into the peritoneum or s.c. skin in rabbits. Pretreatment with blocking mAb against L-selectin (LAM1.3) reduced peritoneal PMN emigration 4 h after i.p. inoculation with 10(10) CFU of Escherichia coli by only 17% compared with animals receiving a nonblocking L-selectin mAb (LAM1.14). Peritoneal PMNs from saline-treated rabbits demonstrated a complete absence of L-selectin, whereas those from LAM1.3-treated animals retained 43% of their baseline L-selectin expression. This suggests that L-selectin shedding is not a requisite event for PMN emigration under these conditions. In rabbits given s.c. inoculations with either Staphylococcus aureus or E coli, pretreatment with mAb LAM1.3 did not significantly impair PMN emigration at 24 h, nor increase the incidence, size, or associated mortality of resulting abscesses at 7 days compared with animals receiving nonblocking mAb LAM1.14. We conclude that: 1) mAb blockade of L-selectin in vivo only modestly affects acute, E. coli-induced peritoneal PMN emigration; and 2) L-selectin blockade does not increase infectious sequelae associated with s.c. bacterial inoculation. These findings of only mildly reduced PMN emigration into the peritoneum and no alteration in s.c. host defense differ from those reported with L-selectin blockade under other, nonbacterial inflammatory conditions, and suggest that redundant selectin-mediated mechanisms (P- and E-selectin) are sufficient for normal PMN emigration in response to bacterial stimulation.