Prevention of post-surgical adhesion formation using aspirin in a rodent model: a preliminary report

Pelvic adhesions are one of the major factors which significantlyand adversely affect surgery outcome due to intra-and postoperativemorbidity and reduce future female fertility. Using a rodentmodel, we evaluated the efficacy of aspirin, a non-steroidalanti-inflammatory drug, in the prevention of adhesion formation.A total of 72 female Wistar rats received a standardized primarytraumatic lesion to the right uterine horn. They were randomlydivided into eight groups: group I (control) had no treatmentand group II received a single pre-operative 0.70 mg aspirin.All the succeeding groups (III-VIII) received aspirin in dosesof 0.35, 0.70, or 1.40 mg every 6 h for either 48 or 96 h inaddition to the pre-operative aspirin (0.70 mg). All animalswere killed 4 weeks later and adhesions were assessed usinga modified adhesion scoring scale. The lowest adhesion scorewas found in the group treated with 0.35 mg of aspirin for 96h, and the highest was found among the groups treated with either0.70 or 1.40 mg for 48–96 h respectively (P < 0.05).These results are in line with the hypothesis that administrationof a low dose of aspirin selectively inhibits the productionof thromboxane A₂, whereas basal prostacyclin biosynthesis ispreserved. This phenomenon might contribute to reducing postoperativeadhesion formation in a rat model. Thus, future studies intothe prevention of adhesion formation may require the additionaluse of a non-steroidal anti-inflammatory drug, for which aspirindeserves further attention, before extrapolation into humantherapy.     

The role of neutrophils in the formation of peritoneal adhesions.

The most common cause of intraperitoneal adhesions which may result in infertility and intestinal obstruction is previous abdominal surgery. Surgical trauma of the peritoneum in the absence of infection elicits a rapid and transient influx of polymorphonuclear leukocytes (PMN) into the peritoneal cavity. The role of neutrophils in intraperitoneal adhesion formation has not been studied. We aimed to study the effects of PMN counts and PMN functions on peritoneal adhesion formation. Forty peritoneal adhesion-induced rats were randomly divided into three groups; group I, receiving saline; group II, receiving cyclophosphamide; and group III, receiving granulocyte-macrophage colony-stimulating factor (GM-CSF). In all groups, peritoneal lavage was performed to determine PMN counts the day after adhesion induction. Blood neutrophil counts and neutrophil functions were also determined. Adhesions were evaluated blindly 14 days after the operation. Adhesion tissue samples were microscopically evaluated. Tissue hydroxyproline and collagen concentrations were measured. The neutrophil counts and phagocytosis significantly increased in group III and neutrophil counts decreased in group II (P < 0.05). The score of adhesion formation in group II was significantly less than that in groups I and III (P < 0.05). Hydroxyproline concentrations of adhesion tissue were significantly decreased in group II when compared with group III (P < 0.05). The present study shows that neutropenia lowers the degree of postoperative adhesion formation. It is concluded that PMN may have a role to play in modulating post-operative adhesion formation.     

Effects of five different barrier materials on postsurgical adhesion formation in the rat

Postsurgical adhesion formation is a significant clinical problem within every surgical specialism. Due to the problems that adhesions cause, a wide variety of adjunctive treatments to prevent the formation and reformation of adhesions have been proposed. One of the modalities that has been studied extensively and that has been showing the most promising results is the so-called barrier method. The purpose of the present study was to compare the efficacy of five of these barrier materials in the prevention of postsurgical adhesion formation in a standardized rat adhesion model. It was concluded that no beneficial effect of Ringer's lactate on adhesion formation was seen. Significant reductions (P < 0.0001) in adhesion percentages compared to control animals were seen with Polyactive((TM)), PRECLUDE Peritoneal Membrane((TM)), Seprafilm((TM)) and Tissucol((TM)), but only PRECLUDE Peritoneal Membrane and Seprafilm significantly reduced adhesions (P < 0.01) when the barrier-treated peritoneal defects were compared with contralateral control-side peritoneal defects. The results of our study suggest that Seprafilm and PRECLUDE Peritoneal Membrane are superior to Tissucol and Polyactive in preventing adhesion formation. When Polyactive was still attached to the site of application during the second laparotomy, similar results to Seprafilm and PRECLUDE Peritoneal Membrane were seen. Future studies on the efficacy of a material to decrease adhesion formation should always include a comparison of several control materials in the same model. Our study indicates that Seprafilm or PRECLUDE Peritoneal Membrane might be used as standards of control.     

Effects of supplemental perioperative oxygen on post-operative abdominal wound adhesions in a mouse laparotomy model with controlled respiratory support

BACKGROUND: Post-operative adhesion formation is a major clinical problem. Tissue oxygenation is one of the most important determinants in adhesion formation. The objective of this study was to investigate whether supplemental perioperative oxygen could reduce post-operative adhesion formation through increasing the peritoneal tissue oxygen tension (PitO(2)) in a mouse model. METHODS: Adult C57BJ6 mice were randomly assigned to two groups: Group 1 (n = 20), Fraction of Inspired Oxygen (FiO(2)): 0.21; Group 2 (n = 20), FiO(2): 0.80. On day 0, over the course of the 90 min procedure including the 60 min of laparotomy, PitO(2) was continuously monitored. On day 7, a second laparotomy was performed to assess abdominal wound adhesions. Real-time RT-PCR was performed to measure expression levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) mRNA in peritoneal tissues. RESULTS: The PitO(2) levels in Group 2 were significantly higher compared to Group 1 (P < 0.001) and controls (P < 0.003). There was no significant difference in the incidence of abdominal wound adhesions; however, the severity of adhesions was significantly reduced in Group 2 compared to Group 1 (P < 0.03). A significantly higher tPA/PAI-1 mRNA ratio was detected in Group 2 and the controls compared to Group 1 (P < 0.02 and P < 0.002, respectively). CONCLUSIONS: Supplemental perioperative oxygen may help to reduce post-operative adhesion formation.     

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.      

Evaluation of a sprayable polyethylene glycol adhesion barrier in a porcine efficacy model.

BACKGROUND: The formation of adhesions following pelvic surgery remains one of the leading causes of infertility, small bowel obstruction and re-operation for pelvic pain. A novel hydrophilic polyethylene glycol based adhesion barrier (SprayGel) is formed by simultaneously spraying two liquid precursors onto surgical sites. The liquids polymerize to form a gel that effectively coats and adheres to tissue. After about 5 days, the hydrogel layer is absorbed and subsequently undergoes renal clearance. It is believed that the presence of such a barrier would inhibit the formation of adhesions following surgical insult. METHODS: A porcine adhesion model was developed wherein bilateral uterine horn transection and re-anastomosis, along with peritoneal side wall excision was performed via laparotomy. In each animal (n = 10, including the pilot study) one pelvic side wall was treated with adhesion barrier, while the contralateral side remained untreated. RESULTS: At second look laparoscopy, 90% of the untreated sites had adhesions, compared with 30% of the treated sites (P = 0.006). Also observed were statistically significant reductions in the adhesion extent (P = 0.029) and adhesion severity scores (P = 0.023) at the treated sites. However, if the pilot study was excluded (n = 8) the differences obtained were no longer significant. CONCLUSIONS: Polyethylene glycol (SprayGel) merits further investigation as an effective barrier to the formation of post-operative adhesions in this porcine model.     

Prevention of postoperative adhesion formation in rat uterine horn model by nimesulide: a selective COX-2 inhibitor

BACKGROUND: Pelvic surgery is one of the main causes of intraperitoneal (i.p.) adhesions that create various medical problems including pelvic pain, bowel obstructions and female infertility. A rat model was used to investigate the efficacy of nimesulide, a selective cyclooxygenase-2 inhibitor, in the prevention of adhesion formation. METHODS: Fifty Wistar-Albino rats underwent bilateral uterine horn injury with a unipolar cautery. Study groups were as follows: (i) control group, no adjuvant therapy; (ii) i.p. Ringer's lactate group, 2 ml Ringer's lactate solution was instilled i.p.; (iii) i.p. Ringer's lactate plus nimesulide group, 1 ml Ringer's lactate plus 1 ml nimesulide (0.5 mg/ml) were given i.p.; (iv) intramuscular (i.m.) nimesulide group, 1 ml i.m. nimesulide (0.5 mg/ml) was given preoperatively for 5 days; and (v) i.p. nimesulide group, 1 ml nimesulide (0.5 mg/ml) was instilled i.p. At the end of the study all animals were killed, and a standard adhesion scoring system was applied by a blinded examiner. RESULTS: The mean adhesion extent in study groups was as follows: 1.33 +/- 0.76 in control group, 1.40 +/- 0.90 in i.p. Ringer's lactate group, 0.75 +/- 0.70 in i.p. Ringer's lactate plus nimesulide group, 0.25 +/- 0.44 in i.m. nimesulide group and 0.31 +/- 0.70 in i.p. nimesulide group. The mean +/- SD adhesion severities of control, i.p. Ringer's lactate, i.p. Ringer's lactate plus nimesulide, i.m. nimesulide, and i.p. nimesulide groups were 0.58 +/- 0.35, 0.30 +/- 0.41, 0.27 +/- 0.3, 0.12 +/- 0.28 and 0.15 +/- 0.35 respectively. The lowest adhesions were found in the groups treated with nimesulide i.m. and nimesulide i.p. ( P < 0.05). CONCLUSIONS: This study showed that preoperative i.m. or postoperative i.p. administration of nimesulide to the site of injury reduced the formation of postoperative adhesions in a rat uterine horn model.     

The impact of peritoneal trauma on intra-abdominal fibrinolytic activity, adhesion formation and early embryonic development in a rabbit longitudinal model

Intra-abdominal adhesions may interfere with fertility following gynaecological surgery and injury to the peritoneum plays a central role in the pathogenesis. Tissue plasminogen activator and its antagonists play a pivotal role in the intra-abdominal balance between fibrinolysis and adhesion formation. This process may be cycle-dependent in women. In order to establish the impact of the fibrinolytic activity on adhesion formation after a standardized trauma, a rabbit longitudinal model was developed, which allowed the study of possible differences between the periods before and after ovulation. The influence of extra-genital adhesions on early embryonic development was investigated. No cycle-dependent changes in fibrinolytic activity of the peritoneal fluid (PF) or of the serum could be demonstrated. No correlation was found between post-operative adhesion formation and the fibrinolytic activity during surgery. Three weeks after surgery, a significant increase in fibrinolytic activity of the PF was observed. The rank order of sampling is suggested to account for these differences. Extra-genital adhesions did not markedly influence ovulation, ovum pick-up and fertilization in this hormonally controlled rabbit model.     

Effectiveness of auto-crosslinked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic surgery: a prospective, randomized, controlled study

BACKGROUND: A prospective, randomized, controlled study was performed to assess the efficacy of auto-crosslinked hyaluronic acid (ACP) gel to prevent the development of de-novo intrauterine adhesions following hysteroscopic surgery. METHODS: One hundred and thirty-two patients with a single surgically remediable intrauterine lesion (myomas, polyps and uterine septa, subgroups I-III) completed the study. Patients were randomized to two different groups: group A underwent hysteroscopic surgery plus intrauterine application of ACP gel (10 ml) while group B underwent hysteroscopic surgery alone (control group). The rate of adhesion formation and the adhesion score was calculated for each group and subgroup 3 months after surgery. RESULTS: Group A showed a significant reduction in the development of de-novo intrauterine adhesions at 3 months follow-up in comparison with the control group. Furthermore, the staging of adhesions showed a significant decrease in adhesion severity in patients treated with ACP gel. CONCLUSIONS: ACP gel significantly reduces the incidence and severity of de-novo formation of intrauterine adhesions after hysteroscopic surgery.     

The role of monocyte chemotactic protein-1 in intraperitoneal adhesion formation

Abdomino-pelvic adhesions arise from infection, endometriosis, or peritoneal injury during surgery, and represent a significant source of morbidity in women of reproductive age. Monocyte chemotactic protein-1 (MCP-1) plays a role in the chemotaxis of mononuclear cells and fibroblasts in a murine wound repair model. To evaluate the role of MCP- 1 in intraperitoneal adhesion formation, we investigated peritoneal fluid MCP-1 levels of women undergoing laparoscopy. Patients without endometriosis were divided into two groups: normal fertile women undergoing bilateral tubal ligation without intraperitoneal adhesions (n=14) and women with pelvic adhesions (n=8). Patients with endometriosis were arranged into two groups: women with (n=17) and without (n=17) adhesions. Peritoneal fluid MCP-1 levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Peritoneal biopsy samples were immunostained for the detection of MCP-1 protein and macrophages, and were also processed for the presence of MCP-1 mRNA expression. Among women without endometriosis, the median peritoneal fluid MCP-1 level was 144 pg/ml (range 54-261) in women without adhesions and was 336 pg/ml (range 130-2494) in women with adhesions (P=0.01). There was a significant correlation between adhesion scores and MCP-1 levels (r=0.50; P=0.018). Among women with endometriosis, peritoneal fluid MCP-1 levels significantly correlated with the stage of the disease. The presence or absence of adhesions did not significantly affect the peritoneal fluid MCP-1 levels in this group of women. In summary, we have found that women with adhesions have elevated peritoneal fluid MCP-1 levels. However, we were not able to show an incremental effect of adhesions on peritoneal fluid MCP-1 levels of patients with endometriosis. Thus, we conclude that factors besides the intraperitoneal adhesions contribute to the elevated peritoneal fluid MCP-1 levels in patients with endometriosis.      

Reduction of adhesion formation in rabbits by intraperitoneal administration of lazaroid formulations

Adhesion formation is a major source of postoperative morbidity and mortality. In this study, the ability of a variety of lazaroid formulations [the antioxidant 21-aminosteroid PNU74006F (tirilazad) and the non-steroidal 2-methylaminochroman derivative PNU83,836E] to reduce i.p. adhesion formation in three rabbit models was examined. In initial studies, PNU83836E was administered via Alzet miniosmotic pump to the site of injury. In the sidewall and double uterine horn models, PNU83,836E was administered via Alzet miniosmotic pump for the entire postoperative interval. In the sidewall model, there was a dose- dependent reduction in the area of the sidewall injury that was involved in adhesions. In the double uterine horn model, PNU83,836E was administered via Alzet miniosmotic pump to the area of injury for 1, 2, 3 or 7 days. Administration for as little as 24 h after surgery significantly reduced the extent of adhesion formation and the reduction was increased if it was administered for longer. Further studies were conducted in which various lazaroid formulations were administered as a bolus at the end of surgery. In both the sidewall and double uterine horn models, administration of either PNU83,386E (in citrate buffer) or PNU74006F (in cyclodextrin or lipid emulsion vehicles) at the end of surgery reduced adhesion formation. Administration of a bolus of PNU74006F 10 min prior to initiation of surgery with or without additional treatment at the end of surgery further increased its efficacy in the reduction of adhesion formation. Administration of a minimum of 1.5 mg before and after surgery (3 mg total) was required for maximal efficacy. These studies demonstrate that pre- and postoperative administration of either a steroidal (PNU74006F) or non-steroidal (PNU83,836E) lazaroid intraperitoneally reduced the formation and reformation of postoperative adhesions in three animal models.      

Peritoneal application of chitosan and UV-cross-linkable chitosan

The suitability of chitosan and UV-cross-linkable chitosan for intraperitoneal use, for example as a barrier device for preventing peritoneal adhesions or for drug delivery, was examined. In vitro experiments using two major cell types present in the peritoneal cavity (mesothelial cells and peritoneal macrophages) revealed neither attractive interactions between cross-linked chitosan gels and the cells nor a proliferative effect. However, the same UV-cross-linked chitosan applied in the peritoneal cavity of rabbits caused a granulomatous reaction with adhesion formation within two weeks in all animals, which persisted up to 4 weeks after exposure. Unmodified chitosan also caused adhesions, while UV irradiation did not. UV-cross-linkable chitosan induced significant elevations in MIP-2 and TNF-alpha from peritoneal macrophages, suggesting that soluble mediators could play a role in inducing adhesion formation. These results reinforce the view that the predictive value of in vitro cytotoxicity assays in matters of biocompatibility may not be sufficient, and suggest that other assays such as cytokine levels may be of value in predicting outcomes in situations involving multiple cell types (i.e. in vivo).     

The correlation of adhesions and peritoneal fluid cytokine concentrations: a pilot study

BACKGROUND: Intra-abdominal adhesion formation and reformation after surgery is a significant cause of morbidity. The greatest problem after the surgical removal of adhesions is their reformation. We examined the concentrations of interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-alpha in the peritoneal fluid throughout the 48 h post-operative period following adhesiolysis, and correlated the results to the extent of adhesion reformation. METHODS: Peritoneal fluid, collected from eight patients following laparoscopy and again at 12, 36 and 48 h after surgery, was analysed using enzyme-linked immunosorbent assay (IL-1 and IL-6) and bioassay (TNF-alpha). At 48 h, a second look laparoscopy was performed to inspect the pelvis for adhesion formation/reformation. RESULTS: Three patients had adhesion reformation >10% at 48 h after surgery. The mean adhesion score 48 h after adhesiolysis was 5 (range 0-17). The mean reduction in adhesion score was 88% (range 83-100%). Newly formed adhesions were filmy, relatively soft and avascular in nature. Adhesion reformation of >10% was associated with (i) high concentrations of IL-6 at 12 h (P < 0.01) and (ii) high concentrations of IL-1 at 48 h (P < 0.001). CONCLUSIONS: Results from this preliminary study suggest that future treatment strategies for adhesion prevention could be aimed at the control of cellular mediators in the peritoneal fluid during the initial adhesion formation period.     

A randomized, controlled pilot study of the safety and efficacy of 4% icodextrin solution in the reduction of adhesions following laparoscopic gynaecological surgery

BACKGROUND: Adhesion-related readmissions are frequent sequelae to gynaecological surgery. Attempts to prevent adhesions by separating healing peritoneal surfaces include site-specific barriers and hydroflotation by instilled solutions. Rapid absorption limits the effectiveness of solutions such as Ringer's lactated saline (RLS). This pilot study assessed the safety, tolerability and preliminary effectiveness of a non-viscous, iso-osmolar solution of 4% icodextrin, an alpha-1,4 glucose polymer with prolonged intraperitoneal residence, in reducing adhesions after laparoscopic gynaecological surgery. METHODS: Women aged > or = 18 years, requiring laparoscopic adnexal surgery (n = 62), were entered into a randomized, open-label, assessor-blinded, multicentre study to compare 4% icodextrin with RLS. Treatments were coded in blocks of four with equal randomization to each group, and pre-allocated to consecutively numbered patients. At least 100 ml per 30 min was used for intra-operative lavage, with 1 l instilled post-operatively. Per protocol analysis included all eligible patients (n = 53); reformation analysis required one or more baseline adhesion (n = 42). Incidence, extent and severity of post-operative adhesions were assessed at second-look laparoscopy after 6-12 weeks. Procedures were video-taped for third party, blinded assessment. RESULTS: Safety and tolerability (laboratory variables, adverse events, clinical follow-up) were good with no difference between treatments. A shift analysis of incidence-ranked adhesions (n = 53) showed apparent improvements in more patients with icodextrin than RLS (37 versus 15%; not significant). Adhesion score reduction (n = 42) was more frequent in icodextrin- than RLS-treated patients: incidence (52 versus 32%), extent (52 versus 47%), and severity (65 versus 37%). Despite greater baseline adhesions, median reformation was less after icodextrin (24%) than RLS (60%). The pilot study group sizes were not powered for statistical significance. CONCLUSIONS: In this preliminary study, 4% icodextrin lavage plus instillation was well tolerated and reduced adhesion formation and reformation following laparoscopic gynaecological surgery. A Phase III pivotal study is currently in progress.     

Adhesion preventive effect of hyaluronic acid after intraperitoneal surgery in mice.

Prevention of intraperitoneal adhesion after gynaecological surgery is essential for maintaining postoperative fertility. In this study, the adhesion prevention effect was examined of a hyaluronic acid (HA) solution obtained from the fermentation method and having a molecular weight of 1.9x10(6) with high viscosity. Laparotomy was conducted on female mice 7 weeks old, whose menstrual periods were synchronized by pregnant mare serum gonadotrophin (PMSG) to injure the uterine horn surface. Intraperitoneal adhesions were favourably formed in 91.7% of cases induced with iodine abrasion, compared with 50% induced by electrosurgery. Intraperitoneal administration of HA was evaluated for its effect on the prevention of adhesions made by iodine abrasion. Adhesion prevention effects of HA were observed at concentrations of 0.3, 0.5, 0.75 and 1.0%, among which the most pronounced effect was with the use of a 0.3% solution (92.3% of cases). Compared with the control group adhesion score of 2.0 +/- 0. 8, significant decreases in adhesion scores were observed at all concentrations. HA with a molecular weight of 1.9x10(6) was recognized to have a definitive prevention effect on postoperative adhesions in mice after laparotomy and is considered to be a prospective material for future clinical use.     

IL-1, IL-6 and TNF-alpha concentrations in the peritoneal fluid of women with pelvic adhesions.

BACKGROUND: Pelvic adhesions are a significant cause of morbidity and are associated with infertility and pain. The three pro-inflammatory cytokines interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-alpha are involved in adhesion formation/reformation. METHODS: The concentration of these three cytokines was examined in the peritoneal fluid of women undergoing laparoscopy, in order to examine the factors affecting their concentrations, with specific reference to the presence or absence of adhesions. RESULTS: We found that the concentration of TNF-alpha in the peritoneal fluid was significantly correlated to the menstrual cycle day (P < 0.01), with increasing concentration as the menstrual cycle progressed from the follicular to the luteal phase. In contrast, IL-1 and IL-6 levels did not show any variation throughout the menstrual cycle. Increased TNF-alpha was found in patients with pelvic adhesions compared with those with normal pelvis; the concentration of TNF-alpha was highest in mild compared with severe adhesions. In contrast, IL-1 concentration was higher in the presence of severe adhesions. IL-6 levels were significantly correlated with the grade of endometriosis (P < 0.05), but there were no significant correlations of either TNF-alpha or IL-1 concentrations with the various grades of endometriosis. CONCLUSION: The exact role of TNF-alpha and IL-1 in adhesion formation is still unknown, but the results from this study suggest that their concentration in the peritoneal fluid is associated with the degree of adhesions present.     

Zn(2+)-SCMC Versus HA for Preventing Intraperitoneal Adhesions: A Rat Model Study

Background: Intraperitoneal adhesion is a serious surgical postoperative complication. Using a rat model, we compared the effectiveness of intraperitoneally administered zinc-modified sodium carboxymethyl cellulose (Zn(2+)-SCMC) and hyaluronic acid (HA) in preventing postoperative intraperitoneal adhesions.Materials and Methods: Peritoneal adhesions were induced in 120 Wistar rats by scraping the cecal mucosa. The rats were randomized into a no treatment group (n = 40) or into a treatment group in which 3 ml of HA (n = 40) or Zn(2+)-SCMC (n = 40) was administered intraperitoneally before the abdominal wall was closed. Following sacrifice two weeks later, the intraperitoneal adhesions were scored and tissues were examined histologically using HE staining.Results: Eight animals died, five in the untreated group (mortality rate, 12.5%), two in the HA group (mortality rate, 5.0%) and one in the Zn(2+)-SCMC group (mortality rate, 2.5%). Relative to the untreated group, the incidence of intraperitoneal adhesions was 77.5% in the HA and 48.7% in the Zn(2+)-SCMC group, with the incidence significantly lower in the Zn(2+)-SCMC group (P < 0.001). Both agents prevented intraperitoneal adhesions by promoting the repair of the abdominal serosa.Conclusions: Administration of Zn(2+)-SCMC was more effective in preventing intraperitoneal adhesions than HA.     

Comparison of Intraperitoneal Honey and Sodium Hyaluronate-Carboxymethylcellulose (Seprafilm™) for the Prevention of Postoperative Intra-Abdominal Adhesions

BACKGROUND:

Abdominal surgery can lead to postoperative intra-abdominal adhesions (PIAAs) with significant morbidity and mortality. This study compares the use of honey with a standard bioresorbable membrane (Seprafilm™) to prevent the formation of PIAAs in rats.

METHODS:

Thirty rats underwent laparotomy, and PIAAs were induced by scraping the cecum. The animals were divided into three groups, each containing ten rats. Group 1 (control) represented the cecal abrasion group, with no intraperitoneal administration of any substance. Group 2 (honey group) underwent cecal abrasion and intraperitoneal administration of honey. Group 3 (Seprafilm™ group) underwent cecal abrasion and intraperitoneal Seprafilm™ application.

RESULTS:

Group 1 exhibited higher adhesion scores for adhesions between the abdominal wall and the organs. Groups 2 and 3 had decreased adhesive attachments to the intra-abdominal structures. Compared to group 1, the incidence of adhesion formation was lower in both group 2 (p=0.001) and group 3 (p=0.001). The incidence of fibrosis was also lower in group 2 (p=0.016) and group 3 (p=0.063) compared to group 1. There was no significant difference between the histopathological fibrosis scores for the rats in group 2 and those in group 3 (p= 0.688).

CONCLUSION:

This study suggests that both honey and Seprafilm™ decrease the incidence of PIAAs in the rat cecal abrasion model. Although the mechanism of action is not clear, intraperitoneal administration of honey reduced PIAAs. The outcome of this study demonstrates that honey is as effective as Seprafilm™ in preventing PIAAs.     

Dose‐dependent effects of prostaglandin E2 in macrophage adhesion and migration

Macrophage migration to the focus of infection is a hallmark of the innate immune response. Macrophage spreading, adhesion, and migration through the extracellular matrix require dynamic remodeling of the actin cytoskeleton associated to integrin clustering in podosomes and focal adhesions. Here, we show that prostaglandin E2 (PGE₂), the main prostaglandin produced by macrophages during inflammation, promote the distinctive dose‐dependent formation of podosomes or focal adhesions in macrophages. Low concentrations of PGE₂ increased p110γ PI3K expression, phosphorylation of actin‐related protein 2, and formation of podosomes, which enhanced macrophage migration in response to chemokines. However, high doses of PGE₂ increased phosphorylation of paxillin and focal adhesion kinase, the expression of serine/threonine protein kinase 1, and promoted focal adhesion formation and macrophage adhesion, reducing macrophage chemotaxis. In summary, we describe the dual role of PGE₂ as a promoter of macrophage chemotaxis and adhesion, proposing a new model of macrophage migration to the inflammatory focus in the presence of a gradient of PGE₂.     

Post-operative adhesions after laparoscopic electrosurgical treatment for polycystic ovarian syndrome with the application of Interceed to one ovary: a prospective randomized controlled study

In this prospective, randomized, controlled clinical study,21 women underwent a second-look laparoscopy 2–11 weeksafter standardized laparoscopic electrosurgical treatment forpolycystic ovarian syndrome (PCOS). Following bilateral ovariantreatment, one ovary was randomly chosen to have Interceed appliedto its surface using a specially designed applicator, with theother ovary serving as a control. Peri-adnexal adhesions ofsignificant extent and severity developed in 57% of the womenand 38% of the adnexa. The incidence of adhesions on the Interceed-treatedside was 43%, while on the control side it was 33%. In addition,the extent and severity of the adhesions appeared to be similaron the Interceed-treated and the control side. However, largernumbers would be required to determine statistically the effectsof Interceed on de-novo adhesion formation after laparoscopicelectro-surgical treatment of PCOS, as described here.