Plasminogen activator/plasminogen activator inhibitor-1 and cytokine modulation by the PROACT System

OBJECTIVE: To examine the effects of the PROACT treatment on the fibrinolytic system and inflammatory cytokines in human peritoneum. DESIGN: Controlled clinical study. SETTING: University hospital. PATIENT(S): Nine subjects undergoing laparotomy had peritoneal samples taken at the incision. INTERVENTION(S): The PROACT applicator was inserted through the peritoneal incision, and treatment of peritoneum was performed twice. A peritoneal sample was taken from one treated area. At closure, the second treated sample and an additional control sample were taken. All four samples were snap frozen in liquid nitrogen. Samples were homogenized and protein content extracted. MAIN OUTCOME MEASURE(S): Concentrations of total and active transforming growth factor-beta 1 (TGF-beta1), tumor necrosis factor-alpha (TNF-alpha), tissue-type plasminogen activator (t-PA), urokinase plasminogen activator (uPA), and plasminogen activator inhibitor 1 (PAI-1) were obtained. RESULT(S): Total TGF-beta1 at opening was 30% less in treated samples. At closure, active TGF-beta1 increased significantly (163%) in control samples and not in treated samples. Tumor necrosis factor alpha was detectable only in control samples at closure. During surgery, tPA levels showed a marked decrease in control samples vs. a small increase in treated samples. Levels of uPA increased significantly only in the control samples. In control samples, tPA/PAI-1 ratio was two thirds of treated sample ratio. CONCLUSION(S): Heating of the peritoneum with the PROACT System modulates the biologic tissue response to induce effects that would be consistent with inhibition of postoperative adhesion development.     

Reduction of adhesion formation with cross-linked hyaluronic acid after peritoneal surgery in rats

OBJECTIVE: To examine the effectiveness of a cross-linked hyaluronan solution (auto-cross-linked polysaccharide [ACP] gel) for the prevention of postsurgical adhesions. DESIGN: A randomized blinded study using a rat model of laparotomy. SETTING: Surgical Research Laboratory in a university medical school. ANIMAL(S): Sixty-seven sexually mature rats. INTERVENTION(S): Standardized surgical trauma was induced in the rat uterine horn to induce adhesion formation. After trauma, group-1 animals (n = 23) received no treatment, group 2 (n = 21) received noncross-linked hyaluronic acid (HA), and group 3 (n = 23) received cross-linked HA applied on the lesion. MAIN OUTCOME MEASURE(S): Six weeks after laparotomy, repeat laparotomy was performed and the adhesions were scored according to Blauer's scoring system. RESULT(S): Overall, 84% of the untreated animals and 65% of the animals treated with noncross-linked HA presented with severe adhesions. The mean (+/-SEM) increase in the adhesion score was 2.46+/-0.23 in the untreated group, 2.23+/-0.29 in the group receiving noncross-linked HA, and 1.27+/-0.12 in the ACP gel group. CONCLUSION(S): ACP gel holds promise as a novel resorbable biomaterial for the reduction of postoperative adhesions after laparotomy.     

Role of microlaparoscopy in the diagnosis of peritoneal and visceral adhesions and in the prevention of bowel injury associated with blind trocar insertion

OBJECTIVE: To determine the frequency of peritoneal and visceral adhesions to the umbilical region according to past surgical history and to estimate the risk of bowel injury with blind insertion of the principal trocar-cannula. DESIGN: Prospective, unicentric study by a single operator. SETTING: Clinique Saint-Sernin and Polyclinique de Bordeaux, Bordeaux, France. PATIENT(s): Eight hundred fourteen patients undergoing diagnostic or operative laparoscopy were classified into four groups based on their history of abdominal surgery: group I (n = 469), no previous abdominal surgery; group II (n = 125), prior laparoscopic surgery; group III (n = 131), previous laparotomy with a horizontal supra-pubic incision; group IV (n = 89), previous laparotomy with a midline incision. INTERVENTION(s): Initial microlaparoscopy performed through the left upper quadrant of the abdomen, inspection of the anterior abdominal wall and particularly the umbilical area for the presence of adhesions. Patients who had adhesions were assessed as to whether or not they were at significant risk of injury from blind insertion of the principal trocar. MAIN OUTCOME MEASURE(s): Incidence of umbilical adhesions and the potential risk of bowel injury with blind insertion of the umbilical (principal) trocar. RESULT(s): Umbilical adhesions were found in 9.82% of the 814 cases. The rates of umbilical adhesions were as follows: group I, 0.68%; group II, 1.6%; group III, 19.8%; and group IV, 51.7%. Severe adhesions with potential risk of bowel injury with blind insertion of the umbilical trocar in the four groups were 0.42%, 0.80%, 6.87%, and 31.46%, respectively. CONCLUSION(s): Women with previous laparotomy have a higher incidence of umbilical adhesions, especially in case of midline incision. Preliminary inspection of the umbilical area with a microlaparoscope and insertion of the umbilical trocar under direct vision are recommended for patients at risk for adhesions to reduce complications associated with insertion of the principal (umbilical) trocar.     

Evaluation of the SprayGel adhesion barrier in the rat cecum abrasion and rabbit uterine horn adhesion models

OBJECTIVE: To evaluate the efficacy of a new adhesion barrier in the prevention of postoperative adhesion formation. DESIGN: A double-blind controlled study of the efficacy of SprayGel in reducing postoperative adhesion formation in two animal models. SETTING: Animal care facility of a contract testing laboratory. ANIMAL(S): Sixteen Sprague-Dawley male rats were randomly allocated into two groups in the cecum abrasion model. Twenty New Zealand white female rabbits were randomly allocated into two groups in the uterine horn abrasion model. INTERVENTION(S): In the rat model, the cecum was abraded with gauze and the abdominal wall was abraded with a scalpel. Treated animals received SprayGel coating on injured surfaces; control animals received no treatment. In the rabbit model, uterine horns were abraded with a scalpel. Treated animals received SprayGel coating on injured surfaces; control animals received no treatment. MAIN OUTCOME MEASURE(S): Postoperative adhesion formation. RESULT(S): In the rat model, SprayGel was found to significantly reduce the incidence of adhesions, which formed in 7 of 8 control rats compared with 1 of 8 treated rats. In the rabbit model, SprayGel was found to significantly reduce both the extent and severity of adhesions. CONCLUSION(S): Application of SprayGel in two animal models reduced formation of postoperative adhesions. Further investigation in large animal and clinical settings is warranted.     

Reduction of postsurgical adhesions with Intergel adhesion prevention solution: a multicenter study of safety and efficacy after conservative gynecologic surgery

OBJECTIVE: To assess the safety and efficacy of the Intergel adhesion prevention solution, a 0.5% ferric hyaluronate gel, in reducing adhesions in patients undergoing peritoneal cavity surgery by laparotomy with a planned second-look laparoscopy. DESIGN: Randomized, third-party blinded, placebo-controlled, parallel group. SETTING: Eleven centers in the United States, and five centers in Europe. PATIENT(S): Women aged 18-46 years who wanted to retain their fertility. INTERVENTION(S): Patients received 300 mL of Intergel solution (n = 143) or lactated Ringer's solution (n = 138) as an intraperitoneal instillate at the completion of surgery. MAIN OUTCOME MEASURE(S): At second-look laparoscopy 6-12 weeks later, the presence of adhesions was evaluated at 24 abdominal sites. RESULT(S): Patients treated with Intergel solution (n = 131) had significantly less adhesions compared to controls (n = 134). Adhesion extent and severity were also significantly reduced. The American Fertility Society score for adnexal adhesions was reduced 59% in the patients in whom the Intergel solution was used. The safety profile of the patients treated with the Intergel solution was comparable to those treated with lactated Ringer's solution. CONCLUSION(S): The Intergel solution was safe and highly efficacious in reducing the number, severity, and extent of adhesions throughout the abdomen after peritoneal cavity surgery.     

Second look for ovarian cancer: laparoscopy or Laparotomy? A prospective comparative study

OBJECTIVE: The objective of this study was to evaluate, for patients with ovarian cancer, the feasibility, reliability, and complications of a laparoscopic second look and to compare them with those of a second look by laparotomy. METHODS: Twenty patients treated by initial surgery and adjuvant chemotherapy for ovarian carcinoma underwent a laparoscopic second look, immediately followed by a comparative laparotomy. All were in complete remission after chemotherapy. Both operations were performed according to a predefined checklist, identical for both surgical techniques and for each patient: after liberation of adhesions, an exhaustive intraperitoneal inspection was performed, with systematic peritoneal cytology and biopsies. Each patient therefore was her own control for the two techniques. RESULTS: The positive predictive value of laparoscopy for the diagnosis of residual disease was 100% (6 of 6 cases), while the negative predictive value was 86% (2 false-negative cases out of 14). Because of the presence of postoperative adhesions, the rate of complete intraperitoneal investigation was 95% for laparotomy versus 41% for laparoscopy. The complication rate of laparoscopy requiring laparotomy was 5.3%. CONCLUSIONS: After treatment of ovarian cancer, a laparoscopic second look appears to be less reliable than one performed by laparotomy. The presence of severe postoperative adhesions is the main obstacle to an exhaustive, reliable, and safe laparoscopic second look.     

A comparative study of postoperative adhesions following laser surgery by laparoscopy versus laparotomy in the rabbit model

In this study, we tested the null hypothesis that intraperitoneal adhesion formation and reduction after laser surgery are the same whether the surgery is performed by laparoscopy or laparotomy. Twenty rabbits were randomly assigned to either laparoscopy or laparotomy and subjected to standardized laser incisions over one uterine horn and over the peritoneal surface of either lower quadrant. Three weeks later, five animals from each group underwent laparoscopy and the other five received laparotomy to score the extent of postoperative adhesions formed and to carry out laser adhesiolysis. The same power density was delivered to tissues in both procedures. Three weeks after the second operative intervention, the animals were killed and the intraperitoneal adhesions blindly scored (scale of 0-3). After the initial procedure, adhesions were absent in the laparoscopy group, but in the laparotomy group, adhesions were frequently present not only at the operative sites of the peritoneal surfaces and uterine horn, but also on the bowel, bladder, and opposite uterine horn where no apparent injury had been inflicted (P less than .005). Three weeks after adhesiolysis, a significant reduction was observed in the mean adhesion scores in the laparoscopy group, but not in the laparotomy group (P = .001). These results lead to the rejection of the null hypothesis and confirm the clinical observation that besides reducing operative trauma, discomfort, and cost, laparoscopic laser surgery is very effective in reducing intraperitoneal adhesions and causes significantly less postoperative adhesion formation than does laparotomy.     

Effects of progesterone on postoperative adhesion formation in hysterectomized rabbits

Progesterone has been reported to have an antiinflammatory as well as immunosuppressive effect, and may prevent adhesion formation. In this study, nine treated and seven control rabbits were randomly selected for either pre- and postoperative progesterone treatment or no treatment. All rabbits underwent hysterectomy, focal peritoneal denudation, and intraabdominal instillation of suspended talc. Adhesion formation was evaluated 1 month postoperatively during repeat exploratory laparotomy. Progesterone-treated and control rabbits did not show any significant difference overall in the incidence of adhesion formation. Subgrouping of adhesion formation into adhesions formed by major surgical tissue trauma or minor peritoneal damage revealed a beneficial effect of progesterone in the reduction of only minor adhesion formation.     

Endometriosis prophylaxis and treatment with the newly developed xenogenic immunomodulator RESAN in an animal model

Objective

The objective was to assess the effectiveness of the newly developed immunomodulator RESAN in the prophylaxis and treatment of endometriosis induced in rats.

Study design

The study was performed on 58 Wistar rats. Twelve weeks before endometriosis induction, the RESAN vaccine was administered to 24 rats (100 mg i.m. and 100 mg s.c.). Endometriosis induction was performed in 48 rats, which were divided into two groups: group I, the prophylaxis group, consisting of 24 previously vaccinated rats; and group II, the treatment group, comprising the other 24 rats, which had not been vaccinated. The graft (4 mm × 4 mm) of endometrium was attached to the parietal peritoneum. A sham operation was performed in 10 rats (group III). After 3 months, a second laparotomy was performed in all animals, and endometriotic foci were excised when present. RESAN was administered to the group II animals. After an additional 3 months, a third laparotomy was performed in all animals of the three groups.

Results

Positive, histologically confirmed endometriosis was found in 4.3% of the animals in group I and in 69.6% of group II rats (p < 0.0001). Macroscopic assessment revealed endometriosis in 21.7% and 91.3% of animals in groups I and II, respectively (p < 0.0001). At final laparotomy, 3 months after excision of the previously suspected foci, no signs of endometriosis were found according to both macroscopic assessment and histological examination. During the second laparotomy intraperitoneal adhesions were present in 13.0% of the animals in group I and in 61.0% of those in group II. No adhesions were present in group III. At the final laparotomy, the adhesions were present in only three of the animals in group II (p < 0.0009).

Conclusions

RESAN seems to be effective in both the prophylaxis and treatment of endometriosis, as well as in the prophylaxis of adhesions. Histological confirmation of endometriosis should be mandatory.     

Hyaluronic acid-carboxymethylcellulose film and perianastomotic adhesions in previously irradiated rats

Objective: Postoperative intra-abdominal adhesions are a major source of postsurgical morbidity. Pelvic irradiation increases the likelihood of adhesion development. The purpose of this study was to evaluate the effects of hyaluronic acid–carboxymethylcellulose film, which was designed as a barrier to prevent adhesions, on the healing of ileal anastomoses performed on irradiated rat bowel. Study Design: Sixty-eight female Sprague-Dawley rats underwent whole pelvic irradiation with a single fraction of 1700 cGy. Twenty weeks later the rats underwent exploratory laparotomy with segmental ileal resection and reanastomosis. Eighteen of the anastomoses were wrapped in hyaluronic acid–carboxymethylcellulose film. Fifty anastomoses were not treated with any adhesion-inhibiting barrier. On the fifth postoperative day the animals underwent another laparotomy for evaluation of the anastomotic sites. Results: At the second laparotomy 93% of the rats treated with hyaluronic acid–carboxymethylcellulose film were found to have perianastomotic abscesses. In the non–hyaluronic acid–carboxymethylcellulose film group the perianastomotic abscess rate was 24% (P < .0001). Conclusion: Among previously irradiated rats undergoing small-bowel resection and anastomosis, hyaluronic acid–carboxymethylcellulose film was associated with a markedly increased rate of abscess formation at the operative site. (Am J Obstet Gynecol 1999;181:1335-8.)     

Evaluation of progestogens for postoperative adhesion prevention

Progesterone (P) has been shown to have potent antiinflammatory and immunosuppressive properties. Previous reports have suggested that the use of P decreases postoperative adhesion formation. To further evaluate the role of pharmacologic doses of progestogens in adhesion prevention, 42 mature New Zealand White rabbits underwent standardized injuries to the uterine horns, fimbriae, and pelvic peritoneum and received one of six treatments. Group S had intraperitoneal placement of normal saline (0.9%); group H received intraperitoneal placement of 32% dextran 70; group IM-P received intramuscular P-in-oil 10 days before and after laparotomy in addition to intraperitoneal saline; group IP-P had intraperitoneal placement of an aqueous P suspension; group DP received medroxyprogesterone acetate intraperitoneally; and group C received no intramuscular or intraperitoneal adhesion-prevention agents. The animals were sacrificed 6 weeks after laparotomy, and the adhesions were scored. Intraperitoneal saline (group S) significantly reduced the amount of adhesions when compared with the control group (C) (P less than 0.05). No significant difference was observed when group S was compared with group H. Intramuscular P added to saline (group IM-P) did not cause further reduction in adhesions when compared with group S. Both group IP-P and group DP had more adhesions than did group S (P less than 0.01). These data fail to support previous claims regarding adhesion prevention by the use of locally or parenterally administered progestogens.     

Surgically induced endometriosis does not alter peritoneal factors in the rabbit model

OBJECTIVE: It was the purpose of this study to examine the cause and effect relationship between alterations in peritoneal factors and the presence of ectopic endometrium in the rabbit model. DESIGN: Forty rabbits had autologous endometrial or omental (control) tissue surgically implanted. Peritoneal fluid (PF) volume, macrophage number, and macrophage activation, as well as the number of implants with adhesions, were compared with values obtained during the initial surgery. The effect of hormonal treatment on these factors was evaluated at a third laparotomy. RESULTS: There was a significant increase (P less than 0.05) of adhesions in animals with endometrial implants. Peritoneal fluid volume, macrophage number, or macrophage activation were not increased in rabbits with endometrial implants as compared with controls, nor was there a response to hormonal manipulation. CONCLUSIONS: These results demonstrate that PF volume, macrophage number, and macrophage activation are not altered by endometrial implants in the rabbit model. This suggests that the increase in these peritoneal factors in women with endometriosis may not be caused exclusively by the presence of ectopic endometrial tissue.     

The effects of carbon dioxide pneumoperitoneum on seeding of tumor in port sites in a rat model

Objectives: The use of laparoscopic surgical techniques for the resection of intraperitoneal malignancies has been rapidly increasing in recent years; concomitantly, tumor recurrences at trocar sites have also been reported. These reports bring into question the appropriateness of pneumoperitoneum and laparoscopic techniques for carcinoma removal. We hypothesized that the carbon dioxide pneumoperitoneum and instrumentation used during laparoscopic procedures contribute to a greater incidence of tumor implantation into the ventral peritoneal wall wound sites than seen with laparotomy. This study, which used port placement and carbon dioxide pneumoperitoneum in an animal model, was designed to determine the relative incidences of tumor implantation into wound sites of the ventral peritoneal wall for laparoscopy and laparotomy. Study Design: Viable MAT B III rat mammary adenocarcinoma cells were injected into the lower right quadrant of the peritoneal cavity of Fisher 344 rats (1 × 10⁵ cells/rat). The animals were then divided into 4 groups: 1 group (n = 9) served as a control group and received no further manipulations; another (n = 8) underwent a midline laparotomy; another (n = 8) had four 18-gauge trocars inserted into the peritoneal cavity; and the last (n = 8) underwent induction of a 7- to 8-mm Hg carbon dioxide pneumoperitoneum in addition to the insertion of four 18-gauge trocars. All animals were maintained under surgical conditions for 2 hours. Animals were killed at 7 days, and the ventral peritoneal wall was examined for macroscopic evidence of tumor formation. Results: A total of 32 possible sites of tumor implantation were measured. The control group showed no significant macroscopic evidence of tumor translocation to the ventral peritoneal wall. Among the 32 measured sites the laparotomy group had an overall lower incidence of tumor implantation at the peritoneal wall wound sites (n = 5) than did the group with the trocars alone (n = 20) group (P = .003) and the group with trocars plus carbon dioxide insufflation (n = 29, P < .0001). The group with trocars alone had a lower incidence of tumor implantation than did the group with trocars plus carbon dioxide pneumoperitoneum (P = .02). Conclusions: Trocar use during laparoscopic surgical procedures led to greater translocation of free tumor cells to peritoneal wall wound sites than did laparotomy in this animal model. The addition of carbon dioxide pneumoperitoneum further increased implantation of tumor cells at trocar sites. These results provide evidence that the use of laparoscopic techniques for resection of intraperitoneal malignancy needs further long-term study. (Am J Obstet Gynecol 1999;181:1329-34.)     

Adhesion prevention by solutions of sodium carboxymethylcellulose in the rat. I

Solutions of sodium carboxymethylcellulose (SCMC) were studied in rats to determine their longevity within the peritoneal cavity and their potential for prevention of postoperative intraperitoneal adhesions. In 18 rats, test solutions of SCMC and 10% dextran 40 were instilled at laparotomy. At 48 hours copious amounts of SCMC remained, whereas no 10% dextran 40 could be detected. In addition, standardized surgical injury was produced on the ceca of 100 rats at laparotomy. All control animals had significant adhesions at 2 weeks. Eighty-two percent of the 10% dextran 40 group had significant adhesions, while only 16% of the 0.9 wt% SCMC and 17% of the 1.0 wt% SCMC groups had significant adhesions. Solutions of SCMC were significantly more effective than 10% dextran 40 in the prevention of adhesions (P less than 0.001). Properties of SCMC and a possible mechanism for its striking effectiveness in adhesion prevention in this study are discussed.     

An evaluation of the Gore-Tex surgical membrane for the prevention of postoperative peritoneal adhesions

The Gore-Tex surgical membrane, expanded polytetrafluoroethylene, has been used as a pericardial graft with minimal adhesion formation reported. The purpose of this study was to assess its efficacy as a barrier method for diminishing postoperative peritoneal adhesions in an animal model. Fifteen New Zealand white rabbits underwent laparotomy, with scrape and cut lesions created bilaterally on the uterine body and horns, respectively. On one side, the lesions were covered with the graft using 7-0 Gore-Tex suture; the contralateral side served as an internal control. After four weeks, the adhesions were graded and mean adhesion scores were calculated. The Gore-Tex score was 4.1 times higher than the control for scrape lesions and 1.9 times higher for cut lesions, but the difference was not statistically significant in either case. Overall, the Gore-Tex mean adhesion score was 2.3 times higher than the control, a statistically significant difference. The Gore-Tex surgical membrane did not appear to be an effective adjuvant for postoperative adhesion prophylaxis in this animal model.     

Calcium channel blockade prevents postsurgical reformation of adnexal adhesions in rabbits

Prevention of postoperative adhesion formation is a subject of concern to the reproductive surgeon. We developed a model to test the efficacy of calcium channel blockade-mediated adhesion prophylaxis after lysis of established pelvic adhesive disease. New Zealand White rabbits received a standardized primary adhesiogenic traumatic lesion to the left uterine horn. One week later, a laparotomy was performed for evaluation (prescore scale: 0 = no adhesions to 4+ = severe) and subsequent lysis of adhesions. Before operative closure, animals were allocated randomly to intraperitoneal treatment with either verapamil 2.5 micrograms/kg/hour or vehicle, delivered by mini-osmotic infusion pumps over the course of 200 hours. Seven days later, the animals were sacrificed and evaluated blindly for extent of adhesion reformation (postscore). Prescores for verapamil and control rabbits were not significantly different (3.3 versus 2.9). Verapamil-treated animals formed considerably fewer adhesions than did controls after adhesiolysis (postscore 0.5 versus 3.5; P less than .001). These data demonstrate a marked inhibition of adhesion reformation after lysis of pelvic adhesions under the influence of verapamil.     

Preoperative versus postoperative dextran 70 for preventing adhesion formation.

Since serosal drying and tissue abrasion play an important role in adhesion formation, we tested the hypothesis that the peritoneal instillation of 32% high-molecular-weight dextran 70 (H) before, rather than after, a surgical procedure results in less postoperative adhesion formation and reformation. Twenty rabbits were subjected to a standardized surgical injury on one ovary, the ipsilateral uterine horn and adjacent parietal peritoneum. Three weeks later the animals underwent a second laparotomy to blindly score the adhesions and subsequently lyse them using microsurgical techniques. The animals were randomly assigned to one of two treatment groups, with H administered either before or at the end of each surgical procedure. Three weeks after the second surgical procedure, the animals were killed to blindly score adhesions. There was no difference in the mean adhesion scores between the two groups after either the first (2.0 versus 2.9, NS) or second surgical procedure (5.5 versus 5.1, NS). Thus, we conclude that preoperative instillation of H does not offer any advantage over postoperative instillation in the prevention of either adhesion formation or reformation.     

The role of intra-peritoneal honey administration in preventing post-operative peritoneal adhesions

OBJECTIVE(S): The accelerative effect of honey in the wound healing process is known. This effect is related to its specific physical properties of hygroscopicity, hypertonicity, lower pH and complex chemical composition. Because peritoneal healing is a kind of wound healing process we hypothesised that post-operative peritoneal adhesions (PPA) may be reduced with intra-peritoneal honey administration. STUDY DESIGN: The study was conducted with 40, 6-month-old, out-bred female Wistar albino rats with a mean weight of 197 +/- 12 g. The rats were divided into two equal groups. An adhesion model was constituted in the cecum and terminal ileum of all rats in each groups. Later the adhesion areas were washed with 0.9% NaCl solution and 5 ml of the same solution was left in the peritoneal cavity in the control group. The same area in the rats in the other group was covered with honey and 5 ml of honey was left in the peritoneal cavity of each animals. Ten days later the rats were sacrificed and the adhesions were graded according to their degree of severity. Statistical analysis was performed with the non-parametric Mann-Whitney U-test. RESULTS: In the control group, there were no rats with grade-0 or grade-1 adhesions but in the honey administered group there were six rats (30%) with grade-0 and 12 rats (60%) with grade-1 adhesions. In the control group, there were six rats (30%) with grade-2 and 14 rats (70%) with grade-3 adhesions. In the honey administered group while two rats (10%) with grade-2 adhesions were present, no rat with grade-3 adhesions was seen. In the comparison, the difference between the groups was found to be highly significant (P < 0.001). CONCLUSION(S): The wound healing accelerative effect and the mechanical barrier formed by the honey, since, it has a high density and, thus, absorbed slowly from peritoneal cavity, may be the reasons for its inhibitory effect on the PPA. This study indicates that though the mechanism is not clear intra-peritoneal honey administration reduces PPA.