Tissue response to five commercially available peritoneal adhesion barriers-A systematic histological evaluation.

Adhesion barriers can be based on numerous substances. In the rat Optimized Peritoneal Adhesion Model (OPAM) the starch-based hemostats 4DryField and Arista were tested for their capability to act in a preventive manner against adhesion formation (applied as a powder that was mixed in situ with saline solution to form a barrier gel). Adhesions were scored using the established scoring systems by Lauder and Hoffmann, as well as histopathologically using the score by Zühlke. Animals receiving saline solution were used as controls. As previously published, 4DryField reduced peritoneal adhesions significantly. However, Arista did not lead to a statistically significant reduction of adhesion formation. When comparing 4DryField and Arista applied in the same manner, only 4DryField was significantly effective in preventing peritoneal adhesions. Histopathological evaluations confirmed the results of the macroscopic investigation, leading to the conclusion that starch-based hemostats do not generally have the capability to function as effective adhesion prevention devices.

The negative impact of postoperative adhesions has long been recognized, but available options for prevention remain limited. Minimally invasive surgery is associated with decreased adhesion formation due to meticulous dissection with gentile tissue handling, improved hemostasis, and limiting exposure to reactive foreign material; however, there is conflicting evidence on the clinical significance of adhesion-related disease when compared to open surgery. Laparoscopic surgery does not guarantee the prevention of adhesions because longer operative times and high insufflation pressure can promote adhesion formation. Adhesion barriers have been available since the 1980s, but uptake among surgeons remains low and there is no clear evidence that they reduce clinically significant outcomes such as chronic pain or infertility. In this article, we review the ongoing magnitude of adhesion-related complications in gynecologic surgery, currently available interventions and new research toward more effective adhesion prevention. Recent literature provides updated epidemiologic data and estimates of healthcare costs associated with adhesion-related complications. There have been important advances in our understanding of normal peritoneal healing and the pathophysiology of adhesions. Adhesion barriers continue to be tested for safety and effectiveness and new agents have shown promise in clinical studies. Finally, there are many experimental studies of new materials and pharmacologic and biologic prevention agents. There is great interest in new adhesion prevention technologies, but new agents are unlikely to be available for clinical use for many years. High-quality effectiveness and outcomes-related research is still needed.

Post-operative adhesions form as a result of normal wound healing processes following any type of surgery. In cardiac surgery, pericardial adhesions are particularly problematic during reoperations, as surgeons must release the adhesions from the surface of the heart before the intended procedure can begin, thereby substantially lengthening operation times and introducing risks of haemorrhage and injury to the heart and lungs during sternal re-entry and cardiac dissection. Here we show that a dynamically crosslinked supramolecular polymer-nanoparticle hydrogel, with viscoelastic and flow properties that enable spraying onto tissue as well as robust tissue adherence and local retention in vivo for two weeks, reduces the formation of pericardial adhesions. In a rat model of severe pericardial adhesions, the hydrogel markedly reduced the severity of the adhesions, whereas commercial adhesion barriers (including Seprafilm and Interceed) did not. The hydrogels also reduced the severity of cardiac adhesions (relative to untreated animals) in a clinically relevant cardiopulmonary-bypass model in sheep. This viscoelastic supramolecular polymeric hydrogel represents a promising clinical solution for the prevention of post-operative pericardial adhesions.

Intra-abdominal adhesions are a costly, long-term sequela of abdominal surgeries. They occur in up to 94% of patients following abdominal operation and cause significant postoperative morbidity including difficult reoperative surgeries, small bowel obstructions, and infertility. The pathophysiology of adhesion formation remains poorly defined, and a uniformly effective method of adhesion prevention does not exist. Research focused on understanding the mechanisms underlying adhesion formation is essential for the development of safe and effective therapeutic approaches to adhesion prevention. The proinflammatory peptide substance P (SP), known to participate in inflammatory and wound-healing events, may contribute to the early processes of adhesion formation. SP is the most widely studied ligand of the neurokinin-1 receptor (NK-1R), and we have determined in a rat model that intraoperative administration of an NK-1R antagonist, CJ-12-255 (Pfizer), that blocks ligand binding to the NK-1R, significantly reduces adhesion formation. It also has been determined that animals administered the NK-1R antagonist intraperitoneally have increased peritoneal fibrinolytic and matrix metalloproteinase activities, and reduced levels of oxidative stress postoperatively, all of which may contribute to the observed reduction in adhesion formation. Studies suggest that intra-abdominal adhesion formation begins within hours of surgery and that the regulation of fibrin deposition, and degradation is of key importance. A pharmacologic agent, such as an NK-1R antagonist, administered at the time of surgery that could augment postoperative peritoneal fibrinolytic activity without compromising wound healing, would be a beneficial tool in the prevention of postoperative adhesions.

Postoperative peritoneal adhesions are major concerns in abdominal surgery. In this experimental study, the effects of 4% icodextrin and omega-3 fatty acids (ω-3 FA) on prevention of postoperative peritoneal adhesions were evaluated. Twenty-four Wistar albino rats were divided into three groups. After laparotomy, serosal abrasion was carried out by cecal brushing. Intraperitoneally 3cm(3) 0.9% NaCl, 3cm(3) 4% icodextrin, and 200mg/kg ω-3 FAs for each group were applied, and then the abdomen was closed. All subjects sacrificed 10days postoperatively. Macroscopic and histopathological cellular reactions as a function of giant cell, lymphocyte/plasmocyte, neutrophil, histiocyte, intracellular adhesion molecule-1 (ICAM-1), and platelet endothelial cell adhesion molecule-1 (PECAM-1) were assessed and hydroxyproline levels were measured in all three groups and compared using Kruskal-Wallis and ANOVA tests when appropriate. Macroscopically, both ω-3 FAs and 4% icodextrin reduced adhesion formation but the difference was not statistically significant (P = 0.253). Histopathological examination revealed that there was no statistical significance in terms of giant cell, lymphocyte/plasmocyte, neutrophil, ICAM-1, and PECAM-1 scores; however, both ω-3 FAs and 4% icodextrin were found to be prone to reduce fibrosis (P = 0.047), whereas in the ω-3 FA group, histiocytic reaction was significantly increased (P = 0.001), and hydroxyproline levels were significantly lower than other groups (P = 0.044). In this study, ω-3 FAs were found to be superior to 4% icodextrin with the lower hydroxyproline level and greater histiocytic reaction. Considering these results, ω-3 FAs can be a promising agent in the prevention of adhesion formation.

Postoperative adhesions develop after nearly every abdominal surgery. The formation of adhesions is associated with the inflammatory response, fibrinolytic system, and extracellular matrix deposition in response to injury. Tanshinone IIA is one of the major extracts obtained from Salvia miltiorrhiza, which has anti-inflammatory effects on many diseases. Postoperative adhesions were induced by injuring the parietal peritoneum and cecum in Wistar rats, followed by the administration of various dosages of tanshinone IIA. The adhesion scores for each group were collected seven days after the initial laparotomy. The activity of the tissue-type plasminogen activator in the peritoneal lavage fluid was measured. The messenger ribonucleic acid expression levels of the tissue-type plasminogen activator, plasminogen activator inhibitor-1, and cyclooxygenase-2 in the ischaemic tissues were measured by quantitative real-time polymerase chain reaction. The intraperitoneal administration of tanshinone IIA is effective for the prevention of the formation of postoperative adhesions in rats. Tanshinone IIA increased fibrinolytic activity in the peritoneal lavage fluid and tissue-type plasminogen activator messenger ribonucleic acid expression in ischaemic peritoneal tissues but decreased the plasminogen activator inhibitor and cyclooxygenase-2 messenger ribonucleic acid expression significantly. These results revealed that tanshinone IIA was a potent postoperative adhesion preventer by enhancing fibrinolytic activity and decreasing cyclooxygenase-2 activity.

Role of the peritoneal cavity in the prevention of postoperative adhesions, pain, and fatigue

Intraperitoneal adhesions are a common problem in abdominal surgery. The aim of this study was to compare the effectiveness of Statofilm, a novel antiadhesive film based on cross-linked carboxymethylcellulose and atorvastatin, with that of sodium hyaluronate-carboxymethylcellulose (Seprafilm(®)) in the prevention of postoperative intraperitoneal adhesions in rats. One hundred male Wistar rats underwent a laparotomy and adhesions were induced by caecal abrasion. The animals were allocated to five groups: a control group with no adhesion barrier, Seprafilm(®) group, placebo group with a film containing carboxymethylcellulose without atorvastatin, and low- and high-dose groups with films containing carboxymethylcellulose and atorvastatin 0·125 and 1 mg per kg bodyweight respectively. Adhesions were classified by two independent surgeons 2 weeks after surgery. Caecal biopsies were obtained for histological evaluation of fibrosis, inflammation and vascular proliferation. All antiadhesive film groups (Seprafilm(®), placebo, low-dose and high-dose) had statistically significant adhesion reduction compared with the control group (P < 0·001, P = 0·015, P < 0·001 and P < 0·001 respectively). The low-dose Statofilm was superior to Seprafilm(®) in terms of adhesion prevention (P = 0·001). Adhesions were present in three-quarters of rats in the Seprafilm(®) group, but only one-quarter in the low-dose Statofilm group. The data suggest that the newly developed adhesion barrier Statofilm has better results than Seprafilm(®) in preventing postoperative adhesions in rats. A low-dose atorvastatin-containing film, such as Statofilm, could be evaluated for future clinical application.

BackgroundAdhesions develop in over 90% of patients after intra-abdominal surgery. Adhesion barriers are rarely used despite the high morbidity caused by intra-abdominal adhesions. Only one of the currently available adhesion barriers has demonstrated consistent evidence for reducing adhesions in visceral surgery. This agent has limitations through poor handling characteristics because it is sticky on both sides. C-Qur™ Film is a novel thin film adhesion barrier and it is sticky on only one side, resulting in better handling characteristics. The objective of this study is to assess efficacy and safety of C-Qur™ Film to decrease the incidence of adhesions after colorectal surgery.Methods/DesignThis is a prospective, investigator initiated, randomized, double-blinded, multicenter trial. Eligible patients undergoing colorectal resection requiring temporary loop ileostomy or loop/split colostomy by laparotomy or hand assisted laparoscopy will be included in the trial. Before closure, patients are randomized 1:1 to either the treatment arm (C-Qur™ Film) or control arm (no adhesion barrier). Patients will return 8 to 16 weeks post-colorectal resection for take down of their ostomy. During ostomy takedown, adhesions will be evaluated for incidence, extent, and severity. The primary outcome evaluation will be assessment of adhesions to the incision site. It is hypothesized that the use of C-Qur™ Film underneath the primary incision reduces the incidence of adhesion at the incision by 30%. To demonstrate 30% reduction in the incidence of adhesions, a sample size of 84 patients (32 + 10 per group (25% drop out)) is required (two-sided test, α = 0.05, 80% power).DiscussionResults of this study add to the evidence on the use of anti-adhesive barriers in open and laparoscopic ‘hand-assisted’ colorectal surgery. We chose incidence of adhesions to the incision site as primary outcome measure since clinical outcomes such as small bowel obstruction, secondary infertility and adhesiolysis related complications are considered multifactorial and difficult to interpret. Incidence of adhesions at repeat surgery is believed to be the most valuable surrogate endpoint for clinically relevant adhesion prevention, since small bowel obstruction and adhesiolysis at repeat surgery are not likely to occur when complete adhesion reduction in a patient is accomplished.Trial registrationClinicalTrials.gov Identifier NCT01872650, registration date 6 June 2013.

Background: This study proposed to identify the possible mechanism of action of novel treatment, alanyl-glutamine (AG) in adhesion prevention. The aim was to outline the natural history of adhesion formation in a randomized animal model and to confirm the effect of peritoneal infiltration of AG on adhesion formation in rats post-laparotomy. The study also challenged the role of macrophage chemotactic protein 1 (MCP-1) on adhesion formation. Method: This study involved open abdominal surgery on 53 Wistar rats. They were assessed for AG's efficacy in preventing adhesion. Rats were randomly assigned to three groups: 1) Open laparotomy (no treatment), 2) Open laparotomy with saline, and 3) Open laparotomy with AG. Tissue explants were analyzed and assessed for fibrosis. Macrophage activity was also evaluated using ED1 and CD68 markers. Results: 6 days after surgery, severe adhesion was evident in the saline and the non-treatment group. This persisted up to day 42, while the treatment group showed minimal evidence of adhesion, with 95%-100% adhesion prevention. MCP-1 did not have a clear role in controlling macrophage infiltration. Conclusion: Our adhesion model showed a better outcome for adhesion prevention in all the rats instilled with AG after laparotomy. While MCP-1 is a marker of inflammation, it does not appear to play a role in preventing intraperitoneal adhesion, nor does it have a clear controlling role in macrophage infiltration.

A variety of nonsteroidal anti-inflammatory drugs (NSAIDs) has been found to inhibit postsurgical peritoneal adhesion formation in a number of animal models. A rabbit uterine horn adhesion model was used to directly compare several commonly used NSAIDs of different chemical classes in a single animal study to evaluate their ability to prevent adhesion formation. The effect of thromboxane inhibitors on adhesion prevention was also evaluated. Each of the NSAIDs tested (tolmetin, ibuprofen, aspirin, and indomethacin) showed significant and comparable efficacy. In this same study, imidazole, a thromboxane synthetase inhibitor, also showed significant efficacy. In a second study, ridogrel, an inhibitor of thromboxane synthetase as well as a thromboxane A2 receptor blocker, also showed significant efficacy in reducing peritoneal adhesion severity. These results further support the view that NSAIDs act to prevent adhesions through a common mechanism. In addition, thromboxane A2 inhibitors were also shown to be efficacious in adhesion prevention, suggesting that platelets may play a substantial role in adhesion formation.

Novel evidence-based prosthetic designs and biomaterials facilitate the performance of highly successful joint replacement (JR) procedures. To achieve this goal, constructs must be durable, biomechanically sound, and avoid adverse local tissue reactions. Different biomaterials such as metals and their alloys, polymers, ceramics, and composites are currently used for JR implants. This review focuses on (1) the biological response to the different biomaterials used for TJR and (2) the chronic inflammatory and foreign-body response induced by byproducts of these biomaterials. A homeostatic state of bone and surrounding soft tissue with current biomaterials for JR can be achieved with mechanically stable, infection free and intact (as opposed to the release of particulate or ionic byproducts) implants. Adverse local tissue reactions (an acute/chronic inflammatory reaction, periprosthetic osteolysis, loosening and subsequent mechanical failure) may evolve when the latter conditions are not met. This article (Part 2 of 2) summarizes the biological response to the non-metallic materials commonly used for joint replacement including polyethylene, ceramics, and polymethylmethacrylate (PMMA), as well as the foreign body reaction to byproducts of these materials. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1685-1691, 2017.

Postoperative adhesions remain an important clinical problem, accounting for infertility, chronic pain and bowel obstruction. Its prevention is still inadequate and overall poorly understood. The aim of this study was to investigate the effect of Reteplase (a recombinant plasminogen activator, r-PA) and of PAI-1 antibodies upon adhesion formation in a laparoscopic model. Pneumoperitoneum-enhanced adhesions were induced by performing a bipolar lesion in female BALB/c mice and by using pure and humidified CO(2) as insufflation gas for 60 min. In experiment 1, four doses of 0.125, 0.25, 0.5 and 1 mg/0.5 ml r-PA and one and two doses of 1 mg r-PA were administrated i.p. Two control groups were included, one without any treatment and the second one receiving four times 0.5 ml of saline. In experiment 2, four doses of 0, 1, 10 and 100 microg/0.5 ml r-PA were administrated i.p. In experiment 3, PAI-1 neutralising and non-neutralising antibodies were injected i.p. after performing the lesion on day 0 and days 2 and 4. Adhesions were scored after 7 days. Adhesion formation was less with the administration of four doses of 1 microg r-PA (proportion, p < 0.04, Wilcoxon). An increase in adhesion formation was observed when higher number of doses and amounts of r-PA were used (Proc GLM, eight groups, two variables, p = 0.05 for the amount of r-PA and p < 0.02 for the number of doses administrated). No effect was observed with the PAI-1 antibodies. Low-dose i.p. administration of rPA is effective in the prevention of adhesions in a laparoscopic mouse model.

In the literature, there is a discussion concerning the prevention, diagnosis and treatment of adhesions of the abdominal cavity and associated with intestinal obstruction, while the question of the pathogenesis of the disease and the true reasons for its development is completely overlooked. Recently, there have been no any significant achievements in solving this problem. The analysis of literature sources revealed a number of shortcomings of the scientific and practical approach associated with outdated fundamental ideas about the causes of the adhesive process, which are based on tissue oxygenation and fibrin organization. So, the healing of the peritoneum and the restoration of the native layer of mesioteliocetes without the formation of adhesions is possible only in the first 3 days from the moment of an injury. At the same time, hypoxia plays an important role in the formation of peritoneal adhesions, affecting the maturation of mesothelial cells and the differentiation of fibroblasts. The solution to the problem of adhesion is possible by influencing the key links of pathogenesis: hypoxia in the abdominal tissue, the system of fibrinolytic and extracellular matrix degradation, the formation and activation of autocoids and regulators of fibrotic tissue. Despite the traditionally established approaches, it is necessary to revise the concept of the pathogenicity theory understanding the cellular and molecular mechanisms of adhesion formation .

Use of fibrinolytic agents in the prevention of postoperative adhesion formation