Preventive Effects of Bioabsorbable Anti-Adhesion Barriers on Bowel Obstruction After Colectomy in Colon Cancer Patients: A Retrospective Cohort Study Using an Insurance Claims Database.

PURPOSE: Postoperative adhesions can be prevented by the use of bioabsorbable anti-adhesion barriers. Although the occurrence of postoperative bowel obstruction is an important concern for patients, at the time of approval of anti-adhesion barriers, its effectiveness in preventing postoperative bowel obstruction had not been evaluated. We aimed to retrospectively evaluate the incidence of bowel obstruction after colectomy in patients with colon cancer using an insurance claims database. METHODS: This retrospective cohort study analyzed the data of colon cancer patients (between 2005 and 2017 from a national insurance claims database) who underwent colectomies to compare the proportion of individuals with postoperative bowel obstruction between the barrier and no barrier groups. RESULTS: Of the 587 patients who met the inclusion criteria, 308 and 279 patients were identified as the barrier and no barrier groups, respectively. The incidence of postoperative bowel obstruction was significantly lower in the barrier group (log-rank test, P = 0.0483). The cumulative incidence of postoperative bowel obstruction 37 months after the initial colectomy was 6.1% and 10.9% in the barrier and no barrier groups, respectively. Moreover, consistent results were obtained in the matched cohort. CONCLUSION: In colectomies for patients with colon cancer, the use of anti-adhesion barriers could significantly reduce the incidence of postoperative bowel obstruction. Evaluations using insurance claims databases could provide important information on outcomes following implementation of medical devices.

Injectable polyamide-amine dendrimer-crosslinked meloxicam-containing poly-γ-glutamic acid hydrogel for prevention of postoperative tissue adhesion through inhibiting inflammatory responses and balancing the fibrinolytic system.

Establishing a physical barrier between the peritoneum and the cecum is an effective method to reduce the risk of postoperative abdominal adhesions. Meloxicam (MX), a nonsteroidal anti-inflammatory drug has also been applied to prevent postoperative adhesions. However, its poor water solubility has led to low bioavailability. Herein, we developed an injectable hydrogel as a barrier and drug carrier for simultaneous postoperative adhesion prevention and treatment. A third-generation polyamide-amine dendrimer (G3) was exploited to dynamically combine with MX to increase the solubility and the bioavailability. The formed G3@MX was further used to crosslink with poly-γ-glutamic acid (γ-PGA) to prepare a hydrogel (GP@MX hydrogel) through the amide bonding. In vitro and in vivo experiments evidenced that the hydrogel had good biosafety and biodegradability. More importantly, the prepared hydrogel could control the release of MX, and the released MX is able to inhibit inflammatory responses and balance the fibrinolytic system in the injury tissues in vivo. The tunable rheological and mechanical properties (compressive moduli: from âˆ¼ 57.31 kPa to âˆ¼ 98.68 kPa;) and high anti-oxidant capacity (total free radical scavenging rate of âˆ¼ 94.56 %), in conjunction with their syringeability and biocompatibility, indicate possible opportunities for the development of advanced hydrogels for postoperative tissue adhesions management.

Coconut leaf midrib skewer as a cause for small bowel obstruction and perforation: A case report.

Foreign body ingestion is an infrequent cause of small bowel obstruction and, rarely, perforation. It is a common occurrence among pediatric patients, mentally impaired and the edentulous elderly population majority of which will pass through the gastrointestinal tract uneventfully. The likelihood of complications such as perforation, bleeding or fistula formation increases markedly particularly for sharp, stiff, and elongated objects (i.e. toothpicks, meat bones, pins, and razor blades). Diagnosis can be difficult as frequently patients are incognizant of the nature and time of ingestion. Imaging is commonly non-specific as well. We present an unusual case of a 65-year-old male who had an ileal perforation secondary to a coconut leaf midrib skewer initially presenting as small bowel obstruction. Intraoperatively, adhesions were seen in the ileum with note of the foreign body perforating two bowel loops that was not identified in preoperative imaging. This case highlights the importance of considering atypical causes of small bowel obstruction even in the background of previous surgery. Finally, early recognition, accurate diagnosis, and timely intervention are essential to improve patient outcomes and decrease mortality in such cases.

Effects of linalool on postoperative peritoneal adhesions in rats.

The current study examines the effects of linalool in preventing postoperative abdominal adhesions. Twenty male Wistar rats were randomly divided into four groups. (1) Sham: in this group, the abdomen was approached, and without any manipulations, it was sutured. (2) Control: rats in this group underwent a surgical procedure to induce adhesions. This involved making three incisions on the right abdominal side and removing a 1×1-cm piece of the peritoneum on the left abdominal side. (3) Treatment groups: these groups underwent the same surgical procedure as the control group to induce adhesions. Animals in these groups received linalool orally with doses of 50 and 100 mg/kg, respectively, for a period of 14 days. Moreover, rats in the sham and control groups received normal saline via gavage for 14 days. The evaluation of TNF-α, TGF-ß, VEGF, and caspase 3 was performed using western blot and IHC methods. Furthermore, oxidative stress biomarkers such as MDA, TAC, GSH, and NO were assessed in the peritoneal adhesion tissue. The findings revealed that linalool significantly reduced peritoneal adhesions by reducing TNF-α, TGF-ß, VEGF, and caspase 3 levels. Moreover, MDA concentration was significantly decreased, while NO, TAC, and GSH levels were notably increased. Overall, linalool was effective in preventing adhesion formation and reduced inflammation, angiogenesis, apoptosis, and oxidative stress. Therefore, linalool as a potent antioxidant is suggested for reducing postoperative adhesions in rats.

Smart hydrogels delivered by high pressure aerosolization can prevent peritoneal adhesions.

Postoperative peritoneal adhesions occur in the majority of patients undergoing intra-abdominal surgery and are one of the leading causes of hospital re-admission. There is an unmet clinical need for effective anti-adhesive biomaterials, which can be applied evenly across the damaged tissues. We examined three different responsive hydrogel types, i.e. a thermosensitive PLGA-PEG-PLGA, a pH responsive UPy-PEG and a shear-thinning hexapeptide for this purpose. More specifically, their potential to be homogeneously distributed in the peritoneal cavity by high pressure nebulization and prevent peritoneal adhesions was evaluated. Solutions of each polymer type could be successfully nebulized while retaining their responsive gelation behavior in vitro and in vivo. Furthermore, none of the polymers caused in vitro toxicity on SKOV3-IP2 cells. Following intraperitoneal administration, both the PLGA-PEG-PLGA and the hexapeptide hydrogels resulted in local inflammation and fibrosis and failed in preventing peritoneal adhesions 7 days after adhesion induction. In contrast, the pH sensitive UPy-PEG formulation was well tolerated and could significantly reduce the formation of peritoneal adhesions, even outperforming the commercially available Hyalobarrier® as positive control. To conclude, local nebulization of the bioresponsive UPy-PEG hydrogel can be considered as a promising approach to prevent postsurgical peritoneal adhesions.

Postsurgical Adhesions: Is There Any Prophylactic Strategy Really Working?

Postoperative adhesions are a frequent complication encountered after surgical procedures, mainly after intraperitoneal interventions. To this day, the pathophysiological mechanism behind the process of adhesions formation is not completely known. There are many strategies proposed as prophylaxis methods, involving surgical techniques, drugs or materials that prevent adhesions and even state of the art technologies such as nanoparticles or gene therapy. The aim of our review is to present these innovative approaches and techniques for postoperative adhesions prevention. After a thorough scientific database query, we selected 84 articles published in the past 15 years that were relevant to our topic. Despite all the recent groundbreaking discoveries, we are at an early stage of understanding the complexity of the adhesion formation mechanism. Further investigations should be made in order to create an ideal product for safe clinical use for prevention.

Does surgeon seniority affect adhesion assessment at cesarean delivery? A prospective study.

BACKGROUND: Intraabdominal adhesions may develop following cesarean delivery and are considered a major concern. OBJECTIVE: This study aimed to determine the effect of surgeon seniority in evaluating intraabdominal adhesions at cesarean delivery. STUDY DESIGN: A prospective study to estimate interrater reliability between surgeons was conducted. Women who underwent cesarean delivery (January-July 2021) in a single tertiary university-affiliated medical center were included. Blinded questionnaires assessing adhesions were completed by the surgeons. Questions were limited to 4 main anatomic sites and 3 possible categories of adhesion (each site was scored between 0 and 2; the sum score range was 0-8). The surgeons were ranked by increasing seniority (1-4) as: (1) junior residents (less than half of residency completed), (2) senior residents (more than half of residency completed), (3) young attending physicians (attending physicians for <10 years), and (4) senior attendings (attending physicians for >10 years). The weighted percentage of agreement was calculated between the 2 surgeons assessing the same adhesions. Scoring differences between the 2 surgeons (senior vs less senior) were also calculated. RESULTS: A total of 96 pairs of surgeons were included in the study. The sum interrater reliability found in the weighted agreement tests between surgeons was 0.918 (confidence interval, 0.898-0.938). When scoring differences between surgeons (senior vs less senior) were calculated, nonsignificant difference was found (mean sum score difference of 0.09 with a standard deviation of 1.03 in favor of the more experienced surgeon). CONCLUSION: Surgeon seniority does not affect subjective scoring of adhesion reports.

Prevention strategies of postoperative adhesion in soft tissues by applying biomaterials: Based on the mechanisms of occurrence and development of adhesions.

Postoperative adhesion (POA) widely occurs in soft tissues and usually leads to chronic pain, dysfunction of adjacent organs and some acute complications, seriously reducing patients' quality of life and even being life-threatening. Except for adhesiolysis, there are few effective methods to release existing adhesion. However, it requires a second operation and inpatient care and usually triggers recurrent adhesion in a great incidence. Hence, preventing POA formation has been regarded as the most effective clinical strategy. Biomaterials have attracted great attention in preventing POA because they can act as both barriers and drug carriers. Nevertheless, even though much reported research has been demonstrated their efficacy on POA inhibition to a certain extent, thoroughly preventing POA formation is still challenging. Meanwhile, most biomaterials for POA prevention were designed based on limited experiences, not a solid theoretical basis, showing blindness. Hence, we aimed to provide guidance for designing anti-adhesion materials applied in different soft tissues based on the mechanisms of POA occurrence and development. We first classified the postoperative adhesions into four categories according to the different components of diverse adhesion tissues, and named them as "membranous adhesion", "vascular adhesion", "adhesive adhesion" and "scarred adhesion", respectively. Then, the process of the occurrence and development of POA were analyzed, and the main influencing factors in different stages were clarified. Further, we proposed seven strategies for POA prevention by using biomaterials according to these influencing factors. Meanwhile, the relevant practices were summarized according to the corresponding strategies and the future perspectives were analyzed.

An endoscopically compatible fast-gelation powder forms Janus-adhesive hydrogel barrier to prevent postoperative adhesions.

Postoperative adhesions occur widely in various tissues, bringing the risk of secondary surgery and increased medical burden. Hydrogel barriers with Janus-adhesive ability can achieve physical isolation of adjacent tissues and are therefore considered an ideal solution. However, integrating endoscopic delivery convenience and viscoelastic Janus hydrogel formation remains a great challenge. Here, we present a report of the in situ formation of Janus-adhesive hydrogel barrier using a sprayable fast-Janus-gelation (FJG) powder. We first methacrylate the polysaccharide macromolecules to break the intermolecular hydrogen bonds and impart the ability of rapid hydration. FJG powder can rapidly absorb interfacial water and crosslink through borate ester bonds, forming a toughly adhesive viscoelastic hydrogel. The Janus barrier can be simply formed by further hydrating the upper powder with cationic solution. We construct rat models to demonstrate the antiadhesions efficiency of viscoelastic FJG hydrogels in organs with different motion modalities (e.g., intestine, heart, liver). We also developed a low-cost delivery device with a standardized surgical procedure and further validated the feasibility and effectiveness of FJG powder in minimally invasive surgery using a preclinical translational porcine model. Considering the advantages in terms of therapeutic efficacy, clinical convenience, and commercialization, our results reveal the great potential of Janus-gelation powder materials as a next-generation antiadhesions barrier.

Lipid emulsions prevent postoperative abdominal adhesions.

INTRODUCTION: Adhesions are the most common cause of long-term morbidity after abdominal surgery and most often cause various forms of intestinal passage disorders ranging from partial obstruction to complete, life-threatening intestinal obstruction. The aim of the present study was to evaluate the protective effect of intraperitoneally administered lipid emulsions on the formation of adhesions in larger animal model, as the lubricating effect of phospholipids and the mechanical barrier of the lipid component are combined with the anti-inflammatory effect of fish oil. METHODS: Thirty-one female domestic pigs were randomly divided into three groups. At the end of the surgical procedure, a lipid emulsion or saline solution was applied intraperitoneally. After 14 days, an independent macroscopic, histological and immunohistochemical evaluation of the adhesions were performed. RESULTS: Intraperitoneal administration of lipid emulsions significantly reduced the incidence of intra-abdominal adhesions. Microscopic examination demonstrated a significant reduction in the number of inflammatory elements and the amount of collagen in the adhesions, especially after administration of the fish oil-based emulsion. A simultaneous decrease in neovascularization was observed in the adhesions. Evaluation of the intestinal anastomosis did not reveal significant differences in healing between the groups. CONCLUSION: Intraperitoneal administration of lipid emulsions can reduce the development of postoperative intra-abdominal adhesions by the combined action of phospholipids as important lubricants and lipids as a mechanical barrier. Their effect is caused by a reduction in proinflammatory and profibrotic mediators. At the same time, intraperitoneal administration of lipid emulsions does not impair healing of the anastomosis in larger animal model.

Self-healing, injectable hydrogel based on dual dynamic covalent cross-linking against postoperative abdominal cavity adhesion.

Clinically, increasing the peritoneal barrier is an effective adjunct to reducing postoperative peritoneal adhesion. This study presents a facile template for preparing a supramolecular hybrid hydrogel through dynamic covalent cross-linking between carboxymethyl chitosan (CMCS), 2-formylphenylboronic acid (2-FPBA), and quercetin (Que). The as-prepared complex CMCS/2-FPBA/Que (CFQ) hydrogel exhibited favorable antibacterial, anti-inflammatory, and antioxidant effects. A L929 cytotoxicity evaluation confirmed the favorable cytocompatibility of the CFQ hydrogel. The postoperative anti-adhesion ability of the CFQ hydrogel was further evaluated in rats with lateral wall defects and cecal abrasions. Compared with control groups, the tissue adhesion rate was significantly reduced by increasing the Que concentration in all the hydrogel-treated groups. Additionally, the sustained-release time of the C3F0.8Q0.08 hydrogel can exceed 14 days, which is highly desirable for clinical wound treatment. STATEMENT OF SIGNIFICANCE: Postoperative adhesions are a very common postoperative complication that seriously affects the quality of life of patients. The currently commonly used methods for preventing adhesion mainly use degradable barrier materials for physical separation. In this study, we prepared a dual dynamic covalently cross-linked CFQ hydrogel, which is not only degradable and injectable, but also has multiple properties such as antibacterial, antioxidant and anti-inflammatory, which can effectively prevent postoperative adhesion and promote wound healing.

The protective and therapeutic effects of 5-androstene3ß, 17ß-diol (ADIOL) in abdominal post-operative adhesions in rat: Suppressing TLR4/NFκB/HMGB1/TGF1 ß/α SMA pathway.

Neurosteroid, 5-androstenediol (ADIOL) had been experimentally applied to protect against many diseases as it had anti-oxidant, anti-inflammatory, and anti-apoptotic effects. In our study, we investigate its role in abdominal postoperative adhesion (APA) formations. Our results demonstrate that ADIOL alleviates APA formation after induction by cecal abrasion (CA) model in the male rat. Interestingly, per administration of ADIOL before APA induction leads to inhibit oxidative stress by increasing superoxide dismutase (SOD) and decreasing Malondialdehyde (MAD) levels to a similar level to the sham group, in addition inhibiting inflammatory pathway by decreasing toll-like receptor 4 (TLR4), nuclear factor kappa-B (NFκB), and High mobility group box 1 (HMGB1) to a similar level to the sham group, furthermore decreasing Transforming growth factor beta 1 (TGFß1) and alpha Smooth muscle -actin (α SMA) levels to similar levels in the sham group. While administration of ADIOL after APA induction lead to decrease adhesions formation by decreasing oxidative stress (↓MDA and ↑SOD levels), inflammatory markers (↓TLR4, ↓NFκB, and ↓HMGB1levels), and collagen deposition by (↓TGF1 ß and↓α SMA levels) is the highly significant manner to those levels in CA model but also significant to those levels in the sham group. Concluded that, pre-administration of ADIOL before APA induction was more effective than its administration after adhesions formations.

Cell Type-Specific Anti-Adhesion Properties of Peritoneal Cell Treatment with Plasma-Activated Media (PAM).

Postoperative abdominal adhesions are responsible for serious clinical disorders. Administration of plasma-activated media (PAM) to cell type-specific modulated proliferation and protein biosynthesis is a promising therapeutic strategy to prevent pathological cell responses in the context of wound healing disorders. We analyzed PAM as a therapeutic option based on cell type-specific anti-adhesive responses. Primary human peritoneal fibroblasts and mesothelial cells were isolated, characterized and exposed to different PAM dosages. Cell type-specific PAM effects on different cell components were identified by contact- and marker-independent Raman imaging, followed by thorough validation by specific molecular biological methods. The investigation revealed cell type-specific molecular responses after PAM treatment, including significant cell growth retardation in peritoneal fibroblasts due to transient DNA damage, cell cycle arrest and apoptosis. We identified a therapeutic dose window wherein specifically pro-adhesive peritoneal fibroblasts were targeted, whereas peritoneal mesothelial cells retained their anti-adhesive potential of epithelial wound closure. Finally, we demonstrate that PAM treatment of peritoneal fibroblasts reduced the expression and secretion of pro-adhesive cytokines and extracellular matrix proteins. Altogether, we provide insights into biochemical PAM mechanisms which lead to cell type-specific pro-therapeutic cell responses. This may open the door for the prevention of pro-adhesive clinical disorders.

Genetic Predisposition of Postoperative Adhesions Varies in Substrains of BALB/c Mice.

Postoperative adhesions are a major clinical problem because of the associated infertility, chronic pain, bowel obstruction, and the associated costs. Variability in adhesion formation was suggested by clinical observations that apparently similar interventions can cause little to severe adhesions. This is supported by the presence of polymorphisms and genetic predisposition to develop adhesions in animal models and humans. We previously demonstrated differences in postoperative adhesions between different mouse strains. In this study, we aimed to investigate the variability in adhesion formation in inbred substrains of BALB/c mice. Since genetic differences in inbred substrains are minimal, they might be an opportunity to tackle the genetics of adhesion formation.

Autologous Blood-Derived Patches Used as Anti-adhesives in a Rat Uterine Horn Damage Model.

BACKGROUND: Intra-abdominal adhesions are frequent side effects of surgery, associated with risks of serious complications such as abdominal pain, infertility, and small bowel obstruction. This study investigated a new autologous blood-based approach to adhesion prophylaxis. MATERIALS AND METHOD: Two autologous blood-derived patches (whole-blood-derived, n = 20, and plasma-derived, n = 20) were evaluated as anti-adhesives. The patches were tested in a rat uterine horn damage model. We simulated an intraabdominal surgery by cauterizing and suturing the uterine horns and created an opposing damage by denuding a part of the abdominal wall. Each rat served as its own control with one treated uterine horn and one untreated. After 14 d of post-surgical recovery, the adhesions were assessed and graded macroscopically and microscopically. Statistical analyses were performed with Wilcoxon signed rank and Mann-Whitney U tests. RESULTS: Both whole-blood and plasma-derived patches resulted in significantly less macroscopic adhesions than were found in untreated uterine horns (P = 0.001 and P = 0.002, respectively). Unpaired analysis found no significant differences between the whole-blood and plasma-derived patch outcomes in this study design. Histopathological evaluation of inflammation and fibrosis did not reveal significant differences between the patches and their matched controls. CONCLUSIONS: The autologous blood-derived patches reduced macroscopic adhesion formation significantly compared with no treatment. There were no adverse events and no histological differences between treatment and control, suggesting that the treatments were feasible and safe. In summary, this study confirms the potential of autologous anti-adhesives for the use in intraabdominal surgery.

Preventing postoperative adhesions after hand tendon repair using acellular dermal matrix.

AIMS: Postoperative tendon adhesions contribute to functional disability and reconstructive failure. In this study, we present the long-term outcomes of a prospective study in which acellular dermal matrix (ADM) was used to prevent postoperative adhesion after tendon injury. METHODS: The study was conducted between March 2014 and February 2017. Patients, aged 19-65 years, with an acute single flexor tendon injury in zones 1 or 2, distal to the palmar digital crease were candidates for the study. Patients were allocated to either an ADM treatment group or a control group without ADM treatment. RESULTS: A total of 37 patients were enrolled in the study: 21 patients in the ADM group and 16 patients in the control group. At six months after surgery, the range of motion in the proximal interphalangeal joint was 81.0±5.1 degrees in the ADM group and 75.8±6.9 degrees in the control group. The range of motion in the distal interphalangeal joint was 79.9±7.1 in the ADM group and 71.2±5.7 degrees in the control group, with significant difference (p=0.03 and p<0.05, respectively). In addition, the total active motion was higher in the ADM group than in the control group. The patients' scores on the Patient Satisfaction Questionnaire were also significantly different, with higher satisfaction scores in the ADM group (p=0.02). The minimal follow-up period was six months. CONCLUSION: The use of ADM after tendon repair has the potential to significantly improve the outcome of tendon surgery in terms of range of motion. DECLARATION OF INTEREST: None of the authors has any financial interest in the products, devices, or drugs mentioned in this article.

Nanoengineered Shear-Thinning Hydrogel Barrier for Preventing Postoperative Abdominal Adhesions.

More than 90% of surgical patients develop postoperative adhesions, and the incidence of hospital re-admissions can be as high as 20%. Current adhesion barriers present limited efficacy due to difficulties in application and incompatibility with minimally invasive interventions. To solve this clinical limitation, we developed an injectable and sprayable shear-thinning hydrogel barrier (STHB) composed of silicate nanoplatelets and poly(ethylene oxide). We optimized this technology to recover mechanical integrity after stress, enabling its delivery though injectable and sprayable methods. We also demonstrated limited cell adhesion and cytotoxicity to STHB compositions in vitro. The STHB was then tested in a rodent model of peritoneal injury to determine its efficacy preventing the formation of postoperative adhesions. After two weeks, the peritoneal adhesion index was used as a scoring method to determine the formation of postoperative adhesions, and STHB formulations presented superior efficacy compared to a commercially available adhesion barrier. Histological and immunohistochemical examination showed reduced adhesion formation and minimal immune infiltration in STHB formulations. Our technology demonstrated increased efficacy, ease of use in complex anatomies, and compatibility with different delivery methods, providing a robust universal platform to prevent postoperative adhesions in a wide range of surgical interventions.

Endostatin in fibrosis and as a potential candidate of anti-fibrotic therapy.

Fibrotic diseases pose significant clinical challenges due to their broadness and complexity. Thus, a better understanding of fibrogenesis and the development of more effective treatments is imperative. Recent evidence suggests a significant antifibrotic potential of an endogenous glycoprotein, endostatin. While endostatin has been widely studied for its role as an anticancer adjuvant by inhibiting tumor angiogenesis, its possible implication in fibrosis remains largely unclear. Here, we review the role of endostatin in various cellular processes and highlight its antifibrotic activity. We hypothesize that endostatin conveys a homeostatic function in the process of fibrosis by regulating (a) TGF-ß1 and its downstream signaling; (b) RhoA/ROCK pathway; (c) NF-κB signaling pathway; (d) expression of EGR-1; (e) PDGF/PDGFR pathway; (f) autophagy-related pathways; (g) pathways associated with cell proliferation and apoptosis. Finally, we propose a schematic model of the antifibrotic roles and mechanisms of endostatin; also, we outline future research directions of endostatin and aim to present a potential therapeutic approach for fibrosis.

Pneumoperitoneum induced mesothelial cell changes in a laparoscopic mouse model.

BACKGROUND: CO2 pneumoperitoneum (PP) during laparoscopic surgery, can cause hypoxia and desiccation in the peritoneal mesothelial cell, resulting in a time-dependent retraction and bulging of these cells, an acute inflammatory reaction and enhanced adhesion formation. Since hypoxia is prevented by adding 4% of oxygen (O2) to the CO2 PP, the aim of this study was to evaluate the effect of adding 4% O2 to the CO2 PP on mesothelial cell morphology. METHODS: In a standardized laparoscopic mouse model (n=8 mice per group), a control group with a 30- or 60-min PP with humidified CO2 + 4% of O2 (groups I and II) was compared to a hypoxic group with 30- or 60-min humidified pure CO2 (groups III and IV) and a desiccation group with 60-min of dry CO2 PP (group V). The effect upon the peritoneum morphology was evaluated by scanning electron microscopy (SEM) of abdominal wall peritoneal biopsies. Biopsies, taken immediately (n=4) and 24 hrs (n=4) after surgery, were compared to a group without PP (group VI, n=4). SEM pictures were blindly scored for cell retraction, deletion of microvilli, fibrin deposition, holes in the epithelial layer and visibility of cell borders using a semi-quantitative scoring system. RESULTS: PP Hypoxia (CO2 PP) has a deleterious effect upon mesothelial morphology, immediately (holes: p= 0.04) and 24 hrs later (cell retraction: p=0.005; total score: p=0.03) . Desiccation has also a deleterious effect immediately (microvilli p=0.0090; fibrin deposition p=0.05) and 24 hrs after surgery (cell retraction: p=0.0036; holes: p=0.0004; microvilli: p< 0.0001, fibrin deposition: p=0.0225; borders: p=0.0007). This deleterious effect increases with duration of CO2 PP, affecting cell retraction (p=0.016), holes (p=0.0441), and the total score (p=0.0488). The addition of 4% of O2 to the CO2 PP failed to reach statistical significance. CONCLUSIONS: These data confirm that CO2 PP and dry gas have a deleterious effect on mesothelial cell morphology. Humidification of the insufflation gas reduces this deleterious effect. The hypothesis of a protective effect of adding O2 failed to reach significance.

Antithrombin Together with NETs Inhibitor Protected Against Postoperative Adhesion Formation in Mice.

BACKGROUND/AIMS: Postoperative adhesions may induce adverse outcomes in patients. Adhesion formation is initiated by fibrin accumulation at the surgical site which is followed by local neutrophilia and the establishment of neutrophil extracellular traps (NET). Previous reports have suggested that the preventive efficacy of reagents designed to reduce postoperative adhesion is inversely correlated with neutrophilia and NET production. Antithrombin (AT) is a natural inhibitor of thrombin, a key factor in coagulation. Here, we evaluate whether treatment with AT and/or NET inhibitors prevent or reduce postoperative adhesion formation in mice. METHODS: Mice were treated with AT and/or NET inhibitors before and/or after cecum cauterization and their adhesion scores were evaluated on day 7 post-operation. Immunochemistry/ immunofluorescence analyses were also performed and we used GSK484, an inhibitor of peptidyl arginine deiminase 4 (PAD4), as the NET inhibitor. RESULTS: AT or GSK484 partially rescued postoperative adhesion formation in mice. AT prevented thrombin-induced plasminogen activator inhibitor 1 and interleukin-6 expression in mesothelial cells in vitro. However, AT could not prevent neutrophilia or NETs formation around the injured serosa. Finally, we investigated a combination of AT and a PAD4 inhibitor and found that this could inhibit almost all adhesion formation in these animals. Since AT-inactivating proteases are liberated following NET release, they might dampen the biological action of the AT treatment. This suggests that NET inhibitors might allow AT to exert its full action in the surgically injured serosa. CONCLUSION: Combined treatment with AT and GSK484 may effectively attenuate postoperative adhesion production in mice.