Prevention Of Adhesion Formation Research Articles

Adhesive small bowel obstruction - an update.

Small bowel obstruction (SBO) accounts for 12–16% of emergency surgical admissions and 20% of emergency surgical procedures. Even with the advent of laparoscopic surgery, intra‐abdominal adhesions remain a significant cause of SBO, accounting for 65% of cases. History and physical examination are essential to identify signs of bowel ischemia as this indicates a need for urgent surgical exploration. Another critical aspect of evaluation includes establishing the underlying cause for obstruction and distinguishing between adhesive and non‐adhesive etiologies as adhesive SBO (ASBO) can be managed non‐operatively in 70–90% of patients. A patient with a history of abdominopelvic surgery along with one or more cardinal features of obstruction should be suspected to have ASBO until proven otherwise. Triad of severe pain, pain out of proportion to the clinical findings, and presence of an abdominal scar suggest possible closed‐loop obstruction. Computed tomography has higher sensitivity and specificity compared to plain films and is recommended by the Bologna guidelines. Correcting fluid and electrolyte imbalance is an initial crucial step to mitigate severe hypovolemia. Patients should proceed with surgery if symptoms of bowel compromise are present, or if symptoms do not resolve or have worsened. Surgery is indicated in patients with ischemia, strangulation, perforation, peritonitis, or failure of non‐operative treatment. With advances in minimal access technology and increasing experience, laparoscopic adhesiolysis is recommended. Mechanical adhesion barriers are an effective measure to prevent adhesion formation.

Flexor Tendon: Development, Healing, Adhesion Formation, and Contributing Growth Factors.

Management of flexor tendon injuries of the hand remains a major clinical problem. Even with intricate repair, adhesion formation remains a common complication. Significant progress has been made to better understand the mechanisms of healing and adhesion formation. However, there has been slow progress in the clinical prevention and reversal of flexor tendon adhesions. The goal of this article is to discuss recent literature relating to tendon development, tendon healing, and adhesion formation to identify areas in need of further research. Additional research is needed to understand and compare the molecular, cellular, and genetic mechanisms involved in flexor tendon morphogenesis, postoperative healing, and mechanical loading. Such knowledge is critical to determine how to improve repair outcomes and identify new therapeutic strategies to promote tissue regeneration and prevent adhesion formation.

Neutrophil and monocyte kinetics play critical roles in mouse peritoneal adhesion formation

Peritoneal adhesions are pathological fibroses that ensnare organs after abdominal surgery. This dense connective tissue can cause small bowel obstruction, female infertility, and chronic abdominal pain. The pathogenesis of adhesions is a fibrotic response to tissue damage coordinated between mesothelial cells, fibroblasts, and immune cells. We have previously demonstrated that peritoneal adhesions are a consequence of mechanical injury to the mesothelial layer sustained during surgery. Neutrophils are among the first leukocytes involved in the early response to tissue damage. Here, we show that when subjected to mechanical stress, activated mesothelial cells directly recruit neutrophils and monocytes through upregulation of chemokines such as CXCL1 and monocyte chemoattractant protein 1 (MCP-1). We find that neutrophils within the adhesion sites undergo cell death and form neutrophil extracellular traps (NETosis) that contribute to pathogenesis. Conversely, tissue-resident macrophages were profoundly depleted throughout the disease time course. We show that this is distinct from traditional inflammatory kinetics such as after sham surgery or chemically induced peritonitis, and suggest that adhesions result from a primary difference in inflammatory kinetics. We find that transient depletion of circulating neutrophils significantly decreases adhesion burden, and further recruitment of monocytes with thioglycolate or MCP-1 also improves outcomes. Our findings suggest that the combination of neutrophil depletion and monocyte recruitment is sufficient to prevent adhesion formation, thus providing insight for potential clinical interventions.

Nasal Adhesions – A New Perspective

Objective: The objective of the study is to explore various causes of adhesions or faults what different surgeons commonly do and how to combat this problem. Study design: Randomized Control Trial. Settings: ENT Unit-I, Allied Hospital, Faisalabad. Duration: July, 2016 to June, 2018. Methodology: 500 patients undergoing septoplasty and SMR, over a period of 2 years were included in this study. Those requiring combination procedures were excluded. The study involved 400 males and 100 females. The age range was 15-75 years with a mean age of 34 years. All patients had a pre-operative nasal packing by undertraining medical officers using a roll gauze soaked in 4% Xylocaine with Topical Adrenaline 1:1000 in a ratio of 50:50 half an hour before surgery. 300 cases were operated under local anesthesia with no intravenous supplement and the remaining 200 under General Anesthesia. Results: 20 patients (04%) presented with adhesions out of which 15 were operated under General Anesthesia and 5 under local anesthesia. All these patients belonged to the non-splinted group. 07 patients (1.4%) complained of slight discomfort due to splints particularly those made of the cut drips. 03 patients (0.6%) complained of the unsightly look of the anterior ends of the splints as they were secured with stitches over the columella. Crust formation was the main problem encountered during the splinting period. Conclusion: Splints have been found to be very effective in preventing adhesion formation which are sometimes very troublesome. However, because of the very low incidence, (04%) in our studies compared to (8.1%) in other series after a single procedure on the nose, one must be very cautious in placing splints and should be placed where the surgeon strongly fears the formation of adhesions, such as in difficult cases. Suggestions: Prevention from unwanted adhesions is the best strategy to avoid adhesions.

Regulation and function of IL-22 in peritoneal adhesion formation after abdominal surgery.

Peritoneal adhesion occurs frequently after gastrointestinal/gynecological surgery. Tissue repair and regeneration are very important during this process. IL-22 is an important cytokine that is secreted from immune cells but functions on mesenchymal cells, such as mesothelial cells. The objective of this study was to investigate the roles of IL-22 and its regulators during adhesion formation. Postsurgical peritoneal drainage fluid from patients and rodent models was examined by enzyme-linked immunosorbent assay and fluorescence-activated cell sorting. It was observed that IL-22 expression in the abdominal cavity was rapidly induced 12 hours after surgery and then slowly decreased to a lower, steady level for up to 7 days after surgery. However, neutralizing IL-22 at the time point at which the highest level of expression was observed failed to reduce adhesion, but neutralizing IL-22 at a later time point, i.e., 3 days after surgery, prevented adhesion significantly. The IL-22 receptor was induced on the mesothelial membrane, and IL-22BP, an inhibitor of IL-22, was reduced 3 days after surgery. Furthermore, IFN-γ was identified to have the ability to induce IL-22R, and IL-18, which was induced by the infiltrating macrophages, was found to inhibit IL-22BP expression both in vivo and in vitro. Together, these data suggest that IL-22 may promote adhesion formation and that the regulation of IL-22, IL-22R, and IL-22BP may have therapeutic potential to prevent adhesion formation after surgery without disturbing the normal immune process.

Preliminary design of a new degradable medical device to prevent the formation and recurrence of intrauterine adhesions

Intrauterine adhesions lead to partial or complete obliteration of the uterine cavity and have life-changing consequences for women. The leading cause of adhesions is believed to be loss of stroma resulting from trauma to the endometrium after surgery. Adhesions are formed when lost stroma is replaced by fibrous tissue that join the uterine walls. Few effective intrauterine anti-adhesion barriers for gynecological surgery exist. We designed a degradable anti-adhesion medical device prototype to prevent adhesion formation and recurrence and restore uterine morphology. We focused on ideal degradation time for complete uterine re-epithelialization for optimal anti-adhesion effect and clinical usability. We developed a triblock copolymer prototype [poly(lactide) combined with high molecular mass poly(ethylene oxide)]. Comparative pre-clinical studies demonstrated in vivo anti-adhesion efficacy. Ease of introduction and optimal deployment in a human uterus confirmed clinical usability. This article provides preliminary data to develop an intrauterine medical device and conduct a clinical trial.

Insights from outside BJOG

Insights from outside BJOG

Role of Topical Mytomycin C Application in Improving Outcome of Functional Endoscopic Sinus Surgery

Background: functional endoscopic sinus surgery, (FESS), is a minimally invasive surgical procedure that opens up the paranasal sinus ostia with an endoscope. Endoscopic sinus surgery is seen as the standard treatment in chronic rhinosinusitis and Sinonasal polyposis. Objective: it was to assess the efficacy of intra and postoperative topical application of Mitomycin C after endoscopic sinus surgery in reducing adhesions and scar formation and improving outcome of FESS. Patients and Methods: this study included 60 cases (24 female (40%) and 36 male (60%) ranging in age from 18 to 50 years) with mean 34 bilateral chronic rhinosinusitis with or without sinonasal polyposis undergoing functional endoscopic sinus surgery. Every patient in this study had been submitted for full history taking, general examination, full ENT examination routine preoperative laboratory investigations and computerized tomography study on the nose and paranasal sinuses. Functional endoscopic sinus surgery had been done for all patients. Results: In our study, bilateral nasal obstruction was presented in 46 patients (76.6%), anterior nasal discharge was presented in 22 patients (36.6%), posterior nasal discharge was presented in 18 patients (30%), headache was presented in 40 patients (66.6%) and facial pain was presented in 12 patients (20%). Endoscopic assessment of the patients 2 months after F.E.S.S revealed that the adhesions presented in 32 sides (26.7%) mainly occurred on the control side 25 (41.7%) while the Mitomycin C side showed minimal adhesions 7 (11.7%) with significant P value (0.04). Conclusion: Topical application of MMC at end of FESS has beneficial role in prevention of adhesion formation and synechiae without any side effects/complications.

Crystalloid fluid suspension results in decreased adhesion burden when compared to bioresorbable membranes in a rat model

IntroductionAdhesion formation represents a major cause of long-term morbidity. Suspension of intra-abdominal contents in fluid medium may effectively prevent adhesion formation. We compare saline hydro-flotation (NS) to hyaluronate bioresorbable membranes (HBM) for adhesion prevention following surgery. MethodsAnimals were randomized to four groups: sham (no injury, n = 5), control (injury without intervention, n = 5), HBM (n = 20) or 10 cc NS (n = 21). Interventions were administered after standardized surgical trauma to the cecum and abdominal wall. Necropsies at two weeks were completed to compare adhesion burden using a customary scoring algorithm. ResultsSignificant adhesion burden was noted in all rats. HBM sustained a more significant adhesion burden with higher total adhesion scores (HBM = 10 vs NS = 8.1/15, p = 0.02). Gross adhesion scores were lower with NS (5.6/9) compared to HBM (7.1/9, p = 0.01). Neo-vascularity was more common in HBM at 2.6/3 versus 1.9/3 with NS (p = 0.01). Percent of the cecum encased with adhesion was higher with HBM (42%) compared to NS (31%, p = 0.05). DiscussionFluid based anti-adhesion methods should be considered for abdominal adhesion formation prevention.

Getting adhesions unstuck

Surgical Adhesions Peritoneal adhesions are ectopic fibrotic tissues induced by surgical perturbations that result in postoperative morbidities such as small bowel obstruction. The cellular origin of adhesions remains unclear. Now, Tsai et al. show that mesothelial cells overlying organs and the abdominal wall give rise to adhesions after surgery in mice. The injured mesothelium up-regulated mesothelial-specific genes known to be highly expressed during fetal development. Targeting adhesions with antibodies against the mesothelial marker mesothelin eliminated adhesions that had formed after surgery. Injured mesothelium responded to hypoxia, and this was mediated by the hypoxia-inducible factor 1 alpha (HIF1α) pathway. Blocking HIF1α with small-molecule inhibitors prevented adhesion formation in mice after surgery. Sci. Transl. Med. 10 , eaan6735 (2018).

The Effect of Single-Dose Intraperitoneal Bevacizumab on Peritoneal Adhesion Formation.

Intra-abdominal adhesions and their complications following abdominal surgery are serious problems, with an incidence of 67-93%. Prevention of peritoneal adhesion formation may eliminate the need for surgical intervention, decreasing complications, morbidity, and cost. Bevacizumab is a recombinant monoclonal antibody which specifically binds vascular endothelial growth factor, an important cytokine in adhesion formation, and neutralizes its biological activity. We developed an experimental model in rats to determine the effect of bevacizumab in preventing adhesion formation and analyzed its effect both micro- and macroscopically. We used 32. Wistar rats randomly divided into two groups: Group A (control) and Group B (bevacizumab), with 16 rats each. A modified cecum abrasion model was developed; 0.9% NaCl solution was administered intraperitoneally to Group A and bevacizumab to Group B. On day 15, adhesion formation was evaluated both macro- and microscopically. Both micro- and macroscopic adhesion grades in Group B were significantly lower than those of control Group A; macroscopic grades were 2.69 ± 0.95 and 0.69 ± 0.8, and microscopic grades were 2.25 ± 1.06 and 0.5 ± 0.52 for Groups A and B, respectively. Bevacizumab was effective in preventing intraperitoneal adhesion formation in our study; however, its inhibitory effects on embryogenesis and the hematopoietic, endocrine, and immune systems may limit its clinical use.

Abstract 17133: A Novel, Shear-Thinning and Rapidly Self-Healing Polymer Nanoparticle Hydrogel Diminishes Post-Operative Adhesions in Rodent and Ovine Models of Cardiac Adhesion Formation

Objective: Adhesions develop after 95% of operations, represent a major clinical challenge, and cost the U.S healthcare system $2.5B annually. In cardiac surgery, adhesions are problematic during re-operations, increasing operative times and posing risks of hemorrhage and injury to the heart and lungs during sternal reentry and cardiac dissection. We hypothesized that shear-thinning, self-healing polymer nanoparticle hydrogels (PNP) would provide a viscoelastic barrier, effectively preventing adhesion formation (Fig 1A). Methods: Multiple PNP formulations underwent rheologic characterization. Male Sprague Dawley rats (n=52) underwent permanent ligation of the LAD to induce robust postinfarct adhesions, followed by epicardial application of PNP (200L), Seprafilm®(1cm 2 ), or no treatment. Male Dorset sheep (n=8) underwent an anterolateral epicardial abrasion followed by application of PNP (25mL), Seprafilm® (12 cm 2 ), or no treatment. Degree of adhesion formation, standardized dissection time, heart function, and immune response were assessed 4-weeks following surgery. Results: PNP exhibited formulation-dependent mechanical properties indicating the effect of hydrogel stiffness on adhesion barrier efficacy (Fig 1B). Infarct size and heart function were controlled to ensure similar inflammatory responses contributing to adhesion formation across treatment groups. Treatment with certain PNP formulations significantly reduced the development of adhesions compared to controls (Fig 1C). Ovine hearts treated with the PNP 1:10 revealed a pristine epicardial surface (Fig 1D, 1E, and 1F) and resulted in a shorter dissection time relative to the controls (Fig 1G). Conclusion: Administration of a shear-thinning, self-healing hydrogel reduces the extent of adhesion formation in the thoracic cavity following surgery in small and large animal models. PNP provides an easily delivered, scalable solution for post-operative adhesion prevention.

Adhesion Prevention to Polypropylene Meshes Using Combined Icodextrin Four Percent and Dimetindene Maleate

BackgroundThe use of surgical meshes in ventral hernia repair has significantly reduced hernia recurrence rates. However, when placed intraperitoneally prosthetic materials can trigger the development of peritoneal adhesions. The present experimental study evaluated the combined icodextrin 4% and dimetindene maleate treatment in preventing peritoneal adhesion formation to polypropylene and titanium-coated polypropylene meshes. Materials and methodsSixty female white rabbits were divided into four groups. A 2 × 2 cm piece of mesh was fixed to intact peritoneum in all animals through a midline laparotomy. A lightweight polypropylene mesh was implanted in groups 1 and 2 and a titanium-coated polypropylene mesh in groups 3 and 4. Groups 2 and 4 were treated, intraoperatively, with intravenous dimetindene maleate (0.1 mg/kg) and intraperitoneal solution of icodextrin 4% (20 mL/kg) and for the next 6 d with dimetindene maleate intramuscularly. The observation period lasted 15 d. Adhesion scores, percentage of mesh affected surface, tissue hydroxyproline levels, and tissue histopathology were examined. ResultsAll animals in group 1 and 57% of animals in group 3 presented postoperative adhesions. The combination of antiadhesives significantly reduced the extent and severity of adhesions as well as the hydroxyproline levels in groups 2 and 4 compared with groups 1 and 3. On microscopic evaluation, animals in group 1 exhibited higher inflammation scores compared with group 2, whereas animals in groups 2 and 4 had better mesotheliazation compared with groups 1 and 3. ConclusionsThe combined administration of icodextrin 4% and dimetindene maleate reduces the extent and severity of adhesions and may be successfully used to prevent adhesion formation after mesh intraperitoneal placement.

An Improved Method for Temporary Suture Medialisation of the Middle Turbinates following Endoscopic Sinus Surgery.

Background Middle turbinate (MT) lateralisation with adhesion formation (MiTLAF) is a common complication following endoscopic sinus surgery, frequently resulting in surgical failure, persistence of preoperative symptoms, and delayed secondary complications. Packing materials, splints, or spacers reduce the risk of MiTLAF but often result in postoperative nasal obstruction and discomfort, along with reduced access for irrigation. Temporary suture medialisation of the MTs reduces the risk of MiTLAF and prevents the problems encountered with packing, splints, or spacers. However, the techniques described in the literature are technically challenging and often ineffectual. Methods We describe a method of suture placement that provides a secure temporary MT medialisation, without the technical challenges of traditional techniques, using a 4-0 Monocryl (Poliglecaprone 25, Ethicon, Somerville, NJ, USA) suture on a 19 mm precision point reverse cutting PS-2 curved needle. We review 25 consecutive patients undergoing sinonasal procedures with our new technique and assess for MiTLAF. Results In our cohort, only one patient experienced MiTLAF which was not clinically significant. Conclusions Our method is simple, easy to perform, and highly effective and prevents adhesion formation without the need for postoperative splints or packing.

Potential Usefulness of Losartan as an Antifibrotic Agent and Adjunct to Platelet-Rich Plasma Therapy to Improve Muscle Healing and Cartilage Repair and Prevent Adhesion Formation.

Postoperative tissue fibrosis represents a major complication in orthopedics. Transforming growth factor beta 1 is a key molecule in the development of postoperative fibrosis. High concentrations of transforming growth factor beta 1 have also been implicated in various diseases. Agents that counteract the actions of transforming growth factor beta 1 have been investigated as potential antifibrotic medications and as adjunct treatment to platelet-rich plasma injections (increased amounts of transforming growth factor beta 1) to improve their effectiveness and/or safety profile. Losartan blocks transforming growth factor beta 1 action and has attracted special interest in orthopedic research that focuses on how to reduce the risk of postoperative fibrosis. [Orthopedics. 2018; 41(5):e591-e597.].

In vitro investigation of chitosan-polygalacturonic acid polyelectrolyte complex (PEC) biomaterials as anti-adhesive substrates for preventing adhesion formation

Adhesions are an abnormal union of membranous surfaces. They are a painful and expensive consequence of abdominal surgeries, specifically in the peritoneal cavity. This complication requires a second surgery to remove the problem, known as adhesiolysis, which we are trying to avoid. Current solutions to adhesion formation either lack efficacy or induce an inflammatory response in the peritoneum. Our focus is to develop a post-surgical adhesion prevention polyelectrolyte complex (PEC) film, composed of an optimal ratio of chitosan (Chi) and polygalacturonic acid (PgA) to prevent adhesion formation. Adhesive properties of fibroblasts and macrophages on the PEC were also studied, since both cell types play a central role in the adhesion formation process. Additionally, we examined PEC attachment methods, ultimately for in vivo application. Current in vitro studies evaluated the material properties of the film to determine the stability of the material. The results of our studies identified certain ratios of Chi-PgA films which are mechanically consistent for use as intra-peritoneal barriers. Furthermore, their potential as anti-adhesive barriers were further supported by the fact that their surfaces are non-permissive for viable fibroblast and macrophage attachment.

Hyaluronic acid and synovial fluid in preventing adhesion formation after tenorrhaphy: An in vivo study on rabbit Achilles tendon

ABSTRACT: Peritendinous adhesions are a significant problem in tendon surgery. One of the most preferred methods for preventing adhesion formation is anti-adhesive applications. This study aimed to investigate the efficacy of natural synovial fluid as an alternative viscoelastic agent for preventing adhesion in the healing period compared to hyaluronic acid. Thirty adult New Zealand rabbits were used in the study to form three experimental models. In all groups, a rupture was induced in the Achilles tendons. Following tenorrhaphy, hyaluronic acid was applied in one group and synovial fluid in the other group for anti-adhesive purposes. In the control group, no viscoelastic application was made. Bandage was applied to the operated extremities for three weeks post-operatively. At the end of five weeks, euthanasia was performed on the animals using pentobarbital sodium. Surgical sites in all groups were macroscopically examined for healing status as well as the presence and extent of adhesions. Biomechanical tests and histopathological examinations were then performed on the tendons in all groups. Findings established once again the positive contribution of hyaluronic acid to preventing adhesion formation as well as to healing and tensile strength in tendon surgery. Although, we found that it is possible to use synovial fluid, which is a natural source of hyaluronic acid, as a viscoelastic material, it is not superior to commercial hyaluronic acid preparation.

PIH20 - Cost-Effectiveness Analysis of Absorbable Adhesion Barrier in Preventing Adhesion Formation after Open Gynecologic Surgeries in China

PIH20 - Cost-Effectiveness Analysis of Absorbable Adhesion Barrier in Preventing Adhesion Formation after Open Gynecologic Surgeries in China

Rapamycin Protects Against Peritendinous Fibrosis Through Activation of Autophagy.

Dysregulation of autophagy plays a pivotal role in fibrosis in multiple organs. However, the role of autophagy in peritendinous fibrosis is not well understood. Here, we hypothesize that autophagy plays a protective role in preventing adhesion formation. In a rat model of tendon injury, we observed dysregulated autophagy during excessive extracellular matrix deposition. Pharmacological induction of autophagy by rapamycin markedly alleviated the severity of peritendinous fibrosis in vivo. In NIH/3T3 fibroblasts and tenocytes, transforming growth factor β1 (TGF-β1) markedly activated myofibroblasts and increased collagen synthesis. Addition of rapamycin activated autophagy, reduced collagen synthesis, and suppressed myofibroblast activation. In vitro experiments also showed that rapamycin decreased cell proliferation and increased the number of cells arrested in G0/G1 phase. However, following pretreatment with the autophagy inhibitor 3-methyladenine (3-MA), rapamycin was unable to repress the fibrotic changes induced by TGF-β1. Autophagy related protein 5 (Atg5) RNA interference in fibroblasts also abolished the protective effects of rapamycin in vitro. In conclusion, our results point to rapamycin as a potential treatment strategy in the prevention of peritendinous fibrosis after tendon injury.

Trametinib prevents mesothelial-mesenchymal transition and ameliorates abdominal adhesion formation

BackgroundIntra-abdominal adhesions are a major cause of morbidity after abdominal or gynecologic surgery. However, knowledge about the pathogenic mechanism(s) is limited, and there are no effective treatments. Here, we investigated a mouse model of bowel adhesion formation and the effect(s) of an Federal Drug Administration-approved drug (trametinib) in preventing adhesion formation. Materials and methodsC57BL/6 mice were used to develop a consistent model of intra-abdominal adhesion formation by gentle cecal abrasion with mortality rates of <10%. Adhesion formation was analyzed histologically and immunochemically to characterize the expression of pro-fibrotic marker proteins seen in pathologic scaring and included alpha smooth muscle actin (αSMA) and fibronectin EDA (FNEDA) which arises from alternative splicing of the fibronectin messenger RNA resulting in different protein isoforms. Trichrome staining assessed collagen deposition. Quantitative polymerase chain reaction analysis of RNA isolated from adhesions by laser capture microscopy was carried out to assess pro-fibrotic gene expression. To block adhesion formation, trametinib was administered via a subcutaneous osmotic pump. ResultsAdhesions were seen as early as post-operative day 1 with extensive adhesions being formed and vascularized by day 5. The expression of the FNEDA isoform occurred first with subsequent expression of αSMA and collagen. The drug trametinib was chosen for in vivo studies because it effectively blocked the mesothelial to mesenchymal transition of rat mesothelium. Trametinib, at the highest dose used (3 mg/kg/d), prevented adhesion formation while at lower doses, adhesions were usually limited, as evidenced by the presence of FNEDA isoform but not αSMA. ConclusionsCecal abrasion in mice is a reliable model to study abdominal adhesions, which can be ameliorated using the MEK1/2 inhibitor trametinib. While blocking adhesion formation at the cell and molecular levels, trametinib, at the therapeutic doses utilized, did not impair the wound healing at the laparotomy site.