Post-Operative Adhesions: A Comprehensive Review of Mechanisms

Post-surgical adhesions are common in almost all surgical areas and are associated with significant rates of morbidity, mortality, and increased healthcare costs, especially when a patient requires repeat operative interventions. Many groups have studied the mechanisms driving post-surgical adhesion formation. Despite continued advancements, we are yet to identify a prevailing mechanism. It is highly likely that post-operative adhesions have a multifactorial etiology. This complex pathophysiology, coupled with our incomplete understanding of the underlying pathways, has resulted in therapeutic options that have failed to demonstrate safety and efficacy on a consistent basis. The translation of findings from basic and preclinical research into robust clinical trials has also remained elusive. Herein, we present and contextualize the latest findings surrounding mechanisms that have been implicated in post-surgical adhesion formation.

Prevention of Post-Operative Adhesions: A Comprehensive Review of Present and Emerging Strategies

Post-operative adhesions affect patients undergoing all types of surgeries. They are associated with serious complications, including higher risk of morbidity and mortality. Given increased hospitalization, longer operative times, and longer length of hospital stay, post-surgical adhesions also pose a great financial burden. Although our knowledge of some of the underlying mechanisms driving adhesion formation has significantly improved over the past two decades, literature has yet to fully explain the pathogenesis and etiology of post-surgical adhesions. As a result, finding an ideal preventative strategy and leveraging appropriate tissue engineering strategies has proven to be difficult. Different products have been developed and enjoyed various levels of success along the translational tissue engineering research spectrum, but their clinical translation has been limited. Herein, we comprehensively review the agents and products that have been developed to mitigate post-operative adhesion formation. We also assess emerging strategies that aid in facilitating precision and personalized medicine to improve outcomes for patients and our healthcare system.

The Therapeutic Potential of Targeting the Angiotensin Pathway as a Novel Therapeutic Approach to Ameliorating Post-Surgical Adhesions

Background: Post-surgical adhesion is a common complication after abdominal or pelvic surgeries. Despite improvements in surgical techniques or the application of physical barriers, little improvements have been achieved. It causes bowel obstruction, pelvic pain, and infertility in women and has an adverse effect on the quality of life. Renin-Angiotensin System (RAS) is traditionally considered as a blood pressure regulator. However, recent studies also indicate that the RAS plays a vital role in other processes, including oxidative stress, fibrosis, proliferation, inflammation, and the wound healing process. Angiotensin II (Ang II) is the main upstream effector of the RAS that can bind to the AT1 receptor (ATIR). A growing body of evidence has revealed that targeting Angiotensin-Converting Enzyme Inhibitors (ACEIs), Angiotensin II type 1 Receptor Blockers (ARBs), and Direct Renin Inhibitors (DRIs) can prevent post-surgical adhesions. Here we provide an overview of the therapeutic effect of RAS antagonists for adhesion. Methods: PubMed, EMBASE, and the Cochrane library were reviewed to identify potential agents targeting the RAS system as a potential approach for post-surgical adhesion. Results: Available evidence suggests the involvement of the RAS signaling pathway in inflammation, proliferation, and fibrosis pathways as well as in post-surgical adhesions. Several FDA-approved drugs are being used for targeting the RAS system. Some of them are being tested in different models to reduce fibrosis and improve adhesion after surgery, including Telmisartan, valsartan, and enalapril. Conclusion: Identification of the pathological causes of post-surgical adhesion and the potential role of targeting Renin–Angiotensin System may help prevent this problem. Based on the pathological function of RAS signaling after surgeries, the administration of ARBs may be considered as a novel and efficient approach to prevent postsurgical adhesions. Pre-clinical and clinical studies should be carried out to have better information on the clinical significance of this therapy against post-surgical adhesion formation.

Relapsing constrictive pericarditis after implantation of an expanded polytetrafluoroethylene surgical membrane

One of the challenges compounding the complexity of reoperative cardiac surgery are the surgical adhesions, which can be responsible for adverse intraoperative events. In such situations implantation of a substitute neo-pericardium has become a frequently used solution for avoiding injuries to the heart and great vessels, with rising numbers of reoperations. The pericardium can be reconstructed using biological (heterologous or autologous) or synthetic material, each having their pros and cons. In this report we present a case of relapsing constrictive pericarditis after implantation of expanded polytetrafluoroethylene neo-pericardium (GORE®). A highly differentiated algorithm and a careful preoperative review of indication is recommended in order to plan the optimal method of pericardioplasty, taking into account the pros and cons of each available material.

Post-surgical adhesions are triggered by calcium-dependent membrane bridges between mesothelial surfaces

Surgical adhesions are bands of scar tissues that abnormally conjoin organ surfaces. Adhesions are a major cause of post-operative and dialysis-related complications, yet their patho-mechanism remains elusive, and prevention agents in clinical trials have thus far failed to achieve efficacy. Here, we uncover the adhesion initiation mechanism by coating beads with human mesothelial cells that normally line organ surfaces, and viewing them under adhesion stimuli. We document expansive membrane protrusions from mesothelia that tether beads with massive accompanying adherence forces. Membrane protrusions precede matrix deposition, and can transmit adhesion stimuli to healthy surfaces. We identify cytoskeletal effectors and calcium signaling as molecular triggers that initiate surgical adhesions. A single, localized dose targeting these early germinal events completely prevented adhesions in a preclinical mouse model, and in human assays. Our findings classifies the adhesion pathology as originating from mesothelial membrane bridges and offer a radically new therapeutic approach to treat adhesions.