Adhesions during and after Surgical Procedures,their Prevention and Impact on Women'S Health

“… adhesion formation is less after laparoscopy compared with laparotomy.”

Adhesion formation following open or laparoscopic surgery remains an almost inevitable consequence of most abdominal procedures. Adhesions resulting from gynecological surgery may well be the most significant iatrogenic factor contributing to small bowel obstruction, chronic pelvic pain, dyspareunia, infertility and a higher complication rate for all following operations. The induction of adhesions was first described in 1889 by von Dembowski in an animal model [1]. Since then many other attempts have been made to define adhesions, but neither a clear definition or established classifications have evolved concerning manifestation and degree of severity. It is estimated that more than 50% of all women undergoing operation will form adhesions. Nevertheless, this rate can only be estimated as the pathogenesis and pathways leading to adhesions are not yet well defined and, therefore, adhesion prophylaxis is still in an experimental stage. However, different methods and approaches have been employed to reduce adhesions but with highly diverging effects.

Pathogenesis of adhesion formation

Many processes occur in response to adhesion stimulation. Peritoneal mesothelial damage leads to an acute inflammatory response promoting the growth of fibrous adhesions.

The fibrinous exudate leads to the formation of fibrin by activation of the coagulation cascade, which transforms prothrombin into thrombin (Factor IIa). Thrombin then triggers the conversion of fibrinogen into monomers of fibrin, which polymerize and are deposited on the wound surface. Polymorphonuclear macrophages and mesothelial cells, which are present in the fibrinous exudate, migrate, proliferate and differentiate. They release a variety of substances, such as plasminogen system components, arachidonic acid metabolites, cytokines and growth factors.

Although fibrinous exudates and fibrin deposition are a part of normal tissue repair, a balance between fibrin deposition and degradation is essential for deciding whether there will be normal peritoneal healing or adhesion formation. Upon full fibrin degradation there will be normal peritoneal healing. If fibrin is not completely degraded, fibroblasts and capillary ingrowths will occur. VEGF has also been implicated in having a role in adhesion formation. Cytokines are produced by fibroblasts and macrophages, which are present within the fibrin meshwork and cause increased collagen synthesis.

Consequences of abdominal adhesions

The following complications may be observed directly due to adhesions from abdominal or pelvic surgeries: bowel obstruction, chronic pelvic pain, dyspareunia, infertility and a higher complication risk in subsequent operations [2,3]. Surgeries on the uterus, ovary and the fallopian tube that involve distortion of the normal anatomy may result in impaired fertility. Patients with a history of various manipulations or surgical procedures are favored subjects for adhesion formation [4]. One-third of all cases of intestinal obstruction are secondary to adhesions [5]. Moderate-to-severe pelvic adhesions may be responsible for 40% of infertility [6]. Successful pregnancy outcome after adhesiolysis in cases of mild filmy adhesions may not improve subsequent pregnancy rates [7]. Some studies have demonstrated that laparoscopic adhesiolysis reduces the subjective assessment of pain [8].

Laparoscopy & adhesion formation

In laparoscopy, trauma to the peritoneum is minimized relative to open surgery. Less hemorrhage results from laparoscopy and the fact that pneumoperitoneum is established may separate healing surfaces and reduce adhesion formation. However, some studies suggest that the pneumoperitoneum used in laparoscopy has some effect on adhesion formation. Elevated intra-abdominal pressure may result in local hypoxia and may potentiate adhesion formation [9]. Most studies indicate that adhesion formation is reduced after laparoscopy compared with laparotomy [10].

Prevention of adhesions

Second-look laparoscopy revealed adhesions in 75% of patients treated at laparotomy compared with 15% in the laparoscopy group [11].

Adhesion reduction agents are of two categories. The first are the pharmacological therapies and the second comprises the topical products that are directly applied during surgery to the operative site. The peritoneum is highly permeable to water, small solutes and proteins and, therefore, is not a physical barrier [12]. This porosity leads to rapid absorption of the intraperitoneal agents, thereby limiting any benefit. Many drugs were trialed extensively to mediate the inflammatory response. Initial attempts used steroids and NSAIDs. Systemic side effects limited the use of these agents. The bleeding with NSAIDs or impaired wound healing with steroids has restricted the use of such agents. Recently free-radical scavengers, including methylene blue [13] and antihistamines, have been trialed [14].

Topical agents

Topical agents are divided into liquids and gels. Liquids are instilled into the abdominal cavity at the end of the surgery. These separate the bowels, which float freely in the liquid based on the principle of hydroflotation. Here, between 500 ml and 3 l of fluid are instilled into the cavity; however, no significant evidence exists to support their use as the absorption rate of the peritoneum ensures that the fluid is absorbed into the vascular system within 24–48 h. Hyperosmolar solutions, such as peritoneal dialysis solution, may be reabsorbed more slowly and have been shown to be effective in rats [15]. Intergel® (Lifecore Biomedical Inc., MN, USA), a solution containing hyaluronic acid, has undergone clinical trials in laparoscopy and laparotomy and has revealed fewer adhesions. Adept®, a 4% icodextrin solution of Baxter Healthcare Corp. (IL, USA), seems promising [16] and the results of the GENEVA study are due to be published shortly [17]. The GENEVA study confirmed the safety of Adept in laparoscopic surgery; however, the proportion of patients with de novo adhesion formation was surprisingly high. No significant difference was found in the reduction of de novo adhesion incidence between Adept and lactated Ringer's solution. A site-specific barrier agent may best be combined with Adept for a wider spectrum of anti-adhesion formation.

Barriers

The basic principle of these agents is that there should be separation of the operative surfaces with a mechanical barrier. There are certain properties that the agents should display to serve as barriers (e.g., the material should be easily degraded without a fibrous reaction). A series of experiments have demonstrated that adhesion formation does not progress after a mesothelial cell layer covers a foreign mesh at approximately 1 week [18].

At present, the following barriers are available: hyaluronic acid, chitosan, carboxymethylcellulose, oxidized regenerated cellulose and expanded polytetrafluoroethylene. The adverse effects of peritonitis and abscesses have hindered the use of hyaluronic acid [19]. Chitosan has an antimicrobial action to bacteria, fungi and viruses and, because of its hemostatic nature, has been successfully used in the dressing of wounds.

“… adhesion formation does not progress after a mesothelial cell layer covers a foreign mesh at approximately 1 week.”

Interceed® (Johnson and Johnson Patient Care Inc., NJ, USA), an oxidized regenerated cellulose, was one of the first barrier agents to be tested. It is a mesh-like barrier that is placed between the traumatized surfaces. It has been used in patients undergoing both laparoscopy and laparotomy for the treatment of conditions such as fibroids, endometriosis and ovarian masses. Larsson concluded that Interceed was safe and effective in controlled human trials; however, it could not eliminate adhesions in all patients and the presence of blood in the matrix of the material negated any benefit [20]. There is also a technical difficulty in introducing the material laparoscopically. However, level 1 evidence revealed a reduction of postoperative adhesions.

Seprafilm® (Genzyme Corp., MN, USA), a hyaluronic acid and carboxymethylcellulose modified to produce a clear film, is another anti-adhesion barrier. Level 1 evidence showed that Seprafilm was safe and effective in reducing postoperative adhesions, but its use was limited due to the difficulty to apply it laparoscopically.

Level 1 evidence also revealed that the barrier Goretex® (WL Gore and Associates, AZ, USA), a polytetrafluoroethylene, reduced the severity of adhesions; however, its usefulness is limited by the need for suturing and later removal. There is also a potential risk of infection and difficulty in applying it laparoscopically.

SprayGel® (Covidien, formerly Confluent Surgical Inc., MN, USA), a polyethylene glycol, is another absorbable barrier. The synthetic gel adhesive barrier is easily applicable after both laparoscopic and open surgery [21,22]. The barrier is formulated to adhere for 5–7 days after which it hydrolyzes to water soluble compounds. Today, Covidien markets a further development of this product under the name of SprayShield® with level 1 evidence.

CoSeal® is a commercially available barrier from Baxter Healthcare Corp. (IL, USA) that has prevented adhesions in 60% of cases in a randomized trial [23].

HYAcorp® endo gel (BioScience GmbH, Ransbach-Baumbach, Germany) is an absorbable, anti-adhesion barrier gel, designed on the basis of hyaluronic acid, and has met with initial clinical success.

In spite of level 1 evidence, so far none of the products are US FDA approved at laparoscopy.

In an interesting monocentric study, Dubuisson et al. evaluated the incidence of intra-abdominal adhesions related to prior abdominal surgery in 1000 gynecological laparoscopic surgical procedures [24]. In 211 cases, intra-abdominal adhesions had to be lyzed (21.1%).

Future perspective

Dubuisson's study provides insight into the incidence of adhesions, which are found in every fifth laparoscopy. One-quarter of these patients had adhesions with bowel involvement. The incidence of adhesions rose with the number of previous surgeries. This article confirms that knowledge of the patient's surgical history is necessary to evaluate the risk of adhesion formation.