** Pelvic Adhesions **
Despite multiple alterations in operative technique, and the recent induction of various adhesion barriers, the issue of adhesion prevention remains at the forefront. All surgeons must deal with the potential for formation of adhesions during surgery, as well as the sequelae of adhesions from previous surgery which may markedly alter the difficulty of a particular surgery.
Post-surgical adhesions often occur following pelvic and abdominal surgery. Data has suggested that 67% to 93% of patients will develop adhesions following abdominal surgery and 55% to 100% of patients will develop adhesions following gynecologic surgery. These issues become critically important from a standpoint of reproductive potential. Additionally, adhesions may be associated with issues such as pelvic pain, as well as abnormalities of bowel function and small bowel obstruction.
** Definitions **
Several definitions of adhesions exist. De novo or new adhesions may form at a site of direct surgical trauma such as a myomectomy incision or an ovarian incision at the time of ovarian cystectomy. De novo adhesions may also develop remote from the site of surgery, such as when adhesions develop surrounding the adnexa at the time of a cesarean section. Adhesions may also reform following adhesiolysis or adhesiectomy.
While three general types of adhesions exist - filmy, vascular, and cohesive, the underlying pathophysiology is similar. The American Fertility Society has attempted to classify disease according to the location and type of adhesions. We have additionally suggested modifications in this standard assessment in an effort to increase reproducibility between surgeons, as well as provide greater levels of information when surgeons communicate.
** The Peritoneum **
An understanding of the anatomy of the peritoneum and the response of the peritoneum to injury is important in understanding how we might prevent adhesion formation. The peritoneum is composed of multiple layers, the mesothelium being the innermost layer, a layer of connective tissue which contains the vascularity and a basement membrane. When the peritoneum is injured (which is inevitable during surgery), during direct incision or indirectly such as with desiccation, there is an inflammatory response.
During this initial phase, inflammatory mediators and histamine are released from mast cells and leukocytes. Capillaries located within the connective tissue dilate and an increased permeability is noted. This allows leukocytes, red blood cells and platelets to become concentrated at the site of an injury. A fibrinous exudate is thus formed at the site of injury. Multiple factors such as prostaglandins, lymphokines, bradykinin, serotonin, transforming growth factor and other chemotactic agents are present within the exudated material.
At this point in time the fibrinous exudate may be cleared through fibrinolysis. In order for this to occur plasminogen must be converted to plasmin by tissue plasminogen activator (t-PA). There is a constant balance in the system between tissue plasminogen activator and plasminogen activator inhibitors. Unfortunately, surgical trauma may have an inherent ability to decrease tissue plasminogen activity while increasing plasminogen activator inhibitors. Under normal circumstances plasmin breaks down exudated fibrin. If this does not occur, the fibrinous exudate is converted into an organized adhesion and fibers of collagen are deposited. Following this, blood vessels begin to form allowing organization of the adhesion.
This process occurs over a one to seven day period of time. In general, at seven days the quantitative development of adhesions is complete. Qualitative changes continue over the next several months with adhesions becoming more dense and vascularized.
Our efforts at adhesion reduction have thus been an attempt to alter the previously described process. These may generally be described as:
1.) minimizing peritoneal injury during surgery, 2.) reducing the local and inflammatory response, 3.) inhibiting the coagulation cascade and promoting fibrinolysis, and 4.) using barriers for separation of surfaces at high risk for adhesion formation.
** Micro and Macro Techniques for Adhesion Reduction **
Various techniques and disease states have been suggested to predispose to adhesion formation. Many studies have been performed to document this. They include incomplete hemostasis, foreign bodies, tissue injury, type of suture utilized, amount of crushing and tissue destruction from instrumentation, tissue desiccation, and underlying infection. Many practical techniques may be utilized to minimize aberration from optimal techniques.
The use of gauze and minimally moistened dry sponges may cause significant peritoneal denudation and surface injury. The use of frequent irrigation has been recommended to limit tissue desiccation and keep tissues moistened. Micro- surgical techniques have been developed in an effort to achieve less tissue destruction during surgery while maintaining precise hemostasis in an effort to decrease subsequent fibrin layering and the potential for adhesions. The use of the most acceptable minimally reactive sutures and an effort to not suture unless necessary helps avoid both tissue reaction and subsequent tissue ischemia from suture placement.
Unfortunately, while the use of such microsurgical techniques are important in and of themselves, they will not completely decrease the risk of adhesions. Indeed, studies have suggested that de novo adhesion rates in patients undergoing laparotomy may be greater than 90% when large numbers of sites are evaluated at the time of second look laparoscopy.
** Risk Factors for Adhesion Formation **
Multiple risks factors have been identified for the formation of adhesions. In one study performed at the time of autopsy the authors reported a 90% incidence of adhesions in patients with multiple previous surgeries, 70% incidence of adhesions in patients with previous gynecologic surgery, a 50% incidence of adhesions with previous appendectomy, and interestingly, a greater than 20% incidence of adhesions in patients with no surgical history. Of even greater interest, a recent publication suggested that myomectomy with a posterior uterine incision may have an incidence of greater than 90% of adhesions from the incision line to bowel, omentum. or the adnexa. Additionally, there has been great interest in the amount of adhesion reformation following lysis of adhesions for laparotomy vs. laparoscopy, as well as the incidence of de novo adhesion formation in laparotomy and laparoscopy.
Compilation studies have suggested that there is a 70% incidence of adhesion reformation with laparotomy and greater than 50% de novo adhesion formation. While adhesion formation has not been found to be significantly altered by laparoscopy, the amount of de novo adhesion has been reported in various studies to be only 10%.
** Pharmacologic Agents in Adhesion Reduction **
In an effort to decrease the adhesions in patients, multiple different methodologies have been utilized. Installation of crystalloid, such a lactated ringers, has been performed. While several animal studies demonstrated a significant reduction in adhesions, multiple studies which utilize crystalloid in control patients, demonstrated no significant effect.
Thirty-two percent Dextran-70 (Hyskon) has been evaluated in multiple studies. The affect of Hyskon to draw fluid into the peritoneal cavity conceptually allows hydro-floatation of viscous structures. It was thought that the separation of viscous structures would not allow fibrin bands to form, thus reducing the risk of adhesion formation. Multiple studies have presented conflicting results from ineffective to statistically effective. In general, it is presently felt that if such therapy is effective, the dependent area of the pelvis may be most positively affected.
Corticosteroids, antihistamines, and non steroidal anti-inflammatories have all been used by various routes in an effort to decrease adhesion formation. The classic regimen of a steroid with antihistamine has been shown to be ineffective in a well done study.
** Barriers for Adhesion Reduction **
Most recently, barriers have been suggested as a means to decrease adherence of one peritoneal structure to another. Presently, two such surgical membranes are marketed in the United States - a Gore-tex surgical membrane composed of expanded polytetrafluoroethylene and Interceed (Johnson and Johnson Medical, Inc. Arlington, TX). The Gore-tex surgical membrane has been used for a number of years and was initially approved for cardiovascular work. This membrane is non-absorbable, non-inflammatory, and because of the small pore size of less than one micron, does not allow infiltration into this sheath. Placement of a surgical membrane requires immobilization by either suture or staple. Several studies have recently demonstrated the efficacy of this membrane. Unfortunately, it is currently recommended that the membrane be removed in patients desiring subsequent fertility.
Interceed barrier is an oxidized regenerated cellulose compound. The exposure of Interceed to peritoneal fluid causes subsequent breakdown and formation of a gelatinous coating over the applied tissue. It is felt that this coating decreases the formation of fibrin bridges which may lead to adhesion formation. Multiple studies have evaluated Interceed as a barrier.
In a study of pelvic sidewall adhesions, applications of Interceed prevented adhesion formation in 51 % of patients vs. 24% of controls where only good surgical technique was utilized. Multiple studies presently exist to document the efficacy in additional procedures, such as endometriosis and in ovarian surgery. It is critically important in the application of Interceed that complete hemostasis be assured. The barrier is then applied, subsequently moistened, and does not require suturing. It is helpful to remove all irrigation fluid by placing the patient in severe reverse Trendelenberg prior to application of these barriers.
Most recently, efforts have been directed to evaluate a solution, film, and gel composed of hyaluronic acid. While initial studies were discouraging, reformulation of the compound have demonstrated excellent results in animal trials. We are presently completing a multicenter randomized double blind study to evaluate both the solution and film. It is hoped that, in the future, applications will obviate the difficult application of membranes, or the need to return for second-look laparoscopy to remove non- absorbable membranes. However, this work remains to be clinically documented.
It remains to be elucidated what the most effective substance will be for adhesion prevention. It is likely that a multifaceted approach, which includes minimization of trauma to tissue, tissue hydration, use of the least reactive sutures, and application of various barriers may yield the best results.