The Online Collection
Surgical Technology International XVI - Surgical Overview
Article title:
Hyaluronan-Based Antiadhesive Agents in Abdominal Surgery: Applications, Results, and Mechanisms of Action









Cornelis J.J.M. Sikkink, M.D.

General Surgeon

Department of Surgery, VU Medical Center, Amsterdam, The Netherlands


Clark J. Zeebregts, M.D., Ph.D.

Staff Surgeon

Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands


Michel M.P.J. Reijnen, M.D., Ph.D.

Staff Surgeon

Department of Surgery, Alysis Zorggroep, Lokatie Rijnstate, Arnhem, The Netherlands


Postsurgical intra-abdominal adhesions cause significant morbidity and mortality, with small bowel obstruction being the most common complication. The urge to prevent adhesion formation has resulted in multiple experimental and clinical trials and the development of numerous antiadhesive agents. Through the years, hyaluronan-based antiadhesives have proved to be successful in the reduction of adhesion formation. Despite the obvious effectiveness of hyaluronan, there is still much debate on its clinical use and mechanisms of action. Various hyaluronan-containing products have been introduced and withdrawn from the market. The application of hyaluronan in combination with meshes for hernia repair appears to be a promising concept. Not all different applications of hyaluronan are well known and its use in patients with a malignancy or abdominal infection remains controversial. Here an overview is given on the effects of hyaluronan-based antiadhesive agents in abdominal surgery, its use in infectious conditions, and its oncologic repercussions. The most important mechanism of action appears to be the mechanical separation of damaged peritoneal surfaces. However, the biological effects of hyaluronan, such as modulation of cell proliferation and peritoneal biology, might also be of influence.



Peritoneal trauma during abdominal surgery and abdominal infection can lead to intra-abdominal adhesion formation (Fig. 1). Adhesions, especially when excessive, can cause severe complications and are responsible for considerable morbidity and mortality. Adhesions are the main cause of intestinal obstruction in the developed world and account for approximately 70% of readmissions for small bowel obstruction.1 After conventional colorectal surgery, one out of five patients is readmitted for reasons directly or indirectly related to adhesions within 4 years after the operation.2 The relative risk of adhesion-related complications in this group is 29.7 per 100 initial procedures over 4 years time. Furthermore, adhesions account for 15% to 20% of cases of secondary infertility in women and are associated with chronic abdominal and pelvic pain.3,4 Relaparotomies are complicated by the presence of adhesions as well; procedures are longer and the risk of inadvertent enterotomy is approximately 20%, which in turn is associated with a higher incidence of postoperative complications, an increased risk of admission to intensive care units, and prolonged hospital stays.5 Complication rates may be even higher when adhesions are accompanied by abdominal infection and abscess formation. The high incidence of adhesion-related complications, their severity, and the obvious impact on the health care burden urge attention for the prevention of postsurgical adhesion formation.

Figure 1. (a) Intra-abdominal adhesion between

small bowel loops. (b) Intra-abdominal adhesion

between omentum and the abdominal wall.

Mechanical separation of adhesiogenic wound surfaces during the first phase of peritoneal healing โ€” which takes 5 days to 7 days โ€” is the most common concept of adhesion prevention. During the last decades, several mechanical barriers have been developed. Membranes of oxidized regenerated cellulose or expanded polytetrafluoroethylene have been demonstrated to decrease the incidence of adhesion formation.6โ€“9 However, oxidized regenerated cellulose was less effective in the presence of blood. Expanded polytetrafluoroethylene may not be the ideal antiadhesive, as it is a permanent device; it remains in situ on the injured site where it is placed, prone for device-related complications.

Figure 2. Hyaluronan is a polysaccharide made up of

repeating disaccharide units of sodium glucuronate

and N-acetyl-glucosamine linked by glycosidic bonds.

Hyaluronan (HA) is a polysaccharide made up of repeating disaccharide units of sodium glucuronate and N-acetyl-glucosamine linked by glycosidic bonds (Fig. 2). In 1934, Meyer and Palmer were the first to describe hyaluronic acid, a polysaccharide isolated from the vitreous fluid (hyalos) that contained uronic acid.10 Later, the name hyaluronan was introduced.11 The intraperitoneal application of HA derivates was considered a promising concept for the reduction of adhesions. Today HA is well known for its antiadhesive properties and has been studied extensively. Currently, HA-based agents are the most frequently used antiadhesive agents worldwide with an undisputed adhesion reducing effect. Use of HA under contaminated or infectious conditions and during oncologic procedures is described as well. However, its use under these conditions is still controversial. In this chapter, an overview is given on the role of HA-based antiadhesive agents in abdominal surgery, with attention for different application forms, mechanisms of action, results, and oncologic repercussions.