Many adhesion mysteries unraveled, but questions remain.

PASADENA, CALIF. -- Adhesion formation probably occurs within the first 3-5 days following surgery, when hypoxia triggers a cascade of cytokines, growth factors, and clotting factors that form a fibrinous, clotlike mass, Dr. Michael P. Diamond said at a meeting of the Obstetrical and Gynecological Assembly of Southern California.

Unless a high level of tissue plasminogen activator (TPA) in relation to plasminogen activator inhibitor-1 (PAI-1) can break up the mass, conditions become ripe for uniquely equipped fibroblasts to proliferate and amass at the site of injury.

Angiogenesis follows, and resilient adhesive bands of tissue are formed that are exceedingly difficult to permanently eradicate through adhesiolysis.

The scenario, based on years of research into the unique properties of adhesion tissue, explains why adhesions are so likely to recur after they are lysed. It also offers guidance in the quest for antiadhesion barriers or medications, since these evidently require only short-term action to prevent long-term problems, said Dr. Diamond, professor and associate chair of obstetrics and gynecology at Wayne State University in Detroit.

The fibroblasts in adhesion tissue and fibroblasts in normal peritoneal tissue differ in fundamental ways. Those differences are exaggerated in the face of hypoxia, Dr. Diamond said. "Years later, there are still molecular and biological differences in these tissues that predispose [patients with adhesions] to further adhesion formation."

Adhesions form after about 60%-80% of laparotomies or laparoscopies, with no meaningful differences seen between the two. "They are not something unique to the work we do as obstetrician gynecologists. Name a surgical specialty and they will have a problem with adhesions," said Dr. Diamond, who also directs the division of reproductive endocrinology and infertility at his university.

Compared with normal tissue, fibroblasts in adhesions have higher basal levels of collagen, fibronectin, transforming growth factor (TGF)-[beta]1, TGF-[beta]2, and PAI-1. Hypoxia--a result of tissue injury during surgery--heightens the disparity in most of these cytokines. Basal TPA levels, critical to breaking up early ...