Painful surgical adhesions may be preventable by taking the COX-2 inhibitor Celebrex, a common oral arthritis drug, just before and immediately after surgery, report researchers at Children's Hospital Boston. Their findings were published in the January 25 online Annals of Surgery.
Adhesions – bands of scar tissue that bind together two internal body surfaces – develop in 55 percent to more than 90 percent of patients undergoing surgery, depending on the type of operation. They are part of normal healing, but when surfaces fuse together that shouldn't, serious pain and complications can result. Adhesions are a major cause of bowel obstruction and infertility, and repeat surgery is often needed to cut through them. Unfortunately, adhesions often recur after these surgeries, and there has been no good way of preventing them.
Investigations led by Dr. Mark Puder and Dr. Arin Greene in the Department of Surgery and the Vascular Biology Program at Children's Hospital Boston tested COX-2 inhibitors in an animal model of abdominal adhesion formation. After undergoing surgery, groups of 6 to 18 mice received either COX-2 inhibitors (Celebrex or Vioxx), non-selective COX inhibitors (such as ibuprofen and aspirin) or placebo for 10 days.
"Results were dramatic," says Puder, senior investigator on the study.
At 10 days, the placebo group had obvious abdominal adhesions. Mice receiving non-selective COX inhibitors had a slight reduction in adhesions, and the COX-2 inhibitor group had a larger reduction. The greatest reduction was in the mice given Celebrex, and 6 of 11 Celebrex-treated mice (55%) were completely adhesion-free.
The researchers then observed the Celebrex, Vioxx, aspirin and placebo groups for an additional 25 days. Again, the Celebrex group had the fewest adhesions. The adhesion score (a measure of both the extent of adhesions and the difficulty of removing them) was only 1 in the Celebrex group, 5 in the Vioxx group, 8 in the aspirin group, and 11 in the placebo group.
Based on these findings, Puder is preparing to set up a multi-institutional clinical trial of Celebrex in adult surgical patients. "If Celebrex works in humans, you could give it to patients on the day of abdominal surgery and the 10 days after surgery," Puder says.
Currently, the most common method of preventing adhesions uses a barrier agent or gel to separate the abdominal surfaces and prevent them from binding together. However, these treatments can suppress the immune system, cause infection, and impair healing.
Although this study looked at abdominal adhesions, Puder believes that COX-2 inhibitors would also reduce adhesions after gynecologic and thoracic surgery, and possibly after orthopedic and plastic surgery.
COX-2 inhibitors are anti-inflammatory drugs best known for their use in arthritis. However, they also inhibit angiogenesis, or formation of blood vessels, and Celebrex also inhibits fibroblast activity, important in scar formation. These three properties make Celebrex a particularly good candidate for testing, Puder says, since adhesions are made up of inflammatory cells, blood vessels, and fibroblasts.
"If you stop each component of the adhesion, then within five days the tissue surface will get a whole new lining of mesothelial cells," Puder says. "Once these cells resurface the area, adhesions won't form."
Puder and colleagues did not set out to study adhesions. They were studying the effects of Celebrex on liver regeneration after injury to the liver. When they went to examine the livers of the mice, they noticed to their surprise that there were no adhesions, an unusual finding. So they decided to do a formal experiment.
"This was an accidental finding," Puder says. "It was just one of those lucky things."