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Fri 1 Jun 2007 12:00 AM

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Postoperative adhesions

Postoperative adhesions are a significant problem after abdominal surgery. Potential solutions include further surgery, barrier agents, and - perhaps, surprisingly - Celebrex.

Postoperative adhesions are a significant problem after abdominal surgery. How do these bands of sticky scar tissue form? The peritoneum (pronounced peri-toe-NEE-um) is a membrane that lines the inside of the abdomen, supporting the abdominal organs and keeping them in place. It also produces a lubricating fluid that makes the organs slippery, so they slide easily against each other and the abdominal wall. This support and the lubrication are important because while the small intestine and other organs need support, they also must be able to move freely in order to function properly.

Careful surgical technique that avoids damaging and jostling tissue presumably helps reduce adhesions.

Peritoneal tissue is delicate. Any surgery can damage it, even when performed through a small incision, using a laparoscope. And the damage isn't just from the incision. The irrigating fluid used in surgery, or tiny bits of gauze - even the powder on surgical gloves - can irritate the peritoneum, causing inflammation and tiny amounts of bleeding.

Bleeding from the peritoneum - or from abdominal organs - results in small deposits of fibrin, the sticky protein that is one of the main components of blood clots. Other factors in the blood tend to break fibrin down, but the trauma of surgery, an infection, or oxygen-poor blood can disrupt that process. When that happens, it gives cells called fibroblasts an opening.

They migrate to the area and busily replace fibrin with collagen, the fibrous tissue found in tendons and other connective tissue. Adhesions are made primarily of the collagen generated by these opportunistic fibroblasts.

Some adhesions are stringy or form thick bands. Others are more diffuse and almost seem to glue organs to one another or to the abdominal wall. The beginnings of adhesion formation may occur right during surgery.

How much they grow and how extensive they are may change over the coming weeks and months. But whether they occur at all is usually determined within the first few days after surgery.

The surgery isn't the only cause. Infections or inflammatory conditions, such as appendicitis, Crohn's disease, or diverticulitis cause adhesions, too. Adhesions also form in response to endometriosis, a condition in which cells from the lining of the uterus (endometrium) also grow on structures outside the uterus.

Bowel obstructions

Most people who have abdominal surgery develop adhesions, and usually they aren't a problem. They don't cause any harm or produce any symptoms. But some adhesions interfere with the normal function of an organ - a problem that may develop years after surgery.

The small intestine is particularly vulnerable because it needs to be mobile so it can push digested food on through. If an adhesion is attached to the small intestine, it may twist and kink, causing a blockage. In the developed world, surgical adhesions are the leading cause of intestinal obstructions. For women, postoperative adhesions affecting the ovaries and fallopian tubes are a common cause of infertility.

For years, physicians have debated whether adhesions alone can be a source of pain.

For bowel obstructions, the choice is fairly straightforward: Cut the adhesions. That will free up the kinked or twisted intestine and end the obstruction. But as with all surgery, there are risks, and bowel perforation is a possibility. Cutting adhesions can sometimes help with infertility if it frees up the ovaries and the fallopian tubes, although good data demonstrating that surgery is effective are hard to come by.

Pain relief

More problematic are adhesions that don't seem to affect the movement or function of any organ in an obvious way, but still cause a patient to feel pain. For years, physicians have debated whether adhesions alone can be a source of pain, and whether surgeons can relieve the pain by cutting the adhesions. Because chronic abdominal or pelvic pain can be so hard to treat, some physicians have cut adhesions, figuring that even if there was a small chance of success, it was worth it.

On the other hand, the value of surgery has been questioned because the operation is likely to trigger the growth of more adhesions in the abdomen, so what has been gained? Moreover, studies of pain treatments have consistently shown a large placebo effect from an intervention. If individual patients feel less pain after adhesions have been cut, it may have little to do with the adhesions and everything to do with relief that something significant has been done to help them.

In 2003, Dutch researchers published a double-blind study in the Lancet that tackled these questions head-on. Diagnostic laparoscopy showed adhesions in 100 patients with chronic abdominal pain. About half of them were given only the diagnostic procedure; the other half, chosen at random, also had surgery to cut the adhesions. A year later, 27% in both groups said their pain was much improved or had gone away. The results look a little more favorable if you include the patients who said their pain was improved. Still, the findings cast doubt on the value of adhesion surgery for pain relief, especially when you consider that it caused complications in five patients (10%). The researchers' conclusion: Laparoscopic adhesiolysis (the medical term for cutting adhesions) cannot be recommended as a treatment for adhesions in patients with chronic abdominal pain.

At a glance: prevention

Whatever the safety or effectiveness of treatment, it would obviously be better to prevent adhesions from forming in the first place. Careful surgical technique that avoids damaging and jostling tissue presumably helps reduce adhesions. Because it is less invasive, laparoscopic surgery would also seem likely to help, although the research on that question is mixed. At one time, there was some hope that nonsteroidal anti-inflammatory drugs (NSAIDs) would be the answer, because by inhibiting prostaglandins they slow down the formation of the fibrin that gets the whole process started. Animal studies were promising, but the results from human trials were not. Doctors have tried using corticosteroids postoperatively, sometimes adding antihistamines, but the results were too mixed for this to be embraced. There's been a lot of interest in barrier agents - small, thin sheets of material positioned to keep tissues from rubbing up against one another.

The materials used in barrier agents range from polytetrafluoroethylene (PTFE - the polymer used to make Teflon and Gore-Tex) to mixtures of chemically modified sugars that the body can absorb in a few days. Some of the early barrier agents actually caused more adhesions. Even the best of these barrier agents haven't been fully embraced by surgeons.Now researchers at Harvard are investigating another possibility: COX-2 inhibitors. Celecoxib (Celebrex), the only drug in the class that's still on the market, impedes the formation of fibroblasts, the cells that start the process leading to adhesions. Drs. Arin Greene and Mark Puder, researchers at Harvard-affiliated Children's Hospital Boston, published a study in the January 2005 Annals of Surgery showing that mice treated with Celebrex formed fewer adhesions during wound healing than those treated with other NSAIDs. As of mid-2005, of course, there's a cloud over the COX-2 drugs because of their cardiovascular side effects, but Dr. Puder believes the risk from taking Celebrex for a week after surgery is likely to be small. In any case, his is only a mouse study. Far more research needs to be done before we'll know how much promise Celebrex has for preventing adhesions in people.

This article is provided courtesy of Harvard Medical International. © 2007 President and Fellows of Harvard College

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