Recurrence of Crohn’s Disease After Surgery
Crohn’s disease and ulcerative colitis are chronic conditions that cause inflammation of the intestinal tract. Up to 70 percent of patients with Crohn’s disease require surgery at some point in their disease course. Unlike people with ulcerative colitis, for whom surgery can offer a cure, people with Crohn’s disease who undergo surgery for removal of diseased intestine are at risk of having the disease return after surgery (recurrence). The Crohn’s typically returns at the same location where the surgery was performed. One notable exception is patients in whom the disease is located only in the colon. Those patients usually are cured by total removal of the colon and rectum, and the creation of an ileostomy, although in a minority of cases the Crohn’s may reappear in another location, usually the small intestine.
The risk of developing recurrent symptoms of Crohn’s disease is approximately 50 percent at five years and 75 percent at 15 years following surgery. In addition, approximately 30 percent of patients will require further surgery within 10 years of the original surgery. Beyond these general numbers, physicians currently cannot accurately predict the risk of Crohn’s disease recurrence for an individual patient. Adding to this unpredictability are rare cases of patients whose Crohn’s disease comes back within a few months of surgery, while at the other extreme are patients who undergo one surgery and never again have significant problems related to Crohn’s disease.
Risk Factors for Disease Recurrence
There are two identifiable factors that seem to be associated with an increased risk of having disease return after surgery. Cigarette smoking is known to be associated with the following increased risks: (1) developing Crohn’s disease, (2) developing more severe Crohn’s disease, and (3) developing fistulas (abnormal channels between the bowel and other organs). Smoking has also been shown to increase the risk of a recurrence of Crohn’s disease after surgery.
In one study, patients who smoked more than 15 cigarettes per day (about three-quarters of a pack) had a two-fold increased risk of developing recurrent symptoms of Crohn’s disease and a four-fold increased risk of requiring further surgery when compared to non-smokers. Patients who smoke fewer cigarettes are also at greater risk of their Crohn’s recurring sooner than nonsmokers. All Crohn’s patients should make smoking cessation a very high priority.
The other factor that seems to determine risk of disease recurrence relates to the type of surgery performed. Surgeries in which an anastomosis is created (connecting the two ends of healthy intestine to each other after removal of the diseased portion) are associated with an increased risk of disease recurrence compared to surgeries where a stoma is created (bringing the intestine through the skin of the abdomen with drainage into a bag). The reason for this difference is not known, but may have something to do with components of stool, including bacteria.
Given the significant risk of developing recurrent disease following surgery for Crohn’s disease, identification of further risk factors and even preventive measures is a high priority. The rest of this article will focus on the role of medications in decreasing the risk of disease recurrence.
Mesalamine
Mesalamine is an agent that helps treat the inflammation that develops in the intestine of patients with Crohn’s disease. Preparations such as Pentasa® or Asacol,® which deliver mesalamine to the area of anastomosis, could theoretically help decrease the risk of recurrent Crohn’s disease following surgery. There have been six published studies that reported on the use of mesalamine in this setting, and four of these studies showed a benefit for mesalamine. The degree of this effect is approximately a 15-percent decrease in the risk of developing further Crohn’s disease compared to patients who receive no therapy. However, patients were taking eight to 16 mesalamine pills daily in these studies.
Because mesalamine is generally very well tolerated with little or no side effects, treatment with this agent should be considered for patients who have undergone recent surgery. However, the use of these medications has to be balanced with two factors: patients’ willingness to take a large number of pills every day when they are otherwise feeling well, and the cost of such therapy (greater than $200 per month depending on the dose used).
Metronidazole
Based on the theory that bacteria in stool contents may play a role in developing recurrent disease following surgery, the use of antibiotics to prevent recurrence appears reasonable. A single study evaluated patients who were treated for a total of three months with either metronidazole (Flagyl,® an antibiotic frequently used among patients with Crohn’s disease) or placebo (sugar pills). Patients treated with metronidazole for three months appeared to have a smaller risk of developing recurrent disease than those who received placebo, and this effect lasted up to one year following surgery. The main drawback to this therapy was mild side effects of the medication. Patients who took the medication for a longer period of time developed more side effects, suggesting that this is probably not a good long-term choice of therapy.
6-mercaptopurine & Azathioprine
6-mercaptopurine (Purinethol®) and azathioprine (Imuran®) are medications that decrease the number and/or activity of the cells responsible for the inflammation associated with Crohn’s. These medications are commonly used to treat people with Crohn’s disease and ulcerative colitis to get them off steroids and to avoid surgery.
Because these medications work well in patients before surgery, it is reasonable to believe that they would also help prevent disease recurrence after surgery. Preliminary studies have suggested that these agents do indeed decrease the risk of Crohn’s disease recurrence, and that these medications are even more effective than mesalamine. It is hoped that further studies will help physicians determine the most effective dose of these drugs in the prevention of Crohn’s recurrence.
Conclusion
Patients with Crohn’s disease who undergo surgery to remove diseased intestine have a moderate risk of developing recurrent disease. There is an important need for a way to identify patients who may be at increased risk for developing recurrent disease in order to maximize and better direct the use of medications in this setting.
Patients often ask what they can do to minimize the chances of Crohn’s coming back after surgery. The answer is: Quit smoking if you already smoke, and don’t start smoking if you are currently a nonsmoker. Medical therapy can be effective in some cases, but the choice of medications needs to be tailored on an individual basis. Be sure to talk to your physician about the treatment that is right for you.
copyright JEAN-PAUL ACHKAR, M.D.
Staff Gastroenterologist
The Cleveland Clinic Foundation
Cleveland, Ohio
Updated July 2003