A Urine Test for Appendicitis

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Correction Appended: June 24, 2009

Appendicitis afflicts roughly one in 10 people during their lifetime and accounts for more emergency abdominal surgeries than any other ailment. Yet, as emergency room doctors know too well, diagnosing the condition is neither easy nor fast.

Doctors use physical exams and CT scans to identify appendicitis, the infection and inflammation of the small, thin pouch attached to a segment of the large intestine in the lower right abdomen, but often, when the diagnosis is less than clear, they err on the side of caution, recommending surgery — the alternative is to risk a burst appendix, which in fact happens frequently enough while patients wait for test results. According to past studies, somewhere between 3% and 30% of all appendectomies may be in patients who do not actually have appendicitis — conditions often mistaken for appendicitis include constipation, gastroenteritis and ovarian cysts, for example — and as many as 45% of surgeries happen too late, after the appendix has already ruptured.

Now, new research by doctors at Children's Hospital Boston may help spur the development of a test for appendicitis that may someday prevent unnecessary surgeries, speed up the diagnostic process and even minimize undue medical costs. "It's very exciting," says Dr. Alex Kentsis, a pediatrician and co-author of the study published online June 23 by the Annals of Emergency Medicine. He estimates that a simple diagnostic test may be as close as three years away, and may be easy enough to administer outside of a hospital's emergency department, in individual doctor's offices or even local clinics.

The test is based on a protein excreted in the urine by patients who have an infection in the appendix. Led by Dr. Richard Bachur, chief of emergency medicine at Children's Hospital Boston, researchers discovered the hallmark protein by collecting and analyzing urine samples from 12 pediatric patients with confirmed cases of appendicitis (determined by inspection of the appendix after surgery). From an initial result involving thousands of different proteins, researchers narrowed the potential candidates by comparing the 12 samples to those from healthy children without appendicitis. "We analyzed the proteins to see which were statistically significant compared with [the controls], and this gave us a short list," explains Hanno Steen, director of the Proteomics Center at Children's and a co-author of the study. That short list, combined with other possible protein candidates identified in previous research on the subject, comprised 57 different possibilities.

Over the next 18 months, researchers analyzed urine samples from 67 pediatric patients who came to Children's emergency room with possible cases of appendicitis. Of those, 25 were confirmed to have the sharply painful condition; samples from the other patients were used as controls. Steen explains that in an emergency room situation, physicians are often faced with distinguishing appendicitis from conditions involving abdominal pain, so it made sense to mimic this contrast in the protein analysis as well.

The results were encouraging. While several proteins were repeatedly found in the urine samples from children with confirmed appendicitis, the most promising was leucine-rich alpha-2-glycoprotein, or LRG, which had statistically negligible rates of false results, meaning that it could correctly identify patients who had appendicitis and those who did not. The researchers were thrilled. "It appears to be accurate in both diagnosing the true positives and the true negatives," says Kentsis.

The reason for LRG's accuracy may have to do with its origin. Kentsis explains that the protein is specific to the immune cells that characterize appendicitis, and is likely a direct result of the infection, unlike other proteins that may be produced in a biological chain reaction, stemming from but distant to the original infection. "It makes good biological sense why LRG would be elevated in patients with appendicitis," he says.

Of course, this research is just the first step of many — including analyses of adult patients and larger study groups — but if these promising results can be replicated, it could mean a dramatic improvement in patient care and a reduction in medical costs. To hasten the process, Kentsis and his colleagues are already planning further studies within the next year or so.

If the research bears out the initial findings, Kentsis foresees the development of "a dip-stick test that can be used in a rapid-care kind of way" to diagnose appendicitis. "Here you have the opportunity to come up with a very quick test," says Steen. "Diagnosis could potentially be down to minutes, and not hours."

The original version of this article misstated that the urine analysis study was published in the Annals of Internal Medicine. It was published in the Annals of Emergency Medicine.