Simple Urine Test May Reduce Unnecessary Childhood Appendectomies

Appendicitis is the most common childhood surgical emergency, but it is also one of the most difficult ailments to diagnose. A misdiagnosis can lead to unnecessary surgery and appendix removal, along with all the dangerous complications surgery entails. On the other hand, a too cautious “wait and see” approach could lead to a ruptured appendix and serious complications. Appendicitis in children has always been tricky for doctors to diagnose. Until now.

According to a June report published in the Annals of Emergency Medicine, emergency medicine physicians and scientists at the Proteomics Center at Children's Hospital Boston may have discovered a way to diagnose appendicitis in children using a simple urine test. Doctors think that a certain protein, detectable in urine, might serve as a “biomarker” for appendicitis.

Despite improvement in imaging technologies, recent figures indicate that 3 to 30 percent of children have unnecessary appendectomies, while 30 to 45 percent of those diagnosed with appendicitis already have a ruptured appendix. Laboratory biomarkers have been identified, but none have proved reliable enough to be clinically useful. Researchers led by Richard Bachur, MD, acting chief of emergency medicine at Children's Hospital Boston, Hanno Steen, PhD, director of the Proteomics Center, and clinical fellow Alex Kentsis, MD, PhD, decided to take a systematic approach, performing a proteomics study using state-of-the are mass spectrometry (a technique that detects and quantifies proteins in a sample). Their two-part study has identified the most accurate biomarker for acute appendicitis known to date.

After performing tests and identifying seven promising urine biomarkers, the two decided that leucine-rich alpha-2-glycoprotein (LRG) was the most promising. This marker appears to be a specific marker for local inflammation. With almost no false positives or false negatives, LRG seemed to indicate to scientists when children were experiencing an inflamed appendix.

Of course, to prevent bias in the clinical trials, researchers were not told each test sample’s actual diagnosis. In the first phase, they examined 12 urine specimens – 6 from patients with appendicitis, taken before and after appendectomy, and 6 from patients without appendicitis –and identified 32 candidate biomarkers, including many proteins associated with immune response and inflammation. To these 32 they added other candidates found through gene expression studies and other means, yielding a total of 57 potential biomarkers. They then sought to validate these markers in 67 children seen at the hospital for suspected appendicitis over an 18-month period, 25 of whom ultimately had proven appendicitis.

These findings suggest that a clinical test, such as a urine dipstick, can be developed through further research. Soon, children could be quickly and efficiently diagnosed when appendicitis is present. (Or, avoid unnecessary surgery when appendicitis is absent.)

As for adults, the jury about urine testing for appendicitis is still out. According to doctors working on the study, biomarkers will likely vary for older patients. Further testing will need to be conducted before a determination can be made about the viability of LRG testing on adults.