Biomarker in urine could minimize unnecessary surgery By Nathan Seppa

A compound identifiable in urine might help doctors distinguish appendicitis from other abdominal problems and avoid needless surgery, researchers report online June 23 in the Annals of Emergency Medicine.

Because signs of appendicitis are particularly difficult to assess in young children and elderly adults, surgeons unnecessarily remove a healthy appendix in 10 to 20 percent of appendectomies performed in the United States, says pediatrician Alex Kentsis of Harvard Medical School and Children’s Hospital Boston.

True appendicitis, on the other hand, often goes untreated because it may cause few symptoms until the appendix ruptures. At that point, a patient risks intestinal infection and severe complications, Kentsis says.

In an effort to find biomarkers that tip off appendicitis better, Kentsis teamed with biochemist Hanno Steen and physician Richard Bachur, both also at Children’s Hospital, to test for 57 compounds in the urine of 67 children being treated for suspected appendicitis. The children had an average age of 11.

Overall, 25 of these patients were found to have appendicitis and underwent surgery. The diagnoses resulted from physical examination, symptom assessment and tests such as CT scans, ultrasounds or other measures. Tissue analysis after surgery confirmed the original diagnoses.

In conducting the urine sample analysis, the researchers didn’t know which children were ultimately diagnosed with appendicitis and which had other diagnoses. These included ovarian cysts, constipation, abdominal pain or other problems that were ascertained by follow-up phone calls six to eight weeks later.

The compound that stood out among the children with appendicitis was leucine-rich alpha-2-glycoprotein, or LRG. Immune cells called neutrophils make LRG. “Release of LRG from neutrophils is a kind of specific feature of appendicitis,” Kentsis says.

LRG is not the only compound overproduced during an attack of appendicitis. But in this analysis, it was the most reliable biomarker to show up in the urine. High levels of LRG in the urine correctly identified a child who had appendicitis and low LRG levels suggested no appendicitis 97 percent of the time, the researchers found.

“They may have found a biomarker that’s really sensitive,” says Robert C. Barber, a geneticist at the University of Texas Southwestern Medical Center at Dallas. “This is a very interesting finding.” Nevertheless, he cautions, “appendicitis is unlikely to have a magic bullet biomarker.” More likely, researchers will eventually need more than one.

Kentsis agrees, noting that other teams have already found some promising biomarkers. “You could imagine using them in combination, if one isn’t sufficient,” he says.

The team will now concentrate on validating the new findings and creating a simpler, clinic-ready kit for testing urine, Kentsis says. Meanwhile, the researchers plan to look at whether the LRG test might also work in adults.

The use of CT scans and ultrasound has improved appendicitis diagnosis in recent years, but these tests still fail to catch some inflamed appendices and wrongly pinpoint healthy ones, the authors note. Also, in some regions of the world, Kentsis says, such high-tech diagnostics just aren’t readily available.


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