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Children's National Studies May Lead To Improved Diagnosis of Appendicitis

Washington, DC - While the purpose of the appendix is largely unknown, Steven L. Zeichner, MD, PhD,  of Children’s National Health System’s Center for Cancer and Immunology Research at Children’s Research Institute, and other researchers from Children’s National and the Institute for Genome Sciences at the University of Maryland School of Medicine have identified potential links between microbes found in the appendix of patients with appendicitis and those found in the rectum in the appendicitis patients. The findings may help guide treatment and lead to the development of new, faster, less expensive and safer tests to diagnose appendicitis.
“An evaluation of the microbiota of the appendix and rectum from patients with and without appendicitis has the potential to open the door to the development of technology that could make costly testing and exploratory surgery in uncertain cases unnecessary,” says Zeichner, who led a study published in PLoS One. The title is “Culture-Independent Evaluation of the Appendix and Rectum Microbiomes in Children With and Without Appendicitis.”

Zeichner is also a professor at the Department of Pediatrics and Microbiology, Immunology and Tropical Medicine at The George Washington University. Besides Zeichner, other co-authors from Children’s National include Hope T. Jackson,  Katherine P. Davenport,  and Anthony D. Sandler, MD, Senior Vice-President of the Joseph E. Robert, Jr, Center for Surgical Care; Chief of Pediatric Surgery, and Principal Investigator for the Immunology Initiative of the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National, together with researchers from the Institute for Genome Sciences at the University of Maryland School of Medicine, Emmanuel Mongodin, an assistant professor, and Claire Fraser, the Director of the Institute.

Appendicitis affects about 77,000 patients a year in the U.S., with annual costs at approximately $680 million.  Generally, the risk of appendicitis in a lifetime has been estimated at 7 percent, with most cases of appendicitis affecting people ages 10 to 30. Appendicitis varies in different populations, in various regions and has been associated with environmental and behavioral factors that include general hygiene, infections and variations in consumption of dietary fiber.

A vast number of microbes and microbiota colonize the body. The largest number of microbes live in the gastrointestinal tract. In recent years, many researchers have shown that the gastrointestinal microbiota play a large role in health and disease, including nutrition, obesity, and other inflammatory disorders. The microbiota of the appendix likely contribute to its function, and an altered microbiota may contribute to the development of appendicitis.

The research team found that the microbiota of the appendicitis patient’s appendices differed from the microbiota of the appendices of patients without appendicitis. Further, the microbiota of the appendices of patients with more severe appendicitis, cases in which the appendix had ruptured, differed from the microbiota of appendices of patients with less severe forms of the disease.

In an unexpected finding, the team found that some of the organisms that differed in the appendices of the patients with appendicitis from the appendices of the patients with normal appendices were also detected in the rectum. This last finding “could suggest a new approach for possible appendicitis molecular diagnostics,” the researchers wrote.  

“Studies of the role of microbes in the appendix and the rectum may lead to improved diagnosis, including a possible reduction of costly CT scans that expose patients to substantial doses of radiation, and exploratory surgery that is sometimes performed to rule out appendicitis when tests and the physical exam do not confidently rule out the possibility of appendicitis,” Zeichner said. “That would be a great help.”

The researchers’ study included participants who ranged in age from 5 months to 18 years. Six patients had normal appendices and 15 patients had appendicitis, nine of which were categorized as perforated based on a pathology report. A total of 42 samples were processed and DNA was extracted and subjected to high throughput DNA sequencing of the genes for the Ribonucleic acid (RNA) that makes up part of the ribosome, the protein synthesis machinery for the cell. The analysis of ribosomal RNA genes using recently available high throughput DNA sequence in recent years has revolutionized the study of microbiota.  The ribosomal RNA gene’s DNA sequence is the sequence that codes for the ribosomal RNA.

The researchers involved in the study have filed a provisional patent application that covers discoveries reported in the manuscript. Children’s National and other institutions involved have not yet licensed the intellectual property and there are no products currently under development. The institutions employing the authors of the paper have intellectual property policies in place that say that the inventors will be given a share of any inducement the institutions receive from the inventions.

Contact: Emily Hartman or Joe Cantlupe at 202-476-4500.

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