Appendicitis is a common and costly disease. About 77,000 patients are diagnosed with appendicitis each year in the US, with annual costs estimated at $680 million/year. Many-fold more patients are evaluated to rule out appendicitis, typically by ultrasonography, which is costly, or by abdominal CT, which is both costly and subjects patients to large radiation doses, which are increasingly appreciated as posing significant long term cancer risks. Recent estimates suggest a ~0.3% lifetime cancer risk resulting from each abdominal/pelvic pediatric CT exam in girls. A better and more accurate approach to the diagnosis of appendicitis is clearly needed. We recently conducted a study that showed that the microbiota of the appendix is different than the microbiota of the rectum, that the microbiota of the diseased appendix is different than the microbiota of the normal appendix and, most interestingly, that the rectal microbiota of patients with appendicitis differed from the rectal microbiota of control patients. These findings suggest that there might be useful rectal bacterial biomarkers for appendicitis that could be developed into a rapid, cheaper and potentially more accurate diagnostic test for appendicitis. While the results are exciting, more data are needed to confirm that biomarkers for appendicitis can be identified in the rectal bacterial communities. We therefore propose to conduct a prospective study examining the rectal microbiota of patients seen in the Children's National Medical Center (CNMC) Emergency Department (ED). We will obtain samples by rectal swab, isolate microbial DNA and obtain the 16S rRNA gene sequences in the sample, and collect associated clinical metadata. We will then compare the rectal microbiota of CNMC ED patients evaluated to rule out appendicitis who have appendicitis ruled in with those who have appendicitis ruled out, based on imaging studies and/or laparotomy/laparoscopy. We will also compare the microbiota of the ED patients with possible appendicitis with a normal control cohort, patients presenting with acute minor trauma. We will create statistical models using the rectal microbiota data, with and without inclusion of clinical metadata that will predict appendicitis diagnosis based on bacterial biomarkers. The deliverable at the conclusion of the proposed study will be data that either confirms or refutes our hypothesis that there are rectal bacterial biomarkers for appendicitis and, if our hypothesis i confirmed, a predictive model for appendicitis diagnosis based on the rectal microbiota biomarkers plus clinical metadata. Significance: Confirmation that there are rectal microbial biomarker signatures for appendicitis will enable future development of a microbial diagnostic test for appendicitis. A rectal bacterial biomarker test for appendicitis would substantially reduc unnecessary harmful radiation exposure, provide more rapid and effective diagnosis for appendicitis, and substantially reduce health care costs.
Appendicitis is a common and costly disease, with about 77,000 patients diagnosed with appendicitis each year in the US, and annual costs estimated at $680 million/year. Patients with suspected appendicitis are typically evaluated with ultrasonography or CT scans, which are expensive and, for CT scans, subject patients to high and potentially harmful radiation doses, but we recently found that there are distinctive microbe populations detectable in the rectum of appendicitis patients, which suggests that it may be possible to develop a test for appendicitis based on an analysis of the microbes in the rectum. We propose to conduct a larger pilot study to either confirm or refute the hypothesis that there are microbial biomarkers present in the rectum that could be useful for the development of a microbial biomarker test for appendicitis, a test which could yield significant improvements in patient care and costs for the health care system.
