Appendicitis treatment usually involves surgery. Some patients with appendicitis have been successfully treated using antibiotics without appendectomy, especially in Europe, but this has been a controversial approach.

A recent randomized trial, the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) study, compared the use of appendectomy with antibiotics alone in treating appendicitis on a larger scale (1552 patients) than previous studies. Long-term results from the CODA study published in December 2021 may help clarify which patients are candidates for treatment without surgery.

Appendicitis surgery and background

Appendicitis is a medical emergency that involves inflammation of the inner lining of the vermiform appendix, which spreads to the remainder of the appendix. Causes include infection, blockage, and less commonly, tumors. It is most common in people between the ages of 10 and 30 but can occur at any age.

Inflamed appendix surgically removed from a 10-year-old boy with acute appendicitis. (Image by Ed Uthman

If not treated quickly, appendicitis can lead to perforation of the appendix, peritonitis, sepsis, and death.6  The primary treatment, removal of the appendix (appendectomy), can be traditional or laparoscopic. Antibiotics are given in advance of the appendectomy.

CODA Study: Comparing appendicitis treatment with and without surgery

The CODA study included adult patients with imaging-confirmed appendicitis in emergency departments. Patients with septic shock, diffuse peritonitis, suspected neoplasm, or several other criteria were excluded. However, the trial did include patients with more severe disease compared with previous studies. Those with an appendicolith – a calcified deposit of feces and minerals in the appendix – were sorted into a prespecified subgroup.

The CODA study’s 2020 primary outcome analysis considered outcomes 90 days post-treatment; it found that antibiotics were non-inferior to appendectomy on the basis of a health status measure, the European Quality of Life–5 Dimensions (EQ-5D) questionnaire. Three in 10 patients required an appendectomy 90 days later, but these patients were largely those with an appendicolith.

The CODA study’s more recent December 2021 article in NEJM provides long-term data; the researchers report that 40% of the patients who received antibiotics alone required appendectomy by one year later, and this increased to 46% of these patients by 2 years after the initial infection. Again, having an appendicolith increased the chances that the patient would eventually require an appendectomy. However, the study did show that some patients can avoid surgery and recover successfully from appendicitis, even in a patient population that is sicker than that included in previous studies.

Appendicolith visible on X-ray. (Image by James Heilman, MD

Risks of appendicitis treatment without surgery

In the CODA trial, patients treated with antibiotics alone had a higher rate of complications, had more visits to the emergency department, and spent more time in the hospital than those in the appendectomy group.

Cancer is the cause of a small percentage of appendicitis cases, and sometimes cancer can mimic appendicitis. Neoplasms are sometimes identified during appendectomy: a study of 21,069 appendectomy specimens found that 0.9% were carrying cancer. Therefore, there is a risk that a neoplasm will be missed during non-surgical appendicitis treatment.

Patient selection in appendicitis treatment without surgery

The CODA researchers gathered input from patients regarding which factors are most important, such as time in the hospital, risks of complications, and missed work, while designing the CODA trial. The Covid-19 pandemic as well as hospital resource and capacity limitations may influence these decisions under some circumstances.

The CODA trial’s main goal was helping individual patients and their doctors select the best treatment plan for their needs. These results could aid in decisions regarding which patients may be appropriately selected for treatment without surgery.

References

  1. https://www.nejm.org/doi/full/10.1056/NEJMe2029126?query=recirc_curatedRelated_article
  2. https://www.nejm.org/doi/full/10.1056/NEJMc2116018
  3. https://www.nejm.org/doi/full/10.1056/nejmoa2014320
  4. https://resident360.nejm.org/clinical-pearls/nonoperative-antibiotic-treatment-of-acute-appendicitis
  5. https://becertain.org/appendicitis-study-coda
  6. https://emedicine.medscape.com/article/773895-overview#a3