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American College of Surgeons

Clinical Congress 2021 

Most patients with appendicitis can have antibiotics as their first treatment, rather than appendectomy

But researchers of U.S. “CODA” trial find that some patients eventually need the operation

Key Takeaways

  • Study results show the safety and sustainability of another treatment option besides surgical removal of the appendix.
  • Study findings highlight the need for increased shared decision making between surgeons and patients on the need for and timing of an appendectomy.
  • To help patients make treatment decisions regarding their appendicitis, CODA investigators developed an online decision-making tool.

Author Interview

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CHICAGO (October 25, 2021): About half of patients with appendicitis do not need an appendectomy procedure up to four years after receiving a course of antibiotics, according to final results of the Comparison of Outcomes of antibiotic Drugs and Appendectomy (CODA) trial. The study findings were presented today at the American College of Surgeons (ACS) virtual Clinical Congress 2021, simultaneous with online publication in the New England Journal of Medicine.1

These results show the safety and sustainability of another treatment option besides surgical removal of the appendix. Appendectomy has been the standard appendicitis treatment for more than 120 years and is the most common emergency abdominal procedure in the U.S.2

The research findings also highlight the need for shared decision making between patients and surgeons, study investigators said.

“Based on their characteristics, circumstances, and priorities, antibiotics will be a good treatment for some, but probably not all patients with appendicitis,” said co-principal investigator David R. Flum, MD, MPH, FACS, professor and associate chair of surgery at University of Washington (UW) School of Medicine in Seattle. David Talan, MD, emergency medicine physician, Geffen School of Medicine at UCLA, is also co-principal investigator.

CODA is the largest randomized clinical trial to explore whether antibiotic treatment is as good as appendectomy in treating appendicitis. The study was conducted at 25 U.S. medical centers in 1,552 adults with appendicitis who were randomly assigned to receive either antibiotics or appendectomy.

Based partly on early CODA results3 and evidence from other studies, the ACS strengthened its guidance for appendicitis treatment during the COVID-19 pandemic last December.4 The College called antibiotics “an acceptable first-line treatment” for most patients with appendicitis.

Higher need for appendectomy with time

Among the study patients who initially received nonoperative treatment, the proportion who eventually underwent an appendectomy increased over time. Preliminary results of the study, reported October 5, 2020, showed only 30 percent of the antibiotics-alone group required an appendectomy within three months.3 Recurrent appendicitis was the primary reason for getting an appendectomy after antibiotic treatment, according to updated results.

With longer-term follow-up, the investigators found appendectomy rates in the antibiotics group were 40 percent one year after antibiotic therapy and 46 percent at two years, rising to 49 percent at three and four years.

“While some clinicians and patients may determine that these longer-term rates of appendectomy make antibiotics a less desirable treatment, a very high proportion of patients report a preference for antibiotics, even if appendectomy may ultimately be necessary,” the study authors wrote. They referred to recent survey results indicating patient preference.5

“Especially in the emergency setting, patients may prefer to avoid or delay an operation for reasons including current demands at work and home, lack of health insurance, or anxiety,” said Giana H. Davidson, MD, MPH, FACS, a co-investigator and an associate professor of surgery at UW School of Medicine.

Complications were uncommon in both treatment groups after the first month, researchers reported. A predictor of antibiotic-treated patients eventually having an appendectomy was the presence in the first 48 hours of an appendicolith, or a small stone in the appendix. After 30 days, that increased risk reportedly decreased.

Decision-making help

To help patients make treatment decisions regarding their appendicitis, CODA investigators developed an online decision-making tool, available at http://www.appyornot.org/. The decision aid includes a video in English and Spanish and provides information about treatment risks and benefits. It also asks users questions about personal preferences, priorities, and resources to help them choose a treatment based on their individual situation.

“Our hope is that a standardized tool that can be easily disseminated across health systems can help patients effectively get information about their diagnosis and clinical outcomes, and help facilitate treatment discussions between patients and their surgeons,” Dr. Davidson said. “It has input from patient stakeholders, surgeons, and emergency medicine doctors to help give patients the information they need to make their choices.”

The online tool will be part of a national implementation program, led partly by the ACS, which will include training clinicians and developing a protocol to standardize appendicitis treatment.

No single patient factor can predict the success or failure of either antibiotic or surgical treatment for every patient, said co-investigator Callie Thompson, MD, FACS, assistant professor of surgery, University of Utah Health, Salt Lake City.

“Picking ‘the best’ candidate for either therapy comes down to having a discussion with each patient about their goals and values for treatment of their appendicitis and discussing the risks and benefits of each treatment with those goals and values in mind,” she said.

The CODA trial showed a higher long-term appendectomy rate in antibiotic-assigned patients than in a large similar study conducted in Europe (“APPAC” trial),6 which had a five-year appendectomy rate of 39 percent in its antibiotics group. The CODA trial differed, however, because it included patients with perforation of the appendix or an appendicolith, said co-investigator Lillian Kao, MD, MS, FACS, professor and division chief of acute care surgery at McGovern Medical School at UTHealth, Houston.

Although the CODA trial did not include children, Dr. Davidson said other studies are ongoing in pediatric patients with appendicitis to determine if initial treatment with antibiotics is right for them.

For a listing of CODA study sites and other study authors, click here.

“FACS” designates that a surgeon is a Fellow of the American College of Surgeons.

The CODA trial is funded through a Patient-Centered Outcomes Research Institute (PCORI) Award (1409-24099).

The authors report no relevant disclosures.

Citation: CODA Collaborative. Antibiotics vs Appendectomy for Acute Appendicitis—Longer Term Outcomes. Research letter. N Engl J Med. 2021.DOI:10.1056/NEJMc2116018

Presented simultaneously at virtual American College of Surgeons Clinical Congress 2021.
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  1. CODA Collaborative. Antibiotics versus Appendectomy for Acute Appendicitis—Longer Term Outcomes. Research letter. N Engl J Med. Posted online October 25, 2021. https://www.nejm.org
  2. Newhall K, Albright B, Tosteson A, Ozanne E, Trus T, Goodney PP. Cost-effectiveness of prophylactic appendectomy: a Markov model. Surg Endosc. 2017 Sep;31(9):3596-3604.
  3. CODA Collaborative. A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis (CODA). N Engl J Med. 2020;383(20):1907-1919. DOI:10.1056/NEJMoa2014320.
  4. American College of Surgeons. ACS Strengthens Its Emergency General Surgery Guidelines for Appendicitis Treatment During COVID-19. Bulletin Brief. Posted online December 8, 2020. Accessed October 19, 2021. http://www.facs.org/publications/bulletin-brief/120820/clinical.
  5. Rosen JE, Agrawal N, Flum Dr, Liao JM. Willingness To Undergo Antibiotic Treatment Of Acute Appendicitis Based on Risk of Treatment Failure. Letter. Br J Surg. Published online August 17, 2021. DOI:10.1093/bjs/znab280.
  6. Salminen P, Paajanen H, Rautio T, et al. Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial. JAMA. 2015;313(23):2340-2348.

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The American College of Surgeons is a scientific and educational organization of surgeons that was founded in 1913 to raise the standards of surgical practice and improve the quality of care for all surgical patients. The College is dedicated to the ethical and competent practice of surgery. Its achievements have significantly influenced the course of scientific surgery in America and have established it as an important advocate for all surgical patients. The College has more than 84,000 members and is the largest organization of surgeons in the world. For more information, visit www.facs.org.

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