Opinion Viewpoint

ARTICLE INFORMATION 3. Di Martino M, Ielpo B, Pata F, et al; MANCTRA-1 uncomplicated appendicitis after laparoscopic
Published Online: April 24, 2024. Collaborative Group. Timing of cholecystectomy appendectomy: a randomized controlled trial.
doi:10.1001/jamasurg.2023.8036 after moderate and severe acute biliary World J Emerg Surg. 2022;17(1):59. doi:10.1186/
pancreatitis. JAMA Surg. 2023;158(10):e233660. s13017-022-00465-5
Conflict of Interest Disclosures: None reported. doi:10.1001/jamasurg.2023.3660 7. Salazar MC, Canavan ME, Chilakamarry S,
REFERENCES 4. Feingold D, Steele SR, Lee S, et al. Practice Boffa DJ, Schuster KM. Appendiceal cancer in the
parameters for the treatment of sigmoid National Cancer Database: increasing frequency,
1. Moris D, Paulson EK, Pappas TN. Diagnosis and diverticulitis. Dis Colon Rectum. 2014;57(3):284-294. decreasing age, and shifting histology. J Am Coll Surg.
management of acute appendicitis in adults: doi:10.1097/DCR.0000000000000075 2022;234(6):1082-1089. doi:10.1097/XCS.
a review. JAMA. 2021;326(22):2299-2311. doi:10. 0000000000000172
1001/jama.2021.20502 5. Dahlstrand U, Wollert S, Nordin P, Sandblom G,
Gunnarsson U. Emergency femoral hernia repair:
2. Davidson GH, Flum DR, Monsell SE, et al; CODA a study based on a national register. Ann Surg.
Collaborative. Antibiotics versus appendectomy for 2009;249(4):672-676. doi:10.1097/SLA.
acute appendicitis—longer-term outcomes. N Engl J 0b013e31819ed943
Med. 2021;385(25):2395-2397. doi:10.1056/
NEJMc2116018 6. Elvira López J, Sales Mallafré R, Padilla Zegarra E,
et al. Outpatient management of acute

Interval Appendectomy After Successful

VIEWPOINT
Antibiotic Treatment?

David A. Talan, MD Offering interval appendectomy to patients who are Successfully helping patients decide between op-
Department of recovered after antibiotic treatment of acute uncompli- erative and nonoperative treatment requires openness
Emergency Medicine, cated appendicitis exposes them to additional risk, dis- to present the advantages and disadvantages of each ap-
Ronald Reagan UCLA
ability, and cost in an attempt to avoid a future illness proach without bias and with empathy to support their
Medical Center,
The David Geffen they most likely would never experience with a surgery outcome priorities. Patients who decide (along with a
School of Medicine at they most likely would never need. child’s parents) to be treated with antibiotics want to
the University of As more patients choose nonoperative treatment, avoid surgery and its associated morbidity and accept
California at Los
Angeles, Los Angeles.
there will be increased opportunity for us to consider the risk that they may not initially respond to antibiot-
interval appendectomy after resolution of appendici- ics or have later recurrence. Although appendectomy is
Peter C. Minneci, tis. Although the extent to which interval appendecto- generally a very safe surgery, it can cause rare serious
MD, MHSc mies in this circumstance are presently being done in complications. Compared with urgent appendectomy,
Nemours Surgical actual practice is unknown, the major randomized clini- nonoperative treatment is associated with more rapid
Outcomes Center and
Department of Surgery, cal trials comparing antibiotics alone with appendec- pain resolution and return to work and school, with many
Nemours Children’s tomy suggest that this surgery was performed to some recovered in a few days and almost all on their feet by 1
Health—Delaware degree. In the Appendicitis Acuta (APPAC) trial, there was week.1-3 Antibiotics lead to fewer complications and
Valley, Willington.
a relatively higher proportion of appendectomies with associated surgeries, with similar 30-day general health
negative pathology among antibiotic-treated patients status. Outpatient antibiotic treatment has recently been
with recurrence compared with surgery-randomized demonstrated to be safe in selected adults allowing pa-
patients (8% vs 0.7%, respectively).1 Salminen and tients to avoid the inconvenience of hospitalization and
Viewpoint page 599
colleagues1 acknowledged that surgeon discretion led to its associated expense.4 Furthermore, recent reports
some patients undergoing appendectomy who did not suggest potential useful functions of the appendix, which
have appendicitis and that, otherwise, the success rate may bring additional benefit to avoiding appendec-
of nonoperative treatment would have been higher. In tomy.
the Comparison of Outcomes of Antibiotic Drugs and For those following up after responding to antibi-
Appendectomy (CODA) trial, surgeons indicated that otic treatment, some satisfaction can be taken in know-
Corresponding approximately 20% of appendectomies were done for ing that we have met a patient’s immediate treatment
Author: David A. Talan,
nonclinical reasons, often due to patient anxiety.2 Al- goals. A patient whose appendicitis is resolved has an in-
MD, Department of
Emergency Medicine, though in most cases the pathology description was creasingly good prognosis, even better than when they
Ronald Reagan UCLA consistent with appendicitis, in the absence of a clinical chose this option. Although investigations have varied
Medical Center, diagnosis, these findings may have represented non- in entry criteria and outcomes, it is clear that only a mi-
The David Geffen
School of Medicine at
specific postinflammatory changes in clinically resolved nority of patients will experience recurrence, with re-
the University of cases. These observations suggest that appendectomy ported later appendectomy rates generally in the range
California at Los rates after initial successful treatment with antibiotics of 20% to 30%.1-4 Recognizing that some appendecto-
Angeles, 1100 Glendon
alone are higher than true recurrence rates, with some mies in these trials were performed in the absence of
Ave, Ste 1200,
Los Angeles, CA 90024 proportion of these appendectomies likely reflecting clinically suspected or pathology-confirmed appendici-
([email protected]). interval appendectomy for nonrecurrence. tis, it may be that as few as 20% will experience true

600 JAMA Surgery June 2024 Volume 159, Number 6 (Reprinted) jamasurgery.com

© 2024 American Medical Association. All rights reserved.

 Opinion

recurrence—and as many as 80% will not. After successfully com- plication rates associated with surgery for recurrence and urgent
pleting a course of antibiotics, beyond 90 days, the chance of fu- surgery at the outset in adults and children, respectively. Retreat-
ture appendectomy is approximately one-quarter of that risk on ini- ment with antibiotics can also be successful. Suggesting interval ap-
tial presentation. After 1 year, recurrence is rare, which Pátková and pendectomy may resurrect and perpetuate these previously rec-
colleagues3 recently confirmed through over 20 years of follow-up.1,2 onciled fears when patients can justifiably be given reassurance.
One worry that may surface after resolution of acute appendi- Explaining to patients with residual nonspecific abdominal symp-
citis is the possibility of missed appendiceal cancer. Interval appen- toms that we cannot help them with surgery will avoid an even more
dectomy is advocated for adults with complicated appendicitis dissatisfied patient later.
because of the high rate of occult neoplasm. However, occult ma- One might wonder if there are special circumstances when even
lignancy has been rarely found among computed tomographic (CT) elective appendectomy may be justified. The National Aeronautics
imaging-screened adults with uncomplicated appendicitis qualify- and Space Administration (NASA) conducted a risk-benefit study
ing for nonoperative treatment (<1%), and this is not an issue in modeling prophylactic appendectomy for astronauts and con-
children.1,5 More evidence from long-term follow-up of CODA par- cluded the risks associated with developing the later complication
ticipants has recently emerged to reassure patients.5 CT imaging was of small-bowel obstruction did not justify the removal of the appen-
found to be near perfect to exclude neoplasms in this cohort, with dix before an extended-duration space mission.7 In fact, 1 interna-
a 99% negative predictive value (95% CI, 99%-99%).6 Among the tional space station astronaut, Chris Hadfield, nearly had a 2013 mis-
antibiotic group in the CODA trial, subsequently discovered cancer sion canceled related to him having experienced a small bowel
occurred in 5 of 1033 participants (0.5%). The median time to diag- obstruction thought to be due to adhesions after a childhood ap-
nosis was 3 months, and there was no evidence of significant pre- pendectomy. Interval appendectomy to escape possible inoppor-
diagnosis progression; all tumors were stage 1 pathology. Pátková tune future illness seems like an expensive convenience that raises
and colleagues3 found no late-detected cancers over their 2-de- questions about the appropriateness of introducing risk as well as
cade surveillance. Repeated imaging and colonoscopy may be inequity. The out-of-pocket costs of interval appendectomy to avoid
considered if there are continued or recurrent symptoms. the unlikely possibility of appendicitis recurrence would make this
We also need to recognize the inertia associated with the com- option prohibitively expensive for many patients, particularly the
mon belief among patients and families of the now disproven tra- uninsured and underinsured.
ditional narrative that, without urgent surgery, the appendix will burst The imperative in treating uncomplicated appendicitis is to ini-
and lead to death. There have been no deaths related to nonoper- tially offer informed shared decision-making. During a patient’s
ative treatment of uncomplicated appendicitis among thousands of follow-up, we can honor that shared decision by reassuring them
patients described in published reports. Should appendicitis recur, that, with each passing day, their risk of appendicitis recurrence
it is no more dangerous or difficult to treat than it was originally. decreases, and they are increasingly likely to realize the outcomes
Salminen et al1 and Minneci and colleagues3 reported similar com- they sought.

ARTICLE INFORMATION Med. 2021;385(25):2395-2397. doi:10.1056/ management of nonoperatively treated patients

Published Online: April 24, 2024. NEJMc2116018 with appendicitis. JAMA Netw Open. 2022;5(7):
doi:10.1001/jamasurg.2023.8033 3. Minneci PC, Hade EM, Lawrence AE, et al; e2220039. doi:10.1001/jamanetworkopen.2022.
Midwest Pediatric Surgery Consortium. Association 20039
Conflict of Interest Disclosures: None reported.
of nonoperative management using antibiotic 6. Writing Group for the CODA Collaborative.
REFERENCES therapy vs laparoscopic appendectomy with Appendiceal neoplasm among those treated with
treatment success and disability days in children antibiotics for appendicitis: secondary analysis of
1. Salminen P, Tuominen R, Paajanen H, et al. with uncomplicated appendicitis. JAMA. 2020;324 the CODA randomized clinical trial. Br J Surg. 2023;
Five-year follow-up of antibiotic therapy for (6):581-593. doi:10.1001/jama.2020.10888 110(12):1659-1662. doi:10.1093/bjs/znad240
uncomplicated acute appendicitis in the APPAC
randomized clinical trial. JAMA. 2018;320(12):1259- 4. Pátková B, Svenningsson A, Almström M, et al. 7. Reyes DP, Carroll DJ, Walton ME, Antonsen EL,
1265. Erratum in: JAMA. 2018 Oct 23;320:1711.17. Long-term outcome of nonoperative treatment of Kerstman EL. Probabilistic risk assessment of
doi:10.1001/jama.2018.13201 appendicitis. JAMA Surg. 2023;158(10):1105-1106. prophylactic surgery before extended-duration
doi:10.1001/jamasurg.2023.2756 spaceflight. Surg Innov. 2021;28(5):573-581. doi:10.
2. Davidson GH, Flum DR, Monsell SE, et al; CODA 1177/1553350620979809
Collaborative. Antibiotics vs appendectomy for 5. Talan DA, Moran GJ, Krishnadasan A, et al;
acute appendicitis—longer-term outcomes. N Engl J The Writing Group for the CODA Collaborative.
Analysis of outcomes associated with outpatient

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