In managing acute uncomplicated appendicitis, patient outcomes are clearly the highest priority. Acute appendicitis ranks among the most common surgical emergencies globally, with an estimated lifespan incidence of 7% to 8% and a peak occurrence between 20 and 40 years of age.
In JAMA Network, Anthony Charles – Department of Surgery, University of Vermont, and JAMA associate editor – discusses a study in this same edition which he strongly believes reaffirms antibiotics as a safe and feasible alternative to appendectomy and underscores the role of shared decision-making in the management of uncomplicated appendicitis.
He writes:
The 2015 Appendicitis Acuta (APPAC) trial, in which adult participants with acute uncomplicated appendicitis without appendicolith were randomised to either open appendectomy or antibiotics (intravenous ertapenem for three days followed by seven days of oral levofloxacin and metronidazole), demonstrated that 72.7% of patients treated with antibiotics did not require an appendectomy within the first year.
The antibiotic treatment success rate was 63% at two years, 62% at three years, and 61% at five years.
Similarly, the 2020 Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial, which included patients with appendicolith, demonstrated that antibiotics were non-inferior to appendectomy; 60% of patients in the antibiotic group did not require an appendectomy by one year, 54% by two years, and 51% at three and four years.
These two major European and American randomised clinical trials (RCTs) found antibiotics to be a feasible and safe alternative to appendectomy in adults with uncomplicated acute appendicitis confirmed by computed tomography, although a milieu of uncertainty regarding recurrent appendicitis has remained.
In this issue of JAMA, Salminen and colleagues present their 10-year follow-up of antibiotic therapy for uncomplicated acute appendicitis in the APPAC trial. The investigators demonstrate a 10-year appendectomy rate of 44.3% and a histological confirmation of recurrent appendicitis rate of 37.8%.
Overall, the 10-year cumulative complication rate after appendectomy was 27.4% (95% CI, 21.6%-33.3%), whereas it was lower in those treated with antibiotics (8.5% [95% CI, 4.8%-12.1%], P < .001). There was no difference in quality of life and patient satisfaction between those treated with antibiotics and those treated with appendectomy.
This study reaffirms antibiotics as a safe and feasible alternative to appendectomy and underscores the role of shared decision-making in the management of uncomplicated appendicitis.
The issue is no longer about a right vs wrong management pathway but between a medically acceptable and a surgically definitive strategy with very different risk-benefit profiles. The two treatment paths have outcomes that are not directly comparable, making it difficult for patients to weigh them. Both clinicians and patients are subject to biases that can skew the shared decision-making process.
Surgeons may determine that the longer-term rates of appendicitis recurrence make antibiotics a less desirable treatment strategy than early appendectomy and may frame these data to favour appendectomy (“Why risk a future recurrence or rupture when we can fix it now?”).
The safe choice from a medico-legal perspective might seem to be surgery. Conversely, an internist might frame antibiotics as the safer option because it “avoids unnecessary surgery”.
Choosing antibiotics requires reliable and prompt access to follow-up care, which can be a significant barrier for underserved populations, patients without insurance, or those without reliable transportation.
When communicating the risks and benefits of either approach, clinicians can improve patient understanding by presenting information numerically rather than using verbal probability terms such as rare, common, or unlikely.
Importantly, clinicians should discuss absolute rather than relative risks while also providing context. The way risk is presented (e.g, 62% success rate vs 38% failure rate) dramatically influences patient choice.
The differences in 10-year cumulative complication rates reported by Salminen et al must be viewed with caution, because open appendectomy is no longer the current standard of care, and the complication profile following laparoscopic appendectomy is indeed much lower than that for open appendectomy.
Interestingly, prior studies have shown that substantial numbers of patients report a preference for antibiotics first, even if appendectomy may ultimately be necessary.
In this study, after successful antibiotic treatment, 90.9% of patients would again select antibiotics. However, less than one-half of the patients who underwent appendectomy after receiving antibiotics alone stated that they would again choose antibiotics in the future.
Unfortunately, determining the factors predictive of recurrence in patients initially treated with antibiotics is challenging.
Uncertainties relating to the risk of missing an underlying malignancy must also be factored into shared decision-making discussions. Studies based on data from North American populations have reported an increase in all histological subtypes of malignant appendiceal tumours.
Marmor et al showed a 54% increase in overall incidence (0.63 to 0.97 per 100 000) of appendiceal cancers among a US population from 2000 to 2009. Incidence rates increased consistently across age and sex.
A subsequent American-Canadian analysis analysis demonstrated an overall 232% increase in incidence rate between 1992 and 2016, in the absence of a concomitant rise in the appendectomy rate. The incidence of an occult malignancy in a surgically removed appendix ranges from less than 1% in children and young adults to 2.5% in adults over 50 who present with acute appendicitis.
Unfortunately, the purported incidence of appendiceal malignancy in the study by Salminen et al is likely an underestimate, given the indeterminate sensitivity of magnetic resonance imaging for appendiceal cancer in an asymptomatic cohort, and must also be assessed against the secular trend for rising incidence of appendiceal cancers in older adults.
Questions remain about the actual incidence of missed malignancy in patients treated with antibiotics and the long-term outcomes for these patients.
Given the higher rates of malignancy in older adults, should this favour surgery in older patients presenting with uncomplicated acute appendicitis? Furthermore, whether the cancer risk is high enough to justify interval appendectomy (planned appendectomy after antibiotic treatment) in certain high-risk groups (e.g, patients over 50) after successful antibiotic management is unknown.
Salminen et al have provided the long-term data required to perform an economic evaluation of an antibiotic-first strategy for uncomplicated acute appendicitis. With a 10-year recurrence rate of 37.8%, antibiotic therapy is highly likely to be cost-effective from a societal perspective.
Even if the recurrence-related appendectomy is more expensive, the initial savings from the 62% who avoid surgery altogether is probably sufficiently substantial that the overall cost is likely to be lower and outweigh the added costs of treating recurrences.
With an economic evaluation that may favour the use of antibiotics for uncomplicated appendicitis, the final management decision must still be shared, because the cost to an individual patient in terms of anxiety, time in the hospital, and potential future illness may outweigh the societal economic benefit.
The decision “to cut or to keep” in the management of acute uncomplicated appendicitis is nuanced and must be individualised, carefully weighing the patient’s values, age, and risk tolerance, with a clear understanding of the uncertainties involved.
Anthony Charles, MD, MPH1 – Department of Surgery, University of Vermont, Burlington, JAMA Associate Editor
Study details
Antibiotic Therapy for Uncomplicated Acute Appendicitis: 10-Year Follow-Up of the APPAC Randomised Clinical trial
Key Points
Question What is the long-term appendicitis recurrence and appendectomy rate in adult patients with uncomplicated acute appendicitis treated with antibiotics?
Findings In this 10-year observational follow-up of patients initially treated with antibiotics for uncomplicated acute appendicitis, the true appendicitis recurrence rate (appendicitis at histopathology) was 37.8% and the cumulative appendectomy rate was 44.3%.
Meaning Long-term follow-up of patients with uncomplicated acute appendicitis supports the use of antibiotics as an option for uncomplicated acute appendicitis in adult patients.
Abstract
Importance
Antibiotic therapy is effective and safe for uncomplicated acute appendicitis in adults, but randomised clinical trial results exceeding five years are missing.
Objective
To determine the 10-year appendicitis recurrence and appendectomy rate in patients with uncomplicated appendicitis treated with antibiotics.
Design, Setting, and Participants
Ten-year observational follow-up of patients in the Appendicitis Acuta (APPAC) multicentre randomised clinical trial comparing appendectomy with antibiotics at six Finnish hospitals from November 2009 to June 2012, where 530 patients (aged 18-60 years) with uncomplicated acute appendicitis diagnosed by computed tomography were randomly assigned to appendectomy (n = 273) or antibiotics (n = 257). Last follow-up was April 29, 2024. This current analysis focused on assessing the 10-year appendicitis recurrence rate among patients assigned to antibiotics.
Interventions
Open appendectomy vs antibiotics with intravenous ertapenem sodium (1 g/d) for three days followed by seven days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times/d).
Main Outcomes and Measures
Prespecified 10-year secondary end points included late (after one year) appendectomy and appendicitis recurrence rate after antibiotics and complications. Post hoc outcomes included the detection of possible appendiceal tumours among patients in the antibiotic group undergoing appendectomy or with an intact appendix using magnetic resonance imaging. Additional post hoc outcomes were quality of life and patient satisfaction.
Results
At 10-year follow-up, 253/257 patients (98.4%) randomised to receive antibiotics (median age, 33 years; 102 [40.3%] female) were assessed for appendicitis recurrence, with a true appendicitis recurrence rate (appendicitis at histopathology) of 37.8% (95% CI, 31.6%-44.1% [87/230]) and a cumulative appendectomy rate of 44.3% (95% CI, 38.2%-50.4% [112/253]). Overall, the 10-year cumulative complication rate in the group randomised to appendectomy was 27.4% (95% CI, 21.6%-33.3% [62/226]) and 8.5% (95% CI, 4.8%-12.1% [19/224]) in the group randomised to receive antibiotics (P < .001). There was no observed significant difference in quality of life between antibiotics and appendectomy (387/530; median health index value, 1.0 [95% CI, 1.0-1.0] for both groups; P = .18).
Conclusions and relevance
Among patients initially treated with antibiotics for uncomplicated acute appendicitis, the rate of recurrence and appendectomy at 10-year follow-up supports the use of antibiotics as an option for uncomplicated acute appendicitis in adult patients.
JAMA Network article – The Appendicitis Gamble—to Cut or to Keep (Open access)
See more from MedicalBrief archives:
Non-operative appendicitis treatment a better option, argue surgeons
Antibiotics effective in 70% of appendix cases with no added risk – Duke study
Royal College Ireland: Surgery best for acute uncomplicated appendicitis