Colon to Rectum
Lancet. 2025;405(10474):233-240
Appendicectomy versus antibiotics for acute uncomplicated appendicitis in children: An open-label, international, multicentre, randomised, non-inferiority trial
Background: Support for the treatment of uncomplicated appendicitis with non-operative management rather than surgery has been increasing in the literature. The aim of this trial was to investigate whether treatment of uncomplicated appendicitis with antibiotics in children is inferior to appendicectomy by comparing failure rates for the 2 treatments. Methods: In this pragmatic, multicentre, parallel-group, unmasked, randomised, non-inferiority trial, children aged 5–16 years with suspected non-perforated appendicitis (based on clinical diagnosis with or without radiological diagnosis) were recruited from 11 children’s hospitals in Canada, the USA, Finland, Sweden, and Singapore. Patients were randomly assigned (1:1) to the antibiotic or the appendicectomy group with an online stratified randomisation tool, with stratification by sex, institution, and duration of symptoms (≥ 48 h vs. < 48 h). The primary outcome was treatment failure within 1 year of random assignment. In the antibiotic group, failure was defined as removal of the appendix, and in the appendicectomy group, failure was defined as a normal appendix based on pathology. In both groups, failure was also defined as additional procedures related to appendicitis requiring general anaesthesia. Interim analysis was done to determine whether inferiority was to be declared at the halfway point. The authors used a non-inferiority design with a margin of 20%. All outcomes were assessed in participants with 12-month follow-up data. Findings: Between January 20, 2016, and December 3, 2021, 936 patients were enrolled and randomly assigned to appendicectomy (n = 459) or antibiotics (n = 477). At 12-month follow-up, primary outcome data were available for 846 (90%) patients. Treatment failure occurred in 153 (34%) of 452 patients in the antibiotic group, compared with 28 (7%) of 394 in the appendicectomy group (difference, 26.7%, 90% confidence interval [CI]: 22.4–30.9). All but 1 patient meeting the definition for treatment failure with appendicectomy were those with negative appendicectomies. Of those who underwent appendicectomy in the antibiotic group, 13 (8%) had normal pathology. There were no deaths or serious adverse events in either group. The relative risk of having a mild-to-moderate adverse event in the antibiotic group compared with the appendicectomy group was 4.3 (95% CI: 2.1–8.7; p < 0.0001).
Interpretation: Based on cumulative failure rates and a 20% non-inferiority margin, antibiotic management of non-perforated appendicitis was inferior to appendicectomy.
DOI: 10.1016/s0140-6736(24)02420-6
Prof. Dr. Peter Hasselblatt
Deputy Director Department of Internal Medicine II, University Medical Center Freiburg (Germany)
What is the optimal treatment for acute appendicitis – antibiotics or surgery?
Recent studies have evaluated the option of conservative antibiotic therapy instead of appendectomy for acute uncomplicated appendicitis. The 2020 multicenter CODA study, which included 1552 patients with acute appendicitis, found that antibiotic therapy was not inferior to appendectomy in terms of health-associated quality of life. However, 30% of patients in the study who initially received antibiotic therapy had to undergo surgery within 90 days. The presence of appendicolithiasis was a risk factor for subsequent surgery or complications. The available evidence on antibiotic therapy versus surgery for uncomplicated appendicitis has now also been evaluated in a meta-analysis that included individual patient data from 2580 adults with uncomplicated appendicitis derived from 6 trials (Scheijmans et al.). The complication rate in patients treated with antibiotics was slightly lower than in those who underwent surgery (5.4% vs. 8.3%). However, according to this meta-analysis, a third of the patients treated with antibiotics also had to undergo surgery within 1 year. Again, the presence of appendicoliths was a significant risk factor for complications or subsequent surgery (around half of the patients receiving antibiotics had to undergo surgery later). Based on these data, adult patients presenting with appendicitis are candidates for conservative management; however, appendicolithiasis should be excluded as a contraindication, and patients should be counseled regarding the approximately 30% risk of progression to appendectomy within the follow-up period.
Do these options also apply to children? To answer this question, a multicenter randomized study involving 936 children with uncomplicated appendicitis was conducted at 11 centers (St. Peter et al.). The primary endpoint was non-inferiority of antibiotic therapy compared to surgery with regard to treatment failure. In patients receiving antibiotic therapy, failure was defined as subsequent surgery, while in patients primarily receiving surgery, it was defined as the absence of inflammatory alterations on histology. Non-inferiority was defined by a margin of 20%. Treatment failure occurred in 34% versus 7% of the children treated by antibiotics versus surgery and the endpoint of non-inferiority was not met. These data indicate that a third of children who received antibiotic therapy also had to undergo surgery later. Although children in the antibiotic group were able to resume their normal daily routine earlier (after 1 day vs. 4 days) and return to school earlier (after 2 days vs. 3 days), these differences were rather small. The duration of hospitalization at first manifestation was also significantly shorter in those receiving antibiotic therapy, but the difference was very small (1.0 day vs. 1.25 days). Given these results and the generally uncomplicated disease course following an appendectomy, we should continue to offer surgery rather than antibiotic therapy for children with uncomplicated appendicitis. The likelihood of requiring surgery after antibiotic therapy remains high, while the associated quality-of-life benefits appear minimal.