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What is the long-term recurrence rate in patients with uncomplicated acute appendicitis treated with antibiotics?
In this 5-year observational follow-up of 257 patients initially treated with antibiotics for uncomplicated acute appendicitis, the cumulative incidence of recurrent appendicitis at 1, 2, 3, 4, and 5 years was 27.3% at 1 year, 34.0% at 2, 35.2% at 3, 37.1% at 4, and 39.1% at 5 years.
Long-term follow up of patients with uncomplicated acute appendicitis suggests that initial treatment with antibiotics rather than surgery may be a feasible alternative.
Short-term results support antibiotics as an alternative to surgery for treating uncomplicated acute appendicitis, but long-term outcomes are not known.
To determine the late recurrence rate of appendicitis after antibiotic therapy for the treatment of uncomplicated acute appendicitis.
Design, Setting, and Participants
Five-year observational follow-up of patients in the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotic therapy, in which 530 patients aged 18 to 60 years with computed tomography–confirmed uncomplicated acute appendicitis were randomized to undergo an appendectomy (n = 273) or receive antibiotic therapy (n = 257). The initial trial was conducted from November 2009 to June 2012 in Finland; last follow-up was September 6, 2017. This current analysis focused on assessing the 5-year outcomes for the group of patients treated with antibiotics alone.
Open appendectomy vs antibiotic therapy with intravenous ertapenem for 3 days followed by 7 days of oral levofloxacin and metronidazole.
Main Outcomes and Measures
In this analysis, prespecified secondary end points reported at 5-year follow-up included late (after 1 year) appendicitis recurrence after antibiotic treatment, complications, length of hospital stay, and sick leave.
Of the 530 patients (201 women; 329 men) enrolled in the trial, 273 patients (median age, 35 years [IQR, 27-46]) were randomized to undergo appendectomy, and 257 (median age, 33 years, [IQR, 26-47]) were randomized to receive antibiotic therapy. In addition to 70 patients who initially received antibiotics but underwent appendectomy within the first year (27.3% [95% CI, 22.0%-33.2%]; 70/256), 30 additional antibiotic-treated patients (16.1% [95% CI, 11.2%-22.2%]; 30/186) underwent appendectomy between 1 and 5 years. The cumulative incidence of appendicitis recurrence was 34.0% (95% CI, 28.2%-40.1%; 87/256) at 2 years, 35.2% (95% CI, 29.3%-41.4%; 90/256) at 3 years, 37.1% (95% CI, 31.2%-43.3%; 95/256) at 4 years, and 39.1% (95% CI, 33.1%-45.3%; 100/256) at 5 years. Of the 85 patients in the antibiotic group who subsequently underwent appendectomy for recurrent appendicitis, 76 had uncomplicated appendicitis, 2 had complicated appendicitis, and 7 did not have appendicitis. At 5 years, the overall complication rate (surgical site infections, incisional hernias, abdominal pain, and obstructive symptoms) was 24.4% (95% CI, 19.2%-30.3%) (n = 60/246) in the appendectomy group and 6.5% (95% CI, 3.8%-10.4%) (n = 16/246) in antibiotic group (P < .001), which calculates to 17.9 percentage points (95% CI, 11.7-24.1) higher after surgery. There was no difference between groups for length of hospital stay, but there was a significant difference in sick leave (11 days more for the appendectomy group).
Conclusions and Relevance
Among patients who were initially treated with antibiotics for uncomplicated acute appendicitis, the likelihood of late recurrence within 5 years was 39.1%. This long-term follow-up supports the feasibility of antibiotic treatment alone as an alternative to surgery for uncomplicated acute appendicitis.
ClinicalTrials.gov Identifier: NCT01022567
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Corresponding Author: Paulina Salminen, MD, PhD, Turku University Hospital, Kiinamyllynkatu 4-8, 20520 Turku, Finland (email@example.com).
Correction: This article was corrected on September 27, 2018, because of incomplete information in Figure 1.
Accepted for Publication: August 16, 2018.
Author Contributions: Drs Salminen and Grönroos had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr Salminen had the final responsibility for the decision to submit the manuscript for publication.
Concept and design: Salminen, Tuominen, Paajanen, Rautio, Nordström, Aarnio, Rantanen, Hurme, Mecklin, Sand, Virtanen, Grönroos.
Acquisition, analysis, or interpretation of data: Salminen, Tuominen, Paajanen, Rautio, Nordström, Rantanen, Hurme, Jartti, Grönroos.
Drafting of the manuscript: Salminen, Tuominen, Paajanen, Nordström, Rantanen, Hurme, Grönroos.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Salminen, Tuominen, Hurme.
Obtained funding: Salminen.
Administrative, technical, or material support: Salminen, Rautio, Nordström, Sand, Virtanen, Grönroos.
Supervision: Salminen, Tuominen, Paajanen, Rautio, Nordström, Rantanen, Sand, Jartti, Grönroos.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Salminen reports receipt of personal fees for lectures from Merck, Lilly, and Orion Pharma. No other disclosures were reported.
Funding/Support: This trial was supported by the Mary and Georg C. Ehrnrooth Foundation, a government research grant (EVO Foundation) awarded to Turku University Hospital, and a Turku University research grant.
Role of the Funder/Sponsor: None of the funding entities had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 2.
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