New long-term results help clarify the trade-offs between surgery and antibiotics for uncomplicated appendicitis.
Over half of patients treated with antibiotics for appendicitis avoided appendectomy for the following decade, according to new follow-up data from the landmark Finnish APPendicitis ACuta (APPAC) trial.
The findings have provided some of the longest follow-up data available to date comparing antibiotic therapy with surgery for uncomplicated acute appendicitis.
Of those who did require subsequent surgical removal of their appendix, just over half (53.4%) said they would not choose initial antibiotic therapy again if given the choice.
However, complication rates remained substantially lower than patients assigned to surgery.
At 10 years, the cumulative complication rate was 27.4% in the appendectomy group compared with 8.5% among patients randomised to antibiotics (P < 0.001).
The trial enrolled 530 adults aged 18 to 60 years across six Finnish hospitals between 2009 and 2012. All participants had CT-confirmed uncomplicated acute appendicitis and were randomly assigned 1:1 to either open appendectomy (273 patients) or antibiotic therapy (257 patients).
Patients in the antibiotic arm received intravenous ertapenem sodium 1g daily for three days, followed by seven days of oral levofloxacin 500mg once daily and metronidazole 500mg three times daily.
At 10-year follow-up, researchers were able to assess 253 of the 257 patients (98.4%) initially randomised to antibiotics.
They found a “true” appendicitis recurrence rate – defined as histologically confirmed appendicitis – of 37.8%.
The cumulative appendectomy rate over 10 years was slightly higher at 44.3%, meaning fewer than half of patients initially treated with antibiotics required surgery over this period.
The appendectomy rate increased progressively over time and most recurrences occurred relatively early. Within the first year, 27.3% of patients in the antibiotic group underwent appendectomy, rising to 39.1% at five years and 44.3% by 10 years.
Seventy patients underwent appendectomy during the first year after antibiotic treatment, with another 30 operations occurring between years one and five. Only 12 additional appendectomies were performed between years six and 10.
Of the 112 patients who ultimately underwent appendectomy after antibiotic treatment, 15 operations occurred during the initial hospitalisation.
Among the remaining 97 delayed appendectomies, uncomplicated acute appendicitis was confirmed histologically in 83 patients – eight patients underwent surgery for suspected recurrence, but appendicitis was not identified histologically.
No patients in the antibiotic group developed complicated appendicitis within the first year and across the entire 10-year follow-up period, only six patients in this group were found to have complicated appendicitis at surgery.
Despite differences in recurrence, overall quality of life was similar between treatment groups at 10 years. Using the validated EQ-5D-5L questionnaire, which measures mobility, self-care, usual activities, pain/discomfort and anxiety/depression, researchers assessed overall QOL.
Among the 387 patients who completed these assessments (217 in the surgery group and 170 in the antibiotics group), the median health index value was identical in both groups at 1.0, indicating overall full health.
However, self-rated health scores were modestly higher among patients randomised to antibiotics.
The median health visual analogue scale (VAS) score – measured on a 100-point scale – was 85 in the antibiotic group compared to 80 in the appendectomy group (P = 0.03).
Patient satisfaction remained relatively high in both groups. Among patients initially randomised to appendectomy, 78% said they would choose the same treatment again. In the antibiotic group, 67.3% would again choose antibiotics.
Unsurprisingly, satisfaction was highest among patients who successfully avoided surgery, with 90.9% saying they would choose antibiotics again. Of those who later required appendectomy, only 46.6% said they would again choose antibiotic therapy.
Tumour prevalence didn’t differ significantly between the treatment groups, with an overall prevalence of 1.2% across the cohort. At the 10-year follow-up, 102 of the 156 patients with intact appendixes underwent MRI imaging.
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While no imaging showed signs of active appendiceal inflammation, imaging for two patients raised alarm. They subsequently underwent appendectomy for suspected tumours and were found to have low-grade appendiceal mucinous neoplasms on histopathology. Neither tumour had been visible on the original CT scans at enrolment.
Comparatively, four tumours were identified in the appendectomy arm within the first year, including three neuroendocrine tumours and one adenoma with low-grade dysplasia.
The researchers concluded that the long-term recurrence and appendectomy rates observed after antibiotic treatment still support antibiotics as a reasonable option for uncomplicated acute appendicitis in adults.
While the findings suggest that antibiotics can spare many patients surgery, clinicians and patients have to weigh this against an approximately 44% cumulative likelihood of appendectomy over the subsequent decade.
