The present meta-analysis indicated a higher treatment success rate and a shorter length of stay in the appendectomy group than those in the antibiotic treatment group. However, the incidences of treatment-related complications and duration of missed work were significantly lower in the antibiotic treatment group than in the appendectomy group. The present study suggested that antibiotics were not inferior to appendectomy for the treatment of AA (especially uncomplicated appendicitis), and long-term quality of life may be higher with the antibiotic treatment.
Since the first report of appendectomy for appendicitis treatment by Mcburney, surgical treatment has become the gold standard for the treatment of AA.27 Eriksson et al.15 conducted RCTs to report for the first time that antibiotics were equally effective with no postoperative pain in AA treatment. Thus, the safety and effectiveness of the two treatments are controversial.3, 9
A RCT allows random grouping of subjects for adopting different interventions. It offers advantages of avoiding various biases, balancing confounding factors, and improving the effectiveness of statistical tests. Thus, RCTs are recognized as the gold standard for evaluating an intervention.28 The present meta-analysis was conducted using RCTs to ensure that the data obtained are convincing and exhibit minimal deviation.
Several studies have exhibited the superiority of appendectomy for several reasons.16, 18, 22–25First, the postoperative recurrence rate associated with appendectomy is negligible. Second, appendiceal tumors and extra-appendiceal pathologies may be detected early after the routine pathological examination, which may affect survival of patients after appendectomy. Third, the global popularization of minimally invasive technology has considerably reduced the incidences of incision infection, abdominal adhesion, and postoperative pain; analgesic use; and hospitalization time after laparoscopic appendectomy compared with those after open appendectomy, which have improved the quality of life of patients.29 Finally, the application of broad-spectrum antibiotics may cause bacterial resistance or contribute to the emergence of superbacteria such as methicillin-resistant Staphylococcus aureus, multidrug-resistant Streptococcus pneumoniae, and vancomycin-resistant enterococci.30 However, appendectomy has numerous limitations. Because most hospitals in developing countries still perform open appendectomy, the postoperative complications cannot be ignored. Simultaneously, the function of the appendix and the influence of its resection on the human body remain unclear.31 Additionally, many patients prefer conservative treatment over surgical treatment.
The present meta-analysis exhibited a statistically significant difference in the 1-year treatment efficacy between the two treatments (P < 0.001; OR < 0.1). However, 70% of the patients with AA in the antibiotic treatment group exhibited no recurrence within 1 year, whereas approximately 60% patients exhibited no recurrence within 5 years.32 Thus, most patients avoided surgical treatment. Nevertheless, the length of hospital stay for the surgical treatment group was shorter than that for the antibiotic treatment group, which may be attributed to the lack of a definite time guideline for the antibiotic treatment. Most clinical centers consider three days as the time point for early treatment, and the length of hospital stay may be greatly reduced in the later treatment stage. In Italy, the use of oral antibiotics in non-surgical treatment was reported to greatly shorten the length of hospital stay.33
Antibiotics therapy offers several theoretical advantages over appendectomy. Compared with surgical resection, conservative treatment exhibited lesser incidences of complications, time missed from work, and hospitalization expenses. Additionally, many patients treated conservatively do not require hospitalization. Because these patients can be treated in the emergency or outpatient department, the treatment efficiency can be improved. This efficient treatment of AA may benefit patients, especially in the COVID-19 pandemic. A high therapeutic effect rate and a low recurrence rate were observed particularly in patients with uncomplicated appendicitis with no appendicolith.26 Incidences of surgical complications do not increase even if appendectomy is delayed in patients treated with antibiotics. Although CT scan exhibits high specificity and sensitivity in AA diagnosis, several patients with normal appendix are still treated with transitional surgery. A retrospective study conducted in 3236 patients who received non-surgical treatment, with the average follow-up period of 7 ± 3.9 years, reported a long-term recurrence rate of only 4.4%.34 Salminen et al.32 reported the late recurrence rate of uncomplicated AA after antibiotic treatment in the APPAC RCT. The author concluded that the possibility of late recurrence within 5 years among patients with simple AA who initially received antibiotic treatment was 39.1%. This long-term follow-up study supported the feasibility of antibiotic treatment as an alternative to surgery for uncomplicated AA. The results of the present meta-analysis may be particularly relevant during the COVID-19 pandemic. Patients and clinicians should weigh the benefits and risks of each method by considering the individual characteristics, preferences, and environment.35
The present meta-analysis has certain limitations. The major source of heterogeneity detected in the sensitivity analysis was the study by Hansson,17 which had a high crossover rate from medical treatment to surgical treatment. The study by Styrud only included male patients, which resulted in a high risk of bias. Additionally, in some RCTs, publication bias or sources of heterogeneity were introduced due to the small sample size and short follow-up time; these factors might have affected the primary results. Furthermore, the antibiotic treatment regimens in all the studies were different. Different antibiotic levels and antimicrobial spectrum may affect the results and serve as a source of heterogeneity. Moreover, only the study by GoryFlum conducted a subgroup analysis for the presence of appendicolith and concluded that patients with an appendicolith detected in preoperative CT examination exhibited a high recurrence rate and were at a high risk of undergoing appendectomy. Although this result is crucial, other studies have not analyzed this aspect. The outcome of health status should be described using the EQ-5D questionnaire,36 which could not be performed in most of the studies included in this meta-analysis due to the lack of original data. Furthermore, although funnel plot comparisons were used and exhibited no publication bias between conservative treatment and appendectomy, Egger and Begg regression tests could not be used to determine publication bias due to the limitations of RevMan software. Finally, due to the restrictions of natural factors, randomized double-blind trials could not be realized in the included RCTs. Therefore, we hope that more clinical centers can do large-sample randomized double-blind controlled trials in the future, and compare the two treatments of appendicitis, so that the evidence level of our meta-analysis will be higher.