Comparing treatment success between the antibiotic and surgical groups, the complication-free cure rate is more objective. The cure rate of antibiotic group in this study is 69.4%, which is consistent with the previous study[24, 57]. In comparision with surgical, the cure rate of the antibiotic group is significantly lower, suggesting that it may not be the optimum treatment for uncomplicated acute appendicitis only considering of recurrence. However, there were certain patients who were not fit or willing for surgery. Bom WJ et al[31] found that about half of the participants preferred antibiotic treatment for avoiding surgery and would accept a recurrence risk of more than 50 percent within 1 year. However, participants who prefer surgery for radical treatment of appendicitis, may tolerate a recurrence risk of no more than 10 percent when treated with antibiotics.
In general, the complications in the antimicrobial therapy group were lower than those in the surgical group. However, the surgical procedures included open and laparoscopic surgery, and the complications of open surgery were higher than those of laparoscopic surgery[58]. Complications of antibiotic therapy were 1.5%-8.2%[24, 36, 42], and 1%~3% of laparoscopic operation[59–61]. According to this study, the complications rates between laparoscopically operated people (4.4%) and antibiotic treated people (3.1%) were similar. With the introduction of laparoscopic surgery, the complications of surgery are greatly reduced compared to conservative treatment, which is a significant advantage of laparoscopic appendectomy.
This study showed that patients who underwent surgery after failing antibiotic treatment had similar surgical complications rates as the surgical group (9.5% vs 11.9%), suggesting that delaying the appendectomy due to antibiotic failure might not possibly result in a higher risk of postoperative complications. The previous study found that the rate of complicated appendicitis was lower in the antibiotics treatment than surgical group (2.7% vs 12.3%)at 1 year. Antibiotics treatment does not increase the rate of complicated appendicitis [62], which is familiar with the present study(antibiotics treatment vs surgery group :5% vs 9.9%). Uncomplicated acute appendicitis treated with antibiotics first was safe and effective with no significant increase in the number of complicated acute appendicitis[7, 36, 63, 64]. Also, evidence suggests that spontaneous resolution of untreated, non-perforated appendicitis is common and the perforation can rarely be prevented[65]. However, the previous Meta-analysis study[24]showed the opposite conclusion because it used the number of surgical patients instead of all patients (which generally applied)of antibiotic group as a parameter. Additionally, it is possible that some patients may have had complicated appendicitis at first that was not diagnosed, as opposed to uncomplicated appendicitis progressing to complicated appendicitis due to antibiotic treatment failure. Therefore, the conclusion that uncomplicated appendicitis will progress to complicated appendicitis can only be overestimated.
Dozens of studies found that the incidence of negative appendicectomies varies greatly from approximately 3.75–21%[61, 66, 67].Normally, there are two reasons for such wide range as follows: (1) preoperative imaging such as CT and ultrasound (US), has widespread used to greatly reduce the proportion of negative appendices in recent years. CT has been shown greater sensitivity and specificity than US for the diagnosis of appendicitis[68, 69, 70]; (2) some considered completely normal appendicitis as a negative appendectomy, while, the others included hyperplasia, atrophy and fibrosis. The present study applies the latter definition. The incidence of negative appendectomy was lower in both groups(antibiotics treatment vs surgery group:4.2%vs 3.7%),similar to another study[61]. In this meta-analysis, ten study reported negative appendicectomies, and only one trials (Styrud2006)[30]did not explicit mention preoperative imaging. Therefore, we should increase the accuracy of preoperative imaging diagnosis, and if US is difficult to clarify, CT, even MRI, can be added [71].
A majority of articles documented similar hospital stay with both treatment methods[26, 36, 41, 72], which is consistent with our study. Some, however, reported that the length of hospital stay in the antibiotics group was longer than that of the surgery group[42, 73], while others reported that the conservative group’s hospital stay was shorter than the surgery group[57].
This meta-analysis only analyzed the quality of life at 1 month and there was no significant difference. Podda M et al. concluded that the score of quality of life was significantly higher in patients with the appendectomy treatment at the 30-day, while the score was lower in the appendectomy group at the 1-year[74]. Minneci PC reported that patients who selected nonoperative management had high quality-of-life scores and remained satisfied with their health care decision at both 30 days and 1 year[70].
Dozens of studies have shown that presence of an appendicolith is associated with both an increased risk of antibiotic failure and recurrence[75–77], which is consistent with this study.
Appendiceal tumors were found in only 2 studies. Salminen 2015[10]reported that four patients had appendiceal tumors in surgical group and no appendiceal tumors were found in antibiotic group, while CODA Collaborative 2020[9]reported seven and two respectively. Fewer appendiceal tumors were reported in the antibiotic group. The rate of misdiagnosis of appendiceal tumors was high, which is reported between 0.7 and 2.5%[78–82]. Currently known risk factors for appendiceal tumors are age and complicated appendicitis[83, 84].
During relapse of failed treatment in the antibiotic group, antibiotics can be treated again. The previous study [48]reported that 2 patients successfully treated with antibiotics again when had recurrence appendicitis. Di Saverio S et al. pointed that a second attempt with antibiotic treatment could be a successful option for over 60% of patients who present with a recurrent episode of appendicitis at follow-up[85]. Poillucci G et al., found that 3.3% of patients who presented with a recurrence at follow-up were successfully treated with a further cycle of antibiotics[86].Antibiotics treatment will not aggravate the progression of uncomplicated appendicitis. Thus, when the patient relapses after initial antibiotic treatment, antimicrobial therapy can be used again if the diagnosis of appendicitis is confirmed.
There are still some limitations in this meta-analysis. The large difference in trial scale for inclusion articles may lead to result bias. Meanwhile, some outcome indicators were included in relatively few articles, which might have an impact on the outcome analysis.