Background
Acute appendicitis is the most common surgical emergency in children [
1]. The lifetime risk of developing appendicitis is 7–8%, and the most common age for developing appendicitis is in the early teens. Appendicectomy is considered the gold standard treatment for acute appendicitis by most surgeons, but many parents and patients find the prospect of the need for emergency surgery frightening and one they are keen to avoid if an alternative is available [
2]. Preliminary work we have already undertaken with children and families confirms a high level of interest in non-operative treatment, and indeed a preference for non-operative treatment so long as clinical outcomes are comparable.
Although appendicectomy is considered a simple procedure, it requires a general anaesthetic and an abdominal operation with its associated risks. The complication rate of appendicectomy (including wound infection, intra-abdominal abscess and adhesional small bowel obstruction) is up to 25% [
3], with a need for hospital readmission in 4–5% of cases [
4,
5]. A contemporary estimation of these risks is available from the National Appendicectomy Audit, a nationwide audit of outcomes of appendicectomy for acute appendicitis in 19 specialist paediatric surgery centres in the United Kingdom [
6]. Over a 2-month period, 242 appendicectomies for acute appendicitis were performed. The negative (histologically normal) appendicectomy rate was 10.3%, and the 30-day adverse event (AE) rate (a composite of readmission, re-intervention, pelvic collection and wound infection) was 15.3%. The economic burden to the healthcare system of paediatric appendicitis in England is in excess of £21 million per year and requires significant resource use, including need for out-of-hours surgery (45% of all paediatric appendicectomies were performed between 1800 and 0800 in the National Appendicectomy Audit).
An alternative approach to treating acute appendicitis in children would be treatment with antibiotics and without an appendicectomy. Whilst there is growing scientific interest in the use of non-operative treatment with antibiotics owing to its potential benefits over surgery and existing data to support its safety, the relative efficacy of this approach compared with appendicectomy is not yet known [
7]. By undergoing a non-operative approach to treatment of their appendicitis, patients may avoid the mental and physical stress and trauma of an operation as well as the associated complications. Non-operative treatment has the potential to reduce the quantity of resources used by the National Health Service (NHS). For example, by reducing the amount of theatre time, staff time and surgical resources used for the treatment of appendicitis, there could be significant savings for the NHS.
It has been known for some time that acute appendicitis can be treated successfully by antibiotics alone in the context of remote environments without surgical service capability [
8]. However, the role of non-operative treatment as primary therapy has only recently come under consideration in developed healthcare systems, initially in adults [
3,
9‐
15] and more recently in children [
16‐
18]. Although studies in adults are sometimes extrapolated to children, to do so is problematic because there are key differences in appendicitis occurring in adults compared with in children. The presentation of appendicitis and the intra-abdominal inflammatory response are different in adults and children [
19,
20] and may be more amenable to antibiotic treatment alone, and the psychosocial and economic impact of appendicitis in children affects the whole family rather than just the individual. Therefore, a paediatric randomised controlled trial (RCT) is necessary to compare both treatment options.
There has been just one pilot RCT, recently performed in Sweden, comparing non-operative treatment with antibiotics with appendicectomy in children with acute appendicitis [
18]. Fifty children (aged 5–15 years) with acute non-perforated appendicitis were randomised to antibiotics (
n = 24) or appendicectomy (
n = 26). All children in the surgery group had histopathologically confirmed acute appendicitis, and none experienced a significant surgical complication. In the antibiotic group, 2 of 24 underwent appendicectomy within the time of primary antibiotic treatment, and 1 further child required appendicectomy for histologically proven, recurrent acute appendicitis 9 months later. Of the eligible participants, the recruitment rate was 40%; the drop-out rate following treatment allocation was 2% (1 patient); and no patient was lost to follow-up by 1 year. This pilot study was not powered sufficiently to compare the efficacy of antibiotics versus surgery, but it was conducted to inform the design of an international, multicentre RCT which is currently recruiting in non-UK centres [
21].
Our group recently performed a systematic review and meta-analysis comparing the efficacy of non-operative treatment and appendicectomy for uncomplicated appendicitis in children [
7]. Whilst there were limitations related to a lack of RCTs, the existing data support a position of equipoise between these two treatment approaches. Neither our review nor any of the contributing studies [
16‐
18,
22‐
24] identified any safety concerns regarding non-operative treatment.
In addition to outcomes of the acute illness, the development of recurrent appendicitis is an important consideration in children who receive non-operative treatment that is not applicable to children treated with appendicectomy. In adults [
9‐
12,
25], the incidence of recurrence (within 1 year) is around 15%. A recent pilot study of non-operative treatment of appendicitis in children with 1 year of follow-up reported a recurrence rate of 5% [
18], and our recent systematic review estimated an incidence of 14% [
7]. This is the best current estimate in children.
Given the current uncertainty regarding the relative efficacy and cost-effectiveness of non-operative treatment compared with appendicectomy in children with uncomplicated acute appendicitis, a definitive RCT is necessary. Although RCTs are ongoing in other countries [
26,
27], there are important differences in diagnostic techniques and healthcare delivery in the United Kingdom that mandate a UK-specific trial. These include a much lower reliance on diagnostic imaging for confirmation of appendicitis in the United Kingdom than in other countries, as well as a higher negative appendicectomy rate and a lower uptake of laparoscopic appendicectomy in the United Kingdom, all of which may influence relative efficacy of non-operative treatment compared with surgery [
6,
28]. Prior to performing a large efficacy trial, we designed this feasibility study, which includes a feasibility RCT, to inform the design and conduct of a future RCT and establish whether a main trial is possible in the United Kingdom.
Acknowledgements
The authors acknowledge the key role played by the following: the sponsor, University Hospitals Southampton NHS Foundation Trust, R&D Department, Southampton General Hospital, Southampton, UK; and all those who provided PPI input, specifically our SSAG.