Aspects of treatment of acute uncomplicated appendicitis in children and adults

Acute appendicitis is a clinical term for inflammation of the vermiform appendix with a sudden onset. Symptoms depend both on the age of a patient and on the position of appendix intraabdominally. The aetiology remains unknown, although, there are multiple theories. The lifetime risk of acute appendicitis in Western countries has been established as 7-8%, with 8.6% for males and 6.7% for females. The standard treatment has been surgery for many decades, but non-operative treatment, in the form of antibiotics, has more recently come to light as a feasible alternative to appendectomies.

Aims: The aim of this thesis was to assess intermediate and long-term outcomes of non- operative treatment in both children and adults. This included assessing safety and feasibility of non-operative treatment and its complications. An additional aim was to ascertain the failure rate of non-operative treatment and recurrence of acute uncomplicated appendicitis in children and try to establish the reasons for the treatment failure.

Methods: Study I was a 5-year follow-up of all participants who underwent surgery or non- operative treatment with antibiotics in a previous randomised controlled pilot trial. Data was extracted from the hospital notes and telephone interviews.

Study II was a long-term follow-up of adults with acute appendicitis who were involved in two randomised controlled trials, which compared non-operative treatment with appendectomy. The first trial consisted of 40 patients (13 female) and second trial was a multicentre study with 252 male patients. National registers were used to retrieve data at follow up, including the Swedish National Patient Register, the Cancer Register, the Cause of Death Register and Statistics Sweden.

Study III was a systematic review that was registered in PROSPERO (CRD42024592607) and done according to PRISMA statement. We searched three databases (PubMed, Medline, Web of Science). Eligible studies were randomised controlled trials or prospective cohort studies with children aged <18 years that received non-operative treatment for uncomplicated appendicitis and reporting at least 30 days follow-up. We carried out a meta- analysis.

Results: In Study I, we followed up all 50 children (26 children in the appendectomy group, 24 children in the nonoperative group) for at least 5 years. The surgical group was without failures and in the nonoperative group there were 11 failures and recurrences. In the first year there were nine failures, two of them had an appendicitis on the histopathology. Another two recurrences, that were histopathologically confirmed appendicitis occurred one to five years after the initial trial. At the 5-year follow-up, 54% of children had been successfully treated nonoperatively with antibiotics alone.

In Study II, in total, we were able to trace down 259 patients in the Patient Register, 137 patients in the non-operative group and 122 in the surgical group. At the end of follow-up, 82 (60%) patients had had successful non-operative treatment without an appendectomy. In the non-operative group there were 21 (15%) failures during the first admission. Thirty-four recurrences happened after discharge, all with a diagnostic code of acute appendicitis. After successful initial treatment, 82/116 (71%) remained without appendectomy.

In Study III, through a systematic search we were able to identify 2343 abstracts. Thirty studies were eligible, 8 randomised controlled trials and 22 prospective cohort studies reporting 27 different patient cohorts. An early failure rate occurred in 10% (95% CI 7-14%) and the recurrence rate was 29% (95% CI 24-34%) at the end of follow-up. When analysing studies with faecalith, a failure rate was higher (17% versus 6.4%) with P-value <0.0001.

Conclusions: Studies I and II demonstrated intermediate- and long-term safety of non- operative treatment alone in children and adults. This treatment does not increase the risk of malignancy and other complications and patients avoid surgery. Study III demonstrated a low initial failure rate and the recurrence rate was 29%. Non-operative treatment was less successful in children with a faecalith, particularly during first admission. These results can be used for discussion about treatment options of uncomplicated appendicitis with child patients and their caregivers.

List of scientific papers

I. Patkova B, Svenningsson A, Almström M, Eaton S, Wester T, Svensson JF. Nonoperative Treatment Versus Appendectomy for Acute Nonperforated Appendicitis in Children: Five-year Follow Up of a Randomized Controlled Pilot Trial. Ann Surg. 2020 Jun;271(6):1030-1035. https://doi.org/10.1097/SLA.0000000000003646

II. Pátková B, Svenningsson A, Almström M, Svensson JF, Eriksson S, Wester T, Eaton S. Long-Term Outcome of Nonoperative Treatment of Appendicitis. JAMA Surg. 2023 Oct 1;158(10):1105-1106. https://doi.org/10.1001/jamasurg.2023.2756

III. Patková B, Svenningsson A, Jumah S, Wester T, Eaton S. Failure and recurrence of non-operative treatment of uncomplicated appendicitis in children; a systematic review and meta-analysis. [Manuscript]