Long-Term Outcome of Nonoperative Treatment of Appendicitis

Abstract

This cohort study uses registry data to report the long-term outcomes of patients who participated in randomized clinical trials of antibiotics vs surgery in Sweden in the 1990s.

The longest outcomes reported of patients receiving nonoperative treatment for acute appendicitis have been at 5 years.¹ We aimed to report long-term outcomes (19-26 years) among participants of the first 2 randomized clinical trials (RCTs) of nonoperative treatment conducted in Sweden in the 1990s.^2,3

Methods

Data for this cohort study were retrieved from the Swedish National Patient Registry on participants (n = 292; 13 female and 279 male) in 2 RCTs of appendectomy vs nonoperative treatment for acute appendicitis (diagnosed clinically in 252, with ultrasound in 40).^2,3 The first was a pilot RCT² with 40 patients (13 female) randomized to appendectomy or antibiotic treatment between May 1992 and March 1994. The second was a multicenter RCT³ with 252 male patients randomized between March 1996 and June 1999. Additional details are described in the eMethods in Supplement 1. This study was approved by the Swedish Ethical Review Authority and National Board of Health and Welfare. Informed consent was waived due to the National Registry nature of the study and anonymization of provided data. We generally followed the STROBE reporting guideline. Demographic characteristics were compared using Mann-Whitney test or by Fisher exact test. A 2-sided P < .05 was considered statistically significant. Statistical analyses were performed in 2022 using SPSS, version 26.0 (IBM).

Results

Initial successful nonoperative treatment was reported in Eriksson and Granström² (19 of 20 patients [95%]) and Styrud et al³ (113 of 128 [88%]) with 1-year recurrence rates of 36.8% (7 of 19 patients) and 14.4% (16 of 111), respectively, in those whose treatment had been initially successfully managed nonoperatively. Of 292 participants, 259 (88.7%) were traceable in the registry, 137 of 148 (92.6%) in the nonoperative group and 122 of 144 (84.7%) in the appendectomy group (Figure 1). In addition to the 21 participants (15%) who had appendectomy due to failure of nonoperative treatment at initial hospital admission, 34 (29%) had a subsequent appendectomy for acute appendicitis, so that 82 of 137 patients (60%) had not undergone appendectomy at the end of follow-up (Figure 2A), and 82 of 116 (71%) who had been successfully discharged without appendectomy remained without appendectomy (Figure 2B). Although the rate of appendectomy was low after the first year, appendectomies continued to occur even up to 20 years later. In addition to those having appendectomy, 13 of 137 patients (9.5%) from the nonoperative group went to a surgical outpatient clinic for abdominal pain, compared with 1 of 122 patients (.01%) from the appendectomy group (P < .002). No patient from either group underwent surgery for bowel obstruction. Although appendiceal neoplasm can manifest as acute appendicitis, no appendiceal tumors were reported in the nonoperative patients who underwent appendectomy during follow-up. Five patients had inflammatory bowel disease; 3 patients with Crohn disease had all undergone appendectomy (2 randomized to appendectomy, 1 following early failure of nonoperative treatment), and 2 patients (1 from each group) had ulcerative colitis.

Figure 1. Flow Diagram of Follow-Up of the Initial Cohort.

RCTs indicates randomized clinical trials.

Figure 2. Cumulative Incidence of Appendectomy Among Patients in the Nonoperative Treatment Group up to 25-Year Follow-Up.

Shaded area represents 95% CI.

Discussion

This study is the first to our knowledge to report truly long-term results of nonoperative treatment of acute appendicitis, by a registry study of patients included in 2 RCTs. Study limitations include that patients could not be followed up prospectively; most patients were male; and we did not have histopathology results after appendectomies in the nonoperative group. In addition, we were looking at results of standards of diagnostics as they were when the initial studies were performed. This renders it difficult to extrapolate to current diagnostic standards, which involve much higher rates of imaging and consequently lower rates of both negative appendectomy and missed perforation.

However, more than half of the patients treated nonoperatively did not experience recurrence and avoided surgery over approximately 2 decades. There is no evidence for long-term risks of nonoperative management other than that of recurrence of appendicitis. The present data will further be beneficial to clinicians as well as patients with acute appendicitis in making a treatment decision.

Supplement 1.

eMethods

eReferences

Supplement 2.

Data Sharing Statement