Five-year follow-up of appendiceal neoplasm risk in periappendicular abscess in the Peri-Appendicitis Acuta Randomized Clinical Trial

from January 2013 to April 2016. This long-term follow-up at a minimum of 5 years was added to the study protocol subsequently targeted to assess the follow-up group patients initially declining to undergo appendectomy after study termination. First, this long-term MRI follow-up was added to ensure patient safety based on the high appendiceal tumor rate at 1-year follow-up. 1 Patients gave a separate written informed consent for this imaging. Second, this observational follow-up assessed the long-term outcomes of the trial patients initially diagnosed with an appendiceal tumor by reviewing their medical records. The detailed methods and primary results have been previously published 1. The difference between groups in age was tested using Mann–Whitney U-test. The study was approved by the Ethical Committee of Turku University Hospital district and conducted in accordance with the Declaration of Helsinki following the relevant portions of the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.


Introduction
2][3][4][5][6] The Peri-Appendicitis Acuta Randomized Clinical Trial (Peri-APPAC RCT) 1 comparing interval appendectomy and follow-up with magnetic resonance imaging (MRI) after the initial successful nonoperative treatment of periappendicular abscess was prematurely terminated in 2016 owing to ethical concerns due to high appendiceal neoplasm rate in the appendectomy group with final overall neoplasm prevalence of 20% (12/60).Out of the 30 patients randomized to MRI follow-up, appendectomy was recommended to all patients.At 5 years, this study reports the long-term outcomes of the follow-up group patients declining to undergo appendectomy after study termination and all the patients diagnosed with an appendiceal tumor.

Methods
This is a post hoc follow-up of the Peri-APPAC RCT comparing interval appendectomy with MRI follow-up for periappendicular abscess after initial successful conservative treatment in adults aged 18 to 60 years in five Finnish hospitals enrolling patients from January 2013 to April 2016.This long-term follow-up at a minimum of 5 years was added to the study protocol subsequently targeted to assess the follow-up group patients initially declining to undergo appendectomy after study termination.First, this long-term MRI follow-up was added to ensure patient safety based on the high appendiceal tumor rate at 1-year follow-up. 1atients gave a separate written informed consent for this imaging.Second, this observational follow-up assessed the long-term outcomes of the trial patients initially diagnosed with an appendiceal tumor by reviewing their medical records.The detailed methods and primary results have been previously published 1.The difference between groups in age was tested using Mann-Whitney U-test.The study was approved by the Ethical Committee of Turku University Hospital district and conducted in accordance with the Declaration of Helsinki following the relevant portions of the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.

Results
Out of the 14 patients with an intact appendix, two had undergone appendectomy after the initial follow-up with no appendiceal tumor findings (Fig. 1).Nine out of the remaining 12 patients with an intact appendix underwent MRI with normal findings.The median age of these patients was 35 years (range 22-58 years), and detailed patient characteristics are presented in Table 1.
Overall initial appendiceal neoplasm rate after premature termination and surgical treatment of the MRI group patients consenting to appendectomy was 20% (12/60, 12 neoplams in 11 patients). 1At 5 years, 3 out of these 11 patients had died, with two deaths related to the appendiceal neoplasm.In the remaining eight patients with appendiceal neoplasms, the long-term follow-up at 5 years after the appendectomy was uneventful (Table 1).The median age of the patients with an appendiceal tumor was significantly higher than that of the patients with an intact appendix undergoing MRI imaging (58 years versus 35 years, p < 0.001).

Discussion
Based on the premature termination of the Peri-APPAC RCT in 2016 due to the high rate of appendiceal neoplasms in the interval appendectomy group, the long-term imaging follow-up of the MRI group patients declining to undergo appendectomy was added to the study protocol to ensure patient safety and ethical conduct of clinical trials.At 5 years, there were no additional appendiceal tumors detected at MRI imaging or in the two additional appendectomies performed between the 1-and 5-year follow-up.The patients declining to undergo appendectomy even after a strong recommendation after study termination were statistically significantly younger than the patients diagnosed with an appendiceal tumor.The main limitation of this study is the small number of patients based on the premature study termination.This long-term follow-up underlines the patient age as a major factor for an appendiceal tumor risk associated with a periappendicular abscess also demonstrated by the initial report1 and other studies. 5,6The rate of appendiceal neoplasms needs to be validated by large prospective cohort studies to further define the necessity of interval appendectomy in all age groups.

Table 1 .
Characteristics of patients with an intact appendix at 5 years and with an initial diagnosis of an appendiceal neoplasm in 2013 -2016.

year follow-up of patients with an initial diagnosis of an appendiceal neoplasm
MRI: magnetic resonance imaging; F: female; M: male; LAMN: low-grade appendiceal mucinous neoplasm; CT: computed tomography.a Mallinen et al.