Appendicolith Characteristics as Predictors of Failure of Non-operative Management in Adults with Uncomplicated Acute Appendicitis: A Systematic Review and Meta-Analysis

Abstract

Background: Non-operative management (NOM) with antibiotics is an accepted option for selected adults with uncomplicated acute appendicitis, but failure is more frequent when an appendicolith is present. Whether appendicolith size, position, number, or obstructive characteristics improve prognostic stratification remains uncertain.
Objective: To evaluate appendicolith presence and characteristics as prognostic factors for NOM failure in adults with imaging-confirmed uncomplicated acute appendicitis, with intraluminal appendiceal air, age, and sex assessed as additional prognostic factors.
Methods: The review was structured as a prognostic-factor systematic review and meta-analysis. Evidence was synthesized from PubMed-indexed records, primary publisher/full-text records, guideline repositories, and backward and forward citation searching through 12 August 2026 using prespecified adult eligibility criteria. Direct studies of NOM failure were separated from indirect radiological or severity studies. Random-effects meta-analysis was undertaken only for compatible effect estimates. Risk-of-bias interpretation incorporated RoB 2 for parent randomized trials and prognostic-factor domains aligned with QUIPS.
Results: Appendicolith presence was the most consistent adverse prognostic marker. In the CODA antibiotic-treated cohort, appendicolith was independently associated with appendectomy within 30 days (adjusted OR 1.99, 95% CI 1.28-3.10). An exploratory synthesis of CODA and Vons data yielded a pooled RR of 2.00 (95% CI 1.54-2.60; I²=0%; k=2) for short-term NOM failure. At one year, pooled individual-participant trial data showed appendectomy in 48.7% of antibiotic-treated patients with an appendicolith versus 30.6% without. Evidence for specific appendicolith characteristics was substantially weaker. Larger size and proximal/base or obstructing location were associated with adverse outcomes mainly in treatment-selection, complicated-disease, or severity cohorts. Intraluminal appendiceal air was not associated with failure, while age and sex effects were inconsistent.
Conclusions: Appendicolith presence is the best-supported imaging prognostic factor for NOM failure. Larger appendicolith size and proximal or obstructive location remain plausible risk refinements but are inadequately validated in strictly uncomplicated adult NOM populations. Intraluminal air, female sex, and older age are not established independent adverse prognostic factors.