Clinical and Laboratory Prediction of Histopathologically Complicated Acute Appendicitis and Associated Surgical Outcomes: A Retrospective Cohort Study

Background/Objectives: Preoperative recognition of complicated acute appendicitis remains difficult, although severity influences treatment and perioperative planning. This study examined clinical and laboratory correlates of histopathologically complicated appendicitis and associated short-term outcomes and developed a preoperative prediction model. Methods: This single-center retrospective cohort included 500 adults undergoing appendectomy for suspected acute appendicitis (2021–2025). The primary outcome was gangrenous or perforated appendicitis on histopathology. Fifty preoperative candidate predictors were analyzed using least absolute shrinkage and selection operator (LASSO) logistic regression with nested cross-validation, calibration and predictor-selection reproducibility assessment, comparison with the Appendicitis Inflammatory Response (AIR) and Alvarado scores, and same-center temporal evaluation (2025 cohort). Results: Complicated histopathology was present in 111 patients (22.2%) and was associated with longer symptom duration, physiological disturbance, peritoneal signs, and systemic inflammation. The LASSO model achieved an out-of-fold area under the curve (AUC) of 0.861 (95% confidence interval [CI], 0.828–0.892; Brier score, 0.129; calibration intercept, −0.158; slope, 0.898), compared with 0.841 for AIR (difference, 0.020; 95% CI, −0.011 to 0.054; p = 0.221) and 0.743 for Alvarado (difference, 0.117; 95% CI, 0.067–0.169; p < 0.001). In the 2025 cohort, the AUC was 0.859 (95% CI, 0.783–0.926), but calibration indicated overprediction (intercept, −0.383; slope, 0.895). Thirty-day complications occurred in 15.3% and 8.0% of patients with complicated and non-complicated histopathology, respectively. Conclusions: Routinely available preoperative variables provided good internally validated discrimination, but the LASSO model did not significantly outperform the simpler AIR score. Overprediction in the later same-center cohort indicates that independent multicenter validation and recalibration are required before clinical use.