Repeat endoscopic ultrasound-guided fine-needle aspiration/biopsy (rEUS-FNA/B) is recommended in solid pancreatic lesions (SPLs) with inconclusive initial results. However, even rEUS-FNA/B cannot completely eliminate false negatives in challenging cases. This study aims to identify risk factors of false-negative results in rEUS-FNA/B and develop a prediction model. 

Data of patients who had initial inconclusive diagnosis and underwent rEUS-FNA/B for SPLs across eight Chinese medical centers from January 2013 to June 2024 were retrospectively reviewed. Logistic regression was performed to identify the risk factors of false-negative results in rEUS-FNA/B. A clinical prediction model using random forest (RF) algorithm was developed with leave-one-hospital-out cross validation.

A total of 230 patients were enrolled in this study. Among them,159 patients (69.1%) were diagnosed with malignancies, while 71 patients (30.8%) had benign lesions. The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of rEUS-FNA were 75.00%, 62.63%, 100%, 100%, and 56.98%, respectively, whereas those of rEUS-FNB were 84.15%, 78.33%, 100%, 100%, and 62.86%. At multivariate analysis, lesion size 20-40mm (OR 0.26), lesion size≥40mm (OR 0.20), ≤2 needle passes (OR 3.1), no liquid-based cytology (LBC) examination (OR 3.95) were found to be independently associated with false-negative results. A final RF model with 4 features (lesion size, rEUS-FNA/B needle type, LBC, smear cytology) showed moderate ability to distinguish false-negative results in both training (AUC=0.78) and validation sets (AUC=0.68).

To minimize false-negative outcomes during rEUS-FNA/B, LBC is strongly recommended. Additionally, SPLs with a maximum diameter of ≤20 mm exhibit a higher probability for producing false-negative results during rEUS-FNA/B procedures.