There are limited data on the efficacy of liquid-based cytology (LBC) for EUS-guided FNA specimens. We aimed to evaluate the diagnostic efficacy of LBC for solid pancreatic neoplasms compared with conventional smears (CSs). In this randomized, crossover, noninferiority trial, we randomly assigned (1:1) patients with suspected pancreatic cancer to the LBC group or the CS group. Aspirates from the first needle pass were processed by one method, aspirates from the second pass by the other method,

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... nd specimens from the last pass were processed as core biopsy samples. The primary endpoint was the diagnostic efficacy of each method, with the final diagnosis as the gold standard. A noninferiority margin of -10% was assumed. Of 170 randomized patients, 165 were classified as malignant and 5 as benign. Unsatisfactory samples were less frequent in the LBC group (1.78%) compared with the CS group (5.33%). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of LBC versus CS were 88.0% versus 83.8% (P = .276), 87.7% versus 83.2% (P = .256), 100% versus 100% (P = .999), 100% versus 100% (P = .999), and 16.7% versus 16.1% (P = .953), respectively. A bloody background was significantly more frequent in the CS group (CS, 85.2%; LBC, 1.8%; P < .001), whereas the nuclear features were similar for both groups. The diagnostic usefulness of LBC was comparable with that of CS. The cytomorphologic features did not differ significantly between the 2 methods, and the reduced bloody backgrounds allowed better visibility in the LBC method. (Clinical trial registration number: NCT03606148.).