Background: The current guideline recommends patients who meet high probability criteria for choledocholithiasis to receive endoscopic retrograde cholangiopancreatography (ERCP). However, adverse events can occur during ERCP. Our goal is to determine whether endoscopic ultrasound (EUS) before ERCP can avoid unnecessary ERCP complications, especially in patients with a negative CT scan. Methods: A total of 604 patients with high probability of choledocholithiasis were screened and 104 patients were prospectively enrolled. Patients with malignant biliary obstruction, altered GI anatomy, and choledocholithiasis on CT scan were excluded. Among them, 44 patients received EUS first, and ERCP if choledocholithiasis present (EUS-first group). The other 60 patients received ERCP directly (ERCP-first group). The baseline characteristics, presence of choledocholithiasis, and complications were compared between groups. All patients were followed for 3 months to determine the difference in recurrent biliary event rate. Cost-effectiveness was compared between the two strategies. Results: There was no marked difference in age, sex, laboratory data, presenting with pancreatitis, and risk factors for choledocholithiasis. Overall, 51 patients (49.0%) had choledocholithiasis, which did not justify the risk of direct ERCP. In the EUS-first group, 27 (61.4%) ERCP procedures were prevented. The overall complication rate was significantly lower in the EUS-first group compared to the ERCP-fist group (6.8% vs. 21.7%, P = 0.04). The number-needed-to-treat to avoid one unnecessary adverse event was 6.71. After a 3-month follow-up, the cumulative recurrence biliary event rates were similar (13.6% vs. 15.0%, P = 0.803). EUS-first strategy was more cost-effective than the ERCP-first strategy (mean cost 2322.89$ vs. 3175.63$, P = 0.002). Conclusions: In high-probability choledocholithiasis patients with a negative CT, the EUS-first strategy is cost-effective, which can prevent unnecessary ERCP procedures and their complications.
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