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Background and study aims: No prospective comparison of endoscopic ultrasonography-guided direct celiac ganglia neurolysis (EUS-CGN) vs. EUS-guided celiac plexus neurolysis (EUS-CPN) has been reported. The aim of the current study was to compare the effectiveness of EUS-CGN and EUS-CPN in providing pain relief from upper abdominal cancer pain in a multicenter randomized controlled trial. Patients and methods: Patients with upper abdominal cancer pain were randomly assigned to treatment using either EUS-CGN or EUS-CPN. Evaluationwas performed at Day 7 postoperatively using a pain scale of 0 to 10.Patients for whom pain decreased to⩽3 were considered to have a positive response, and those experiencing a decrease in pain to⩽1 were considered to be completely responsive. Comparison between the two groups was performed using intention-to-treat analysis. The primary endpoint was the difference in treatment response rates between EUS-CGN and EUS-CPN at postoperative Day 7.Secondary endpoints included differences in complete response rates, pain scores, duration of pain relief, and incidence of adverse effects. Results: A total of 34 patients were assigned to each group. Visualization of ganglia was possible in 30 cases (88 %) in the EUS-CGN group.The positive response ratewas significantly higher in the EUS-CGN group (73.5 %) than in the EUS-CPN group (45.5 %; P=0.026). The complete response rate was also significantly higher in the EUS- CGN group (50.0 %) than in the EUS-CPN group (18.2 %; P=0.010). There was no difference in adverse events or duration of pain relief between the two groups. Conclusions: EUS-CGN is significantly superior to conventional EUS-CPN in cancer pain relief. [ABSTRACT FROM AUTHOR]