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Background  Bleeding after endoscopic submucosal dissection (ESD) in antithrombotic drug users is still one of the important issues to be solved. We performed scheduled second-look endoscopy (SLE) 5 days after ESD, when the resumption of antithrombotic agents is assumed to have achieved a steady state, rather than on the day after ESD. We investigated bleeding incidence and the status of ulcers.    Methods  A total of 299 lesions in 299 patients subjected to ESD for gastric neoplasms were enrolled. A double dose of proton pump inhibitors was administered after ESD. SLE was planned 5 days after ESD. Post-ESD bleeding occurring before SLE was defined as early phase post-ESD bleeding, whereas bleeding after SLE was defined as later phase post-ESD bleeding. Forrest IIa and IIb ulcers are defined as high-risk ulcers requiring prophylactic hemostasis. We investigated risk factors for post-ESD bleeding, particularly focusing on the use of antithrombotic agents and the presence of high-risk ulcers requiring prophylactic hemostasis during SLE.    Results  Under a double dose of proton pump inhibitors, early phase post-ESD bleeding occurred in 2.3% of non-users (5/218) and 6.2% of users of antithrombotic agents (5/81). High-risk ulcers were found in 19.0% of the cases during scheduled SLE (55/289). Later phase bleeding occurred in 5.5% of cases [2.8% of non-users (6/213) and 13.2% of users of antithrombotic agents (10/76)]. Cox regression analysis revealed that the risk factor for post-ESD bleeding was antithrombotic treatment (HR: 3.56; 95% CI: 1.63–8.02,  p  = 0.002) alone. Among patients with high-risk ulcers, a statistically significant increase in bleeding was observed in the later phase in patients under antithrombotic therapy, compared to those not receiving any antithrombotic agents ( p  = 0.001).    Conclusions  Antithrombotic treatment is a risk factor for post-ESD bleeding despite SLE being scheduled 5 days after ESD. Later phase post-ESD bleeding was observed in 13.2% of the patients under antithrombotic treatment even after prophylactic hemostasis for high-risk ulcers.    Trial registration  This study was registered in the UMIN Clinical Trials Registry System ( 000023306 ). Retrospectively registered on 23rd July 2016.

Bleeding in patients who underwent scheduled second-look endoscopy 5 days after endoscopic submucosal dissection for gastric lesions