Several studies have reported the usefulness of second-look endoscopy following endoscopic hemostasis to prevent bleeding in patients with hemorrhagic peptic ulcer–. Based on such studies, second-look endoscopy has come to be conventionally performed after ESD as well. Recently, we found reports, albeit only a few, of the benefit of second-look endoscopy following ESD. Kim et al. support the performance of second-look endoscopy following ESD, whereas Goto et al. and Ryu et al. reported that second-look endoscopy was not effective for preventing post-ESD bleeding[24, 25]. In our study, no difference was observed in the postoperative bleeding rate between the groups that did and did not undergo second-look endoscopy. Consistent with the reports of Goto et al. and Ryu et al., our results suggested that second-look endoscopy following ESD did not reduce the risk of postoperative bleeding. One of the possible reasons is the effect of the gastric pH. Control of bleeding is known to be difficult in the presence of a low gastric pH[13, 26]. As the gastric pH is low in patients undergoing endoscopic treatment for peptic ulcer, rebleeding is prone to occur in these patients, and second-look endoscopy is considered to be useful. In contrast, the gastric pH is high at the time of ESD due to the PPI therapy initiated from the previous day, and the risk of rebleeding is lower; therefore, second-look endoscopy may not be required. As the base of a peptic ulcer in the active phase is often covered with a white moss, it is difficult to visually recognize the narrow blood vessels, though thick blood vessels can be visually recognized. Therefore, it is difficult to treat narrow vessels. On the other hand, no white moss is observed in ulcers at the end of the ESD and the narrow vessels can be more clearly recognized, and, therefore, can also be treated. It has been reported that treatment of the visualized blood vessels using hemostatic forceps or a clip at the end of ESD is very useful for reducing post-ESD bleeding[19, 20]. Furthermore, Tsuji et al. reported that postoperative bleeding is more common at the margin than at the center of the ulcer base. At our hospital, we treat the visible blood vessels focusing on the ulcer margin in all patients at the end of ESD. As it is possible to treat more blood vessels at the end of ESD than at the time of endoscopic treatment of peptic ulcers, performance of second-look endoscopy following ESD may not have any influence on the incidence of postoperative bleeding.
There are many reports of the risk factors for post-ESD bleeding, including flat or depressed-type lesions, lesions in the L segment, large resected specimens, long operative time, beginner surgeons, patients under maintenance dialysis, and oral intake of antiplatelet agents[5, 24, 28, 29]. Among these, lesions in the L segment and large resected specimens have been reported from multiple researches. In our study, postoperative bleeding was more common in patients with a large resected specimen, lesion in the L segment, and young patients. As bleeding within 24 hours of the ESD procedure accounts for approximately half of all cases of postoperative bleeding, the risk factors for bleeding within 24 hours of ESD (immediate bleeding) and those for bleeding occurring later (delayed bleeding) were investigated. This is the first report of investigation of patients with post-ESD bleeding in detail over time. In this study, immediate bleeding occurred significantly more frequently in patients with lesions in the L segment, large resected specimens, and large tumor size. On the other hand, delayed bleeding was significantly more common in younger patients and patients with concomitant renal disease. In other words, lesion factors predominantly affected the bleeding risk in the early stage after the ESD and patient factors predominantly affected the bleeding risk in the later stages after the procedure. In the case of large resected specimens, multiple blood vessels are present in the ulcer base, according to their size, increasing the risk of bleeding. Okada et al. reported that the volume of postoperative bleeding was 8.2-fold higher when the resected specimen was larger than 4 cm in diameter. It has been shown that the number and diameter of submucosal arteries in the L segment are less and smaller, respectively, than those in the other gastric segments, suggesting that lesions in the L segment of the stomach may be associated with less intraoperative bleeding and therefore less hemostatic intervention. As lesions in the L segment are prone to bile exposure which refluxes into the stomach, and a large amount of local injection solution enters the submucosal layer in this segment, blood vessels that cannot be confirmed immediately after the procedure may be exposed as the volume of the local injection solution decreases. With regard to age, Jang et al. reported that the frequency of ESD-associated bleeding (including intraoperative bleeding) was higher in patients younger than 65 years of age as compared with that in patients who were 65 years of age or older. This may be attributable to the higher post-ESD physical activity as compared to elderly patients undergoing the procedure, and also the greater acid secretion in young people than in the elderly. Patients with renal disease have delayed wound healing as a result of tissue fragility, hypoproteinema, and vascular disorders, as well as more marked aggressive factors such as enhanced acid secretion and increased gastrin levels, and reduced defense factors such as prostaglandins, all of which may be expected to lead to a delay in histological restoration of the ulcer and delayed postoperative bleeding[5, 32].
In order to minimize the risk of postoperative bleeding, we administer oral PPIs from the day before the operation and use hemostatic treatment with hemostatic forceps or a clip for exposed vessels at the base of the ulcer immediately after the procedure. In addition to ensuring these measures, we believe that some additional measures would be required in patients with large resected specimens or lesions in the L segment and younger patients, who were found in this study to be more prone to postoperative bleeding. For example, it is necessary to identify blood vessels at the ulcer base after ESD, that are prone to cause postoperative bleeding, using endoscopic Doppler ultrasound or infrared imaging system[33, 34], and to use over-the-scope-clip for cerclage of the ESD ulcer and medical adhesives for covering the ulcer[35, 36]. As these devices and drugs have been examined in only a small number of patients, further study is desired. Second-look endoscopy may be useful in patients who are prone to develop postoperative bleeding 24 hours or later after ESD, such as young patients and patients with renal disease; therefore, further studies are required.
A limitation of this study was that it was a retrospective single-institution study. Furthermore, the number of patients undergoing second-look endoscopy was lower in the first half of the study period than in the second half of the study period, which may have caused a bias.