DISCUSSION
blood spurting, bleeding, death, blood oozing
SECONDARY, RECTAL TUMORS, BLEEDING
This study showed that TDM-621 is a useful hemostatic peptide for blood oozing during ESD for gastric or rectal tumors and that severe AE do not occur with this peptide solution.This is the first multicenter, randomized, parallel-group comparative study to directly compare the efficacy and safety of TDM-621 with those of conventional hemostatic methods for blood oozing during endoscopic resection. In this study, the number of coagulations with hemostatic forceps (the primary efficacy end point) was significantly reduced in the TDM-621 group compared with that in the control group. TDM-621 showed the efficacy to reduce the number of coagulations with hemostatic forceps by both highly and less experienced endoscopists.A significant decrease in the number of cauterizations (the secondary efficacy end point) was shown, as determined by the operator, verifying the usefulness of TDM-621. The degree of dispersion of the number of cauterizations was markedly smaller in the TDM-621 group than in the control group. This result provides evidence that TDM-621 treatment reduced the number of coagulations considerably and suggests that treatment with TDM-621 can reduce the physical burden on patients during the procedure. There was no difference in the incidence of postcoagulation bleeding between the TDM-621 and control groups, which suggests that the hemostatic effects of TDM-621 were similar to those of the usual hemostasis methods during the procedure. The hemostasis achievement rate with TDM-621 treatment alone was 62.2%.The time from blood oozing to achievement of hemostasis was significantly longer in the TDM-621 group than in the control group. This result may be because we set the time from the beginning of the TDM-621 treatment to the achievement of hemostasis to a maximum of 3 minutes. Furthermore, the time required for coagulation might increase while preparing the hemostatic forceps for coagulation in cases where hemostasis is not achieved. In clinical practice, the use of TDM-621 is expected to reduce the overall duration of ESD. For patients in the TDM-621 group in whom hemostasis was achieved, the operator's opinion was that the use of TDM-621 weakened the bleeding momentum and made it easier to identify the bleeding site. Consequently, TDM-621 might have contributed to the reduction in the number of coagulations even when hemostasis was not achieved.TDM-621 has been available for use in preventing intraoperative ESD and post-ESD bleeding in the colon in 28 countries, including the United Kingdom, Germany, France, and Italy, since 2014, and was approved for use in Canada in 2019. In 2021, the US Food and Drug Administration approved this solution as a hemostatic agent. In Japan, TDM-621 has been found effective in achieving hemostasis in 25 patients who underwent cardiovascular surgery (The incidence of AE was not significantly different between the TDM-621 and control groups. No defects derived from TDM-621 treatment were observed. No AE requiring discontinuation of the clinical trial or leading to death occurred. These findings confirm the safety of using TDM-621 for the treatment of blood oozing occurring during ESD, which had been established in previous clinical trials (This study has several limitations. First, the trial was not double-blind because the purpose of this study was to compare the hemostatic methods. Second, the study targeted only blood oozing and did not include blood spurting. It may be difficult for TDM-621 to completely stop the latter. However, based on our experience, we believe a coagulation hemostat would stop blood spurting because the bleeding site would be easily identified. In addition, it may be possible to reduce blood spurting with TDM-621 (In conclusion, TDM-621 was shown to be a useful hemostatic peptide with easy operability and no crucial technical and safety problems in the endoscopic treatment of gastric and rectal tumors. We expect that TDM-621 alone will be applied to a wide range of clinical fields as a hemostatic agent in the future.