Minami Hashimoto1,2, Waku Hatta3, Yosuke Tsuji4, Toshiyuki Yoshio5, Yohei Yabuuchi6, Shu Hoteya7, Hisashi Doyama8, Yasuaki Nagami9, Takuto Hikichi1, Masakuni Kobayashi10, Yoshinori Morita11,12, Tetsuya Sumiyoshi13, Mikitaka Iguchi14, Hideomi Tomida15,16, Takuya Inoue17, Tatsuya Mikami18, Kenkei Hasatani19, Jun Nishikawa20, Tomoaki Matsumura21, Hiroko Nebiki22, Dai Nakamatsu23, Ken Ohnita24, Haruhisa Suzuki25, Hiroya Ueyama26, Yoshito Hayashi27, Mitsushige Sugimoto28,29, Mitsuhiro Fujishiro30, Atsushi Masamune3, Hiromasa Ohira2. 1. Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan. 2. Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan. 3. Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan. 4. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 5. Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. 6. Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan. 7. Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan. 8. Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan. 9. Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan. 10. Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan. 11. Department of Gastroenterology, Kobe University International Clinical Cancer Research Center, Hyogo, Japan. 12. Department of Gastroenterology, Kobe University Graduate School of Medicine, Hyogo, Japan. 13. Department of Gastroenterology, Tonan Hospital, Hokkaido, Japan. 14. Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan. 15. Gastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan. 16. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan. 17. Division of Gastroenterology and Hepatology, Osaka General Medical Center, Osaka, Japan. 18. Division of Endoscopy, Hirosaki University Hospital, Aomori, Japan. 19. Department of Gastroenterology, Fukui Prefectural Hospital, Fukui, Japan. 20. Faculty of Laboratory Science, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan. 21. Department of Gastroenterology, Chiba University Graduate School of Medicine, Chiba, Japan. 22. Department of Gastroenterology, Osaka City General Hospital, Osaka, Japan. 23. Department of Gastroenterology, Toyonaka Municipal Hospital, Osaka, Japan. 24. Department of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan. 25. Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan. 26. Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan. 27. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan. 28. Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan. 29. Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Shiga, Japan. 30. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan.
Abstract
OBJECTIVES: Delayed bleeding is a major adverse event in endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Some patients may experience rebleeding after successful hemostasis for delayed bleeding, yet the details of rebleeding remain unclear. We aimed to clarify the frequency and risk factors of rebleeding. METHODS: Among 11,452 patients who underwent ESD for EGC at 33 institutions in Japan between 2013 and 2016, we analyzed 489 patients showing delayed bleeding. The rate of rebleeding was investigated. Subsequently, 15 candidate variables were evaluated for their influence on the risk of rebleeding via logistic regression analysis. RESULTS: Rebleeding occurred in 11.2% (55/489) of the enrolled patients. Multivariate analysis revealed that warfarin [odds ratio (OR), 2.71; 95% confidence interval (CI), 1.26-5.84] and a resection size >40 mm (OR, 1.99; 95% CI, 1.08-3.67) were independent risk factors for rebleeding. In the analysis of the management of warfarin after index bleeding, only warfarin discontinuation (OR, 3.66; 95% CI, 1.37-9.78) was significantly associated with rebleeding in comparison with no use of warfarin. However, many rebleeding events (75.0%) occurred following the resumption of warfarin. The rebleeding rate during discontinuation status and that in taking warfarin (continuation or resumption) were 6.1% and 20.0%, respectively. CONCLUSIONS: Rebleeding was not a rare event in patients experiencing delayed bleeding after ESD for EGC. In addition to having a resection size >40 mm, warfarin usage placed patients at high risk for rebleeding, especially at the timing of its resumption following discontinuation as well as its continuation.
OBJECTIVES: Delayed bleeding is a major adverse event in endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Some patients may experience rebleeding after successful hemostasis for delayed bleeding, yet the details of rebleeding remain unclear. We aimed to clarify the frequency and risk factors of rebleeding. METHODS: Among 11,452 patients who underwent ESD for EGC at 33 institutions in Japan between 2013 and 2016, we analyzed 489 patients showing delayed bleeding. The rate of rebleeding was investigated. Subsequently, 15 candidate variables were evaluated for their influence on the risk of rebleeding via logistic regression analysis. RESULTS: Rebleeding occurred in 11.2% (55/489) of the enrolled patients. Multivariate analysis revealed that warfarin [odds ratio (OR), 2.71; 95% confidence interval (CI), 1.26-5.84] and a resection size >40 mm (OR, 1.99; 95% CI, 1.08-3.67) were independent risk factors for rebleeding. In the analysis of the management of warfarin after index bleeding, only warfarin discontinuation (OR, 3.66; 95% CI, 1.37-9.78) was significantly associated with rebleeding in comparison with no use of warfarin. However, many rebleeding events (75.0%) occurred following the resumption of warfarin. The rebleeding rate during discontinuation status and that in taking warfarin (continuation or resumption) were 6.1% and 20.0%, respectively. CONCLUSIONS: Rebleeding was not a rare event in patients experiencing delayed bleeding after ESD for EGC. In addition to having a resection size >40 mm, warfarin usage placed patients at high risk for rebleeding, especially at the timing of its resumption following discontinuation as well as its continuation.