Rebleeding in patients with delayed bleeding after endoscopic submucosal dissection for early gastric cancer
Minami Hashimoto
Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
Search for more papers by this authorWaku Hatta
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
Search for more papers by this authorYosuke Tsuji
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Search for more papers by this authorToshiyuki Yoshio
Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
Search for more papers by this authorYohei Yabuuchi
Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
Search for more papers by this authorShu Hoteya
Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
Search for more papers by this authorHisashi Doyama
Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan
Search for more papers by this authorYasuaki Nagami
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorCorresponding Author
Takuto Hikichi
Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
Corresponding: Takuto Hikichi, Department of Endoscopy, Fukushima Medical University Hospital, 1 Hikarigaoka, Fukushima 960-1295, Japan. Email: [email protected]
Search for more papers by this authorMasakuni Kobayashi
Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
Search for more papers by this authorYoshinori Morita
Department of Gastroenterology, Kobe University International Clinical Cancer Research Center, Hyogo, Japan
Department of Gastroenterology, Kobe University Graduate School of Medicine, Hyogo, Japan
Search for more papers by this authorTetsuya Sumiyoshi
Department of Gastroenterology, Tonan Hospital, Hokkaido, Japan
Search for more papers by this authorMikitaka Iguchi
Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
Search for more papers by this authorHideomi Tomida
Gastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
Search for more papers by this authorTakuya Inoue
Division of Gastroenterology and Hepatology, Osaka General Medical Center, Osaka, Japan
Search for more papers by this authorTatsuya Mikami
Division of Endoscopy, Hirosaki University Hospital, Aomori, Japan
Search for more papers by this authorKenkei Hasatani
Department of Gastroenterology, Fukui Prefectural Hospital, Fukui, Japan
Search for more papers by this authorJun Nishikawa
Faculty of Laboratory Science, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
Search for more papers by this authorTomoaki Matsumura
Department of Gastroenterology, Chiba University Graduate School of Medicine, Chiba, Japan
Search for more papers by this authorHiroko Nebiki
Department of Gastroenterology, Osaka City General Hospital, Osaka, Japan
Search for more papers by this authorDai Nakamatsu
Department of Gastroenterology, Toyonaka Municipal Hospital, Osaka, Japan
Search for more papers by this authorKen Ohnita
Department of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan
Search for more papers by this authorHaruhisa Suzuki
Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
Search for more papers by this authorHiroya Ueyama
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorYoshito Hayashi
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorMitsushige Sugimoto
Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Shiga, Japan
Search for more papers by this authorMitsuhiro Fujishiro
Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
Search for more papers by this authorAtsushi Masamune
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
Search for more papers by this authorHiromasa Ohira
Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
Search for more papers by this authorCollaborators
Search for more papers by this authorMinami Hashimoto
Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
Search for more papers by this authorWaku Hatta
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
Search for more papers by this authorYosuke Tsuji
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Search for more papers by this authorToshiyuki Yoshio
Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
Search for more papers by this authorYohei Yabuuchi
Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
Search for more papers by this authorShu Hoteya
Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan
Search for more papers by this authorHisashi Doyama
Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan
Search for more papers by this authorYasuaki Nagami
Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorCorresponding Author
Takuto Hikichi
Department of Endoscopy, Fukushima Medical University Hospital, Fukushima, Japan
Corresponding: Takuto Hikichi, Department of Endoscopy, Fukushima Medical University Hospital, 1 Hikarigaoka, Fukushima 960-1295, Japan. Email: [email protected]
Search for more papers by this authorMasakuni Kobayashi
Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
Search for more papers by this authorYoshinori Morita
Department of Gastroenterology, Kobe University International Clinical Cancer Research Center, Hyogo, Japan
Department of Gastroenterology, Kobe University Graduate School of Medicine, Hyogo, Japan
Search for more papers by this authorTetsuya Sumiyoshi
Department of Gastroenterology, Tonan Hospital, Hokkaido, Japan
Search for more papers by this authorMikitaka Iguchi
Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
Search for more papers by this authorHideomi Tomida
Gastroenterology Center, Ehime Prefectural Central Hospital, Ehime, Japan
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
Search for more papers by this authorTakuya Inoue
Division of Gastroenterology and Hepatology, Osaka General Medical Center, Osaka, Japan
Search for more papers by this authorTatsuya Mikami
Division of Endoscopy, Hirosaki University Hospital, Aomori, Japan
Search for more papers by this authorKenkei Hasatani
Department of Gastroenterology, Fukui Prefectural Hospital, Fukui, Japan
Search for more papers by this authorJun Nishikawa
Faculty of Laboratory Science, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
Search for more papers by this authorTomoaki Matsumura
Department of Gastroenterology, Chiba University Graduate School of Medicine, Chiba, Japan
Search for more papers by this authorHiroko Nebiki
Department of Gastroenterology, Osaka City General Hospital, Osaka, Japan
Search for more papers by this authorDai Nakamatsu
Department of Gastroenterology, Toyonaka Municipal Hospital, Osaka, Japan
Search for more papers by this authorKen Ohnita
Department of Gastroenterology and Hepatology, Nagasaki University Hospital, Nagasaki, Japan
Search for more papers by this authorHaruhisa Suzuki
Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
Search for more papers by this authorHiroya Ueyama
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan
Search for more papers by this authorYoshito Hayashi
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorMitsushige Sugimoto
Department of Gastroenterological Endoscopy, Tokyo Medical University Hospital, Tokyo, Japan
Division of Digestive Endoscopy, Shiga University of Medical Science Hospital, Shiga, Japan
Search for more papers by this authorMitsuhiro Fujishiro
Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Aichi, Japan
Search for more papers by this authorAtsushi Masamune
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
Search for more papers by this authorHiromasa Ohira
Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
Search for more papers by this authorCollaborators
Search for more papers by this authorThe authors Minami Hashimoto and Waku Hatta are considered as co-first authors.
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.
Conflict of Interest
Mitsuhiro Fujishiro declared that he received lecture honoraria from Takeda Pharmaceutical, EA Pharma, Nihon Pharmaceutical and his department received research grants from HOYA Pentax, EA Pharma, Eisai, Taiho Phamaceutical, AbbVie GK, Nippon Kayaku, Chugai Pharmaceutical, Gilead Sciences, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma outside the submitted work. Atsushi Masamune declared that he received lecture honoraria from EA Pharma, Takeda Pharmaceutical, Daiichi Sankyo Co., and Lylan.co.jp and he received commercial research funding from Otsuka Pharmaceutical, EA Pharma, Gilead Sciences, Asahi Kasei Pharma, Eisai, AbbVie GK, Takeda Pharmaceutical, and Daiichi Sankyo, outside the submitted work. The other authors declare no competing interests.
Supporting Information
| Filename | Description |
|---|---|
| den13943-sup-0001-SupInfo.docxWord 2007 document , 32.8 KB |
Table S1 Clinical differences of the patients between early and late rebleeding. CKD, chronic kidney disease; P2Y12RA, P2Y12 receptor antagonist; DOAC, direct oral anticoagulant; SM1, submucosal invasion <500 μm from the muscularis mucosa; SM2, tumor invasion depth of ≥500 µm from the muscularis mucosa; ESD, endoscopic submucosal dissection. Table S2 Rebleeding after ESD for EGC in patients who took multiple antithrombotic agents. A. Rebleeding rate in the combination of two kinds of antithrombotic agents. B. Interaction between two kinds of antithrombotic agents. ESD, endoscopic submucosal dissection; EGC, early gastric cancer; P2Y12RA, P2Y12 receptor antagonist; DOAC, direct oral anticoagulants. Table S3 The rebleeding rates according to the hospital volume. ESD, endoscopic submucosal dissection. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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