A Prospective Observational Study on Gastric Endoscopic Submucosal Dissection under Continuous Administration of Antithrombotic Agents
Abstract
:1. Introduction
2. Materials and Methods
2.1. Prospective Observational Study on Gastric ESD in Patients Undergoing Continuous Antithrombotic Therapy
2.2. Retrospective Observational Study on Gastric ESD in Patients without Antithrombotic Therapy
2.3. ESD Procedure
2.4. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 2015, 136, E359–E386. [Google Scholar] [CrossRef]
- Plummer, M.; de Martel, C.; Vignat, J.; Ferlay, J.; Bray, F.; Franceschi, S. Global burden of cancers attributable to infections in 2012: A synthetic analysis. Lancet Glob. Health 2016, 4, e609–e616. [Google Scholar] [CrossRef] [PubMed]
- Shimizu, S.; Tada, M.; Kawai, K. Early gastric cancer: Its surveillance and natural course. Endoscopy 1995, 27, 27–31. [Google Scholar] [CrossRef]
- Noguchi, Y.; Yoshikawa, T.; Tsuburaya, A.; Motohashi, H.; Karpeh, M.S.; Brennan, M.F. Is gastric carcinoma different between Japan and the United States? Cancer 2000, 89, 2237–2246. [Google Scholar] [CrossRef]
- Gotoda, T.; Yanagisawa, A.; Sasako, M.; Ono, H.; Nakanishi, Y.; Shimoda, T.; Kato, Y. Incidence of lymph node metastasis from early gastric cancer: Estimation with a large number of cases at two large centers. Gastric Cancer 2000, 3, 219–225. [Google Scholar] [CrossRef]
- Hirasawa, T.; Gotoda, T.; Miyata, S.; Kato, Y.; Shimoda, T.; Taniguchi, H.; Fujisaki, J.; Sano, T.; Yamaguchi, T. Incidence of lymph node metastasis and the feasibility of endoscopic resection for undifferentiated-type early gastric cancer. Gastric Cancer 2009, 12, 148–152. [Google Scholar] [CrossRef]
- Oka, S.; Tanaka, S.; Kaneko, I.; Mouri, R.; Hirata, M.; Kawamura, T.; Yoshihara, M.; Chayama, K. Advantage of endoscopic submucosal dissection compared with EMR for early gastric cancer. Gastrointest. Endosc. 2006, 64, 877–883. [Google Scholar] [CrossRef] [PubMed]
- Watanabe, K.; Ogata, S.; Kawazoe, S.; Watanabe, K.; Koyama, T.; Kajiwara, T.; Shimoda, Y.; Takase, Y.; Irie, K.; Mizuguchi, M.; et al. Clinical outcomes of EMR for gastric tumors: Historical pilot evaluation between endoscopic submucosal dissection and conventional mucosal resection. Gastrointest. Endosc. 2006, 63, 776–782. [Google Scholar] [CrossRef] [PubMed]
- Park, Y.M.; Cho, E.; Kang, H.Y.; Kim, J.M. The effectiveness and safety of endoscopic submucosal dissection compared with endoscopic mucosal resection for early gastric cancer: A systematic review and meta-analysis. Surg. Endosc. 2011, 25, 2666–2677. [Google Scholar] [CrossRef]
- Tsuji, Y.; Ohata, K.; Ito, T.; Chiba, H.; Ohya, T.; Gunji, T.; Matsuhashi, N. Risk factors for bleeding after endoscopic submucosal dissection for gastric lesions. World J. Gastroenterol. 2010, 16, 2913–2917. [Google Scholar] [CrossRef]
- Koh, R.; Hirasawa, K.; Yahara, S.; Oka, H.; Sugimori, K.; Morimoto, M.; Numata, K.; Kokawa, A.; Sasaki, T.; Nozawa, A.; et al. Antithrombotic drugs are risk factors for delayed postoperative bleeding after endoscopic submucosal dissection for gastric neoplasms. Gastrointest. Endosc. 2013, 78, 476–483. [Google Scholar] [CrossRef]
- Gotoda, T.; Hori, K.; Iwamuro, M.; Kono, Y.; Miura, K.; Kanzaki, H.; Kawano, S.; Kawahara, Y.; Okada, H. Evaluation of the bleeding risk with various antithrombotic therapies after gastric endoscopic submucosal dissection. Endosc. Int. Open 2017, 5, E653–E662. [Google Scholar] [CrossRef]
- Matsumura, T.; Arai, M.; Maruoka, D.; Okimoto, K.; Minemura, S.; Ishigami, H.; Saito, K.; Nakagawa, T.; Katsuno, T.; Yokosuka, O. Risk factors for early and delayed post-operative bleeding after endoscopic submucosal dissection of gastric neoplasms, including patients with continued use of antithrombotic agents. BMC Gastroenterol. 2014, 14, 172. [Google Scholar] [CrossRef]
- Sato, C.; Hirasawa, K.; Koh, R.; Ikeda, R.; Fukuchi, T.; Kobayashi, R.; Kaneko, H.; Makazu, M.; Maeda, S. Postoperative bleeding in patients on antithrombotic therapy after gastric endoscopic submucosal dissection. World J. Gastroenterol. 2017, 23, 5557–5566. [Google Scholar] [CrossRef]
- Ueki, N.; Futagami, S.; Akimoto, T.; Maruki, Y.; Yamawaki, H.; Kodaka, Y.; Nagoya, H.; Shindo, T.; Kusunoki, M.; Kawagoe, T.; et al. Effect of antithrombotic therapy and long endoscopic submucosal dissection procedure time on early and delayed postoperative bleeding. Digestion 2017, 96, 21–28. [Google Scholar] [CrossRef]
- Lim, J.H.; Kim, S.G.; Kim, J.W.; Choi, Y.J.; Kwon, J.; Kim, J.Y.; Lee, Y.B.; Choi, J.; Im, J.P.; Kim, J.S.; et al. Do antiplatelets increase the risk of bleeding after endoscopic submucosal dissection of gastric neoplasms? Gastrointest. Endosc. 2012, 75, 719–727. [Google Scholar] [CrossRef] [PubMed]
- Igarashi, K.; Takizawa, K.; Kakushima, N.; Tanaka, M.; Kawata, N.; Yoshida, M.; Ito, S.; Imai, K.; Hotta, K.; Ishiwatari, H.; et al. Should antithrombotic therapy be stopped in patients undergoing gastric endoscopic submucosal dissection? Surg. Endosc. 2017, 31, 1746–1753. [Google Scholar] [CrossRef] [PubMed]
- Oh, S.; Kim, S.G.; Kim, J.; Choi, J.M.; Lim, J.H.; Yang, H.J.; Park, J.Y.; Han, S.J.; Kim, J.L.; Chung, H.; et al. Continuous Use of Thienopyridine May Be as Safe as Low-Dose Aspirin in Endoscopic Resection of Gastric Tumors. Gut Liver 2018, 12, 393–401. [Google Scholar] [CrossRef] [PubMed]
- Harada, H.; Suehiro, S.; Murakami, D.; Nakahara, R.; Nagasaka, T.; Ujihara, T.; Sagami, R.; Katsuyama, Y.; Hayasaka, K.; Amano, Y. Feasibility of gastric endoscopic submucosal dissection with continuous low-dose aspirin for patients receiving dual antiplatelet therapy. World J. Gastroenterol. 2019, 25, 457–468. [Google Scholar] [CrossRef]
- Miura, Y.; Tsuji, Y.; Yoshio, T.; Hatta, W.; Yabuuchi, Y.; Hoteya, S.; Kikuchi, D.; Tsuji, S.; Nagami, Y.; Hikichi, T.; et al. Association between perioperative management of antiplatelet agents and risk of post-endoscopic submucosal dissection bleeding in early gastric cancer: Analysis of a nationwide multicenter study. Gastrointest. Endosc. 2023, 97, 889–897. [Google Scholar] [CrossRef] [PubMed]
- Fujimoto, K.; Fujishiro, M.; Kato, M.; Higuchi, K.; Iwakiri, R.; Sakamoto, C.; Uchiyama, S.; Kashiwagi, A.; Ogawa, H.; Murakami, K.; et al. Japan Gastroenterological Endoscopy Society. Guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. Dig. Endosc. 2014, 26, 1–14. [Google Scholar] [CrossRef]
- Veitch, A.M.; Radaelli, F.; Alikhan, R.; Dumonceau, J.M.; Eaton, D.; Jerrome, J.; Lester, W.; Nylander, D.; Thoufeeq, M.; Vanbiervliet, G.; et al. Endoscopy in patients on antiplatelet or anticoagulant therapy: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guideline update. Endoscopy 2021, 53, 947–969. [Google Scholar]
- ASGE Standards of Practice Committee; Acosta, R.; Abraham, N.S.; Chandrasekhara, V.; Chathadi, K.V.; Early, D.S.; Eloubeidi, M.A.; Evans, J.A.; Faulx, A.L.; Fisher, D.A.; et al. Management of antithrombotic agents in patients undergoing GI endoscopy. Gastrointest. Endosc. 2016, 83, 3–16. [Google Scholar]
- Mannen, K.; Tsunada, S.; Hara, M.; Yamaguchi, K.; Sakata, Y.; Fujise, T.; Noda, T.; Shimoda, R.; Sakata, H.; Ogata, S.; et al. Risk factors for complications of endoscopic submucosal dissection in gastric tumors: Analysis of 478 lesions. J. Gastroenterol. 2010, 45, 30–36. [Google Scholar] [CrossRef]
- Fujishiro, M.; Chiu, P.W.; Wang, H.P. Role of antisecretory agents for gastric endoscopic submucosal dissection. Dig. Endosc. 2013, 25, 86–93. [Google Scholar] [CrossRef]
- Isomoto, H.; Shikuwa, S.; Yamaguchi, N.; Fukuda, E.; Ikeda, K.; Nishiyama, H.; Ohnita, K.; Mizuta, Y.; Shiozawa, J.; Kohno, S. Endoscopic submucosal dissection for early gastric cancer: A large-scale feasibility study. Gut 2009, 58, 331–336. [Google Scholar] [CrossRef]
- Takizawa, K.; Oda, I.; Gotoda, T.; Yokoi, C.; Matsuda, T.; Saito, Y.; Saito, D.; Ono, H. Routine coagulation of visible vessels may prevent delayed bleeding after endoscopic submucosal dissection--an analysis of risk factors. Endoscopy 2008, 40, 179–183. [Google Scholar] [CrossRef] [PubMed]
- Chung, I.K.; Lee, J.H.; Lee, S.H.; Kim, S.J.; Cho, J.Y.; Cho, W.Y.; Hwangbo, Y.; Keum, B.R.; Park, J.J.; Chun, H.J.; et al. Therapeutic outcomes in 1000 cases of endoscopic submucosal dissection for early gastric neoplasms: Korean ESD Study Group multicenter study. Gastrointest. Endosc. 2009, 69, 1228–1235. [Google Scholar] [CrossRef] [PubMed]
- Toyokawa, T.; Inaba, T.; Omote, S.; Okamoto, A.; Miyasaka, R.; Watanabe, K.; Izumikawa, K.; Horii, J.; Fujita, I.; Ishikawa, S.; et al. Risk factors for perforation and delayed bleeding associated with endoscopic submucosal dissection for early gastric neoplasms: Analysis of 1123 lesions. J. Gastroenterol. Hepatol. 2012, 27, 907–912. [Google Scholar] [CrossRef]
- Higashiyama, M.; Oka, S.; Tanaka, S.; Sanomura, Y.; Imagawa, H.; Shishido, T.; Yoshida, S.; Chayama, K. Risk factors for bleeding after endoscopic submucosal dissection of gastric epithelial neoplasm. Dig. Endosc. 2011, 23, 290–295. [Google Scholar] [CrossRef]
- Miyahara, K.; Iwakiri, R.; Shimoda, R.; Sakata, Y.; Fujise, T.; Shiraishi, R.; Yamaguchi, K.; Watanabe, A.; Yamaguchi, D.; Higuchi, T.; et al. Perforation and postoperative bleeding of endoscopic submucosal dissection in gastric tumors: Analysis of 1190 lesions in low- and high-volume centers in Saga, Japan. Digestion 2012, 86, 273–280. [Google Scholar] [CrossRef] [PubMed]
- Okada, K.; Yamamoto, Y.; Kasuga, A.; Omae, M.; Kubota, M.; Hirasawa, T.; Ishiyama, A.; Chino, A.; Tsuchida, T.; Fujisaki, J.; et al. Risk factors for delayed bleeding after endoscopic submucosal dissection for gastric neoplasm. Surg. Endosc. 2011, 25, 98–107. [Google Scholar] [CrossRef] [PubMed]
- Takeuchi, T.; Ota, K.; Harada, S.; Edogawa, S.; Kojima, Y.; Tokioka, S.; Umegaki, E.; Higuchi, K. The postoperative bleeding rate and its risk factors in patients on antithrombotic therapy who undergo gastric endoscopic submucosal dissection. BMC Gastroenterol. 2013, 13, 136. [Google Scholar] [CrossRef] [PubMed]
- Ono, S.; Fujishiro, M.; Yoshida, N.; Doyama, H.; Kamoshida, T.; Hirai, S.; Kishihara, T.; Yamamoto, Y.; Sakae, H.; Imagawa, A.; et al. Thienopyridine derivatives as risk factors for bleeding following high risk endoscopic treatments: Safe Treatment on Antiplatelets (STRAP) study. Endoscopy 2015, 47, 632–637. [Google Scholar] [CrossRef]
- Ono, S.; Myojo, M.; Harada, H.; Tsuji, K.; Murakami, D.; Suehiro, S.; Doyama, H.; Ando, J.; Saito, I.; Fujishiro, M.; et al. Is it possible to perform gastric endoscopic submucosal dissection without discontinuation of a single antiplatelet of thienopyridine derivatives? Endosc. Int. Open 2017, 5, E943–E949. [Google Scholar] [CrossRef]
- Tounou, S.; Morita, Y.; Hosono, T. Continuous aspirin use does not increase post-endoscopic dissection bleeding risk for gastric neoplasms in patients on antiplatelet therapy. Endosc. Int. Open. 2015, 3, E31–E38. [Google Scholar] [CrossRef]
- Ono, H.; Yao, K.; Fujishiro, M.; Oda, I.; Uedo, N.; Nimura, S.; Yahagi, N.; Iishi, H.; Oka, M.; Ajioka, Y.; et al. Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer (second edition). Dig. Endosc. 2021, 33, 4–20. [Google Scholar] [CrossRef]
Continuous Antithrombotic Agent Group 88 Patients, 100 Lesions | Non-Antithrombotic Agent Group 479 Patients, 534 Lesions | p-Value | ||||
---|---|---|---|---|---|---|
Age (years), median (range) | 79 | (60–92) | 74 | (33–94) | <0.001 | |
Sex, male, n (%) | 62 | (70) | 349 | (73) | 0.642 | |
Habit | ||||||
Smoking, n (%) | 14 | (16) | 91 | (19) | 0.493 | |
Alcohol consumption, n (%) | 25 | (28) | 184 | (38) | 0.074 | |
Comorbidities | ||||||
Hypertension, n (%) | 60 | (68) | 268 | (56) | 0.033 | |
Diabetes mellitus, n (%) | 25 | (28) | 113 | (24) | 0.333 | |
Cerebrovascular disease, n (%) | 47 | (53) | 15 | (3) | <0.001 | |
Ischemic heart disease, n (%) | 22 | (25) | 16 | (4) | <0.001 | |
Atrial fibrillation, n (%) | 24 | (27) | 1 | (0.2) | <0.001 | |
Antithrombotic agent | ||||||
Antiplatelet agents, n (%) | 63 | (72) | ||||
Aspirin, n (%) | 35 | (40) | ||||
Cilostazol, n (%) | 17 | (19) | ||||
Thienopyridine derivatives, n (%) | 17 | (19) | ||||
Anticoagulant agent | 27 | (31) | ||||
Warfarin, n (%) | 11 | (13) | ||||
Apixaban, n (%) | 9 | (10) | ||||
Rivaroxaban, n (%) | 4 | (5) | ||||
Dabigatran, n (%) | 3 | (3) | ||||
Number of antithrombotic agents | ||||||
Single, n (%) | 80 | (91) | ||||
Multiple, n (%) | 8 | (9) | ||||
Dual antiplatelet agents | 6 | (7) | ||||
Aintiplatelet plus anticoagulant | 2 | (2) | ||||
Lesion size (mm), median (range) | 12 | (2–140) | 12 | (1–64) | 0.343 | |
Number of lesions | 0.731 | |||||
Single, n (%) | 76 | (86) | 420 | (88) | ||
Multiple, n (%) | 12 | (14) | 59 | (12) | ||
Acid-suppressive agent | <0.001 | |||||
Lansoprazole | 26 | (30) | 479 | (100) | ||
Vonoprazan | 62 | (70) | 0 | 0 |
Continuous Antithrombotic Agent Group 88 Patients, 100 Lesions | Non-Antithrombotic Agent Group 479 Patients, 534 Lesions | p-Value | |||
---|---|---|---|---|---|
En bloc resection, n (%) | 100 | (100) | 534 | (100) | 1.000 |
R0 resection, n (%) | 97 | (97.0) | 514 | (96.3) | 0.715 |
Specimen size (mm), median (range) | 35.5 | (22–150) | 35.0 | (17–96) | 0.205 |
Procedure time (min), median (range) | 71.5 | (23–273) | 75.0 | (22–445) | 0.876 |
Adverse event | |||||
Perforation, n (%) | 0 | (0) | 11 | (2.3) | 0.151 |
Postoperative bleeding, n (%) | 9 | (10.2) | 20 | (4.2) | 0.018 |
Incidence of Postoperative Bleeding (%) | |
---|---|
Antithrombotic agents, overall | 9/88 (10.2) |
Antiplatelet agents | 7/63 (11.1) |
Aspirin | 3/35 (8.6) |
Cilostazol | 1/17 (5.9) |
Thienopyridine derivatives | 5/17 (29.4) |
Anticoagulant agents | 2/27 (7.4) |
Warfarin | 0/11 (0) |
Apixaban | 1/9 (11.1) |
Dabigatran | 0/3 (0) |
Rivaroxaban | 1/4 (25.0) |
Number of antithrombotic agent | |
Multiple | 2/8 (25.0) |
Dual antiplatelet agents | 2/6 (33.3) |
Antiplatelet + anticoagulant | 0/2 (0) |
Postoperative Bleeding n = 9 | No Postoperative Bleeding n = 79 | p-Value | |||
---|---|---|---|---|---|
Age (years), median (range) | 77 | (69–89) | 79 | (60–92) | 0.634 |
Sex, male, n (%) | 7 | (78) | 55 | (70) | 1.000 |
Habit | |||||
Smoking, n (%) | 0 | (0) | 14 | (18) | 0.344 |
Alcohol consumption, n (%) | 1 | (11) | 24 | (30) | 0.436 |
Helicobacter pylori infection status | |||||
Positive, n (%) | 3 | (33) | 25 | (32) | 1.000 |
Comorbidity | |||||
Hypertension, n (%) | 6 | (67) | 54 | (68) | 1.000 |
Diabetes mellitus, n (%) | 2 | (22) | 23 | (29) | 1.000 |
Cerebrovascular disease, n (%) | 6 | (67) | 41 | (52) | 0.494 |
Ischemic heart disease, n (%) | 0 | (0) | 22 | (28) | 0.105 |
Atrial fibrillation, n (%) | 2 | (22) | 22 | (28) | 1.000 |
Antithrombotic agent | |||||
Antiplatelet agent | 7 | (78) | 56 | (71) | 1.000 |
Aspirin, n (%) | 3 | (33) | 32 | (41) | 1.000 |
Cilostazol, n (%) | 1 | (11) | 16 | (20) | 1.000 |
Thienopyridine derivatives, n (%) | 5 | (56) | 12 | (15) | 0.012 |
Anticoagulant agents | 2 | (22) | 25 | (32) | 0.716 |
Warfarin, n (%) | 0 | (0) | 11 | (14) | 0.595 |
Apixaban, n (%) | 1 | (11) | 8 | (10) | 1.000 |
Dabigatran, n (%) | 0 | (0) | 3 | (4) | 1.000 |
Rivaroxaban, n (%) | 1 | (11) | 3 | (4) | 0.356 |
Number of antithrombotic agent | |||||
Multiple, n (%) | 2 | (22) | 6 | (8) | 0.188 |
Dual antiplatelet agents | 2 | (22) | 4 | (5) | 0.113 |
Antiplatelet + anticoagulant | 0 | (0) | 2 | (3) | 1.000 |
Location of lesion (n = 100) | |||||
Upper third, n (%) | 2 | (20) | 10 | (11) | 0.644 |
Middle third, n (%) | 5 | (50) | 43 | (48) | |
Lower third, n (%) | 3 | (30) | 37 | (41) | |
Lesion size (mm), median (range) | 16 | (12–40) | 13 | (4–140) | 0.119 |
Number of lesions | |||||
Multiple, n (%) | 1 | (11) | 11 | (14) | 1.000 |
Acid-suppressive agent | |||||
Vonoprazan | 6 | (67) | 56 | (71) | 1.000 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kawai, D.; Iwamuro, M.; Takenaka, R.; Obata, T.; Yamamoto, T.; Hirata, S.; Miura, K.; Takemoto, K.; Tsugeno, H.; Fujiki, S. A Prospective Observational Study on Gastric Endoscopic Submucosal Dissection under Continuous Administration of Antithrombotic Agents. J. Clin. Med. 2024, 13, 1886. https://doi.org/10.3390/jcm13071886
Kawai D, Iwamuro M, Takenaka R, Obata T, Yamamoto T, Hirata S, Miura K, Takemoto K, Tsugeno H, Fujiki S. A Prospective Observational Study on Gastric Endoscopic Submucosal Dissection under Continuous Administration of Antithrombotic Agents. Journal of Clinical Medicine. 2024; 13(7):1886. https://doi.org/10.3390/jcm13071886
Chicago/Turabian StyleKawai, Daisuke, Masaya Iwamuro, Ryuta Takenaka, Taisuke Obata, Takashi Yamamoto, Shoichiro Hirata, Ko Miura, Koji Takemoto, Hirofumi Tsugeno, and Shigeatsu Fujiki. 2024. "A Prospective Observational Study on Gastric Endoscopic Submucosal Dissection under Continuous Administration of Antithrombotic Agents" Journal of Clinical Medicine 13, no. 7: 1886. https://doi.org/10.3390/jcm13071886
APA StyleKawai, D., Iwamuro, M., Takenaka, R., Obata, T., Yamamoto, T., Hirata, S., Miura, K., Takemoto, K., Tsugeno, H., & Fujiki, S. (2024). A Prospective Observational Study on Gastric Endoscopic Submucosal Dissection under Continuous Administration of Antithrombotic Agents. Journal of Clinical Medicine, 13(7), 1886. https://doi.org/10.3390/jcm13071886