Digestive Endoscopy 2014; ••: ••–••
doi: 10.1111/den.12410
Review
Second-look endoscopy after endoscopic submucosal dissection for gastric neoplasms Toshihiro Nishizawa,1,2 Hidekazu Suzuki,2 Satoshi Kinoshita,1,2 Osamu Goto,1 Takanori Kanai2 and Naohisa Yahagi1 1
Division of Research and Development for Minimally Invasive Treatment, Cancer Center and 2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
Routine second-look endoscopy after gastric endoscopic submucosal dissection (ESD) remains controversial. The aim of the present study was to systematically evaluate the efficacy of second-look endoscopy for gastric ESD. PubMed, the Cochrane library, and the Igaku-chuo-zasshi database were searched in order to identify randomized trials eligible for inclusion in the systematic review. Data were combined to calculate a pooled odds ratio (OR) for developing post-ESD bleeding. The database search yielded three randomized trials (854 patients). Compared with second-look endoscopy, the pooled OR for post-ESD bleeding without second-look endoscopy was 0.69 (95%
INTRODUCTION
E
NDOSCOPIC SUBMUCOSAL DISSECTION (ESD) is a recently developed technique that enables en bloc endoscopic resection of large lesions.1,2 We used ESD instead of open surgery to carry out curative resection of node-negative early gastric cancer.3 One of the major concerns regarding gastric ESD is delayed bleeding. Recent studies showed that proton pump inhibitors more effectively prevented bleeding as a result of ESD-induced gastric ulcers than histamine H2-receptor antagonists.4,5 However, delayed bleeding occurs in approximately 5% of patients who undergo gastric ESD.6 Several previous studies reported that second-look endoscopy prevents further bleeding after endoscopic treatment of peptic ulcer bleeding in the stomach.7 A significant
bs_bs_banner
Corresponding: Hidekazu Suzuki, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Email: [email protected] Received 22 October 2014; accepted 21 November 2014.
confidence interval [CI]: 0.38–1.26, P = 0.228), without significant heterogeneity. There were no significant differences between second-look endoscopy and no second-look endoscopy with regard to large tumor size (>20 mm). This systematic review and meta-analysis showed that second-look endoscopy had no advantage for the prevention of post-ESD bleeding in patients without a high risk of bleeding. Key words: bleeding, endoscopic submucosal dissection (ESD), meta-analysis, second-look endoscopy, systematic review
number of authors recommended carrying out second-look endoscopy for ESD-induced ulcer,8,9 especially for lesions with significant risk factors for delayed bleeding including tumor size,10,11 specimen size,12,13 and tumor location.6 According to our previous survey, most institutions continue to carry out second-look endoscopy.14 By contrast, our previous retrospective analysis suggested that the incidence of post-ESD bleeding was not significantly different before and after second-look endoscopy.15 Furthermore, several randomized controlled trials (RCT) evaluated the efficacy of second-look endoscopy for ESD-induced ulcer.16–18 However, most studies have been limited by relatively small sample sizes. We propose that the systematic pooling of data from all available studies may provide better insight into second-look endoscopy after ESD. The avoidance of unnecessary second-look endoscopies after gastric ESD could save unnecessary cost, patient burden, and endoscopist workload. If this systematic review and meta-analysis clarifies the role of second-look endoscopy with greater evidence, endoscopists would likely change their daily practice. Our objective was to carry out a systematic review of RCT comparing second-look endoscopy and no second-look endoscopy after ESD.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
1
2
T. Nishizawa et al.
METHODS
B
EFORE CARRYING OUT the meta-analysis, we developed a simplified protocol including search strategies, criteria for study selection, and methods for relevant data extraction, quality assessment, and statistical analysis.
Search strategy Electronic databases including PubMed, the Cochrane library, and the Igaku-chuo-zasshi database in Japan (from 1950 to October 2014) were used to carry out a systematic literature search. A search strategy was constructed using a combination of the following words: (endoscopic submucosal dissection) AND (second-look). Articles published in any language were included.
Digestive Endoscopy 2014; ••: ••–••
examined was the odds ratio (OR) for post-ESD bleeding with no second-look endoscopy versus second-look endoscopy. We used a random-effects model to calculate summary OR and 95% CI. Between-study heterogeneity was assessed using Cochrane’s Q and I-squared tests. Because of the low power of the Q test, a cut-off value (20 mm) included 56 patients who did not receive secondlook endoscopy and 63 patients who received second-look endoscopy.17,18 Compared to second-look endoscopy, the pooled OR for post-ESD bleeding with no second-look endoscopy was 1.39 (95% CI: 0.31–6.21), indicating no significant difference between the two groups (Fig. 3).
DISCUSSION
T
HIS SYSTEMATIC REVIEW and meta-analysis indicates that second-look endoscopy confers no advantage for the clinical outcome of patients who undergo gastric ESD. The incidence of post-ESD bleeding tended to be higher with second-look endoscopy than with no second-look endoscopy, although the difference was not statistically significant. Prophylactic hemostasis for adherent clots during second-look endoscopy may be an unnecessary procedure. Prophylactic coagulation for adherent clots may induce tissue damage and even increase the incidence of post-ESD bleeding. The natural healing response may be among the major contributors to the prevention of post-ESD bleeding.12 In this meta-analysis, two trials evaluated the efficacy of second-look endoscopy with respect to tumor size (>20 mm). There were no significant differences between
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
4
T. Nishizawa et al.
Digestive Endoscopy 2014; ••: ••–••
Table 2 Evaluation of bias of RCT included in the present systematic review Author/Year
Random sequence generation
Allocation concealment
Blinding of participants and personnel
Blinding of outcome assessment
Adequate assessment of incomplete outcome
Selective reporting avoided
No other bias
Ryu et al. 201316 Kim et al. 201417 Mochizuki et al. 201418
Yes No Yes
Yes Yes Yes
No No No
No No No
Yes Yes Yes
Yes Yes Yes
Yes Yes Yes
No, high risk of bias; RCT, randomized controlled trial; Yes, low risk of bias.
Description
Figure 2 Forest plot displaying the odds ratios and 95% CI of each study for post- endoscopic submucosal dissection bleeding. SLE, second-look endoscopy.
Non-SLE
SLE
Odds ratio meta-analysis plot
Odds ratio
n/N
n/N
(random effects, 95% CI)
(95% CI)
Ryu 2013
9/81
12/74
Kim 2014
6/217
8/220
0.75 (0.21, 2.53)
Mochizuki 2014
5/132
7/130
0.69 (0.17, 2.61)
Total
20/430
27/424
0.69 (0.38, 1.26)
Test for heterogeneity: χ2=0.05, df=2, p=0.98
0.1
0.2
0.5
1
2
5
I2=0%
Description
Figure 3 Forest plot displaying the odds ratios and 95% CI of each study for post-endoscopic submucosal dissection bleeding with large tumor size (>20 mm). SLE, second-look endoscopy.
0.65 (0.22, 1.80)
Non-SLE
SLE
Odds ratio meta-analysis plot
Odds ratio
n/N
n/N
(random effects, 95% CI)
(95% CI)
Kim
3/35
3/45
Mochizuki
1/21
0/18
1.75 (0.01, 144.85)
Total
4/56
3/63
1.39 (0.31, 6.21)
Test for heterogeneity: χ2=0.02, df=1, p=0.88 0.01
second-look endoscopy and no second-look endoscopy with regard to large tumor size. However, because only a few trials were included, these results should be interpreted with caution, and more studies are needed. With regard to cost-effectiveness, the Japanese national insurance system has set fees of 11 400 JPY for a diagnostic esophagogastroduodenoscopy and 46 000 JPY for
1.31 (0.16, 10.43)
0.1 0.2 0.5 1 2
5 10
100
1000
I2=0%
endoscopic hemostasis or coagulation.18 Thus, the avoidance of unnecessary second-look endoscopies after gastric ESD may result in substantial savings of both money and human resources. In clinical practice, it is important to discuss how to lessen post-ESD bleeding. A new method for preventing post-ESD bleeding using medical adhesive such as
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2014; ••: ••–••
Second-look endoscopy after ESD 5
n-butyl-2-cyanoacrylate was reported.26 The prospective study revealed that medical adhesive spray is effective in preventing post-ESD bleeding (medical adhesive group 0% [0/89] vs control group 4.88% [4/82]; P = 0.035). Medical adhesives are usually used to treat gastric varices, and medical adhesive spray could be an option for preventing post-ESD bleeding. As high-dose proton pump inhibitor was quite effective in cases of peptic ulcer bleeding,27–29 highdose proton pump inhibitor might lessen post-ESD bleeding. The present systematic review had several limitations that should be taken into account. Differing definitions of postESD bleeding used in the three studies may be considered a source of heterogeneity. In addition, as a result of the limited number of eligible studies, it might be underpowered to assess their summary statistics. One trial excluded patients with high risk of bleeding, such as those who had chronic renal failure or liver cirrhosis. In all three RCT, the patients who took antiplatelet drugs or antithrombotic drugs during the perioperative period were excluded. Therefore, it may be necessary to carry out second-look endoscopy in patients with a high risk of bleeding. Further studies with large numbers of patients are warranted to clarify the efficacy of second-look endoscopy after ESD. In conclusion, second-look endoscopy has no advantage for the prevention of post-ESD bleeding. Based on these results, routine second-look endoscopy after ESD is not recommended in patients without a high risk of bleeding.
CONFLICT OF INTERESTS
D
URING THE LAST 2 years, Author H.S. has received scholarship funds for the research from Astellas Pharm Inc., Astra-Zeneca K.K., Otsuka Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, and Zeria Pharmaceutical Co., Ltd and has received service honoraria from Astellas Pharm Inc., Astra-Zeneca K.K., Eisai Co., Otsuka Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, and Zeria Pharmaceutical Co., Ltd. Author T.K. has received scholarship funds for the research from Astellas Pharm Inc., AstraZeneca K.K., Otsuka Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, Eisai Pharmaceutical Co., Ltd, Zeria Pharmaceutical Co., Ltd, Tanabe Mitsubishi Pharmaceutical Co., Ltd, JIMRO Co., Ltd, Kyorin Pharmaceutical Co. Ltd, and has received service honoraria from Astellas Pharm Inc., Eisai Pharmaceutical Co., Ltd, JIMRO Co., Ltd, Tanabe Mitsubidhi Pharmaceutical Co. Ltd, Otsuka Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, Miyarisan Pharmaceutical Co. Ltd, and Zeria Pharmaceutical Co., Ltd. Author N.Y. has received scholarship funds for the research from Astra-Zeneca K.K., Takeda Pharmaceutical Co., Ltd, Eisai Co., Top Corporation, Kaigen Pharm Co., Ltd, ASKA
Pharmaceutical Co., Ltd, FUJIFILM Corporation, Boston Scientific Japan K.K., Century Medical Inc., and Covidien Japan Inc. The funding source had no role in the design, practice or analysis of this study. There are no other conflicts of interests for this article.
REFERENCES 1 Kodashima S, Fujishiro M, Yahagi N, Kakushima N, Omata M. Endoscopic submucosal dissection using flexknife. J. Clin. Gastroenterol. 2006; 40: 378–84. 2 Uraoka T, Parra-Blanco A, Yahagi N. Colorectal endoscopic submucosal dissection in Japan and Western countries. Dig. Endosc. 2012; 24 (Suppl 1): 80–3. 3 Gotoda T, Yanagisawa A, Sasako M et al. Incidence of lymph node metastasis from early gastric cancer: Estimation with a large number of cases at two large centers. Gastric Cancer 2000; 3: 219–25. 4 Yang Z, Wu Q, Liu Z, Wu K, Fan D. Proton pump inhibitors versus histamine-2-receptor antagonists for the management of iatrogenic gastric ulcer after endoscopic mucosal resection or endoscopic submucosal dissection: A meta-analysis of randomized trials. Digestion 2011; 84: 315–20. 5 Nishizawa T, Suzuki H, Kanai T, Yahagi N. Proton pump inhibitor alone vs proton pump inhibitor plus mucosal protective agents for endoscopic submucosal dissection-induced ulcer: A systematic review. J. Clin. Biochem. Nutr. (in press). 6 Takizawa K, Oda I, Gotoda T et al. Routine coagulation of visible vessels may prevent delayed bleeding after endoscopic submucosal dissection–an analysis of risk factors. Endoscopy 2008; 40: 179–83. 7 Chiu PW, Lam CY, Lee SW et al. Effect of scheduled second therapeutic endoscopy on peptic ulcer rebleeding: A prospective randomised trial. Gut 2003; 52: 1403–7. 8 Muraki Y, Enomoto S, Iguchi M, Fujishiro M, Yahagi N, Ichinose M. Management of bleeding and artificial gastric ulcers associated with endoscopic submucosal dissection. World J. Gastrointest. Endosc. 2012; 4: 1–8. 9 Tsuji Y, Ohata K, Ito T et al. Risk factors for bleeding after endoscopic submucosal dissection for gastric lesions. World J. Gastroenterol. 2010; 16: 2913–7. 10 Chung IK, Lee JH, Lee SH 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: 1228–35. 11 Uedo N, Takeuchi Y, Yamada T et al. Effect of a proton pump inhibitor or an H2-receptor antagonist on prevention of bleeding from ulcer after endoscopic submucosal dissection of early gastric cancer: A prospective randomized controlled trial. Am. J. Gastroenterol. 2007; 102: 1610–6. 12 Kim HH, Park SJ, Park MI, Moon W. Clinical impact of secondlook endoscopy after endoscopic submucosal dissection of gastric neoplasms. Gut Liver 2012; 6: 316–20.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
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13 Kim SE, Kim HH, Kim JH et al. The role of second-look endoscopy in endoscopic submucosal dissection for early gastric cancer. Turk. J. Gastroenterol. 2013; 24: 218– 23. 14 Goto O, Fujishiro M, Oda I et al. A multicenter survey of the management after gastric endoscopic submucosal dissection related to postoperative bleeding. Dig. Dis. Sci. 2012; 57: 435–9. 15 Goto O, Fujishiro M, Kodashima S et al. A second-look endoscopy after endoscopic submucosal dissection for gastric epithelial neoplasm may be unnecessary: A retrospective analysis of postendoscopic submucosal dissection bleeding. Gastrointest. Endosc. 2010; 71: 241–8. 16 Ryu HY, Kim JW, Kim HS et al. Second-look endoscopy is not associated with better clinical outcomes after gastric endoscopic submucosal dissection: A prospective, randomized, clinical trial analyzed on an as-treated basis. Gastrointest. Endosc. 2013; 78: 285–94. 17 Kim JS, Chung MW, Chung CY et al. The need for second-look endoscopy to prevent delayed bleeding after endoscopic submucosal dissection for gastric neoplasms: a prospective randomized trial. Gut Liver 2014; 8: 480–6. 18 Mochizuki S, Uedo N, Oda I et al. Scheduled second-look endoscopy is not recommended after endoscopic submucosal dissection for gastric neoplasms (the SAFE trial): a multicentre prospective randomised controlled non-inferiority trial. Gut Published online: 9 Oct 2014; doi: 10.1136/gutjnl-2014-307552 19 Higgins JPT, Green S (eds). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www .cochrane-handbook.org 20 Nishizawa T, Suzuki H, Matsuzaki J, Kanai T, Yahagi N. Propofol versus traditional sedative agents for endoscopic submucosal dissection. Dig. Endosc. 2014; 26: 701–6.
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21 Harbord RM, Egger M, Sterne JA. A modified test for smallstudy effects in meta-analyses of controlled trials with binary endpoints. Stat. Med. 2006; 25: 3443–57. 22 Choi CW, Kim HW, Kang DH et al. Clinical outcomes of second-look endoscopy after gastric endoscopic submucosal dissection: Predictive factors with high risks of bleeding. Surg. Endosc. 2014; 28: 2213–20. 23 Park CH, Park JC, Lee H, Shin SK, Lee SK, Lee YC. Secondlook endoscopy after gastric endoscopic submucosal dissection for reducing delayed postoperative bleeding. Gut Liver Published online: 23 Apr 2014; doi: 10.5009/gnl13252 24 Takahashi F, Yoshitake N, Akima T et al. A second-look endoscopy may not reduce the bleeding after endoscopic submucosal dissection for gastric epithelial neoplasm. BMC Gastroenterol. 2014; 14: 152. 25 Kim ER, Kim JH, Kang KJ et al. Is a second-look endoscopy necessary after endoscopic submucosal dissection for gastric neoplasm? Gut Liver Published online: 25 Jul 2014; doi: 10.5009/gnl13422 26 Zhang Y, Chen Y, Qu CY, Zhou M, Ni QW, Xu LM. Effects of medical adhesives in prevention of complications after endoscopic submucosal dissection. World J. Gastroenterol. 2013; 19: 2704–8. 27 Lau JY, Leung WK, Wu JC et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding. N. Engl. J. Med. 2007; 356: 1631–40. 28 Fujishiro M, Chiu PW, Wang HP. Role of antisecretory agents for gastric endoscopic submucosal dissection. Dig. Endosc. 2013; 25 (Suppl 1): 86–93. 29 Chan WH, Khin LW, Chung YF, Goh YC, Ong HS, Wong WK. Randomized controlled trial of standard versus high-dose intravenous omeprazole after endoscopic therapy in high-risk patients with acute peptic ulcer bleeding. Br. J. Surg. 2011; 98: 640–4.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
doi: 10.1111/den.12410
Review
Second-look endoscopy after endoscopic submucosal dissection for gastric neoplasms Toshihiro Nishizawa,1,2 Hidekazu Suzuki,2 Satoshi Kinoshita,1,2 Osamu Goto,1 Takanori Kanai2 and Naohisa Yahagi1 1
Division of Research and Development for Minimally Invasive Treatment, Cancer Center and 2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
Routine second-look endoscopy after gastric endoscopic submucosal dissection (ESD) remains controversial. The aim of the present study was to systematically evaluate the efficacy of second-look endoscopy for gastric ESD. PubMed, the Cochrane library, and the Igaku-chuo-zasshi database were searched in order to identify randomized trials eligible for inclusion in the systematic review. Data were combined to calculate a pooled odds ratio (OR) for developing post-ESD bleeding. The database search yielded three randomized trials (854 patients). Compared with second-look endoscopy, the pooled OR for post-ESD bleeding without second-look endoscopy was 0.69 (95%
INTRODUCTION
E
NDOSCOPIC SUBMUCOSAL DISSECTION (ESD) is a recently developed technique that enables en bloc endoscopic resection of large lesions.1,2 We used ESD instead of open surgery to carry out curative resection of node-negative early gastric cancer.3 One of the major concerns regarding gastric ESD is delayed bleeding. Recent studies showed that proton pump inhibitors more effectively prevented bleeding as a result of ESD-induced gastric ulcers than histamine H2-receptor antagonists.4,5 However, delayed bleeding occurs in approximately 5% of patients who undergo gastric ESD.6 Several previous studies reported that second-look endoscopy prevents further bleeding after endoscopic treatment of peptic ulcer bleeding in the stomach.7 A significant
bs_bs_banner
Corresponding: Hidekazu Suzuki, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Email: [email protected] Received 22 October 2014; accepted 21 November 2014.
confidence interval [CI]: 0.38–1.26, P = 0.228), without significant heterogeneity. There were no significant differences between second-look endoscopy and no second-look endoscopy with regard to large tumor size (>20 mm). This systematic review and meta-analysis showed that second-look endoscopy had no advantage for the prevention of post-ESD bleeding in patients without a high risk of bleeding. Key words: bleeding, endoscopic submucosal dissection (ESD), meta-analysis, second-look endoscopy, systematic review
number of authors recommended carrying out second-look endoscopy for ESD-induced ulcer,8,9 especially for lesions with significant risk factors for delayed bleeding including tumor size,10,11 specimen size,12,13 and tumor location.6 According to our previous survey, most institutions continue to carry out second-look endoscopy.14 By contrast, our previous retrospective analysis suggested that the incidence of post-ESD bleeding was not significantly different before and after second-look endoscopy.15 Furthermore, several randomized controlled trials (RCT) evaluated the efficacy of second-look endoscopy for ESD-induced ulcer.16–18 However, most studies have been limited by relatively small sample sizes. We propose that the systematic pooling of data from all available studies may provide better insight into second-look endoscopy after ESD. The avoidance of unnecessary second-look endoscopies after gastric ESD could save unnecessary cost, patient burden, and endoscopist workload. If this systematic review and meta-analysis clarifies the role of second-look endoscopy with greater evidence, endoscopists would likely change their daily practice. Our objective was to carry out a systematic review of RCT comparing second-look endoscopy and no second-look endoscopy after ESD.
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
1
2
T. Nishizawa et al.
METHODS
B
EFORE CARRYING OUT the meta-analysis, we developed a simplified protocol including search strategies, criteria for study selection, and methods for relevant data extraction, quality assessment, and statistical analysis.
Search strategy Electronic databases including PubMed, the Cochrane library, and the Igaku-chuo-zasshi database in Japan (from 1950 to October 2014) were used to carry out a systematic literature search. A search strategy was constructed using a combination of the following words: (endoscopic submucosal dissection) AND (second-look). Articles published in any language were included.
Digestive Endoscopy 2014; ••: ••–••
examined was the odds ratio (OR) for post-ESD bleeding with no second-look endoscopy versus second-look endoscopy. We used a random-effects model to calculate summary OR and 95% CI. Between-study heterogeneity was assessed using Cochrane’s Q and I-squared tests. Because of the low power of the Q test, a cut-off value (20 mm) included 56 patients who did not receive secondlook endoscopy and 63 patients who received second-look endoscopy.17,18 Compared to second-look endoscopy, the pooled OR for post-ESD bleeding with no second-look endoscopy was 1.39 (95% CI: 0.31–6.21), indicating no significant difference between the two groups (Fig. 3).
DISCUSSION
T
HIS SYSTEMATIC REVIEW and meta-analysis indicates that second-look endoscopy confers no advantage for the clinical outcome of patients who undergo gastric ESD. The incidence of post-ESD bleeding tended to be higher with second-look endoscopy than with no second-look endoscopy, although the difference was not statistically significant. Prophylactic hemostasis for adherent clots during second-look endoscopy may be an unnecessary procedure. Prophylactic coagulation for adherent clots may induce tissue damage and even increase the incidence of post-ESD bleeding. The natural healing response may be among the major contributors to the prevention of post-ESD bleeding.12 In this meta-analysis, two trials evaluated the efficacy of second-look endoscopy with respect to tumor size (>20 mm). There were no significant differences between
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
4
T. Nishizawa et al.
Digestive Endoscopy 2014; ••: ••–••
Table 2 Evaluation of bias of RCT included in the present systematic review Author/Year
Random sequence generation
Allocation concealment
Blinding of participants and personnel
Blinding of outcome assessment
Adequate assessment of incomplete outcome
Selective reporting avoided
No other bias
Ryu et al. 201316 Kim et al. 201417 Mochizuki et al. 201418
Yes No Yes
Yes Yes Yes
No No No
No No No
Yes Yes Yes
Yes Yes Yes
Yes Yes Yes
No, high risk of bias; RCT, randomized controlled trial; Yes, low risk of bias.
Description
Figure 2 Forest plot displaying the odds ratios and 95% CI of each study for post- endoscopic submucosal dissection bleeding. SLE, second-look endoscopy.
Non-SLE
SLE
Odds ratio meta-analysis plot
Odds ratio
n/N
n/N
(random effects, 95% CI)
(95% CI)
Ryu 2013
9/81
12/74
Kim 2014
6/217
8/220
0.75 (0.21, 2.53)
Mochizuki 2014
5/132
7/130
0.69 (0.17, 2.61)
Total
20/430
27/424
0.69 (0.38, 1.26)
Test for heterogeneity: χ2=0.05, df=2, p=0.98
0.1
0.2
0.5
1
2
5
I2=0%
Description
Figure 3 Forest plot displaying the odds ratios and 95% CI of each study for post-endoscopic submucosal dissection bleeding with large tumor size (>20 mm). SLE, second-look endoscopy.
0.65 (0.22, 1.80)
Non-SLE
SLE
Odds ratio meta-analysis plot
Odds ratio
n/N
n/N
(random effects, 95% CI)
(95% CI)
Kim
3/35
3/45
Mochizuki
1/21
0/18
1.75 (0.01, 144.85)
Total
4/56
3/63
1.39 (0.31, 6.21)
Test for heterogeneity: χ2=0.02, df=1, p=0.88 0.01
second-look endoscopy and no second-look endoscopy with regard to large tumor size. However, because only a few trials were included, these results should be interpreted with caution, and more studies are needed. With regard to cost-effectiveness, the Japanese national insurance system has set fees of 11 400 JPY for a diagnostic esophagogastroduodenoscopy and 46 000 JPY for
1.31 (0.16, 10.43)
0.1 0.2 0.5 1 2
5 10
100
1000
I2=0%
endoscopic hemostasis or coagulation.18 Thus, the avoidance of unnecessary second-look endoscopies after gastric ESD may result in substantial savings of both money and human resources. In clinical practice, it is important to discuss how to lessen post-ESD bleeding. A new method for preventing post-ESD bleeding using medical adhesive such as
© 2014 The Authors Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society
Digestive Endoscopy 2014; ••: ••–••
Second-look endoscopy after ESD 5
n-butyl-2-cyanoacrylate was reported.26 The prospective study revealed that medical adhesive spray is effective in preventing post-ESD bleeding (medical adhesive group 0% [0/89] vs control group 4.88% [4/82]; P = 0.035). Medical adhesives are usually used to treat gastric varices, and medical adhesive spray could be an option for preventing post-ESD bleeding. As high-dose proton pump inhibitor was quite effective in cases of peptic ulcer bleeding,27–29 highdose proton pump inhibitor might lessen post-ESD bleeding. The present systematic review had several limitations that should be taken into account. Differing definitions of postESD bleeding used in the three studies may be considered a source of heterogeneity. In addition, as a result of the limited number of eligible studies, it might be underpowered to assess their summary statistics. One trial excluded patients with high risk of bleeding, such as those who had chronic renal failure or liver cirrhosis. In all three RCT, the patients who took antiplatelet drugs or antithrombotic drugs during the perioperative period were excluded. Therefore, it may be necessary to carry out second-look endoscopy in patients with a high risk of bleeding. Further studies with large numbers of patients are warranted to clarify the efficacy of second-look endoscopy after ESD. In conclusion, second-look endoscopy has no advantage for the prevention of post-ESD bleeding. Based on these results, routine second-look endoscopy after ESD is not recommended in patients without a high risk of bleeding.
CONFLICT OF INTERESTS
D
URING THE LAST 2 years, Author H.S. has received scholarship funds for the research from Astellas Pharm Inc., Astra-Zeneca K.K., Otsuka Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, and Zeria Pharmaceutical Co., Ltd and has received service honoraria from Astellas Pharm Inc., Astra-Zeneca K.K., Eisai Co., Otsuka Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, and Zeria Pharmaceutical Co., Ltd. Author T.K. has received scholarship funds for the research from Astellas Pharm Inc., AstraZeneca K.K., Otsuka Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, Eisai Pharmaceutical Co., Ltd, Zeria Pharmaceutical Co., Ltd, Tanabe Mitsubishi Pharmaceutical Co., Ltd, JIMRO Co., Ltd, Kyorin Pharmaceutical Co. Ltd, and has received service honoraria from Astellas Pharm Inc., Eisai Pharmaceutical Co., Ltd, JIMRO Co., Ltd, Tanabe Mitsubidhi Pharmaceutical Co. Ltd, Otsuka Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, Miyarisan Pharmaceutical Co. Ltd, and Zeria Pharmaceutical Co., Ltd. Author N.Y. has received scholarship funds for the research from Astra-Zeneca K.K., Takeda Pharmaceutical Co., Ltd, Eisai Co., Top Corporation, Kaigen Pharm Co., Ltd, ASKA
Pharmaceutical Co., Ltd, FUJIFILM Corporation, Boston Scientific Japan K.K., Century Medical Inc., and Covidien Japan Inc. The funding source had no role in the design, practice or analysis of this study. There are no other conflicts of interests for this article.
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