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Nakamura et al. Mini-invasive Surg 2022;6:50 https://dx.doi.org/10.20517/2574-1225.2022.38 Page 13 of 20

Table 4. Predictors for delayed bleeding after ESD for EGC
Variables Adjusted odds ratio 95%CI P-value β regression coefficient Point
CKD with hemodialysis Yes 4.33 2.71-6.91 < 0.001 1.464 3
Aspirin Yes 2.24 1.55-3.24 < 0.001 0.807 2
P2Y12RA Yes 3.13 1.91-5.12 < 0.001 1.140 2
Cilostazol Yes 2.04 1.09-3.80 0.025 0.712 1
Warfarin Yes 8.74 4.92-15.54 < 0.001 2.168 4
DOAC Yes 8.16 4.74-14.04 < 0.001 2.099 4
Interruption of AT agents Each kind of agents 0.67 0.46-0.97 0.033 -0.403 -1
The number of tumors Multiple 1.38 1.04-1.85 0.028 0.324 1
Tumor size > 30 mm 1.72 1.28-2.31 < 0.001 0.545 1
Tumor location Lower third 1.68 1.35-2.10 < 0.001 0.520 1
[30]
This table is modified from Ref. . CKD: Chronic kidney disease; P2Y12RA: P2Y12 receptor antagonist; DOAC: direct oral anticoagulant; AT:
antithrombotics.

Several studies have indicated that the incidence of post-gastric ESD bleeding does not differ between
patients treated with PPI and those treated with potassium-competitive acid blockers (P-CABs) [31-33] . A
recent large-scale study using propensity score matching analysis suggested a significant reduction in post-
gastric ESD bleeding in patients treated with P-CAB compared to those using PPI . The use of
[34]
antithrombotic agents is also a risk factor for delayed bleeding following gastric ESD. However, the Japanese
Gastroenterological Endoscopy Society (JGES), European Society of Gastroenterological Endoscopy
(ESGE), and American Society for Gastroenterological Endoscopy (ASGE) guidelines recommend
performing high-bleeding-risk procedures without interruption of low-dose aspirin (LDA) therapy in
patients who are at high risk for thromboembolic events [35-37] . Two meta-analyses of observational studies
indicated similar delayed bleeding rates after gastric ESD between groups that continued and groups that
interrupted their LDA therapy [38,39] . In terms of multiple antithrombotic therapies, the JGES, ESGE, and
ASGE guidelines recommend that thienopyridine be withdrawn or replaced with aspirin monotherapy for
high-bleeding-risk procedures. A meta-analysis indicated that the risk of delayed bleeding after gastric ESD
in regular users of multiple antithrombotic drugs was significantly higher than that in non-users [odds ratio:
5.17 (95%CI: 3.13-8.54)] .
[38]

In a recently reported multicenter retrospective study including 728 patients who received anticoagulants,
delayed bleeding occurred in 14% of patients taking direct oral anticoagulants (DOACs), which was not
considerably different from delayed bleeding rates in patients receiving warfarin (18%) . The ESGE and
[40]
ASGE guidelines recommend heparin bridging therapy during high-bleeding-risk endoscopic procedures,
while the supplementary issue of the JGES guidelines for the management of patients taking anticoagulants
suggests the possibility of continuation of warfarin instead of heparin bridging therapy . Many studies
[41]
have shown a high incidence of delayed bleeding after gastric ESD in patients receiving heparin bridging
therapy (10.8%-61.5%) [42-49] .

Some reports have described a new endoscopic method for the prevention of post-ESD bleeding in high-
risk patients. Tissue shielding using polyglycolic acid (PGA) sheets and fibrin glue is one of the approaches
to the prevention of post-ESD bleeding. Two prospective, non-randomized studies that enrolled patients
taking antithrombotic agents showed that the delayed bleeding rate was significantly lower in the tissue
shielding group than in the control group (6.7% vs. 22.0%, P = 0.04, and 5.8% vs. 20.8%, P = 0.041,
respectively) [50,51] . Kikuchi et al. also reported favorable results for the PGA sheet shielding method in a
single-arm study . The PGA sheet delivery to post-ESD wounds through the working channel was
[52]