Severity of gastric mucosal atrophy affects the healing speed of post-endoscopic submucosal dissection ulcers

Table 1 Characteristics of enrolled patients with gastric tumor

Parameter
Number	132
Age (yr)	71.0 ± 8.6
Gender (male/female)	100/32 (75.8%/34.2%)
H. pylori status (positive/negative)	68/64 (51.5%/48.5%)
Anti-coagulant administration (+/-)	22/110 (16.7%/83.3%)
Acid suppressant post-ESD (lansoprazole/vonoprazan)	97/35 (73.5%/26.5%)
CYP2C19 genotype (EM/IM/PM)	40/51/22 (35.4%/45.1%/19.5%)
Endoscopic background of gastric mucosa
Atrophy (Kyoto A0+A1/Kyoto A2)	20/112 (15.2%/84.8%)
Intestinal metaplasia (none + mild/severe)	72/55 (56.7%/43.3%)
Diffuse redness (none/mild/severe)	65/62 (51.2%/48.8%)
Tumor
Types (adenoma/cancer)	16/116 (12.1%/87.9%)
Depth (mucosa/submucosa)	118/14 (89.4%/10.6%)
Location of tumors (upper/middle/lower third)	15/67/50 (11.4%/50.8%/37.8%)
ESD
Mean procedure time (min)	76.4 ± 56.7
Mean resected ulcer area (mm2)	671.9 ± 720.9
ESD-induced ulcer area
Reduction at 4 wk	90.4% ± 10.7%
Mean ulcer area at 4 wk (mm2)	71.3 ± 135.6
Reduction at 8 wk	99.8% ± 0.6%
Mean ulcer area at 8 wk (mm2)	2.8 ± 15.6

EM: Extensive metabolizer of CYP2C19; ESD: Endoscopic submucosal dissection; IM: Intermediate metabolizer of CYP2C19; PM: Poor metabolizer of CYP2C19.

Table 2 Characteristics of patients who achieved early healing of artificial ulcer area after endoscopic submucosal dissection

	Reduction rate over 90% at 4 wk			Reduction rate 100% at 8 wk
Characteristic	Achieved (n = 82)	Not achieved (n = 45)	P value	Achieved (n = 110)	Not achieved (n = 16)	P value
Age (yr)	70.9 ± 9.3	71.2 ± 7.3	0.831	70.4 ± 8.9	74.1 ± 6.2	0.047
Gender (male/female)	62/20 (75.6%/24.4%)	33/12 (73.3%/26.7%)	0.777	86/24 (78.2%/21.8%)	8/8 (50.0%/50.0%)	0.021
H. pylori (positive/negative)	42/40 (51.2%/48.8%)	24/21 (53.3%/46.7%)	0.82	54/56 (49.1%/50.9%)	12/4 (75.0%/25.0%)	0.053
Anti-coagulants	13 (15.9%)	8 (17.8%)	0.78	16 (14.5%)	4 (25.0%)	0.231
PPI or PCAB (post-ESD)	60/22 (73.2%/26.8%)	32/13 (71.1%/28.9%)	0.804	82/28 (74.5%/25.5%)	14/2 (87.5%/12.5%)	0.210
CYP2C19 type (EM/IM/PM)	27/28/15 (38.6/40/21.4)	12/20/7 (30.8/51.3/17.9)	0.522	35/39/19 (37.6/41.9/20.5)	4/9/1 (28.6%/64.3%/7.1%)	0.249
Gastric mucosa
Trophy (Kyoto A0+A1/Kyoto A2)	18/64 (22.0%/78.0%)	2/43 (4.0%/96.0%)	0.01	19/91 (17.3%/82.7%)	1/15 (6.3%/93.7%)	0.233
Metaplasia (none-mild/severe)	51/31 (62.2/37.8)	21/24 (46.7/53.3)	0.091	64/46 (58.2/41.8)	8/8 (50.0/50.0)	0.537
Diffuse redness (none-mild/severe)	44/38 (53.7/46.3)	21/24 (46.7/53.3)	0.451	60/50 (54.5/45.5)	7/9 (43.8/56.2)	0.419
Tumor
Depth (mucosa/submucosa)	78/4 (95.1/4.9)	35/10 (77.8/22.2)	0.004	101/9 (91.8 /8.2)	15/1 (93.8/6.2)	0.629
Location (upper/middle/lower third)	7/39/36/ (8.5/47.6/43.9)	7/26/12 (15.6/57.8/26.6)	0.124	12/58/40 (10.9/52.7/36.4)	2/7/7 (12.4/43.8/43.8)	0.797
ESD
Mean procedure time (min)	65.6 ± 41.1	89.7 ± 64.0	0.026	73.9 ± 52.3	76.1 ± 41.4	0.872
Mean resected ulcer area (mm2)	544.7 ± 387.1	809.8 ± 849.8	0.053	567.3 ± 435.2	1178.5 ± 1520.1	0.130

EM: Extensive metabolizer; ESD: Endoscopic submucosal dissection; IM: Intermediate metabolizer; PCAB: Potassium competitive acid blocker; PM: Poor metabolizer; PPI: Proton pump inhibitor; H. pylori: Helicobacter pylori.

Table 3 Univariate analysis of factors preventing healing of ulcers after endoscopic submucosal dissection

	Reduction rate over 90% at 4 wk		Reduction rate 100% at 8 wk
Variable	Not achieved (n = 45)	P value	Not achieved (n = 16)	P value
Age (yr)	1.004 (0.963-1.048)	0.841	1.058 (0.987-1.135)	0.113
Gender (female vs male)	1.127 (0.491-2.588)	0.777	3.583 (1.218-10.545)	0.021
Helicobacter pylori	1.088 (0.525-2.255)	0.820	3.111 (0.945-10.244)	0.053
Lansoprazole vs vonoprazan	1.108 (0.493-2.488)	0.804	0.418 (0.089-1.956)	0.210
Anti-coagulants	1.148 (0.436-3.018)	0.780	1.958 (0.561-6.832)	0.231
CYP2C19 type (EM vs IM/PM)	1.084 (0.635-1.850)	0.768	0.921 (0.420-2.020)	0.838
Atrophy (Kyoto A0+A1 vs Kyoto A2)	6.047 (1.334-27.403)	0.010	3.132 (0.390-25.163)	0.233
Tumor located in upper and middle third (vs lower third)	0.465 (0.211-1.026)	0.055	1.361 (0.471-3.934)	0.568
Mean procedure time (min)	1.009 (1.002-1.017)	0.018	1.001 (0.991-1.011)	0.871
Mean resected ulcer area (mm2)	1.001 (1.000-1.001)	0.032	1.001 (1.000-1.001)	0.013

EM: Extensive metabolizer; IM: Intermediate metabolizer; PM: Poor metabolizer.

Table 4 Multivariate analysis of factors preventing healing of ulcers after endoscopic submucosal dissection

	Reduction rate over 90% at 4 wk		Reduction rate 100% at 8 wk
Variable	Not achieved (n = 45)	P value	Not achieved (n = 16)	P value
Gender (male vs female)	1.833 (0.715-4.698)	0.207	4.438 (1.253-15.724)	0.021
Helicobacter pylori	1.012 (0.463-2.213)	0.976	3.340 (0.866-12.885)	0.080
Atrophy (Kyoto A0+A1 vs Kyoto A2)	5.678 (1.190-27.085)	0.029	2.764 (0.309-24.711)	0.363
Tumor located in upper and middle third (vs lower third)	0.698 (0.283-1.724)	0.436	1.848 (0.493-6.933)	0.362
Mean procedure time (min)	1.007 (0.997-1.017)	0.194	0.998 (0.982-1.015)	0.850
Mean resected ulcer area (mm2)	1.000 (1.000-1.001)	0.443	1.001 (1.000-1.002)	0.023