Reevaluation of the expanded indications in undifferentiated early gastric cancer for endoscopic submucosal dissection

Table 1 Clinical and endoscopic features of the patients according to the presence of lymph node metastasis

Variables	LNM- (n = 73)	LNM+ (n = 14)	P value
Age at diagnosis, yr (median, IQR)	47.0 (41.0-52.0)	43.5 (37.0-51.0)	0.276
Lesion size, cm (median, IQR)	1.5 (1.2-1.7)	1.5 (1.3-1.8)	0.485
Male, n (%)	25 (34.2)	4 (28.6)	0.918
Longitudinal location, n (%)			0.269
Upper	4 (5.5)	0 (0.0)
Middle	22 (30.1)	2 (14.3)
Lower	47 (64.4)	12 (85.7)
Cross-sectional circumference, n (%)			0.421
Anterior wall	16 (21.9)	6 (42.9)
Great curvature	16 (21.9)	2 (14.3)
Posterior wall	23 (31.5)	3 (21.4)
Lesser curvature	18 (24.7)	3 (21.4)
Gross type, n (%)			0.440
Depressed	42 (57.5)	10 (71.4)
Flat	25 (34.2)	4 (28.6)
Elevated	6 (8.2)	0 (0.0)
Number of retrieved LNs (median, IQR)	30.0 (25.0-37.0)	30.5 (25.5-37.0)	0.862
Endoscopic appearances, n (%)
Exudate	6 (8.2)	1 (7.1)	> 0.999
Endoscopic ulcer	30 (41.1)	7 (50.0)	0.747
Converging fold	11 (15.1)	1 (7.1)	0.715
Tumor island	14 (19.2)	3 (21.4)	> 0.999

LNM: Lymph node metastasis; IQR: Interquartile range.

Table 2 Detailed clinical information of the 14 patients with lymph node metastasis

Case No.	Age (yr)	Sex	Type	Size (cm)	Location	Histology	Depth of invasion	Total number of dissected LNs	Number of metastatic LNs
1	59	Female	IIb	1.5	Middle	PD with SRC	LP	31	3
2	41	Female	IIc	1.3	Lower	PD with SRC	LP	18	3
3	57	Male	IIc	1.3	Lower	SRC	LP	21	1
4	47	Female	IIc	1.8	Middle	PD with SRC	LP	21	3
5	46	Female	IIb	2.0	Lower	PD with SRC	LP	25	6
6	37	Female	IIc	1.5	Lower	PD with SRC	MM	31	3
7	48	Female	IIc	1.5	Lower	PD with SRC	LP	37	1
8	35	Male	IIc	0.9	Lower	PD with SRC	LP	38	1
9	35	Female	IIc	1.5	Lower	PD with SRC	LP	27	1
10	52	Female	IIb	0.7	Lower	PD with SRC	LP	29	1
11	60	Male	III	0.6	Lower	PD with SRC	MM	30	1
12	39	Female	IIc	2.0	Lower	PD with SRC	LP	37	1
13	37	Female	IIb	1.8	Lower	PD with SRC	LP	42	1
14	33	Male	IIc	2.0	Lower	PD with SRC	LP	48	3

LNM: Lymph node metastasis; PD: Poorly differentiated carcinoma; SRC: Signet ring cell; SRCC: Signet ring cell carcinoma; LP: Lamina propria; MM: Muscularis mucosa.

Table 3 Histologic features of the tumors and background stomach according to the presence of lymph node metastasis

Variables	LNM- (n = 73)	LNM+ (n = 14)	P value
Depth of invasion			0.503
LP	53 (72.6)	12 (85.7)
MM	20 (27.4)	2 (14.3)
Size, cm	1.5 (1.2-1.7)	1.5 (1.3-1.8)	0.642
% of SRCs			0.157
< 10%	17 (23.3)	0 (0)
≥ 10% and < 50%	35 (47.9)	10 (71.4)
≥ 50% and < 90%	14 (19.2)	3 (21.4)
≥ 90%	7 (9.6)	1 (7.1)
Diagnostic category according to the proportion of SRCs			0.059
Non-mixed (SRCC and PD)	24 (32.9)	1 (7.1)
Mixed (PD with SRC component)	49 (67.1)	13 (92.9)
Background stomach			0.278
Mild CG	8 (11.0)	0 (0)
Moderate CG or IM	24 (32.9)	3 (21.4)
CAG	22 (30.1)	4 (28.6)
CAG with visible H. pylori	19 (26.0)	7 (50.0)
H. pylori abundance, n/total n			0.263
0	23/71 (32.4)	2/14 (14.3)
1+	14/71 (19.7)	3/14 (21.4)
2+	14/71 (19.7)	6/14 (42.9)
3+	20/71 (28.2)	3/14 (21.4)
TP53 expression, n/total			> 0.999
Loss (0)	3/70 (4.3)	0/14 (0)
Wildtype pattern (1+/2+)	63/70 (90.0)	13/14 (92.9)
Overexpression (3+)	4/70 (5.7)	1/14 (7.1)

LNM: Lymph node metastasis; IQR: Interquartile range; LP: Lamina propria; MM: Muscularis mucosa; SRC: Signet ring cell; SRCC: Signet ring cell carcinoma; PD: Poorly differentiated carcinoma encompassing adenocarcinoma and non-signet ring cell type of poorly cohesive carcinoma; CG: Chronic gastritis; IM: Intestinal metaplasia; CAG: Chronic active gastritis; H. pylori: Helicobacter pylori.

Table 4 Histologic features of the tumor microenvironment according to the presence of lymph node metastasis

Variables	LNM- (n = 73)	LNM+ (n = 14)	P value
TIL abundance			0.438
< 10%	25 (34.2)	7 (50.0)
10%-20%	33 (45.2)	6 (42.9)
≥ 20%	15 (20.5)	1 (7.1)
Degree of central fibrosis			0.522
Mild	6 (8.5)	2 (14.3)
Moderate	35 (49.3)	8 (57.1)
Marked	30 (42.3)	4 (28.6)
Degree of peripheral fibrosis
Mild	11 (15.5)	2 (14.3)	0.495
Moderate	53 (74.6)	9 (64.3)
Marked	7 (9.9)	3 (21.4)
Distribution of fibrosis
Central = peripheral	32 (45.1)	7 (50.0)	0.204
Central > peripheral	33 (46.5)	4 (28.6)
Central < peripheral	6 (8.5)	3 (21.4)
Fibrosis score	0.55 (0.38-0.83)	0.53 (0.31-0.77)	0.273
Blurring of MM, n/total			0.028
Non-diffuse (absent/focal)	43/71 (60.6)	13/14 (92.9)
Diffuse	28/71 (39.4)	1/14 (7.1)

LNM: Lymph node metastasis; TIL: Tumor-infiltrating lymphocytes; IQR: Interquartile range; MM: Muscularis mucosa.

Table 5 Logistic regression analysis for the risk of Lymph node metastasis

Variable	OR	95%CI	P value
Depth of invasion
LP	1
MM	0.44	0.09-2.15	0.312
Diagnostic category according to % of SRCs
Non-mixed (SRC and PD)	1
Mixed (PD with SRC component)	6.37	0.79-51.6	0.083
Background stomach
CG	1
CAG	2.86	0.74-11.1	0.129
Presence of H. pylori
Absent (0)	1
Present (≥ 1+)	2.88	0.59–13.9	0.190
TIL abundance			0.409
< 10%	1
10%-20%	0.65	0.19-2.17	0.484
≥ 20%	0.24	0.03-2.13	0.199
Fibrosis score	0.34	0.05-2.49	0.285
Blurring of MM
Non-diffuse (absent/focal)	1
Diffuse	0.12	0.02-0.95	0.045

LNM: Lymph node metastasis; OR: Odds ratio; LP: Lamina propria; MM: Muscularis mucosa; SRC: Signet ring cell; SRCC: Signet ring cell carcinoma; PD: Poorly differentiated carcinoma encompassing adenocarcinoma and non-signet ring cell type of poorly cohesive carcinoma; CG: Chronic gastritis; CAG: Chronic active gastritis; TIL: Tumor-infiltrating lymphocytes; H. pylori: Helicobacter pylori.