Endoscopic submucosal dissection for undifferentiated-type early gastric cancer: Do we have enough data to support this?

Table 1 Curability for endoscopic resection of early gastric cancer

Curability criteria
Curative resection	En bloc resection, no lateral and vertical margin positivity, no lymphovascular invasion
	Intramucosal cancer, differentiated histology, size ≤ 20 mm, No ulcerative finding
Curative resection for expanded indications	En bloc resection, no lateral and vertical margin positivity, no lymphovascular invasion
	Intramucosal cancer, differentiated histology, size > 20 mm, no ulcerative finding
	Intramucosal cancer, differentiated histology, size ≤ 30 mm, presence of ulcerative finding
	SM 1 depth of invasion, differentiated histology, size ≤ 30 mm, no ulcerative finding
	Intramucosal cancer, undifferentiated histology, size ≤ 20 mm, no ulcerative finding
Non-curative resection	Any resection that does not satisfy one of the above criteria

SM: Submucosa.

Table 2 Proposed criteria for endoscopic resection of undifferentiated type early gastric cancer

Study	Year	Country	No. of patients with UD-EGC	No. of patients with PD/SRC/MC	LNM in UD-EGC, n (%)	LNM in proposed criteria	Risk factors related to LNM in UD-EGC	Proposed criteria of ER for UD-EGC
								Size, mm	Depth of invasion	Ulcer	LVI
Tong et al[53]	2011	China	193	81/102/7/31	46 (23.8)	0/72	Size, depth of invasion, LVI, Histologic type	NS or ≤ 20	M or SM	NS	No
Kim et al[54]	2011	South Korea	707	288/419/0	65 (9.2)	0/101	Size, depth of invasion, LVI, Age2	153	M	NS	No
Li et al[55]	2010	China	108	85/16/7	16 (14.8)	0/25	Size, depth of invasion, LVI	20	M	NS	No
Park et al[56]	2009	South Korea	215	Only SRC	17 (7.9)	0/57	Depth of invasion, LVI	25	SM2	NS	No
Kunisaki et al[57]	2009	Japan	573	182/378/13	74 (12.9)	0/85	Size, depth of invasion, LVI	20	M	NS	No
Hirasawa et al[26]	2009	Japan	3843	NA	504 (13.1)	0/310	Size, depth of invasion, LVI	20	M	No	No
Hanaoka et al[58]	2009	Japan	143	NA	35 (24.5)	0/41	Size, depth of invasion, LVI, Histologic type	30	≤ 500 μm4	NS	No5
Ye et al[59]	2008	South Korea	591	266/316/9	79 (13.4)	0/119	Size, depth of invasion, LVI	25	M	NS	No
Park et al[60]	2008	South Korea	234	Only PD	25 (21.6)	0/56	Size, depth of invasion, LVI	15	M or ≤ 500 μm	NS	No
Li et al[61]	2008	China	85	Only PD	12 (14.1)	0/25	Size, depth of invasion, LVI	20	M	NS	No
Li et al[62]	2008	South Korea	646	307/330/9	61 (9.4)	1/201	Size, depth of invasion, LVI	20	M	NS	No
Ha et al[63]	2008	South Korea	641	248/388/5	100 (15.6)	0/77	Size, depth of invasion, LVI, histologic type	20	M	NS	No
Hyung et al[64]	2004	South Korea	289	NA	43 (14.9)	NA	Size, depth of invasion, LVI, histologic type	15	M	NS	No
Abe et al[65]	2004	Japan	175	68/104/3	32 (18.3)	0/6	Size, LVI	10	M	NS	No
Gotoda et al[23]	2000	Japan	2341	NA	243 (10.4)	0/141	Size, depth of invasion, LVI, histologic type, ulcer, macroscopic type	20	M	No	No

¹Three patients had EGCs with histology of undifferentiated adenocarcinoma;

²Young age less than 45 years was related to the lymph node metastasis of only poorly-differentiated carcinoma;

³Size criteria were ≤ 25 mm in poorly-differentiated adenocarcinomas and ≤ 15 mm in signet-ring cell carcinomas, respectively;

⁴The depth of invasion in proposed criteria was ≤ 500 μm or no more from the lower margin of the muscularis mucosae;

⁵Hanaoka et al also suggested the proportion of undifferentiated components < 50% as one of criteria. UD-EGC: Undifferentiated type early gastric cancer; PD: Poorly-differentiated adenocarcinoma; SRC: Signet-ring cell carcinoma; MC: Mucinous carcinoma; LNM: Lymph node metastasis; ER: Endoscopic resection; LVI: Lymphovascular invasion; M: Mucosa; SM: Submucosa; NS: Not significant; NA: Not available.

Table 3 Clinical characteristics of representative studies on endoscopic resection for undifferentiated type early gastric cancer

Study	Year	Country	No. of patients with UD-EGC	No. of patients with PD/SRC	Age (yr)1	Sex (male)	SM invasion	Ulcer	Size (mm)1	Size > 20 mm
Kim et al[80]	2013	South Korea	74	55/19	61.8 ± 12.0	40 (54.1)	16 (21.6)	11 (14.9)	19.9 ± 12.5	36 (48.6)
Abe et al[87]	2013	Japan	97	18/77/22	62.0 (35.0-88.0)3	55 (56.7)	19 (19.6)	9 (9.3)	12.03	14 (14.4)
Park et al[88]	2012	South Korea	77	47/154	60.9 (33.0-82.0)	49 (63.6)	12 (15.6)	4 (5.2)	23.3 ± 14.0	35 (45.5)
Okada et al[89]	2012	Japan	1035	12/91	59.0 (34.0-91.0)	48 (46.6)	10 (9.7)	1 (1.0)	8.0 (1.0-33.0)3	NA
Kamada et al[76]	2012	Japan	46	NA	65.5 (29.0-90.0)	24 (52.2)	7 (15.2)	1 (2.2)	NA	8 (17.4)
Yamamoto et al[90]	2010	Japan	58	48/10	64.0 (33.0-81.0)	31 (53.4)	7 (12.1)	2 (3.4)	11.0 (2.0-28.0)	5 (8.6)
Kang et al[73]	2010	South Korea	60	30/30	56.7 ± 10.4	31 (51.7)	17 (28.3)	17 (28.3)	26.3 ± 12.9	31 (51.7)
Kim et al[74]	2009	South Korea	58	17/41	55.0 (26.0-81.0)	26 (44.8)	NA	0 (0)	13.3 ± 6.5	4 (6.9)

Data are expressed as absolute numbers (percentage) or mean ± SD.

¹Data are expressed as mean with standard deviation or range;

²Two patients had EGCs with histology of moderately to poorly differentiated adenocarcinoma;

³Data are expressed as median with or without range;

⁴Fifteen patients had EGCs with mixed type histology;

⁵A total of 103 EGCs in 101 patients were enrolled. UD-EGC: Undifferentiated typr early gastric cancer; PD: Poorly-differentiated adenocarcinoma; SRC: Signet-ring cell carcinoma; SM: Submucosa; NA: Not available.

Table 4 Short-term outcomes of endoscopic resection for undifferentiated early gastric cancer n (%)

Study	LMP	VMP	LVI	En bloc resection	Complete resection	Curative resection	OP after ER1	Residual tumor2	LNM2	Bleeding	Perforation
Kim et al[80]	NA	NA	10 (12.5)	67 (90.5)	54 (73.0)	23 (31.1)	19/51 (37.3)	NA	NA	1 (1.4)	3 (4.1)
Abe et al[87]	5 (5.2)	4 (4.1)	3 (3.1)	96 (99.0)	88 (90.7)	62 (63.9)	21/35 (60.0)	1/21 (4.8)	2/21 (9.5)	4 (4.1)	4 (4.1)
Park et al[88]	12 (15.6)3		5 (6.5)	64 (83.1)	NA	35 (45.5)	11/42 (26.2)	NA	0/11 (0.0)	NA	NA
Okada et al[89]	5 (4.9)3		2 (2.0)	102 (99.0)	NA	85 (82.5)	10/18 (55.6)	2/10 (20.0)	0/10 (0.0)	9 (8.7)	1 (1.0)
Kamada et al[76]	5 (10.9)	4 (8.7)	4 (8.7)	42 (91.3)	NA	NA	5	1/5 (20.0)	NA	2/46 (4.3	2 (4.3)
Yamamoto et al[90]	1 (1.7)	0 (0.0)	2 (3.4)	57 (98.3)	52 (89.7)	46 (79.3)	8/12 (66.7)	2/8 (25.0)	0/8 (0.0)	5 (8.6)	2 (3.4)
Kang et al[73]	14 (23.3)	11 (18.3)	15 (25.0)	60 (100)	33 (55.0)	NA	15/27 (55.6)	6/15 (40.0)	2/15 (13.3)	1 (1.7)	1 (1.7
Kim et al[74]	10 (52.6)	9 (47.4)	NA	49 (84.5)	39 (67.2)	NA	9/19 (47.4)	4/9 (44.4)	1/9 (11.1)	8 (13.8)	1 (1.7)

¹Proportions are ratio of additional operation to incomplete or non-curative endoscopic resection;

²Data are the incidence of residual tumor or lymph node metastasis in specimens obtained by additional operation;

³Data are cases with lateral and/or vertical margin positivity. LMP: Lateral margin positivity; VMP: Vertical margin positivity; LVI: Lymphovascular invasion; OP: Operation; ER: Endoscopic resection; LNM: Lymph node metastasis; NA: Not available.