Endoscopic submucosal dissection of gastric tumors: A systematic review and meta-analysis

Table 1 Search query

Medline	(“endoscopic submucosal dissection”[tiab] OR “endoscopic submucosal resection”[tiab] OR “submucosal dissection”[tiab] OR “ESD”[tiab]) AND (“stomach”[Mesh] OR gastr*[tiab] OR “foregut”[tiab])
Ovid	(endoscopic submucosal dissection OR endoscopic submucosal resection OR submucosal dissection OR endoscopic dissection OR ESD) AND (stomach OR gastr* OR foregut)
CINAHL	(endoscopic submucosal dissection OR endoscopic submucosal resection OR submucosal dissection OR endoscopic dissection OR ESD) AND (stomach OR gastr* OR foregut)
Cochrane	(endoscopic submucosal dissection OR endoscopic submucosal resection OR submucosal dissection OR endoscopic dissection OR ESD) AND (stomach OR gastr* OR foregut)

Table 2 Characteristics of studies included in the meta-analysis of gastric endoscopic submucosal dissection

Ref.	Data period, yr	Country	Patients, n	Age, mean (range), yr	Female, %	Tumor, n	Tumor size, mean (range), mm	Procedure length, mean (range), min
Sattianayagam et al[21]	2008-2012	Australia	10	75 (43-86)	NA	12	35 (15-65)	NA
Cardoso et al[22]	2005-2007	Brazil	12	71.2 (27-91)	50	15	16.8 (8-20)	140
Chaves et al[23]	2007-2009	Brazil	15	67.1 (32-81)	20	16	16.2 (6-35)	85 (20-150)
Santos et al[24]	2010-2011	Brazil	9	65 (58-73)	0	9	28.6 (20-45)	103 (60-240)
Xu et al[25]	2006-2009	China	120	51.5 (26-75)	40	120	18.8 (8-30)	64.6 (30-120)
He et al[26]	2008-2012	China	144	55.8 (18-78)	72	145	15.14	63.4 (20-180)
Zhang et al[27]	2008-2011	China	18	65.3 (30-71)	61	18	26 (10-35)	90 (50-120)
Probst et al[28]	2003-2010	Germany	83	68.6 (41-87)	40	91	NA	142 (60-420)
Schumacher et al[29]	2008-2010	Germany	30	61 (35-93)	43	30	25 (20-70)	74 (15-402)
Catalano et al[30]	2005-2007	Italy	12	68 (38-83)	100	12	NA	111 (62-150)
Coda et al[31]	2007-2009	Italy	7	72 (61-83)	43	7	26 (15-50)	123 (50-360)
Hirasaki et al[32]	2000-2004	Japan	144	70 (45-91)	NA	144	13	73
Yokoi et al[33]	1999-2003	Japan	46	67 (45-89)	9	46	NA	NA
Ono et al[34]	2000-2007	Japan	408	67	NA	444	NA	NA
Hirasawa et al[35]	2000-2009	Japan	58	69.3	21	58	20.3 (3-50)	82 (22-275)
Yoshinaga et al[36]	2001-2006	Japan	24	61.7 (37-85)	8	25	16.5 (3-60)	NA
Takenaka et al[37]	2001-2005	Japan	275	NA	NA	306	NA	NA
Miyahara et al[38]	2001-2010	Japan	1082	71.7 (36-92)	29	1190	NA	99.8 (10-675)
Ohnita et al[39]	2001-2010	Japan	1209	72 (33-95)	27	1322	NA	NA
Oka et al[40]	2002-2004	Japan	185	NA	NA	195	19.4 (5-100)	84.4
Shimura et al[41]	2002-2005	Japan	55	71.4 (46-91)	22	59	15.5	58 (7-640)
Hirasaki et al[42]	2002-2006	Japan	112	70 (45-89)	NA	112	19	69
Ohta et al[43]	2002-2010	Japan	1500	NA	NA	1795	NA	NA
Kamada et al[44]	2002-2010	Japan	46	65.5 (29-90)	48	46	NA	NA
Toyonaga et al[45]	2002-2007	Japan	821	71 (31-93)	34	1136	13 (1-105)	NA
Kosaka et al[46]	2002-2007	Japan	438	69.4	26	438	14.6	47 (8-345)
Yamaguchi et al[47]	2003-2005	Japan	54	NA	NA	54	19.1 (30-70)	129 (29-440)
1Akasaka et al[48]	2003-2008	Japan	1188	71	27	1188	20 (2-105)	90 (6-750)
Ono et al[49]	2003-2011	Japan	80	69.6	20	80	NA	83.7
1Toyokawa et al[50]	2003-2010	Japan	967	NA	32	1123	18	98
Tanabe et al[51]	2003-2007	Japan	421	69 (41-91)	23	421	NA	67 (7-360)
Shimamura et al[52]	2004-2012	Japan	521	NA	NA	616	NA	NA
Takahashi et al[53]	2004-2013	Japan	459	71.4	25	459	17.2	NA
Yamamoto et al[54]	2005-2011	Japan	1430	69.6	28	1520	15.3	101
Higashimaya et al[55]	2005-2011	Japan	891	69.1	27	1027	18.3	NA
Hoteya et al[56]	2005-2010	Japan	1224	68	24	1463	21	89
Matsumura et al[57]	2005-2014	Japan	413	72.1	30	425	18.4	NA
Sohara et al[58]	2006-2011	Japan	681	70.9 (45-91)	40	850	20.8 (2-150)	42 (4-360)
1Nishimura et al[59]	2006-2012	Japan	669	71	27	750	NA	NA
Tsuji et al[60]	2007-2009	Japan	328	68	29	398	43	69
Akahoshi et al[61]	2007-2009	Japan	35	72 (52-85)	34	35	15.6	104 (33-264)
Mukai et al[62]	2007-2010	Japan	142	72.4	32	161	NA	81
Tanaka et al[63]	2008-2011	Japan	32	71 (56-84)	63	33	17 (4-67)	111 (23-399)
Okamoto et al[64]	2009-2010	Japan	45	69 (49-83)	29	45	14 (10-35)	80
Watari et al[65]	2010-2012	Japan	94	70.9 (48-87)	24	98	NA	NA
Sumiyama et al[66]	2010-2012	Japan	100	NA	18	105	18 (3-53)	34 (4-151)
Kusano et al[67]	2011-2012	Japan	10	69.2	20	10	16.3	130.5
Kawamura et al[68]	NA	Japan	4	NA	25	4	24 (14-36)	50.5 (28-72)
Lee et al[69]	2003-2008	South Korea	461	62	30	487	NA	NA
Kim et al[70]	2003-2006	South Korea	337	NA	23	337	16	49
1Shin et al[71]	2003-2010	South Korea	1105	65 (27-87)	32	1105	NA	NA
Jang et al[72]	2004-2007	South Korea	402	60 (34-84)	37	402	NA	NA
Kim et al[73]	2004-2007	South Korea	142	62	34	142	NA	NA
Kang et al[74]	2005-2008	South Korea	456	62.4	23	456	20.6	NA
Goh et al[75]	2005-2009	South Korea	210	NA	NA	210	NA	NA
Ahn et al[76]	2005-2008	South Korea	889	62.8	23	916	21.5	37.5
Yoo et al[77]	2005-2010	South Korea	729	64 (55-70)	26	823	18 (12-25)	52 (33-84)
Lim et al[78]	2005-2011	South Korea	24	63 (56-75)	21	24	16 (4-52)	42 (16-103)
Park et al[79]	2005-2011	South Korea	916	62	73	931	NA	NA
Chung et al[80]	2005-2010	South Korea	76	61.1	42	76	NA	NA
Kim et al[81]	2007-2012	South Korea	126	55 (28-85)	44	126	12 (1-50)	NA
Min et al[82]	2007-2011	South Korea	1527	63 (27-87)	21	1577	16 (1-110)	NA
Kim et al[83]	2008-2010	South Korea	440	64	29	450	19	48
Yoon et al[84]	2008-2010	South Korea	1319	63	34	1443	15.7	61.8
Choi et al[85]	2008-2012	South Korea	616	NA	26	616	12.9	27.7
Chun et al[86]	2009-2012	South Korea	35	54.15	NA	35	18	32.3 (7-84)
1Chung et al[87]	2010-2012	South Korea	76	64	36	76	NA	44
Kim et al[88]	2012-2013	South Korea	446	NA	34	446	NA	NA
Bialek et al[89]	2007-2010	Poland	37	63 (24-86)	62	37	25 (10-60)	NA
Dinis-Ribeiro et al[90]	2005-2008	Portugal	19	74	NA	19	NA	90 (40-300)
Lee et al[91]	2004-2006	Taiwan	25	69 (36-82)	44	25	19	NA
1Chang et al[92]	2004-2007	Taiwan	70	66.5 (35-84)	36	70	18.5 (8-40)	92.4 (25-210)
Chu et al[93]	2009-2011	Taiwan	16	51.9 (35-65)	63	16	26.1 (20-42)	52 (30-120)
González et al[94]	NA	Uruguay	5	NA	NA	5	25.2	85 (30-180)

¹Multicenter studies. NA: Not available.

Table 3 Rates of adverse outcomes in patients undergoing gastric endoscopic submucosal dissection between 1998 and 2014

Adverse outcomes	Studies, n	Patients, n	Tumor, n	Rate (95%CI), %1
Immediate2
Perforation3	66	24855	27118	2.7 (2.1, 3.3)
Major bleeding4	19	3815	3943	2.9 (1.3, 6.6)
Delayed5
Perforation	13	2570	2852	0.39 (0.06, 2.4)
Major bleeding6	63	21612	23338	3.6 (3.1, 4.3)
Recurrence7
Among tumors with R0	17	-	2027	0.02 (0.001, 1.4)
Among tumors without R0	13	-	203	7.7 (3.6, 16)
Irrespective of R0 status8	33	11256	12398	0.75 (0.42, 1.3)

¹The rates are calculated as a percentage of the total number of tumors operated;

²Immediate refers to adverse outcomes occurring within 24 h of the procedure;

³The rate (95%CI) of immediate perforation was significantly lower with epithelial [2.7% (2.2%-3.6%)] compared with subepithelial tumors [8.9% (2.7%-15%)] (P = 0.02) and declined by 0.29% (0.05%-0.54%) per year over the duration of study (P = 0.02);

⁴The rate (95%CI) of major immediate bleeding declined by 2.3% (0.72%-3.9%) per year over the duration of study (P = 0.007);

⁵Delayed refers to adverse outcome occurring 24 h after the procedure;

⁶The rate (95%CI) of delayed bleeding increases by 1.3% (0.07%-2.5%) for every 10 year increase in age;

⁷Average follow-up was 26, 28 and 32 mo for assessment of recurrence among tumors with R0, without R0, and irrespective of R0 status respectively;

⁸The rate (95%CI) of recurrence decreases by 0.4% (0.1%-0.7%) for every 10 year increase in age (P = 0.01) and there was a trend towards higher rate in Western countries [5.1% (0.5%-11%)] compared with Asia [0.5% (0.3%-0.6%)] (P = 0.06). R0: Histologically-confirmed en bloc resection.

Table 4 Clinical outcomes among patients with gastric cancers who underwent endoscopic submucosal dissection

Outcomes	Studies, n	Tumor, n	Rate (95%CI)1
Efficacy measures
R0 resection	24	8520	87 (84-90)
Endoscopic en bloc resection	29	9652	94 (91-96)
Curative resection	10	5234	83 (80-86)
Safety measures
Immediate perforation2	31	12076	3.1 (2.4-3.9)
Immediate major bleeding2	6	303	2.9 (0.24-27)
Delayed perforation3	6	1486	0.15 (0.01-3.8)
Delayed bleeding3	29	11925	3.8 (3.0-4.7)
Recurrence (if R0)4	8	724	0.14 (0.004-4.6)
Recurrence (if not R0)4	7	152	8.5 (3.6-19)
Recurrence (irrespective of R0 status)4	18	7681	0.77 (0.39-1.5)

¹The rates are calculated as a percentage of the total number of tumors operated;

²Immediate refers to adverse outcomes occurring within 24 h of the procedure;

³Delayed refers to adverse outcome occurring 24 h after the procedure;

⁴Average follow-up was about 26, 24 and 37 mo for assessment of recurrence among tumors with R0, without R0, and irrespective of R0 status respectively. R0: Histologically-confirmed en bloc resection.