Chemoprevention of gastric cancer development after Helicobacter pylori eradication therapy in an East Asian population: Meta-analysis

Table 1 Characteristics of the studies

Ref.	Country	Primary or metachronous cancer	Design	Disease at basement	Follow-up periods (yr)	Patients number	Age (yr)	Sex (male/ female)	Regimen of eradication therapy	Eradication rate (%)
Fukase et al[31], 2006	Japan	Metachronous	RCT	Gastric cancer	3	544	68 (62-73)	386/119	LPZ(30)/AMPC(750)/CAM(200), BID, 7D	75.0
Choi et al[32], 2018	South Korea	Metachronous	RCT	Gastric cancer	5.9	396	59	298/104	RPZ(10)/AMPC(1000)/CAM(500), BID 7D	80.4
Choi et al[33,69]	South Korea	Metachronous	RCT	Gastric cancer	6	898	60.4	594/283	OPZ(20)/AMPC(1000)/CAM(500), BID 7D	82.6
Uemura et al[70], 1997	Japan	Metachronous	Cohort	Gastric cancer	3	132	69 (44-85)	97/35	1st: OPZ(20)/CAM(400) 14D, 2nd: OPZ(20)/AMPC(1500)/MNZ(500), BID 14D	46.2
Nakagawa et al[71], 2006	Japan	Metachronous	Cohort	Gastric cancer	2	2825	NA	NA	NA	NA
Shiotani et al[72], 2008	Japan	Metachronous	Cohort	Gastric cancer	2.75	100	69	67/13	PPI/AMPC(750)/CAM(200), BID 7D	81.3
Han et al[73], 2011	South Korea	Metachronous	Cohort	Gastric cancer	2.7	176	61.8 (43-83)	112/64	NA	NA
Kim et al[74], 2011	South Korea	Metachronous	Cohort	Gastric cancer	5.1	55	60.7 (43-81)	36/19	NA	50.9
Maehata et al[75], 2012	Japan	Metachronous	Cohort	Gastric cancer	3	268	69 (49-90)	194/74	PPI/AMPC(750)/CAM(200), BID 7D	78.2
Seo et al[76], 2013	South Korea	Metachronous	Cohort	Gastric cancer	2.27	74	62	55/19	PPI/AMPC(1000)/CAM(500), BID 7-14D	82.4
Kato et al[77], 2013	Japan	Metachronous	Cohort	Gastric cancer	2.23	368	70.5	953/305	NA	NA
Bae et al[78], 2014	South Korea	Metachronous	Cohort	Gastric cancer	5	1007	63 (28-88)	785/222	PPI/AMPC(750)/CAM(200), BID 7-14D	NA
Kim et al[79], 2014	South Korea	Metachronous	Cohort	Gastric cancer	4.3	374	64 (35-87)	278/96	PPI/AMPC(1000)/CAM(500), BID 7D	72.1
Kwon et al[80], 2014	South Korea	Metachronous	Cohort	Gastric cancer	3.4	283	59	190/93	PPI/AMPC(750)/CAM(200), BID 7D	68.9
Jung et al[27], 2015	South Korea	Metachronous	Cohort	Gastric cancer	3.36	1041	62.7	773/268	LPZ(30)/AMPC(1000)/CAM(500), BID 7-14D	NA
Lim et al[28], 2015	South Korea	Metachronous	Cohort	Gastric cancer	3.1	933	63.0 ± 9.51	512/250	NA	NA
Kim et al[81], 2016	Korea	Metachronous	Cohort	Gastric cancer	2.5	257	67	189/68	PPI/AMPC(1000)/CAM(500), BID 7D	86.3
Ami et al[82], 2017	Japan	Metachronous	Cohort	Gastric cancer	4.47	438	69.4 ± 8.7	421/118	LPZ(30) or RPZ(10)/AMPC(750)/CAM(200), BID 7-14D	NA
Kwon et al[29], 2017	South Korea	Metachronous	Cohort	Gastric cancer	3.725	590	63	398/192	RPZ(20)/AMPC(1000)/CAM(500), BID 7D	81.8
Chung et al[30], 2017	South Korea	Metachronous	Cohort	Gastric cancer	5.125	185	67.4 (45-87)	141/44	PPI/AMPC/CAM, BID 7D	NA
Han et al[83], 2018	South Korea	Metachronous	Cohort	Gastric cancer	5	565	61	440/125	NA	NA
Cho et al[17], 2013	South Korea	Metachronous	RCT	Gastric cancer	3	169	56	117/52	RPZ(10)/AMPC(1000)/CAM(500), BID 7D	77
Wong et al[18], 2004	China	Primary	RCT	Gastritis alone	7.5	1630	42.2 (35-65)	880/750	OPZ(20)/AMPC(750)/MNZ(400), BID 14D	82.5
Ma et al[23], You et al[84] and Li et al[85]	China	Primary	RCT	Non-gastric cancer	14.3	2258	47.1	1808/1603	OPZ(20)/AMPC(1000), BID 7D	66.2
Wong et al[19], 2012	China	Primary	RCT	With/without metaplasia	2	1024	53.0 (35-64)	473/551	PPI/AMCP(1000)/CAM(500), BID 7D	71.3
Zhou et al[24], 2014, Leung et al[86], 2004	China	Primary	RCT	Non-gastric cancer	10	554	53.35 ± 8.49	268/284	OPZ(20)/AMPC(1000)/CAM(500), BID 7D	88.9
Saito et al[22], 2000	Japan	Primary	Cohort	Gastric adenoma	2	64	79.2 (68-92)	35/29	OPZ(20)/AMCP(1000)/CAM(400), BID 7D	75
Uemura et al[52], 2001	Japan	Primary	Cohort	With/without PU	7.7	1526	52.4	869/657	NA	NA
Kato et al[87], 2006	Japan	Primary	Cohort	With/without PU	5.9-7.7	3021	54	1868/1153	LPZ(30)/AMPC(750)/CAM(200), BID 7-14D	NA
Takenaka et al[88], 2007	Japan	Primary	Cohort	With/without PU	3.17	1807	53.6 ± 12.4	1289/518	Dual therapy or PPI/AMPC(750)/CAM(200 or 400), BID 7D	82.9
Ogura et al[89], 2008	Japan	Primary	Cohort	With/without PU	3.2	708	62	400/308	LPZ(30)/AMPC(750/1000)/CAM(400) or MNZ(250), BID 7D	74
Kim et al[90], 2008	South Korea	Primary	Cohort	With/without PU	9.4	1790	46.7	1483/297	Tripotassi-um dicitrate bismuthate (300, QID)/MNZ(500, TID)/TC(500, QID), 5D or OPZ(20)/CAM(500)/AMPC(1000)BID 7D	NA
Mabe et al[53], 2009	Japan	Primary	Cohort	With/without PU	5.6	4133	52.9 (13-91)	2964/1169	LPZ(30) or OPZ(20)/AMPC(750)/CAM(200 or 400), BID 7D	64.8
Yanaoka et al[25], 2009	Japan	Primary	Cohort	Non-gastric cancer	9.3	4129	49.8	5560/107	OPZ(20)/AMPC(750 or 500), BID 14D, OPZ(20)/AMPC(750)/CAM(200), BID 7D	87.2
Watanabe et al[26], 2012	Japan	Primary	Cohort	Non-gastric cancer	5.4	823	NA	NA	OPZ(20, BID)/AMPC(750 or 500, BID) 14D or OPZ(20)/AMPC(750)/CAM(200), BID 7D	82.0
Lee et al[20], 2013	China	Primary	Cohort	With/without PU or dysplaisa	5	8242	49.2 ± 12.8	1888/2233	PPI/AMCP(1000)/CAM(500), BID 7D	78.7
Shichijo et al[21], 2015	Japan	Primary	Cohort	Intestinal metaplasia	6.7 ± 4.7	659	60.1 ± 11.0	374/355	LPZ(30)/AMPC(750 or 1000)/CAM(200) or MNZ(250), BID 7D	NA
Take et al[91-94]	Japan	Primary	Cohort	Peptic ulcer	9.9	1222	49.9 ± 8.3	1087/135	Dual or Triple therapy	NA

Non-gastric cancer: patients had no history of gastric cancer, but were unknown to have peptic ulcer and dysplasia. AMPC: Amoxicillin; BID: Twice-daily dosing; CAM: Clarithromycin; D: Day; LPZ: Lansoprazole; MNZ: Metronidazole; NA: Not available; OPZ: Omeprazole; PPI: Proton pump inhibitor; PU: Peptic ulcer; QID: Four-times daily dosing; RCT: Randomized control trial; RPZ: Rabeprazole; TID: Three-times daily dosing; TC: Tetracycline.

Table 2 Gastric cancer development and histological characteristics

Ref.	Design	Follow-up periods (yr)	Eradicated group		Non-eradicated control group		Eradicated group		Non-eradicated control group
			Cancer/ Total	Cancer incidence, /100000 PY	Cancer/ Total	Cancer incidence, /100000 PY	Intestinal type	Diffuse type	Intestinal type	Diffuse type
Patients after resection for gastric cancer
Fukase et al[31], 2006	RCT	3	9/272	1102.9	24/272	2941.2	9	0	23	1
Choi et al[32], 2018	RCT	5.9	14/194	1223.1	27/202	2265.5	14	0	25	1
Choi et al[33,69]	RCT	6	18/442	678.7	36/456	1315.8	13	5	26	8
Uemura et al[70], 1997	Cohort	3	0/65	0	6/67	2985.1	0	0	6	0
Nakagawa et al[71], 2006	Cohort	2	8/356	864.3	129/2469	2902.7	NA	NA	NA	NA
Shiotani et al[72], 2008	Cohort	2.75	9/80	4090.9	1/11	3305.8	9	0	1	0
Han et al[73], 2011	Cohort	2.7	4/94	1576	2/22	3367	NA	NA	NA	NA
Kim et al[74], 2011	Cohort	5.1	0/28	0	5/27	3631.1	0	0	NA	NA
Maehata et al[75], 2012	Cohort	3	15/177	2824.9	13/91	4761.9	14	1	13	0
Seo et al[76], 2013	Cohort	2.27	6/61	4333.1	3/13	10166	NA	NA	NA	NA
Kato et al[77], 2013	Cohort	2.23	24/263	4092.1	6/105	2562.5	NA	NA	NA	NA
Bae et al[78], 2014	Cohort	5	34/485	1402.1	24/182	2637.4	NA	NA	NA	NA
Kim et al[79], 2014	Cohort	4.3	2/49	770.1	16/107	3250.7	NA	NA	NA	NA
Kwon et al[80], 2014	Cohort	3.4	18/214	2473.9	13/69	5541.3	8	2	6	4
Jung et al[27], 2015	Cohort	3.36	21/506	1235.2	10/169	1761.1	NA	NA	NA	NA
Lim et al[28], 2015	Cohort	3.1	7/236	956.8	6/276	701.3	NA	NA	NA	NA
Kim et al[81], 2016	Cohort	2.5	3/120	902.5	1/42	872.1	NA	NA	NA	NA
Ami et al[82], 2017	Cohort	4.47	25/212	2638.1	1/14	1598	NA	NA	NA	NA
Kwon et al[29], 2017	Cohort	3.725	33/368	2255.9	8/27	7454	10	6	3	2
Chung et al[30], 2017	Cohort	5.125	17/167	1986.3	7/18	7588.1	NA	NA	NA	NA
Han et al[83], 2018	Cohort	5	12/212	1132.1	18/196	1836.7	11	1	18	0
Cho et al[17], 2013	RCT	3	3/87	1149.4	1/82	406.5	1	2	1	0
Patients with gastritis
Wong et al[18], 2004	RCT	7.5	7/817	114.2	11/813	180.4	NA	NA	NA	NA
Ma et al[23], You et al[84] and Li et al[85]	RCT	14.3	34/1130	210.4	52/1128	322.4	NA	NA	NA	NA
Wong et al[19], 2012	RCT	2	6/510	588.2	3/514	291.8	6	0	2	1
Zhou et al[24], 2014, Leung et al[86], 2004	RCT	10	2/276	72.5	7/276	253.6	NA	NA	NA	NA
Saito et al[22], 2000	Cohort	2	0/32	0	4/32	6250	0	0	4	0
Uemura et al[52], 2001	Cohort	7.7	0/253	0	36/993	424.4	0	0	23	13
Kato et al[87], 2006	Cohort	5.9-7.7	23/1788	218	44/1233	467.2	19	4	32	12
Takenaka et al[88], 2007	Cohort	3.17	6/1519	121.5	5/288	598.7	4	2	4	1
Ogura et al[89], 2008	Cohort	3.2	6//404	464.1	13/304	1379.5	3	3	11	2
Kim et al[90], 2008	Cohort	9.4	1/476	22.3	4/977	43.6	0	1	3	1
Mabe et al[53], 2009	Cohort	5.6	47/3781	222	9/352	491.7	35	10	5	4
Yanaoka et al[25], 2009	Cohort	9.3	5/473	113.7	55/3656	161.8	4	1	36	19
Watanabe et al[26], 2012	Cohort	5.4	0/327	0	7/496	261.4	0	0	1	6
Lee et al[20], 2013	Cohort	5	15/4121	72.8	16/4121	77.7	NA	NA	NA	NA
Shichijo et al[21], 2015	Cohort	6.7 ± 4.7	4/260	229.6	13/203	955.8	NA	NA	NA	NA
Take et al[91-94]	Cohort	9.9	24/1133	214	6/89	681	14	10	5	1

NA: Not available; RCT: Randomized control trial; PY: Person-year.