Endoscopic and surgical resection of T1a/T1b esophageal neoplasms: A systematic review

Table 1 Forty-two studies were included in the analysis of endoscopically resected patients

Author	EMR/ESD	Patients	Surgery	ADC/SCC	Positive resection margin	Other therapy	Local recurrence	Meta-chronous	N (+)	L (+)	Re-classification	Grade 3	In situ	Piecemeal resection
Buttar et al[10]	EMR	17	0	ADC	3	PDT					8		0
Chaves et al[11]	ESD	5		SCC	0		0						3	1
Chennat et al[12]	EMR	49	3	ADC			0				22		0
Ciocirlan et al[13]	EMR	51	2	SCC	14	CHEMO	8	2				0	4	36
Conio et al[14]	EMR	39	3	ADC			0	1		2	10	5	0
Ell et al[15]	EMR	64	5	ADC		PDT/APC	6	3			6	6	0
Espinel et al[16]	EMR	4	1	ADC							1	0	0
Fujishiro et al[17]	ESD	43		SCC	7		1	1		1			24	0
Gerke et al[18]	EMR	41		ADC	9	RFA	3	0					0
Goda et al[19]	EMR	58	1	SCC		CRT				1			0
Higuchi et al[20]	EMR	20	0	SCC	6	CRT/APC	0	0	0	6		1	0
Hull et al[52]	EMR	10		ADC							2		0
Iguchi et al[21]	EMR	8	1	SCC								0	4
Ishihara et al[22]	EMR/ESD	70		SCC		CRT	12			0			40
Ishii et al[23]	ESD	35	1	SCC	2	CHEMO	0			1			28	0
Larghi et al[24]	EMR	40	5	ADC		PDT/APC	0				6		19
Lewis et al[25]	EMR	100	1	ADC	1	PDT			1		8
Lin et al[26]	EMR	9	1	SCC	0		1		0	0	1	0	7
Lopes et al[27]	EMR	41	1	ADC		APC/CRT	4	2			14		2
Maish et al[28]	EMR	7	7	ADC	1				0		4		0
Manner et al[6]	EMR/ESD	21	1	ADC	27	APC	3	2		0		0	0
Naritaka et al[29]	EMR	13	1	SCC	2	RT	1						7	9
Nijhawan et al[30]	EMR	25	2	ADC		PDT	0				11
Noguchi et al[31]	EMR	33	5	SCC		CRT			0	5	14		15
Nomura et al[32]	EMR	51	1	SCC		CRT	4						30	41
Nonaka et al[33]	ESD	25	1	SCC	3	RT/CRT	0				10		0	0
Ohashi et al[90]	EMR	179		SCC						13			68
Ono et al[34]	ESD	84	9	SCC	7	CRT	1	2	2				0	0
Ota et al[35]	EMR	18	0	SCC	5	CRT	0		4	11		3	0
Pech et al[3]	EMR/ESD	39		SCC	20	PDT/CHEMO	5		2	7		1	10
Peters et al[53]	EMR/ESD	141		ADC	37					1	73	14
Pouw et al[37]	EMR/ESD	34	1	ADC		APC	3				14		10
Prasad et al[39]	EMR	25	25	ADC	17				5		16
Repici et al[51]	ESD	20	2	SCC	1		0	0	1			2	3	0
Scheil-Bertram et al[40]	EMR	16	16	ADC					16				1
Schröder et al[41]	EMR	16		ADC/SCC	9				3	13		1
Shimizu et al[42]	EMR	82		SCC		APC	2	12					16
Takeo et al[44]	EMR	29	5				0		0		15		10
Tanabe et al[46]	EMR	85	0	SCC	15	APC/CRT	5						0	41
Teoh et al[47]	EMR/ESD	28		SCC	6	RT/CRT	1			1
Urabe et al[48]	EMR/ESD	122		SCC			6						56
Vieth et al[54]	EMR	295		ADC	210					10		22
Yokoyama et al[49]	EMR	17	0	SCC		RT							7
Zehetner et al[50]	EMR	28	3	ADC	0	RFA	5	3		2		2

EMR: Endoscopic mucosal resection; ESD: Endoscopic submucosal dissection; SCC: Squamous carcinoma; ADC: Adenocarcinoma; APC: Argon plasma coagulation; PDT: Photodynamic therapy; CRT: Chemoradiation therapy; RFA: Radiofrequency ablation; RT: Radiology; CHEMO: Chemotherapy.

Table 2 Meta-regression analysis of the methods of endoscopic resection according to the published studies (the random effects model was used)

EMR vs ESD	Coefficient	95%CI	P value	Favors
Patients submitted to surgery	0.401	-2.912964, 3.714436	0.806	None
Positive margin	-0.741	-3.362995, 1.881024	0.558	None
Local recurrence	-1.713	-4.420582, 0.9937198	0.201	None
Lymph node metastasis	0.905	-5.762587, 7.573427	0.762	None
Metachronous cancer	-1.804	-4.350273, 0.7420371	0.143	None
Procedural complications	1.397	-1.264597, 4.058631	0.289	None
Stenosis	7.322	3.810146, 10.83439	< 0.001	EMR
Piecemeal resection1
Number of cases	-7.709	-11.03803, -4.380844	< 0.001	ESD
Local recurrence	-4.034	-6.151498, -1.915559	< 0.01	ESD
Resection margins	0.837	-3.725993, 5.39999	0.678	None

¹Data available only for squamous cell carcinoma studies. EMR: Endoscopic mucosal resection; ESD: Endoscopic submucosal dissection.

Table 3 Meta-regression analysis of the outcomes of endoscopic resection according to the histologic type of early esophageal cancer (the random effects model was used)

Outcome	Histologic type	Log-odds ratio	SE	95.0% lower confidence limit	95.0% upper confidence limit	Odds	Favors
Patients submitted to surgery	ADC	-2.1206	0.6249	-3.3454	-0.8958	12%	ADC
	SCC	4.1356	0.4038	-4.9271	-3.3440	37%	P < 0.05
Positive margins	ADC	-2.3761	1.0181	-4.3716	-0.3806	9%	None
	SCC	-2.5689	0.6973	-3.9357	-1.2022	7%
Local recurrence	ADC	-4.8189	0.1469	-5.1068	-4.5309	0.80%	None
	SCC	-4.3347	0.2792	-4.8819	-3.7874	1%
Lymph node metastasis	ADC	-3.0565	0.7714	-4.5685	-1.5445	5%	None
	SCC	-4.7682	0.4413	-5.6332	-3.9032	0.90%
Metachronous cancer	ADC	-2.8017	0.2384	-3.2690	-2.3344	6%	None
	SCC	-4.6030	0.6059	-5.7905	-3.4155	1%
Pre- vs post-endoscopic tumor stage	ADC	-0.5449	0.4316	-1.3909	0.3011	53%	-
	SCC	-0.8267	0.3324	-1.4782	-0.1752	39%

SCC: Squamous cell carcinoma; ADC: Adenocarcinoma.

Table 4 Thirty-eight studies were included in the analysis of surgically resected patients

Study	SCC/ADC	sm	sm1	sm2	sm3	N+ sm	N+ sm1	N+ sm2	N+ sm3	L+ sm	L+ sm1	L+ sm2	L+ sm3	V+ sm	V+ sm1	V+ sm2	V+ sm3	Grade III
Amano et al[55]	SCC	83	10	10	63	47	4	4	39	15				23				6
Araki et al[56]	SCC	58	12	18	28	15	1	4	10	12	0	4	8	6	0	2	4
Bollschweiler et al[57] (ADC)	ADC	22	9	4	9	9	2	0	7									5
Bollschweiler et al[57] (SCC)	SCC	22	3	6	13	11	1	1	9									8
Buskens et al[58]	ADC	42	16	13	13	12	0	3	9	16	0	4	12					17
Cen et al[59]	ADC	51				12				14								20
Chino et al[91]	SCC	22	5	8	9	11	1	6	4	17	5	6	6	6	0	2	4
Eguchi et al[61]	SCC	364	32			196	17			11	11
Endo et al[92]	SCC	121	18	48	55	51	2	15	34					95	6	35	54
Gockel et al[63]	ADC	15	8	2	5	3	1	1	1
Gockel et al[63]	SCC	15	7	4	4	2	1	1	0
Goseki et al[64]	SCC	30				15				21				22				8
Higuchi et al[20]	SCC	15	15			3	3			14	14			7	7
Ide et al[65]	SCC	85				26				54				23
Ikeda et al[66]	SCC	45				19								23
Kim et al[67]	SCC	133	36	27	69	39	6	5	28	30								18
Kimura et al[68]	SCC	26				9				11				5
Kuwano et al[93]	SCC	26	4	2	20	10				18				10				6
Liu et al[71]	ADC	37				10				15								0
Makuuchi et al[72]	SCC	81	18	25	38	33	4	11	18	60	13	19	28	31	2	9	20
Matsumoto et al[73]	SCC	87	15	26	46	41				48				26
Nakajima et al[74]	SCC	84	9	29	46	33	0	5	28	60				42				9
Natsugoe et al[75]	SCC	92	21	28	43	42	6	11	25	51				25				21
Noguchi et al[31]	SCC	38	6	10	22	20	1	3	16	31	4	8	19	10	1	1	8
Ohno et al[76]	SCC	16				2				6				4				5
Paraf et al[77]	ADC	12				1								5
Rice et al[78]	ADC	24				5												123
Rice et al[78]	SCC	3				1												13
Scheil-Bertram et al[40]	ADC	21	7	2	12	5	1	0	4	9	2	0	7	1	1	0	0	12
Schmidt et al[79]	SCC	5				2				3
Shiozaki et al[81]	SCC	180	21	73	86	92	8	37	47	119	11	51	57	45	3	18	24	54
Soga et al[82]	SCC	4				2				3								2
Tomita et al[83]	SCC	89	11	10	68	51	5	4	42	32				44				7
Tsutsui et al[84]	SCC	38				8								17
Westerterp et al[85]	ADC	66	25	23	18	18	0	6	12									59
Yoshikane et al[86]	SCC	17				12				11				4				1
Sepesi et al[80]	ADC	29	14	11	4	9	3	4	2
Leers et al[70]	ADC	51	19	9	23	11	4	1	6

SCC: Squamous cell carcinoma; ADC: Adenocarcinoma; L+: Lymphovascular invasion; V+: Microvascular invasion; sm: Submucosal layer.

Table 5 Meta-regression analysis of histologic parameters between adenocarcinoma and squamous cell carcinoma patients according to the published studies (the random effects model was used)

Comparison of ADC vs SCC	Coefficient	95%CI	P value	Better status
Positive lymph nodes	1.890	0.3945146, 3.384624	< 0.01	ADC
Lymphovascular invasion	0.626	-0.7032339, 1.956155	0.340	None
Microvascular invasion	1.114	-0.2682334, 2.496538	0.108	None
Grade 3	0.305	-1.584654, 2.195142	0.731	None

SCC: Squamous cell carcinoma; ADC: Adenocarcinoma.

Table 6 Number of patients with lymph node metastasis and lymphatic and vascular invasion according to the depth of tumor in the submucosal layer

Patients with diseases
Lymph node metastasis
sm (38 studies: n = 2149)1		sm1 (n = 308)		sm2 (n = 349)		sm3 (n = 624)
SCC	ADC	SCC	ADC	SCC	ADC	SCC	ADC
793/1779 (45%)	95/370 (26%)	60/224 (27%)	8/84 (10%)	107/296 (36%)	11/53 (21%)	301/544 (55%)	39/80 (49%)
Lymphovascular invasion
sm (n = 1286)1		sm1 (n = 134)		sm2 (n = 150)		sm3 (n = 209)
627/1090 (56%)	76/196 (39%)	58/111 (52%)	2/23 (9%)	88/135 (65%)	4/15 (27%)	118/184 (64%)	19/25 (76%)
Microvascular invasion
sm (n = 1194)1		sm1 (n = 104)		sm2 (n = 185)		sm3 (n = 251)
468/1161 (40%)	6/33 (18%)	19/97 (20%)	1/7 (14%)	67/183 (37%)	0/2 (0%)	114/239 (48%)	0/12 (0%)

¹Total numbers of patients differ since not all studies provide relevant information. sm: Submucosal layer; SCC: Squamous cell carcinoma; ADC: Adenocarcinoma.