Meta-analysis of lymph node metastasis in Siewert type I and II T1 adenocarcinomas

Table 1 Characteristics of patients with Siewert type I and II pT1 adenocarcinomas

Characteristic	Data
n	85
Median age (range), yr	67 (38-84)
Male sex, n (%)	69 (81.1)
Depth, n (%)
T1a	22 (25.9)
T1b	63 (74.1)
Differentiation, n (%)
Differentiated	72 (84.7)
Undifferentiated	13 (15.3)
Median size (SD), mm	26 (± 14.6)
Lymphovascular invasion, n (%)	50 (58.8)
Underlying Barrett's esophagus, n (%)	43 (50.5)
Lymph node metastasis, n (%)	11 (12.9)

Table 2 Studies of patients who underwent surgery for Siewert type I and II pT1 adenocarcinomas with lymph node status

Ref.	n	Siewert classification	TNM classification		SM subdivision
			T1a, n (%)	T1b, n (%)	SM1, n (%)	SM2, n (%)	SM3, n (%)
Westerterp et al[6]	120	I, II	1/54 (1.8)	18/66 (27.2)	0/25 (0)	6/23 (20)	12/18 (56)
Barbour et al[7]	85	I, II	0/35 (0)	9/50 (18)	-	-	-
Lees et al[8]	126	I, II	1/75 (1.3)	11/51 (21.6)	4/19 (21)	1/9 (11.1)	6/23 (26.1)
Griffin et al[9]	119	I, II	0/54 (0)	8/65 (12.3)	-	-	-
Lee et al[10]	258	I, II	9/122 (7.3)	35/136 (25.7)	-	-	-
Present study	85	I, II	1/15 (6.6)	10/70 (14.2)	0/7 (0)	4/43 (9.3)	6/20 (30)
Total	793	I, II	12/355	91/438
			(3.4%, 95%CI: 1.5-5.2)	(20.7%, 95%CI: 16.9-24.5)

TNM: Tumor-node-metastasis; SM: Submucosal; SM: Subdivision defines 3 sections of equivalent thickness of submucosa: Superficial (SM1), middle (SM2) and deep (SM3).

Table 3 Frequencies of lymph node metastasis and lymphovascular invasion per depth of invasion in this study

Invasion depth (μm)	Lymphatic invasion frequency	Venous invasion frequency	Frequency of lymph node metastasis
SM < 500, n (%, 95%CI)	7/30 (23.3, 8.1-38.4)	2/30 (6.6, 0-15.5)	1/30 (3.3, 0-9.7)
SM < 1000, n (%, 95%CI)	11/46 (23.9, 11.5-36.2)	7/46 (15.2, 4.5-25.5)	2/46 (4.3, 0-10.2)

SM: Submucosal.

Table 4 Univariate and multivariate analysis of potential risk factors for lymph node metastasis

Statistical test	OR	Lower 95%CI	Upper 95%CI	P value
Univariate analysis
Age (< 70 or ≥ 70 yr)	0.32	0.03	1.75	0.19
Sex (male or female)	1.04	0.18	11	1
Location of tumor center (Siewert type I or II)	2.1	0.31	10.8	0.37
Depth of invasion (M or SM)	2.3	0.28	108.3	0.67
Depth of invasion (≥ 500 μm or < 500 μm)	4.89	0.58	40.8	0.14
Differentiation (undifferentiated or differentiated)	6.6	1.29	33.7	0.01
Tumor size (< 30 mm or ≥ 30 mm)	3.1	0.72	14.8	0.08
Macroscopic tumor type (elevated or depressed)	1.43	0.31	9.1	0.74
Ulceration (yes or no)	1.91	0.44	8.7	0.33
Barrett’s esophageal adenocarcinoma (yes or no)	0.79	0.17	3.42	0.75
Lymphovascular invasion (yes or no)	5.1	1.04	25.1	0.02
Multivariate analysis
Differentiation (undifferentiated or differentiated)	6.08	1.4	26.4	0.01
Lymphovascular invasion (yes or no)	4.66	1.09	19.9	0.03

M: Mucosal; SM: Submucosal; OR: Odds ratio.