Clinicopathological features and clinical outcomes
A total of 303 patients underwent radical surgery plus 14v dissection in the study and clinicopathological features were shown in Table 1. Most patients were male (66.0%) and their age ranged from 28 to 75 years old (mean: 55.92 y). A majority of tumors were located in L area (67.7%), presented with poor differentiation (77.2%) and canalicular adenocarcinoma histological type (73.9%). A minority of patients underwent total or proximal gastrectomy surgery (24.1%). And cases were classified into stage Ⅰ (17.5%), Ⅱ (20.1%), Ⅲ (62.4%) (postsurgical pathological stage). The metastastic incidence of No.14v lymph node was 15.8% and the micrometastatic incidence was 3.9%. The total metastatic rate of 14v was 19.1%. The median number of overall harvested lymph nodes and harvested 14v lymph nodes was 28.48 and 2.03, respectively. Patients were followed up every 3 months during the first 3 years, subsequently every 6 months for the following 2 years and once a year after 5 years until the time of death or the deadline, December 31th, 2018. The following-up time ranged from 3 to 178 months (median: 46m). And the 3-, 5-year overall survival rate of patients with radical gastrectomy plus 14v dissection was 71.2% and 50.7%, respectively.
Table 1
Clinicopathological features of patients with gastric cancer undergoing radical gastrectomy plus 14v dissection
Clinicopathological characteristics
|
Value
|
Percentage(%)
|
Age (y)
|
55.92 ± 10.74
|
|
Gender
|
|
|
Male
|
200
|
66.0
|
Female
|
103
|
34.0
|
Tumor size (cm)
|
6.02 ± 10.74
|
|
Location
|
|
|
U
|
14
|
4.6
|
M
|
84
|
27.7
|
L
|
205
|
67.7
|
Histological type
|
|
|
Adenocarcinoma
|
224
|
73.9
|
Signet-ring or mucinous carcinoma
|
79
|
26.1
|
Grade of differentiation
|
|
|
Well or moderate
|
69
|
22.8
|
Poor
|
234
|
77.2
|
Borrmann type
|
|
|
Ⅰ、Ⅱ
|
178
|
58.7
|
Ⅲ
|
108
|
35.6
|
Ⅳ
|
17
|
5.6
|
Postoperative T category (pT)
|
|
|
T1-2
|
81
|
26.7
|
T3-4
|
222
|
73.3
|
Postoperative N category(pN)
|
|
|
N0
|
89
|
29.4
|
N1
|
41
|
13.5
|
N2
|
63
|
20.8
|
N3
|
110
|
36.3
|
Extent of resection
|
|
|
Total or proximal
|
73
|
24.1
|
Distal
|
230
|
75.9
|
Pathological stage(pTNM)
|
|
|
Ⅰ
|
53
|
17.5
|
Ⅱ
|
61
|
20.1
|
Ⅲ
|
189
|
62.4
|
The number of harvested lymph nodes
|
28.48 ± 10.52
|
|
The number of metastatic lymph nodes
|
6.28 ± 7.51
|
|
Without 14v micrometastasis
|
245
|
80.9
|
With 14v micrometastasis
|
10
|
3.3
|
With 14v metastasis
|
48
|
15.8
|
The number of harvested lymph nodes of 14v
|
2.03 ± 1.439
|
|
Location, U/M/L, the upper/middle/lower third of stomach |
Clinicopathological characteristics associated with 14v metastasis or micrometastasis
We sought to identify subgroups that were likely to be presented with 14v metastasis or micrometastasis. It revealed the metastasis or micrometastasis of 14v was associated with tumor size (P = 0.001), location (P = 0.027), Borrmann type (P = 0.003), pT category (P = 0.001), pN category (P = 0.000), pTNM stage (P = 0.000) and the number of metastatic lymph node (P = 0.000) (Table 2.). Logistic regression analysis demonstrated that location (P = 0.004, RR: 0. 320, 95%CI: 0.146-0.700), Borrmann type (P = 0.010, RR: 0.010, 95%CI: 1.104–2.089) and pN category (P = 0.000, RR: 3.709, 95%CI: 2.326–5.914) were significantly correlated with 14v metastasis or micrometastasis (Table 3.).
Table 2
Univariate analysis of clinicopathological features associated with 14v metastatic status
Variable
|
14v micrometastasis (-)
|
14v micrometastasis or metastasis (+)
|
P value
|
Age (y)
|
|
|
|
<60
|
159
|
36
|
0.686
|
≧60
|
86
|
22
|
Gender
|
|
|
|
Male
|
162
|
38
|
0.930
|
Female
|
83
|
20
|
Tumor size (cm)
|
|
|
|
<5.0
|
127
|
16
|
0.001
|
≧5.0
|
118
|
41
|
Location
|
|
|
|
U
|
14
|
0
|
0.027
|
M
|
73
|
11
|
L
|
158
|
47
|
Histological type
|
|
|
|
Adenocarcinoma
|
179
|
45
|
0.480
|
Signet-ring or mucinous carcinoma
|
66
|
13
|
Grade of differentiation
|
|
|
|
Well or moderate
|
57
|
12
|
0.674
|
Poor
|
118
|
46
|
Borrmann type
|
|
|
|
Ⅰ、Ⅱ
|
154
|
24
|
0.003
|
Ⅲ、
|
81
|
27
|
Ⅳ
|
10
|
7
|
Postoperative T category (pT)
|
|
|
|
T1-2
|
77
|
4
|
0.000
|
T3-4
|
168
|
54
|
Postoperative N category(pN)
|
|
|
|
N0
|
89
|
0
|
0.000
|
N1
|
37
|
4
|
N2
|
55
|
8
|
N3
|
64
|
46
|
Extent of resection
|
|
|
|
Total or proximal
|
62
|
11
|
0.310
|
Distal
|
183
|
47
|
Pathological stage(pTNM)
|
|
|
|
Ⅰ
|
52
|
1
|
0.000
|
Ⅱ
|
59
|
2
|
Ⅲ
|
134
|
55
|
The number of harvested lymph nodes
|
28.90 ± 10.419
|
26.72 ± 10.843
|
0.157
|
The number of metastatic lymph nodes
|
4.56 ± 6.034
|
13.55 ± 8.728
|
0.000
|
The number of harvested lymph nodes of 14v
|
|
|
|
1
|
120
|
33
|
0.120
|
2
|
57
|
15
|
≧3
|
67
|
8
|
Location, U/M/L, the upper/middle/lower third of stomach |
Table 3
Univariate analysis of regional lymph nodes associated with 14v metastatic status
Lymphatic metastasis
|
14v micrometastasis (-)
|
14v micrometastasis or metastasis (+)
|
P value
|
No.1
|
|
|
|
(+)
|
23
|
17
|
0.000
|
(-)
|
179
|
30
|
No.2
|
|
|
|
(+)
|
10
|
1
|
0.001
|
(-)
|
41
|
3
|
No.3
|
|
|
|
(+)
|
90
|
39
|
0.000
|
(-)
|
142
|
11
|
No.4
|
|
|
|
(+)
|
79
|
37
|
0.000
|
(-)
|
154
|
14
|
No.5
|
|
|
|
(+)
|
46
|
29
|
0.000
|
(-)
|
103
|
9
|
No.6
|
|
|
|
(+)
|
96
|
50
|
0.000
|
(-)
|
135
|
6
|
No.7
|
|
|
|
(+)
|
63
|
29
|
0.000
|
(-)
|
167
|
20
|
No.8a
|
|
|
|
(+)
|
42
|
40
|
0.000
|
(-)
|
189
|
11
|
No.9
|
|
|
|
(+)
|
15
|
23
|
0.000
|
(-)
|
178
|
22
|
No.10
|
|
|
|
(+)
|
1
|
2
|
0.005
|
(-)
|
10
|
0
|
No.11
|
|
|
|
(+)
|
16
|
17
|
0.000
|
(-)
|
164
|
17
|
No.12a
|
|
|
|
(+)
|
14
|
17
|
0.000
|
(-)
|
127
|
19
|
No.1, right paracardial lymph node; No.2, left paracardial lymph node; No.3, lymph node along the lesser curvature; No.4 (4sa, 4sb, 4sd), lymph node along the short gastric vessels, the left gastroepiploic vessels and the right gastroepiploic vessels; No.5, the suprapyloric lymph node; No.6, the infrapyloric lymph node; No.7, lymph node along the left gastric artery; No.8a, lymph node along the common hepatic artery; No.9, lymph node around the celiac artery; No.10, lymph node at the splenic hilum; No.11 (11p and 11d); lymph node along the proximal splenic artery and distal splenic artery; No.12a, lymph node in the hepatoduodenal ligament (along the hepatic artery); No.14v, lymph node along the superior mesenteric vein. |
Regional lymph nodes associated with 14v metastasis or micrometastasis
In order to investigate 14v lymphatic drainage pathway, the study included lymph node, No.1, No.2, No.3, No.4 (4sa, 4sb and 4sd), No.5, No.6, No.7, No.8a, No.9, No.10, No.11, No.12a to conduct univariate and multivariable analysis. It demonstrated that the metastatic status of LN14v was significantly correlated with that all regional nodes (all P < 0.05, Table 4.). Multivariable analysis results revealed that the metastasis of LN6 and LN9 to be independent variables associated with LN14v metastasis or micrometastasis (P = 0.003,RR: 0.101, 95%CI: 0.022–0.496; P = 0.013,RR: 0.093, 95%CI: 0.014–0.608) (Table 5.). Of 146 patients with LN6 metastasis, 34.2% cases had the metastasis or micrometastasis of LN14v. And LN6 status showed the low false negative rate (10.7%) to predict the absence of metastasis or micrometastasis of LN14v.
Table 4
Multivariate analysis of clinicopathological features associated with 14v metastatic status
Variable
|
β
|
RR(95%CI)
|
P value
|
Tumor size
|
0.331
|
1.392(0.649–2.988)
|
0.396
|
Location
|
-0.139
|
0.320(0.146-0.700)
|
0.004
|
Borrmann type
|
0.418
|
1.519(1.104–2.089)
|
0.010
|
Postoperative T category (pT)
|
0.624
|
1.866(0.565–6.160)
|
0.306
|
Postoperative N category(pN)
|
1.311
|
3.709(2.326–5.914)
|
0.000
|
Pathological stage(pTNM)
|
-0.747
|
0.474(0.097–2.313)
|
0.356
|
Table 5
Multivariate analysis of regional lymph nodes associated with 14v metastatic status
Lymphatic metastasis
|
β
|
RR(95%CI)
|
P value
|
No.1
|
1.378
|
3.968(0.340-46.257)
|
0.271
|
No.3
|
-0.172
|
0.842(0.054–13.085)
|
0.902
|
No.4
|
1.464
|
4.325(0.206–90.878)
|
0.346
|
No.5
|
-0.189
|
0.150(0.010–2.203)
|
0.167
|
No.6
|
-2.294
|
0.101(0.022–0.496)
|
0.003
|
No.7
|
1.062
|
2.891(0.118–71.054)
|
0.516
|
No.8a
|
-1.395
|
0.248(0.037–1.681)
|
0.153
|
No.9
|
-2.38
|
0.093(0.014–0.608)
|
0.013
|
No.11
|
2.048
|
7.750(0.203-295.209)
|
0.270
|
No.12a
|
-0.345
|
0.708(0.029–17.523)
|
0.833
|
No.1, right paracardial lymph node; No.3, lymph node along the lesser curvature; No.4 (4sa, 4sb, 4sd), lymph node along the short gastric vessels, the left gastroepiploic vessels and the right gastroepiploic vessels; No.5, the suprapyloric lymph node; No.6, the infrapyloric lymph node; No.7, lymph node along the left gastric artery; No.8a, lymph node along the common hepatic artery; No.9, lymph node around the celiac artery; No.11 (11p and 11d); lymph node along the proximal splenic artery and distal splenic artery; No.12a, lymph node in the hepatoduodenal ligament (along the hepatic artery); No.14v, lymph node along the superior mesenteric vein. |
Prognostic value of metastatic status of 14v in gastric cancer
The 5-year overall survival rate of patients with LN14v metastasis and LN14v micrometastasis was 12.9% and 10.0%. And the 5-year survival rate of patients of positive group (LN14v micrometastasis or metastasis) was 12.4%. The negative group (neither LN14v metastasis nor micrometastasis) had a more favorable survival in comparison to the positive group (LN14v micrometastasis or metastasis) (P = 0.000, HR = 4.001, 95%CI = 2.789–5.739, Fig. 1). In stratified analysis, the negative group showed higher overall survival rate (60.1%) than that of LN14v micrometastasis or metastasis group (P = 0.000, HR = 2.093, 95%CI = 1.480–2.961; P = 0.000, HR = 3.931, 95%CI = 2.671–5.787, Fig. 2). But the difference between patients with 14v micrometastasis and 14v metastasis was not significant (P = 0.901, HR = 1.047, 95%CI = 0.501–2.171). Univariate analysis results showed age, gender, tumor size, Borromann type, pT stage, pN stage, pTNM stage, and pathological type were correlated to the prognosis. Furthermore, multivariable Cox proportional hazard model analysis demonstrated that LN14v metastatic status (P = 0.001, HR = 1.936, 95%CI = 1.323–2.834), pT stage (P = 0.003, HR = 2.725, 95%CI = 1.416–5.244), pN stage (P = 0.000, HR = 2.090, 95%CI = 1.688–2.588), pathological type (P = 0.043, HR = 1.448, 95%CI = 1.012–2.072) and Borromann type (P = 0.000, HR = 1.341, 95%CI = 1.148–1.566) were significant prognostic variables (Table 6.). Even having underwent radical gastrectomy plus the LN14v dissection, patients with 14v metastasis or micrometastasis had worse survival than that of patients of stageⅠ, Ⅱ and Ⅲ neither with LN14v metastasis nor micrometastasis (P = 0.000, Fig. 3).
Table 6
Univariate and multivariate analysis of overall survival in patients with gastric cancer undergoing radical gastrectomy plus 14v dissection
Characteristics
|
Univariate analysis
|
Multivariate analysis
|
β
|
HR (95%CI)
|
P value
|
β
|
HR (95%CI)
|
P value
|
Gender
|
0.354
|
0.702(0.503–0.980)
|
0.037
|
0.081
|
0.922(0.773–1.110)
|
0.366
|
Age
|
0.378
|
1.459(1.052–2.023)
|
0.024
|
0.268
|
1.307(0.932–1.832)
|
0.12
|
Tumor size
|
0.919
|
2.506(1.761–3.567)
|
0.001
|
0.04
|
1.040(0.695–1.557)
|
0.847
|
Location
|
0.09
|
1.094(0.823–1.454)
|
0.537
|
|
|
|
Borrmann type
|
0.409
|
1.505(1.294–1.751)
|
0.001
|
0.293
|
1.341(1.148–1.566)
|
0.000
|
Postoperative T category (pT)
|
1.757
|
5.797(3.267–10.286)
|
0.001
|
1.003
|
2.725(1.416–5.244)
|
0.003
|
Postoperative N category(pN)
|
0.908
|
2.480(2.058–2.989)
|
0.001
|
0.737
|
2.090(1.688–2.588)
|
0.000
|
Micro- or metastasis Status of 14v
|
1.386
|
4.001(2.7894–5.739)
|
0.000
|
0.661
|
1.936(1.323–2.834)
|
0.001
|
Histological type
|
0.582
|
1.789(1.269–2.524)
|
0.001
|
0.37
|
1.448(1.012–2.072)
|
0.043
|
Grade of differentiation
|
0.542
|
1.719(1.101–2.684)
|
0.017
|
0.102
|
1.107(0.679–1.806)
|
0.684
|
Extent of resection
|
0.461
|
1.586(1.107–2.271)
|
0.012
|
0.264
|
1.302(0.883–1.921)
|
0.183
|
The benefit of lymphadenectomy of LN14v in gastric cancer
Having established that 14v metastatic status was prognosis significance for adequately staged patients treated by radical gastrectomy plus the 14v dissection, we sought to identify patient subgroups for whom the benefit was maximized and those for whom TRG was not of prognostic significance. In matched analysis, patients with gastric cancer of stage Ⅲ, U/M area, pN2-3 and LN 6(+) underwent lymphadenectomy of 14v suffered better survival than those without lymphadenectomy of 14v (P = 0.006, Fig. 4).