Optimal proximal resection margin distance for gastrectomy in advanced gastric cancer

Table 1 The basic demographics and clinicopathologic characteristics of patients who underwent distal and total gastrectomy with curative intent for gastric adenocarcinoma, n (%)

Variables	Distal gastrectomy (n = 859)	Total gastrectomy (n = 659)
Age (yr; median) at operation	60 (23-87)	57 (22-86)
Sex
Male	603 (70.2)	441 (66.9)
Female	256 (29.8)	218 (33.1)
BMI (kg/m2, median)	23.2 (16.0-36.2)	23.4 (13.4-36.0)
ASA
1	246 (28.6)	213 (32.3)
2	571 (66.5)	427 (64.8)
3	39 (4.5)	17 (2.6)
4	3 (0.3)	2 (0.3)
Tumor location
Upper 1/3	8 (0.9)	266 (40.4)
Middle 1/3	225 (26.2)	320 (48.6)
Lower 1/3	626 (72.9)	73 (11.1)
Reconstruction
Billroth I	610 (71.0)
Billroth II	137 (15.9)
RYGJ	112 (13.0)
RY		659 (100.0)
Bormann classification
I	14 (1.6)	14 (2.1)
II	162 (18.9)	66 (10.0)
III	660 (76.8)	499 (75.7)
IV	23 (2.7)	80 (12.1)
Tumor size (cm, median)	5.0 (0.8-18)	6.0 (0.7-24)
CLN	27 (15-75)	30 (15-106)
PLN	2 (0-49)	3 (0-101)
T stage
T2	288 (33.5)	110 (16.7)
T3	370 (43.1)	310 (47.0)
T4a	195 (22.7)	226 (34.3)
T4b	6 (0.7)	13 (2.0)
N stage
N0	308 (35.9)	203 (30.8)
N1	181 (21.1)	110 (16.7)
N2	173 (20.1)	128 (19.4)
N3a	159 (18.5)	133 (20.2)
N3b	38 (4.4)	85 (12.9)
AJCC stage
Stage I	155 (18.0)	66 (10.0)
Stage II	336 (39.1)	235 (35.7)
Stage III	368 (42.8)	358 (54.3)
PRM (cm; median)	4.8 (0.3-17)	3.5 (0.1-18.5)
DRM (cm; median)	3.2 (0.2-19)	9.4 (0.3-27)
Histology
Differentiated	351 (40.9)	192 (29.1)
Undifferentiated	508 (59.1)	467 (70.9)
Lymphovascular invasion	413 (48.1)	360 (54.6)
Perineural invasion	368 (42.8)	344 (52.2)
Recurrence	220 (25.6)	251 (38.1)
Locoregional recurrence	60	41
Hematogenous metastasis	74	83
Extra-abdominal LN metastasis	2	1
Peritoneal metastasis	74	1
Mixed	10	17

RYGJ: Roux-en-Y gastrojejunostomy; RY: Roux-en-Y esophagojejunostomy; CLN: Total number of collected lymph nodes; PLN: Total number of positive lymph nodes; PRM: Proximal resection margin; DRM: Distal resection margin; AJCC: American Joint Committee on Cancer.

Table 2 Clinicopathologic factors depending on the distance from the proximal resection margin in patients who underwent curative distal gastrectomy, n (%)

Variables	PRM (cm)						P value
	≤ 1.0 (n = 17)	1.1-3.0 (n = 170)		3.1-5.0 (n = 287)	> 5.0 (n = 385)
Age (yr)1 at operation	59.7 ± 3.4	57.2 ± 1.0		58.2 ± 0.7	59.0 ± 0.6		0.416
Sex							0.279
Male	9 (52.9)		116 (68.2)	199 (69.3)		279 (72.5)
Female	8 (47.1)		54 (31.8)	88 (30.7)		106 (27.5)
Tumor location							< 0.001
Upper 1/3	1 (5.9)		3 (1.8)	3 (1.0)		1 (0.3)
Middle 1/3	9 (52.9)		74 (43.5)	86 (30.0)		56 (14.5)
Lower 1/3	7 (41.2)		93 (54.7)	198 (69.0)		328 (85.2)
Reconstruction							0.004
Billroth I	12 (70.6)		101 (59.4)	218 (76.0)		279 (72.5)
Billroth II	3 (17.6)		32 (18.8)	38 (13.2)		64 (16.6)
RYGJ	2 (11.8)		37 (21.8)	31 (10.8)		42 (10.9)
Borrmann type IV	1 (5.9)		6 (3.5)	7 (2.4)		9 (2.3)	0.461
Tumor size (cm)1	6.5 ± 0.8		5.8 ± 0.2	5.3 ± 0.1		5.2 ± 0.1	0.004
T stage							0.768
T2	5 (29.4)		56 (32.9)	89 (31.0)		138 (35.8)
T3	7 (41.2)		75 (44.1)	123 (42.9)		165 (42.9)
T4	5 (29.4)		39 (22.9)	75 (26.1)		82 (21.3)
CLN1	26.6 ± 2.0		29.3 ± 0.8	29.4 ± 0.6		28.8 ± 0.5	0.612
N stage							0.971
N0	5 (29.4)		61 (35.9)	101 (35.2)		141 (36.6)
N1	2 (11.8)		36 (21.2)	63 (22.0)		80 (20.8)
N2	4 (23.5)		36 (21.2)	55 (19.2)		78 (20.3)
N3	6 (35.3)		37 (21.8)	68 (23.7)		86 (22.3)
AJCC stage							0.551
Stage I	4 (23.5)		31 (18.2)	52 (18.1)		68 (17.7)
Stage II	3 (17.6)		65 (38.2)	108 (37.6)		160 (41.6)
Stage III	10 (58.8)		74 (43.5)	127 (44.3)		157 (40.8)
Differentiation							0.023
Differentiated	4 (23.5)		64 (37.6)	105 (36.6)		178 (46.2)
Undifferentiated	13 (76.5)		106 (62.4)	182 (63.4)		207 (53.8)
LVi	8 (47.1)		75 (44.1)	142 (49.5)		188 (48.8)	0.706
PNi	9 (52.9)		80 (47.1)	138 (48.1)		141 (36.6)	0.010
Recurrence	4 (23.5)		52 (30.6)	69 (24.0)		95 (24.7)	0.765
Local recurrence	1 (5.9)		11 (6.5)	24 (8.4)		24 (6.2)	0.727

¹mean ± standard error. PRM: Proximal resection margin; RYGJ: Roux-en-Y gastrojejunostomy; CLN: Total number of collected lymph nodes; AJCC: American Joint Committee on Cancer; LVi: Lymphovascular invasion; PNi: Perineural invasion.

Table 3 Clinicopathologic factors depending on the distance from the proximal resection margin in patients who underwent curative total gastrectomy, n (%)

Variables	PRM (cm)				P value
	≤ 1.0 (n = 90)	1.1-3.0 (n = 209)	3.1-5.0 (n = 146)	> 5.0 (n = 214)
Age (yr)1 at operation	57.1 ± 1.2	55.0 ± 0.9	54.6 ± 0.9	56.3 ± 0.9	0.330
Sex					0.364
Male	64 (71.1)	135 (64.6)	92 (63.0)	150 (70.1)
Female	26 (38.9)	74 (35.4)	54 (37.0)	64 (29.9)
Tumor location					< 0.001
Upper 1/3	81 (90.0)	127 (60.8)	32 (21.9)	26 (12.1)
Middle 1/3	8 (8.9)	75 (35.9)	103 (70.5)	134 (62.6)
Lower 1/3	1 (1.1)	7 (3.3)	11 (7.5)	54 (25.2)
Borrmann type IV	17 (18.9)	37 (17.7)	14 (9.6)	12 (5.6)	< 0.001
Tumor size (cm)1	8.1 ± 0.5	7.6 ± 0.3	7.0 ± 0.3	5.9 ± 0.2	< 0.001
T stage					0.873
T2	14 (15.6)	30 (14.4)	24 (16.4)	42 (19.6)
T3	44 (48.9)	100 (47.8)	67 (45.9)	99 (46.3)
T4	32 (35.6)	79 (37.8)	55 (37.7)	73 (34.1)
CLN1	30.7 ± 1.1	33.1 ± 1.0	32.2 ± 1.0	31.0 ± 0.7	0.216
N stage					0.495
N0	23 (25.6)	74 (35.4)	47 (32.2)	59 (27.6)
N1	14 (15.6)	35 (16.7)	21 (14.4)	40 (18.7)
N2	15 (16.7)	41 (19.6)	30 (20.5)	42 (19.6)
N3	38 (42.2)	59 (28.2)	48 (32.9)	73 (34.1)
AJCC stage					0.587
Stage I	8 (8.9)	19 (9.1)	14 (9.6)	25 (11.7)
Stage II	29 (32.2)	85 (40.7)	53 (35.3)	68 (31.8)
Stage III	53 (58.9)	105 (50.2)	79 (54.1)	121 (56.5)
Differentiation					0.082
Differentiated	29 (32.2)	55 (26.3)	34 (23.3)	74 (34.6)
Undifferentiated	61 (67.8)	154 (73.7)	112 (76.7)	140 (65.4)
LVi	57 (63.3)	108 (51.7)	75 (51.4)	120 (56.1)	0.231
PNi	54 (60.0)	101 (48.3)	92 (63.0)	97 (45.3)	0.002
Recurrence	44 (48.9)	80 (38.3)	48 (32.9)	79 (36.9)	0.648
Local recurrence	8 (8.9)	10 (4.6)	11 (6.9)	14 (6.2)	0.637

¹mean ± standard error. PRM: Proximal resection margin; RYGJ: Roux-en-Y gastrojejunostomy; CLN: Total number of collected lymph nodes; AJCC: American Joint Committee on Cancer; LVi: Lymphovascular invasion; PNi: Perineural invasion.

Table 4 Analysis of the risk factors associated with overall survival in patients who underwent distal gastrectomy using the Cox proportional hazard model

	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
Age	1.04 (1.03-1.05)	< 0.001	1.04 (1.03-1.05)	< 0.001
Female sex	0.89 (0.69-1.15)	0.367
BMI	0.94 (0.90-0.98)	0.002
Tumor location
Upper 1/3	Ref.
Mid 1/3	3.11 (0.43-22.4)	0.260
Lower 1/3	3.54 (0.50-25.2)	0.208
Reconstruction
Billroth I	Ref.		Ref.
Billroth II	1.66 (1.26-2.20)	< 0.001	1.40 (1.04-1.87)	0.025
RYGJ	1.34 (0.96-1.86)	0.083	1.45 (1.04-2.03)	0.030
Tumor size	1.11 (1.06-1.16)	< 0.001
Borrmann type IV	0.96 (0.48-1.94)	0.914
CLN	0.99 (0.98-1.00)	0.045	0.99 (0.98-1.00)	0.034
T stage
T2	Ref.		Ref.
T3	1.36 (1.01-1.83)	0.044	1.08 (0.79-1.48)	0.612
T4	3.02 (2.24-4.06)	< 0.001	1.90 (1.38-2.62)	< 0.001
N stage
N0	Ref.		Ref.
N1	1.07 (0.73-1.56)	0.739	0.92 (0.63-1.36)	0.686
N2	2.33 (1.67-3.25)	< 0.001	2.06 (1.46-2.90)	< 0.001
N3	3.74 (2.77-5.05)	< 0.001	3.10 (2.25-4.28)	< 0.001
Diffuse type histology	1.00 (0.79-1.25)	0.967
LVi	1.82 (1.44-2.29)	< 0.001
PNi	1.32 (1.06-1.66)	0.015
PRM (cm)
0-1.0	Ref.
1.1-3.0	0.57 (0.27-1.19)	0.134
3.1-5.0	0.59 (0.29-1.23)	0.162
> 5.0	0.61 (0.30-1.25)	0.175

PRM: Proximal resection margin; RYGJ: Roux-en-Y gastrojejunostomy; CLN: Total number of collected lymph nodes; LVi: Lymphovascular invasion; PNi: Perineural invasion.

Table 5 Analysis of the risk factors associated with overall survival in patients who underwent total gastrectomy using the Cox proportional hazard model

	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
Age	1.02 (1.01-1.03)	< 0.001	1.03 (1.02-1.04)	< 0.001
Female sex	1.03 (0.81-1.30)	0.834
BMI	0.95 (0.92-0.99)	0.009
Tumor location
Upper 1/3	Ref.
Mid 1/3	0.76 (0.60-0.95)	0.018
Lower 1/3	0.94 (0.65-1.35)	0.723
Tumor size	1.09 (1.07-1.12)	< 0.001
Borrmann type IV	2.21 (1.66-2.94)	< 0.001	1.93 (1.43-2.60)	< 0.001
CLN	1.00 (0.99-1.01)	0.548	0.99 (0.98-1.00)	0.035
T stage
T2	Ref.		Ref.
T3	1.67 (1.14-2.45)	0.008	1.21 (0.81-1.81)	0.352
T4	3.24 (2.22-4.72)	< 0.001	1.85 (1.22-2.79)	0.004
N stage
N0	Ref.		Ref.
N1	1.11 (0.74-1.68)	0.617	1.03 (0.67-1.57)	0.900
N2	1.73 (1.21-2.46)	0.003	1.48 (1.01-2.18)	0.045
N3	3.87 (2.88-5.19)	< 0.001	2.81 (1.98-3.98)	< 0.001
Diffuse type histology	1.23 (0.96-1.58)	0.103
LVi	2.09 (1.65-2.64)	< 0.001	1.43 (1.10-1.86)	0.008
PNi	1.60 (1.27-2.00)	< 0.001
PRM (cm)
0-1.0	Ref.
1.1-3.0	0.80 (0.57-1.10)	0.164
3.1-5.0	0.65 (0.45-0.93)	0.019
> 5.0	0.81 (0.58-1.12)	0.202

PRM: Proximal resection margin; RYGJ: Roux-en-Y gastrojejunostomy; CLN: Total number of collected lymph nodes; LVi: Lymphovascular invasion; PNi: Perineural invasion.

Table 6 Analysis of the risk factors associated with recurrence-free survival in patients who underwent distal gastrectomy using the Cox proportional hazard model

	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
Age	1.02 (1.00-1.03)	0.011	1.02 (1.00-1.03)	0.012
Female sex	0.93 (0.69-1.25)	0.636
BMI	0.96 (0.92-1.00)	0.068
Tumor location
Upper 1/3	Ref.
Mid 1/3	2.32 (0.32-16.77)	0.403
Lower 1/3	2.35 (0.33-16.76)	0.395
Reconstruction
Billroth I	Ref.		Ref.
Billroth II	1.90 (1.37-2.64)	< 0.001	1.50 (1.08-2.10)	0.016
RYGJ	1.87 (1.31-2.67)	0.001	1.72 (1.20-2.47)	0.003
Tumor size	1.16 (1.10-1.21)	< 0.001
Borrmann type IV	1.04 (0.46-2.33)	0.931
CLN	1.00 (0.99-1.01)	0.91
T stage
T2	Ref.		Ref.
T3	2.61 (1.72-3.96)	< 0.001	1.92 (1.25-2.95)	0.003
T4	6.17 (4.08-9.34)	< 0.001	3.42 (2.21-5.31)	< 0.001
N stage
N0	Ref.		Ref.
N1	1.23 (0.75-2.03)	0.415	1.03 (0.62-1.70)	0.92
N2	3.42 (2.26-5.19)	< 0.001	2.55 (1.67-3.89)	< 0.001
N3	5.75 (3.92-8.42)	< 0.001	3.88 (2.59-5.80)	< 0.001
Diffuse type histology	1.19 (0.91-1.57)	0.206	1.05 (0.79-1.39)	0.758
LVi	2.29 (1.73-3.02)	< 0.001
PNi	1.63 (1.25-2.12)	< 0.001
PRM (cm)
0-1.0	Ref.
1.1-3.0	1.03 (0.37-2.86)	0.949
3.1-5.0	0.78 (0.29-2.15)	0.633
> 5.0	0.84 (0.31-2.29)	0.734

PRM: Proximal resection margin; RYGJ: Roux-en-Y gastrojejunostomy; CLN: Total number of collected lymph nodes; LVi: Lymphovascular invasion; PNi: Perineural invasion.

Table 7 Analysis of the risk factors associated with recurrence-free survival in patients who underwent total gastrectomy using the Cox proportional hazard model

	Univariate		Multivariate
	HR (95%CI)	P value	HR (95%CI)	P value
Age	1.01 (1.00-1.02)	0.071	1.01 (1.00-1.02)	0.032
Female sex	1.23 (0.95-1.56)	0.118
BMI	0.96 (0.92-1.00)	0.067
Tumor location
Upper 1/3	Ref.
Mid 1/3	0.67 (0.51-0.87)	0.002
Lower 1/3	0.86 (0.57-1.30)	0.859
Tumor size	1.11 (1.08-1.14)	< 0.001	1.03 (1.00-1.07)	0.075
Borrmann type IV	2.84 (2.10-3.83)	< 0.001	1.91 (1.32-2.76)	0.001
CLN	1.00 (0.99-1.01)	0.612
T stage
T2	Ref.		Ref.
T3	2.20 (1.36-3.54)	0.001	1.31 (0.90-2.16)	0.289
T4	4.18 (2.60-6.72)	< 0.001	1.90 (1.14-3.18)	0.014
N stage
N0	Ref.		Ref.
N1	1.43 (0.89-2.31)	0.139	1.27 (0.77-2.07)	0.348
N2	2.35 (1.55-3.56)	< 0.001	1.68 (1.06-2.65)	0.026
N3	4.90 (3.43-6.99)	< 0.001	2.84 (1.87-4.32)	< 0.001
Diffuse type histology	1.14 (0.86-1.50)	0.357
LVi	2.41 (1.84-3.15)	< 0.001	1.44 (1.08-1.91)	0.013
PNi	1.71 (1.33-2.21)	< 0.001
PRM (cm)
0-1.0	Ref.
1.1-3.0	0.80 (0.55-1.15)	0.225
3.1-5.0	0.63 (0.42-0.95)	0.028
> 5.0	0.74 (0.51-1.07)	0.104

PRM: Proximal resection margin; RYGJ: Roux-en-Y gastrojejunostomy; CLN: total number of collected lymph nodes; LVi: Lymphovascular invasion; PNi: Perineural invasion.