Prognostic significance of systemic immune-inflammation index in patients with intrahepatic cholangiocarcinoma undergoing hepatic resection

Table 1 Baseline characteristics of included patients

Variables	All patients (n = 530)	Derivation cohort (n = 265)	Validation cohort (n = 265)	P value
Patient factors/laboratory parameters
Age, yr	57.2 (10.7)	57.9 (10.5)	56.5 (10.8)	0.131
Male gender, n (%)	256 (48.3)	134 (50.6)	122 (46.0)	0.339
HBsAg (positive), n (%)	153 (29.0)	80 (30.3)	73 (27.7)	0.565
Hepatolithiasis, n (%)	89 (16.8)	42 (15.6)	47 (17.9)	0.487
CA-199 < 22, n (%)	150 (29.0)	77 (30.0)	73 (28.0)	0.738
Platelet	178 (72)	179 (73)	177 (71)	0.778
Neutrophil	4.6 (2.1)	4.6 (2.3)	4.6 (2.0)	0.976
Lymphocyte	1.6 (0.9)	1.6 (1.2)	1.6 (0.5)	0.641
NLR	3.38 (2.95)	3.34 (2.22)	3.42 (3.54)	0.746
PLR	126 (68)	127 (65)	125 (70)	0.716
SII	612 (635)	605 (495)	619 (751)	0.803
Histological and gross features of tumors
Tumor size, cm	6.0 (2.7)	6.0 (2.7)	6.0 (2.7)	0.783
Solitary tumor, n (%)	373 (70.4)	196 (74.0)	177 (66.8)	0.087
Well tumor differentiation, n (%)	22 (4.2)	11 (4.2)	11 (4.2)	1.000
Macrovascular invasion, n (%)	123 (23.2)	71 (26.8)	52 (19.6)	0.064
Microvascular invasion, n (%)	54 (10.2)	27 (10.2)	27 (10.2)	1.000
Node positive, n (%)	129 (24.3)	61 (23.0)	68 (25.7)	0.544
Perineural invasion, n (%)	80 (15.1)	38 (14.3)	42 (15.8)	0.716
TNM stage, n (%)				0.902
IA	63 (11.9)	33 (12.5)	30 (11.3)
IB	38 (7.2)	21 (7.9)	17 (6.4)
II	56 (10.6)	26 (9.8)	30 (11.3)
IIIA	242 (45.7)	122 (46.0)	120 (45.3)
IIIB	131 (24.7)	63 (23.8)	68 (25.7)
Follow-up, median (range)	18.0 (1.0-115.4)	18.2 (1.0-115.4)	17.8 (1.2-104.5)

Age, platelet, neutrophil and lymphocyte were shown as mean (SD). M: Male; F: Female; CA-199: Carbohydrate antigen-199; TNM: Tumor-node-metastasis; NLR: Neutrophil to lymphocyte ratio; PLR: Platelet to lymphocyte ratio; SII: Systemic immune-inflammation index; HR: Hazard ratio; CI: Confidence interval.

Table 2 Correlation between systemic immune-inflammation index and clinicopathological characteristics in derivation and validation cohort

Variables	Derivation			Validation
	SII ≤ 450	SII > 450	P value	SII ≤ 450	SII > 450	P value
Total patients	123	142		130	135
Age, yr	57.89 (9.5)	57.98 (11.3)	0.943	57.79 (10.7)	55.41 (10.9)	0.074
Male gender, n (%)	67 (54.5)	67 (47.2)	0.268	61 (46.9)	61 (45.2)	0.806
HBsAg, n (%)	45 (36.9)	35 (24.6)	0.033	39 (30.2)	34 (25.2)	0.413
Hepatolithiasis, n (%)	15 (12.2)	27 (19.0)	0.164	22 (16.9)	25 (18.5)	0.758
CA-199 < 22, n (%)	40 (33.1)	37 (27.2)	0.010	45 (34.9)	28 (21.2)	0.002
Platelet	139 (45)	214 (75)	< 0.001	141 (50)	213 (70)	< 0.001
Neutrophil	3.34 (1.0)	5.65 (2.5)	< 0.001	3.46 (1.3)	5.66 (1.9)	< 0.001
Lymphocyte	1.81 (1.7)	1.43 (0.5)	0.009	1.73 (0.5)	1.41 (0.5)	< 0.001
Tumor size, cm	5.2 (2.3)	6.5 (2.9)	< 0.001	5.40 (2.2)	6.36 (3.0)	0.007
Solitary tumor, n (%)	99 (80.5)	97 (68.3)	0.025	92 (70.8)	86 (63.0)	0.197
Well tumor differentiation, n (%)	7 (5.7)	4 (2.8)	0.357	8 (6.2)	3 (2.2)	0.110
Macrovascular invasion, n (%)	33 (26.8)	38 (26.8)	1.000	23 (17.7)	29 (21.5)	0.449
Microvascular invasion, n (%)	12 (9.8)	15 (10.6)	0.844	9 (6.9)	18 (13.3)	0.103
Node positive, n (%)	20 (16.3)	41 (28.9)	0.020	27 (20.8)	41 (30.4)	0.089
Perineural invasion, n (%)	19 (15.4)	19 (13.4)	0.732	22 (16.9)	20 (14.8)	0.745
TNM stage, n (%)			0.017			0.123
IA	22 (17.9)	11 (7.7)		16 (12.3)	14 (10.4)
IB	11 (8.9)	10 (7.0)		8 (6.2)	9 (6.7)
II	14 (11.4)	12 (8.5)		11 (8.5)	19 (14.1)
IIIA	56 (45.5)	66 (46.5)		68 (52.3)	52 (38.5)
IIIB	20 (16.3)	43 (30.3)		27 (20.8)	41 (30.4)

Age, platelet, neutrophil and lymphocyte were shown as mean (SD). M: Male; F: Female; CA-199: Carbohydrate antigen-199; TNM: Tumor-node-metastasis; SII: Systemic immune-inflammation index; HR: Hazard ratio; CI: Confidence interval.

Table 3 Univariate analysis in the derivation cohort

Variables	Overall survival			Recurrence-free survival
	HR	95%CI	P value	HR	95%CI	P value
Age, yr (> 60/≤ 60)	0.917	0.669-1.258	0.592	0.998	0.749-1.330	0.991
Gender (F/M)	0.747	0.546-1.023	0.069	0.791	0.594-1.052	0.107
HBsAg	1.347	0.966-1.878	0.079	1.289	0.947-1.753	0.106
Hepatolithiasis	1.775	1.179-2.675	0.006	1.357	0.913-2.018	0.131
CA-199 (≥ 22/< 22)	1.631	1.122-2.370	0.010	1.357	0.981-1.876	0.065
Tumor size (≥ 5/< 5)	1.171	0.853-1.608	0.328	1.359	1.016-1.818	0.039
Tumor number (multiple/single)	1.686	1.204-2.362	0.002	1.953	1.436-2.658	< 0.001
Tumor differentiation (moderate-poor/well)	5.326	1.318-21.519	0.019	4.498	1.434-14.110	0.010
Macrovascular invasion	1.076	0.753-1.538	0.688	1.014	0.756-1.453	0.776
Microvascular invasion	1.683	1.062-2.667	0.027	2.022	1.325-3.088	0.001
Node positive	2.696	1.928-3.769	< 0.001	1.955	1.424-2.684	< 0.001
Perineural invasion	1.174	0.832-1.656	0.360	1.443	0.976-2.134	0.066
TNM stage (III/I-II)	1.663	1.090-2.539	0.018	1.529	1.130-2.068	0.006
NLR (> 2.65/≤ 2.65)	1.609	1.171-2.212	0.003	1.482	1.111-1.978	0.007
PLR (> 110/≤ 110)	1.482	1.069-2.055	0.018	1.325	0.989-1.776	0.060
SII (> 450/≤ 450)	1.774	1.285-2.449	< 0.001	1.455	1.088-1.946	0.011

M: Male; F: Female; CA-199: Carbohydrate antigen-199; TNM: Tumor-node-metastasis; NLR: Neutrophil to lymphocyte ratio; PLR: Platelet to lymphocyte ratio; SII: Systemic immune-inflammation index; HR: Hazard ratio; CI: Confidence interval.

Table 4 Multivariate analysis in the derivation cohort

Variables	Overall survival			Recurrence-free survival
	HR	95%CI	P value	HR	95%CI	P value
Hepatolithiasis	1.348	0.870-2.088	0.182
CA-199 (≥ 22/< 22)	1.458	0.979-2.170	0.064
Tumor size (≥ 5/<5)				0.873	0.556-1.371	0.555
Tumor number (multiple/single)	1.666	1.140-2.434	0.008	1.679	1.200-2.348	0.002
Tumor differentiation (moderate-poor/well)	3.061	0.739-12.675	0.123	2.813	0.877-9.022	0.082
Microvascular invasion	0.938	0.556-1.582	0.809
Node positive	2.377	1.586-3.562	< 0.001	1.881	1.316-2.688	0.001
TNM stage (III/I-II)	0.682	0.456-1.022	0.064	0.756	0.527-1.085	0.129
SII (> 450/≤ 450)	1.774	1.245-2.528	0.002	1.385	1.005-1.909	0.046

M: Male; F: Female; CA-199: Carbohydrate antigen-199; TNM: Tumor-node-metastasis; SII: Systemic immune-inflammation index; HR: Hazard ratio; CI: Confidence interval.