Lymphocyte to C-reactive protein ratio as a novel inflammatory biomarker: Validation and clinical relevance as an independent prognostic factor in cholangiocarcinoma

Table 1 Clinicopathological characteristics of 76 patients with cholangiocarcinoma, n (%)

Variables	Number of patients	Low LCR	High LCR	P value
Age				0.287
≤ 70	58 (76.32)	43 (56.58)	15 (19.74)
> 70	18 (23.68)	11 (14.47)	7 (9.21)
Sex				0.870
Male	46 (60.53)	33 (43.42)	13 (17.11)
Female	30 (39.47)	21 (27.63)	9 (11.84)
Obstructive jaundice				0.432
Yes	50 (65.79)	37 (48.7)	13 (17.1)
No	26 (34.21)	17 (22.4)	9 (11.8)
CEA				0.989
Normal	45 (59.21)	32 (42.1)	13 (17.1)
Abnormal	31 (40.79)	22 (28.9)	9 (11.8)
CA199
Normal	23 (30.26)	17 (22.4)	6 (7.9)	0.717
Abnormal	53 (69.74)	37 (48.7)	16 (21.1)
CA125				0.606
Normal	52 (68.42)	36 (47.4)	16 (21.1)
Abnormal	24 (31.58)	18 (23.7)	6 (7.9)
CRP				< 0.001a
Normal	33 (43.42)	11 (14.5)	22 (28.9)
Abnormal	43 (56.58)	43 (56.6)	0 (0.0)
WBC count (109/L)				0.343
Normal	35 (46.05)	23 (30.3)	12 (15.8)
Abnormal	41 (53.95)	31 (40.8)	10 (13.2)
Albumin (g/L)				0.471
Normal	58 (76.32)	40 (52.6)	18 (23.7)
Abnormal	18 (23.68)	14 (18.4)	4 (5.3)
Hemoglobin (g/L)				0.851
Normal	23 (30.26)	16 (21.1)	7 (9.2)
Abnormal	53 (69.74)	38 (50.0)	15 (19.7)
Tumor location				0.277
Intrahepatic	21 (27.63)	13 (17.1)	8 (10.5)
Extrahepatic	55 (72.37)	41 (53.9)	14 (18.4)
Number of tumor
1	71 (93.42)	51 (67.1)	20 (26.3)	0.573
≥ 2	5 (6.58)	3 (3.9)	2 (2.6)
Tumor size				0.900
Largest diameter ≥ 5 cm	18 (23.68)	13 (17.1)	5 (6.6)
Largest diameter < 5 cm	58 (76.32)	41 (53.9)	17 (22.4)
Surrounding vascular invasion				0.188
Yes	18 (23.68)	15 (19.7)	3 (3.9)
No	58 (76.32)	39 (51.3)	19 (25.0)
Surrounding tissues invasion				0.307
Yes	64 (84.21)	44 (57.9)	20 (26.3)
No	12 (15.79)	10 (13.2)	2 (2.6)
Lymph node metastasis				0.666
Yes	27 (35.52)	20 (26.3)	7 (9.2)
No	49 (64.48)	34 (44.7)	15 (19.7)
Tumor stage
II	38 (50.00)	27 (34.5)	11 (14.5)	1.0
III	38 (50.00)	27 (34.5)	11 (14.5)
Tumor grade				0.404
I	26 (34.21)	16 (21.1)	10 (13.2)
II	39 (51.32)	30 (39.5)	9 (11.8)
III	11 (14.47)	8 (10.5)	3 (3.9)
R0 resection				0.115
Yes	66 (86.84)	49 (64.5)	17 (22.3)
No	10 (13.16)	5 (6.6)	5 (6.6)

^aP < 0.05.

LCR: Lymphocyte to C-reactive protein ratio; CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen; CRP: C-reactive protein; WBC: White blood cell.

Table 2 Univariate and multivariate analyses of surgical site infection predictors

Variables	Univariate			Multivariate
	OR	95%CI	P value	OR	95%CI	P value
Age
> 70	2.436	0.628-9.448	0.098	2.520	0.592-10.734	0.211
Sex
Female	2.400	0.872-6.603	0.190
Obstructive jaundice
Yes	2.600	0.932-7.255	0.068	2.437	0.707-8.394	0.158
CEA
Abnormal	1.007	0.367-2.761	0.989
CA199
Abnormal	1.978	0.695-5.626	0.201
CA125
Abnormal	1.800	0.638-5.081	0.267
CRP
Abnormal	1.156	0.423-3.158	0.778
WBC count (109/L)
Abnormal	1.034	0.382-2.799	0.947
Albumin (g/L)
Abnormal	1.824	0.598-5.564	0.291
Hemoglobin (g/L)
Abnormal	2.443	0.722-8.265	0.151
Tumor location
Intrahepatic	2.423	0.835-7.028	0.099	2.094	0.568-7.726	0.267
Number of tumors
≥ 2	1.700	0.264-10.947	0.577
Tumor size
Largest diameter ≥ 5 cm	1.312	0.421-4.090	0.639
Surrounding vascular invasion
Yes	1.575	0.455-5.457	0.474
Surrounding tissues invasion
Yes	1.975	0.552-7.065	0.295
Lymph node metastasis
Yes	1.697	0.573-5.028	0.340
Tumor stage
III	1.292	0.478-3.494	0.613
Tumor grade
III vs II vs I	1.050	0.501-2.2	0.897
R0 resection
Yes	1.739	0.339-8.390	0.507
LCR
Low	3.438	0.901-13.125	0.071	4.412	1.035-18.806	0.045

OR: Odds ratio; CI: Confidence interval; CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen; CRP: C-reactive protein; WBC: White blood cell; LCR: Lymphocyte to C-reactive protein ratio.

Table 3 Univariate and multivariate analyses of predictors of hospital stay

Variables	Univariate			Multivariate
	OR	95%CI	P value	OR	95%CI	P value
Age
> 70	1.538	0.531-4.458	0.427
Sex
Male	1.190	0.474-2.991	0.711
Obstructive jaundice
Yes	1.174	0.455-3.032	0.740
CEA
Abnormal	1.161	0.464-2.908	0.749
CA199
Normal	1.252	0.468-3.351	0.655
CA125
Abnormal	1.094	0.415-2.886	0.856
CRP
Abnormal	3.267	1.267-8.419	0.414
WBC count (109/L)
Abnormal	1.353	0.547-3.346	0.513
Albumin (g/L)
Abnormal	2.985	0.942-9.458	0.063	4.306	1.062-17.454	0.041
Hemoglobin (g/L)
Abnormal	1.696	0.632-4.551	0.294
Tumor location
Extrahepatic	1.014	0.371-2.775	0.978
Number of tumors
1	4.875	0.519-45.821	0.166
Tumor size
Largest diameter ≥ 5 cm	2.143	0.708-6.483	0.177
Surrounding vascular invasion
Yes	1.167	0.403-3.377	0.766
Surrounding tissues invasion
No	2.000	0.547-7.312	0.295
Lymph node metastasis
Yes	1.515	0.586-3.919	0.391
Tumor stage
III	1.894	0.761-4.716	0.070	1.695	0.574-5.004	0.339
Tumor grade
III vs II vs I	1.412	0.713-2.797	0.323
R0 resection
Yes	1.800	0.464-6.976	0.395
LCR
Low	4.533	1.526-13.467	0.007	8.511	2.403-30.149	0.001
Complication
Yes	3.367	1.177-9.631	0.024	8.392	2.246-31.359	0.002

OR: Odds ratio; CI: Confidence interval; CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen; CRP: C-reactive protein; WBC: White blood cell; LCR: Lymphocyte to C-reactive protein ratio.

Table 4 Univariate and multivariate analyses of predictors of overall survival

Variables	Median OS	Univariate			Multivariate
		HR	95%CI	P value	HR	95%CI	P value
Age
≤ 70/> 70	21.86/17.03	0.919	0.489-1.728	0.793
Sex
Male/female	22.80/17.03	0.799	0.447-1.359	0.379
Obstructive jaundice
Yes/no	16.47/22.70	1.129	0.635-2.010	0.679
CEA
Abnormal/normal	21.86/22.80	1.02	0.575-1.811	0.946
CA199
Abnormal/normal	17.33/28.90	1.434	0.774-2.658	0.252
CA125
Abnormal/normal	19.43/22.80	1.118	0.593-2.108	0.729
CRP
Abnormal/normal	11.73/39.93	1.695	0.962-2.987	0.068
WBC count (109/L)
Abnormal/normal	19.43/22.80	1.09	0.626-1.899	0.760
Albumin (g/L)
Abnormal/normal	10.03/22.70	1.104	0.577-2.111	0.766
Hemoglobin (g/L)
Abnormal/normal	19.43/22.70	1.2	0.675-2.133	0.535
Tumor location
Extrahepatic/intrahepatic	25.53/19.43	0.787	0.551-1.125	0.189
Number of tumors
≥ 2/1	19.43/22.80	1.552	0.555-4.339	0.402
Tumor size
Largest diameter ≥ 5 cm/< 5 cm	8.27/22.80	1.528	0.813-2.873	0.188
Surrounding vascular invasion
Yes/no	7.37/24.87	2.07	1.130-3.793	0.019	1.292	0.629-2.655	0.486
Surrounding tissues invasion
Yes/no	19.10/32.03	1.565	0.667-3.674	0.304
Lymph node metastasis
Yes/no	17.03/24.87	1.605	0.913-2.820	0.100
Tumor stage
III/II	13.93/32.03	1.728	0.992-3.008	0.053	2.017	1.051-3.871	0.035
Tumor grade
III/II/I	15.70/22.70/46.51	1.497	1.003-2.234	0.094
R0 resection
No/ yes	7.37/24.87	2.156	1.042-4.461	0.038	3.547	1.567-8.029	0.002
LCR
Low/high	14.93/46.67	2.025	1.159-3.539	0.022	3.204	1.546-6.643	0.002
Complication
Yes/no	17.03/21.86	1.406	0.563-1.941	0.024	1.261	0.663-2.395	0.480
Postoperative adjuvant therapy
Yes/no	22.80/15.40	0.721	0.405-1.284	0.267

OS: Overall survival; HR: Hazard ratio; CI: Confidence interval; CEA: Carcinoembryonic antigen; CA: Carbohydrate antigen; CRP: C-reactive protein; WBC: White blood cell; LCR: Lymphocyte to C-reactive protein ratio.