Prognostic significance of combined preoperative fibrinogen and CA199 in gallbladder cancer patients

Table 1 Baseline characteristics of 154 patients who underwent potential curative cholecystectomy n (%)

Characteristic	Patients (n = 154)
Age (yr)	64 (29-85)
≤ 60	56 (36.4)
> 60	98 (63.6)
Sex
Male	63 (40.9)
Female	91 (59.1)
Cholecystolithiasis
Absent	79 (51.3)
Present	75 (48.7)
Diabetes
Absent	116 (75.3)
Present	38 (24.7)
Jaundice
Absent	129 (83.8)
Present	25 (8.9)
Blood groups
A	43 (27.9)
B	56 (36.4)
AB	9 (5.8)
O	46 (29.9)
Pathological types
Adenosquamous carcinoma	3 (1.9)
Adenocarcinoma	150 (97.4)
Papillocarcinoma	1 (0.6)
Degree of differentiation
Poor	60 (39.0)
Moderate-well	94 (61.0)
Resection margin status
Negative	96 (62.3)
Positive	58 (37.7)
Maximum tumor diameter (cm)	3 (0.2-13)
≤ 2.45	68 (44.2)
> 2.45	86 (55.8)
T stage
Tis-T1a	10 (6.5)
T1b-T2b	29 (18.8)
T3	103 (66.9)
T4	12 (7.8)
N stage
0	98 (63.6)
1	47 (30.5)
2	9 (5.8)
Distant metastasis
Absent	142 (92.2)
Present	12 (7.8)
TNM stage
0-I stage	16 (10.4)
IIA-IIB stage	16 (10.4)
IIIA-IIIB stage	92 (59.7)
IVA-IVB stage	30 (19.5)
CA199 (U/mL)	69.3 (0.6-10524)
≤ 25.45	57 (37.0)
> 25.45	97 (63.0)
Fibrinogen concentration (g/L)	3.54 (1.71-7.47)
≤ 3.47	75 (48.7)
> 3.47	79 (51.3)

Table 2 Correlation between fibrinogen concentration and clinicopathological characteristics in gallbladder carcinoma patients n (%)

Characteristics	Fibrinogen concentration		P value
	≤ 3.47 g/L (n = 75)	> 3.47 g/L (n = 79)
Age (yr)
≤ 60	31 (20.1)	25 (16.2)	0.243
> 60	44 (28.6)	54 (35.1)
Sex
Male	33 (21.4)	30 (19.5)	0.513
Female	42 (27.3)	49 (31.8)
Cholecystolithiasis
Absent	38 (24.7)	41 (26.6)	0.878
Present	37 (24.0)	38 (24.7)
Diabetes
Absent	57 (37.0)	59 (38.3)	0.850
Present	18 (11.7)	20 (13.0)
Jaundice
Absent	68 (44.2)	61 (39.6)	0.029
Present	7 (4.5)	18 (11.7)
Blood groups
A	19 (12.3)	24 (15.6)	0.145
B	33 (21.4)	23 (14.9)
AB	2 (1.3)	7 (4.5)
O	21 (13.6)	25 (16.2)
Pathological types
Adenosquamous carcinoma	0 (0)	3 (1.9)	0.142
Adenocarcinoma	75 (48.7)	75 (48.7)
Papillocarcinoma	0 (0)	1 (0.6)
Degree of differentiation
Poor	23 (14.9)	37 (24.0)	0.048
Moderate-well	52 (33.8)	42 (27.3)
Resection margin status
Negative	56 (36.4)	40 (26.4)	0.003
Positive	19 (12.3)	39 (25.3)
Maximum tumor diameter (cm)
≤ 2.45	34 (22.1)	34 (22.1)	0.871
> 2.45	41 (26.6)	45 (29.2)
T stage
Tis-T1a	8 (5.2)	2 (1.3)	< 0.001
T1b-T2b	22 (14.3)	7 (4.5)
T3	43 (27.9)	60 (39.0)
T4	2 (1.3)	10 (6.5)
N stage
N0	50 (32.5)	48 (31.2)	0.748
N1	21 (13.6)	26 (16.9)
N2	4 (2.6)	5 (3.2)
Distant metastasis
Absent	69 (44.8)	73 (47.4)	0.925
Present	6 (3.9)	6 (3.9)
TNM stage
0-I stage	12 (7.8)	4 (2.6)	0.011
IIA-IIB stage	12 (7.8)	4 (2.6)
IIIA-IIIB stage	39 (25.3)	53 (34.4)
IVA-IVB stage	12 (7.8)	18 (11.7)
CA199 (U/mL)
≤ 25.45	37 (24.0)	20 (13.0)	0.003
> 25.45	38 (24.7)	59 (38.3)

Table 3 Correlation between CA199 level and clinicopathological characteristics in gallbladder carcinoma patients n (%)

Characteristics	CA199 level		P value
	≤ 25.45 U/mL (n = 57)	> 25.45 U/mL (n = 97)
Age (yr)
≤ 60	24 (15.6)	32 (20.8)	0.299
> 60	33 (21.4)	65 (42.2)
Sex
Male	23 (14.9)	40 (26.0)	0.914
Female	34 (21.1)	57 (37.0)
Cholecystolithiasis
Absent	32 (20.8)	47 (30.5)	0.406
Present	25 (16.2)	50 (32.5)
Diabetes
Absent	45 (29.2)	71 (46.1)	0.447
Present	12 (7.8)	26 (16.9)
Jaundice
Absent	53 (34.4)	76 (49.4)	0.022
Present	4 (2.6)	21 (13.6)
Blood groups
A	19 (12.3)	24 (15.6)	0.303
B	21 (13.6)	35 (22.7)
AB	1 (0.6)	8 (5.2)
O	16 (10.4)	30 (19.5)
Pathological types
Adenosquamous carcinoma	0 (0)	3 (1.9)	0.299
Adenocarcinoma	57 (37.0)	93 (60.4)
Papillocarcinoma	0 (0)	1 (0.6)
Degree of differentiation
Poor	33 (21.4)	61 (39.6)	0.069
Moderate-well	24 (15.6)	36 (23.4)
Resection margin status
Negative	45 (29.2)	51 (33.1)	0.001
Positive	12 (7.8)	46 (29.9)
Maximum tumor diameter (cm)
≤ 2.45	30 (19.5)	38 (24.7)	0.131
> 2.45	27 (17.5)	59 (38.3)
T stage
Tis-T1a	7 (4.5)	3 (1.9)	< 0.001
T1b-T2b	18 (11.7)	11 (7.1)
T3	32 (20.8)	71 (46.1)
T4	0 (0.0)	12 (7.8)
N stage
N0	43 (27.9)	55 (35.7)	0.056
N1	11 (7.1)	36 (23.4)
N2	3 (1.9)	6 (3.9)
Distant metastasis
Absent	53 (34.4)	89 (57.8)	0.783
Present	4 (2.6)	8 (5.2)
TNM stage
0-I stage	11 (7.1)	5 (3.2)	< 0.001
IIA-IIB stage	12 (7.8)	4 (2.6)
IIIA-IIIB stage	27 (17.5)	65 (42.2)
IVA-IVB stage	7 (4.5)	23 (14.9)
Fibrinogen concentration (g/L)
≤ 3.47	37 (24.0)	38 (24.7)	0.003
> 3.47	20 (13.0)	59 (38.3)

Table 4 Univariate analysis of overall survival in gallbladder cancer patients

Characteristics	HR (95%CI)	P value
Age (yr)	1.473 (0.973-2.230)	0.067
≤ 60
> 60
Sex	0.995 (0.670-1.477)	0.981
Male
Female
Cholecystolithiasis	1.198 (0.814-1.764)	0.360
Absent
Present
Diabetes	1.028 (0.651-1.623)	0.906
Absent
Present
Jaundice	2.598 (1.644-4.106)	< 0.001
Absent
Present
Blood groups	-	0.113
A
B
AB
O
Pathological types	-	0.165
Adenosquamous carcinoma
Adenocarcinoma
Papillocarcinoma
Degree of differentiation	1.527 (1.031-2.261)	0.035
Poor
Moderate-well
Resection margin status	3.683 (2.468-5.496)	< 0.001
Negative
Positive
Maximum tumor diameter (cm)	1.101 (0.744-1.630)	0.631
≤ 2.45
> 2.45
T stage	-	< 0.001
Tis-T1a
T1b-T2b
T3
T4
N stage	-	< 0.001
N0
N1
N2
Distant metastasis	2.550 (1.388-4.684)	< 0.003
Absent
Present
TNM stage	-	< 0.001
0-I stage
IIA-IIB stage
IIIA-IIIB stage
IVA-IVB stage
CA199 (U/mL)	3.570 (2.213-5.760)	< 0.001
≤ 25.45
> 25.45
Fibrinogen concentration (g/L)	2.790 (1.853-4.214)	< 0.001
≤ 3.47
> 3.47

Table 5 Multivariate analysis of overall survival in gallbladder cancer patients

Characteristics	HR (95%CI)	Wald	P value
Resection margin status	1.971 (1.288-3.017)		0.002
Negative
Positive
TNM stage		11.299	0.003
IIA-IIB stage/0-1 stage	1.336 (0.317-5.627)	0.156	0.693
IIIA-IIIB stage/0-1 stage	3.831 (1.167-12.571)	4.907	0.027
IVA-IVB stage/0-1 stage	5.204 (1.497-18.093)	6.730	0.009
Fibrinogen concentration (g/L)	1.711 (1.114-2.627)		0.014
≤ 3.47
> 3.47
CA199 (U/mL)	1.842 (1.111-3.056)		0.018
≤ 25.45
> 25.45

Table 6 Univariate and multivariate analysis of overall survival in gallbladder cancer patients according to the combination of fibrinogen and CA199

Characteristics	HR (95%CI)	Wald	P value
Univariate analysis
Combined fibrinogen and CA199	-		< 0.001
0
1
1.1
2.1
Multivariate analysis
Resection margin status	1.973 (1.289-3.020)		0.002
Negative
Positive
TNM stage	11.299		0.011
IIA-IIB stage/0-1 stage	1.342 (0.318-5.659)	0.160	0.689
IIIA-IIIB stage/0-1 stage	3.812 (1.158-12.545)	4.848	0.028
IVA-IVB stage/0-1 stage	5.189 (1.491-18.055)	6.699	0.010
Combined fibrinogen and CA199	14.218		0.003
1/0	1.784 (0.775-4.104)	1.854	0.173
1.1/0	1.895 (0.943-3.806)	3.222	0.073
2.1/0	3.195 (1.676-6.090)	12.454	0.000

The number 0 for fibrinogen concentration > 3.47g/L with CA199 level > 25.45 U/mL group, number 1 for fibrinogen concentration > 3.47 g/L with CA199 level ≤ 25.45 U/mL group, number 1.1 for fibrinogen concentration ≤ 3.47g/L with CA199 level > 25.45 U/mL group, and number 2.1 for fibrinogen concentration ≤ 3.47 g/L with CA199 level ≤ 25.45 U/mL group.