Risk factors for occult metastasis detected by inflammation-based prognostic scores and tumor markers in biliary tract cancer

Table 1 Patients' demographics

	Type of operations
Characteristics	EL (n = 26)	R (n = 210)	P value
Age, yr1	69 (55-83)	70 (25-89)	0.57
Sex (male / female)	12/14	122/88	0.29
BMI (kg/m2)1	21.8 (18-31.6)	21.8 (15.6-40.1)	0.98
Location of the tumor, n
Intrahepatic bile duct (n = 39)	6	33
Perihilar bile duct (n = 55)	3	52
Distal bile duct (n = 55)	8	47
Gallbladder (n = 50)	9	41
Papilla of Vater (n = 37)	0	37

¹Data are presented as median (range). EL: Exploratory laparotomy; R: Resected.

Table 2 Comparison of laboratory findings and inflammation-based prognostic scores

	Type of operations
Variables	EL (n = 26)	R (n = 210)	P value
Hb (g/dL)1	12.0 ± 0.33	12.3 ± 0.11	0.78
Plt (10000/μL)1	24.4 ± 1.53	22.1 ± 0.54	0.079
PT-INR1	0.97 ± 0.03	0.99 ± 0.01	0.72
Albumin (mg/dL)1	3.73 ± 0.11	3.79 ± 0.04	0.66
ALP (IU/L)1	641 ± 98	564 ± 34	0.22
γ-GTP (IU/L)1	223 ± 51	192 ± 17	0.28
T-bil (mg/dL)1	1.74 ± 0.34	1.24 ± 0.11	0.083
LDH (IU/L)1	212 ± 16	187 ± 5.6	0.079
CRP (mg/dL)1	0.88 ± 0.93	1.23 ± 0.33	0.63
Creatinine clearance (mL/min)1	212 ± 16	187 ± 5.6	0.079
Tumor markers
CA19-9 (IU/mL)1	5198 ± 2767	777 ± 357	0.014
CEA (ng/mL)1	12.3 ± 3.1	5.1 ± 1.0	0.0054
Inflammation-based prognostic scores
NLR1	3.92 ± 0.40	2.81 ± 0.14	0.0018
PLR1	190 ± 18	166 ± 6.4	0.15
PNI1	43.4 ± 3.4	46.7 ± 1.2	0.82
mGPS (A / B, C, D)	9 / 17	126 / 84	0.012

¹Data are presented as the mean ± SD. CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen; NLR: Neutrophil-lymphocyte ratio; PLR: Platelet-lymphocyte ratio; PNI: Prognostic nutrition index; mGPS: Modified Glasgow prognostic score; EL: Exploratory laparotomy; R: Resected.

Table 3 Cut-off values of each variables determined using receiver operator characteristic curves for all BTC patients

Variables	Cut-off value	Sensitivity	Specificity	PPV	AUC
CA19-9	255 IU/mL	0.423	0.823	0.229	0.688
CEA	7 ng/mL	0.346	0.919	0.346	0.645
NLR	3	0.615	0.71	0.208	0.667

PPV: Positive predictive value; AUC: Area under the curve; BTC: Biliary tract cancer.

Table 4 Tumor markers, inflammation-based prognostic scores and survival time according to type of biliary tract cancers

Variables	Type of cancer
	IBDC	EBDC	GBC	Vater C
	(n = 39)	(n = 110)	(n = 50)	(n = 37)
Tumor markers
CA19-9 (IU/mL)1	7904 ± 3316	1356 ± 506	832 ± 371	22 ± 36
CEA (ng/mL) 1	12.2 ± 26.8	4.0 ± 7.5	8.4 ± 22.0	3.2 ± 3.5
Inflammation-based prognostic scores
NLR1	3.04 ± 1.60	2.83 ± 2.20	3.22 ± 2.27	2.74 ± 2.04
PLR1	151.1 ± 56.9	174.0 ± 95.4	176.6 ± 99.2	163.2 ± 109.9
PNI1	48.0 ± 5.5	45.3 ± 24.5	46.7 ± 7.0	47.1 ± 7.1
mGPS (A / B, C, D)	10/29	47/63	32/18	10/27
Cumulative survival time (%)2
1-year	65.0	80.1	82.6	94.6
3-year	48.3	35.7	63.2	75.3
5-year	31.3	26.4	45.8	75.3

¹Data are presented as the mean ± SD.

²Kaplan-Meier analysis. IBDC: Intrahepatic bile duct cancer; EBDC: Extrahepatic bile duct cancer; GBC: Gallbladder cancer; Vater C: Cancer of the papilla of Vater; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen; NLR: Neutrophil-lymphocyte ratio; PLR: Platelet-lymphocyte ratio; PNI: Prognostic nutrition index; mGPS: Modified Glasgow prognostic score.

Table 5 Sensitivity, Specificity and PPV for each biliary cancer

Variables (cut-off value)	Sensitivity	Specificity	PPV
Intrahepatic bile duct cancer
CA19-9 (255 IU/mL)	0.833	0.667	0.313
CEA (7 ng/mL)	0.500	0.849	0.333
NLR (3)	0.500	0.636	0.200
Extrahepatic bile duct cancer
CA19-9 (255 IU/mL)	0.273	0.787	0.125
CEA (7 ng/mL)	0.273	0.939	0.333
NLR (3)	0.455	0.727	0.152
Gallbladder cancer
CA19-9 (255 IU/mL)	0.444	0.878	0.444
CEA (7 ng/mL)	0.444	0.878	0.444
NLR (3)	0.889	0.659	0.364

PPV: Positive predictive value; CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen; NLR: Neutrophil-lymphocyte ratio.

Table 6 Occult liver and peritoneal metastasis according to each criteria, n (%)

Factor	n of patients	No. of patients with occult liver or peritoneal metastasis	Estimated reduction rate of exploratory laparotomy
CA19-9 > 255 U/mL	48 (20)	7	7/48 (14.6)
CEA > 7 ng/mL	26 (11)	6	6/26 (23.1)
NLR > 3	77 (33)	11	11/77 (14.3)
mGPS = B, C, D	101 (43)	5	5/101 (5.0)
Positive factors ≥ 2	73 (31)	11	11/73 (15.1)
Positive factors ≥ 3	26 (11)	7	7/26 (26.9)
Positive factors ≥ 4	6 (3)	2	2/6 (33.3)

CA19-9: Carbohydrate antigen 19-9; CEA: Carcinoembryonic antigen; NLR: Neutrophil-lymphocyte ratio.