Carbohydrate antigen 19-9 as a novel prognostic biomarker in distal cholangiocarcinoma

Table 1 Demographic and pathological findings in patients with distal cholangiocarcinoma

Variables	Group 1 (n = 81)	Group 2 (n = 105)	P
Gender (M/F)	50/31	63/42	0.811
Age, mean ± SD, yr	63.7 ± 9.1	65.8 ± 8.1	0.093
Smoking (Y/N)	24/57	38/67	0.347
Diabetes (Y/N)	18/63	35/70	0.096
PBD (Y/N)	35/46	55/50	0.215
TB (μmol/L)	76.7 (35.4–211.3)	110.0 (24.1–203.4)	0.78
CA19-9 (U/mL)	27.3 (11.7–45.6)	139.8 (42.7–316.2)	0
γ-GGT (U/L)	706 (395–1194)	207 (80–446)	0
Tumor size, mean ± SD, cm	2.1 ± 0.9	2.2 ± 1.1	0.82
Tumor differentiation (poor/moderate & high)	20/61	32/73	0.412
Nerve invasion (Y/N)	68/13	Nov-94	0.261
Intraoperative blood loss (mL)	500 (400–600)	500 (400–800)	0.222
Blood transfusion (Y/N)	30/51	36/69	0.697
OP time, mean ± SEM, h	9.5 ± 1.4	10.0 ± 2.1	0.079
LN metastasis (+/–)	18/63	57/48	0
Resection margin (R0/R1)	Jan-80	Jul-98	0.141
Postoperative chemotherapy (Y/N)	20/61	19/86	0.273

PBD: preoperative biliary drainage; TB: total bilirubin; CA19-9: carbohydrate antigen 19-9; γ-GGT: γ-glutamyltransferase; OP: operation; LN: lymph node; R: resection margin.

Table 2 Univariate analysis of risk factors for distal cholangiocarcinoma recurrence

Variable	n	1-yr OS (%)	3-yr OS (%)	χ2	P
Gender				2.434	0.119
Male	113	69.6	42.9
Female	73	63	23.3
Age, yr				1.155	0.283
≤ 60	53	67.7	39.7
> 60	133	66.8	31.8
Smoking				0.883	0.347
Yes	62	69.3	32
No	124	65.9	35.5
Diabetes				0.734	0.391
Yes	53	61.6	32.7
No	133	69.1	34.9
PBD				0.519	0.471
Yes	90	67	31.3
No	96	67.1	36.8
TB (μmol/L)				2.556	0.11
≤ 21	38	82.4	34.3
> 21	148	63.3	32.4
CA19-9 (U/mL)				5.688	0.017
≤ 37	69	83.5	43.7
> 37	117	56.5	28
γ-GGT (U/L)				0.06	0.806
≤ 45	11	51.1	51.1
> 45	175	68	34
CA19-9/GGT				26.824	0
≤ 0.12	81	84.2	51
> 0.12	105	52.9	20.1
OP time, h				0.299	0.585
≤ 9	83	65.4	36.3
> 9	103	68.2	31.5
Intraoperative blood loss (mL)				1.282	0.258
≤ 500	117	69.3	35.5
> 500	69	62.6	30.7
Blood transfusion				7.235	0.007
Yes	66	56.3	24.7
No	120	72.7	37.9
Degree of differentiation				20.848	0
Poor	52	34.2	22.2
Moderate & high	134	79.9	39
Tumor size, cm				3.313	0.069
≤ 2	114	72.7	39.6
> 2	72	57.7	24.5
LN metastasis				32.491	0
Yes	75	45.6	15.4
No	111	81.1	47.8
Nerve invasion				4.963	0.026
Yes	162	65.4	31.8
No	24	80	60
Resection margin				0.943	0.332
R0	178	67	34.8
R1	8	66.7	16.7
Postoperative complication				0.197	0.657
Yes	54	75.2	30.1
No	132	64.3	34.9
Postoperative chemotherapy				0.011	0.917
Yes	39	65.7	36.5
No	147	67.4	33.5

OS: overall survival; PBD: preoperative biliary drainage; TB: total bilirubin; CA19-9: carbohydrate antigen 19-9; γ-GGT: γ-glutamyltransferase; OP: operation; LN: lymph node; R: resection margin.

Table 3 Morbidity and mortality between two groups in patients with distal cholangiocarcinoma

Variables	Group 1 (n = 81)	Group 2 (n = 105)	P
Postoperative hospital stay (d)	21 (16–24)	20 (16–29)	0.368
In-hospital death	1	6	0.229
Complications	20	34	0.252
Biochemical fistula	12	7	0.069
Pancreatic fistula
Grade B	4	2	0.458
Grade C	3	4	0.726
Delayed gastric emptying	2	6	0.473
Intra-abdominal infection	7	9	0.986
Abdominal hemorrhage	4	7	0.856

Table 4 Multivariate analysis of independent risk factors for distal cholangiocarcinoma recurrence

Variable	RR	95%CI	P
CA19-9	0.921	0.578–1.468	0.728
CA19-9/GGT	2.134	1.319–3.451	0.002
Blood transfusion	0.74	0.497–1.103	0.139
Degree of differentiation	1.695	1.115–2.576	0.013
LN metastasis	2.145	1.404–3.277	0
Nerve invasion	1.238	0.520–2.951	0.63

RR: relative risk; CI: confidence interval; CA19-9: carbohydrate antigen 199; GGT: γ-glutamyltransferase; LN: lymph node.

Table 5 Univariate analysis of long-term survival in patients with distal cholangiocarcinoma

Variable	n	1-yr OS (%)	3-yr OS (%)	χ2	P
Gender				1.351	0.245
Male	113	76.1	40.8
Female	73	67.9	25.9
Age, yr				2.381	0.123
≤ 60	53	80.9	36.4
> 60	133	69.5	32.3
Smoking				0.822	0.364
Yes	62	78.2	27.3
No	124	70.2	36.1
Diabetes				0.014	0.906
Yes	53	70.8	32.6
No	133	73.5	34.6
PBD				1.217	0.27
Yes	90	70.2	27.7
No	96	75.1	39.9
TB (μmol/L)				0.623	0.43
≤ 21	38	78.9	44.4
> 21	148	70.9	32.3
CA19-9 (U/ml)				8.239	0.004
≤ 37	69	85	49
> 37	117	65.5	25.5
γ-GGT (U/L)				0.169	0.681
≤ 45	11	71.6	43
> 45	175	72.9	34.1
CA19-9/GGT				38.091	0
≤ 0.12	81	88.3	59.2
> 0.12	105	61	13.6
OP time, h				0.008	0.929
≤ 9	83	68.8	38.4
> 9	103	76	31.6
Intraoperative blood loss (mL)				2.693	0.101
≤ 500	117	72.8	39.1
> 500	69	72.5	26.2
Blood transfusion				8.307	0.004
Yes	66	65.1	26.1
No	120	76.9	37.3
Degree of differentiation				21.212	0
Poor	52	51.5	19.4
Moderate & high	134	80.9	40
Tumor size, cm				1.544	0.214
≤ 2	114	78.4	35.7
> 2	72	63.6	31.3
LN metastasis				30.845	0
Yes	75	59.8	15.8
No	111	81.4	48.4
Nerve invasion				1.861	0.173
Yes	162	73.7	30.3
No	24	66.2	66.2
Resection margin				3.343	0.067
R0	178	73.2	35.2
R1	8	62.5	12.5
Postoperative complication				2.357	0.125
Yes	54	67.8	28.8
No	132	74.9	36.3
Postoperative chemotherapy				0.073	0.788
Yes	39	70.4	36.8
No	147	73.4	33.5

OS: overall survival; PBD: preoperative biliary drainage; TB: total bilirubin; CA19-9: carbohydrate antigen 19-9; γ-GGT: γ-glutamyltransferase; OP: operation; LN: lymph node; R: resection margin.

Table 6 Multivariate analysis of long-term survival in patients with distal cholangiocarcinoma

Variable	RR	95%CI	P
CA19-9	0.974	0.607–1.561	0.911
CA19-9/GGT	2.837	1.727–4.660	0
Blood transfusion	0.763	0.513–1.135	0.182
Degree of differentiation	1.725	1.140–2.609	0.01
LN metastasis	2.05	1.336–3.144	0.001

CA19-9: carbohydrate antigen 19-9; GGT: γ-glutamyltransferase; LN: lymph node.