Comorbidity negatively influences prognosis in patients with extrahepatic cholangiocarcinoma

Table 1 The Charlson comorbidity index (CCI)[12]

Weight1	Comorbid condition
1	Myocardial infarction
	Congestive heart failure
	Peripheral vascular disease
	Cerebrovascular disease (except hemiplegia)
	Dementia
	Chronic obstructive pulmonary disease
	Connective tissue disease
	Peptic ulcer disease
	Mild liver disease
	Diabetes (without complications)
2	Hemiplegia
	Moderate or severe renal disease
	Diabetes with end-organ damage (retinopathy, neuropathy, etc)
	Any second solid tumor (nonmetastatic), leukemia or lymphoma
3	Moderate or severe liver disease
6	Metastatic solid tumor
	AIDS

¹Optionally, the age index leads to adding 1 point for each decade over 40 years.

Table 2 Demographic, clinical, and laboratory data of patients at baseline (mean ± SD) n (%)

Variable	Perihilar (n = 37)	Distal (n = 31)	Total (n = 68)
Age (yr)	74.2 ± 10.5	72.4 ± 12.6	73.4 ± 11.5
Sex (M/F)	18/19	16/15	34/34
Smoking	13 (35.1)	8 (25.8)	21 (30.9)
Predisposing factor	5 (13.5)	1 (3.2)	6 (8.8)
Family history of malignancy	1 (2.7)	4 (12.9)	5 (7.4)
Clinical manifestations
Jaundice	33 (89.2)	26 (83.9)	59 (86.8)
Abdominal pain	16 (43.2)	9 (29.0)	25 (36.7)
Weight loss	11 (29.7)	8 (25.8)	19 (27.9)
Fever	0 (0)	3 (9.7)	3 (4.4)
Casual diagnosis	0 (0)	1 (3.2)	1 (1.5)
Symptoms duration (mo) [median (range)]	0.3 (0.01-12)	0.5 (0.05-3.5)	0.5 (0.01-12)
AST (IU/L)	146 ± 104	129 ± 121	138 ± 111
ALT (IU/L)	211 ± 166	172 ± 139	193 ± 144
γ-GT (IU/L)	629 ± 377	811 ± 660	712 ± 529
LDH (IU/L)a	269 ± 180	169 ± 54	223 ± 174
Albumin (g/dL)	3.3 ± 0.4	3.2 ± 0.7	3.2 ± 0.6
Bilirubin (mg/dL)	15.6 ± 9.1	12.6 ± 9.5	14.2 ± 9.3
Hemoglobin (g/dL)	13.4 ± 1.4	12.7 ± 2.3	13.1 ± 1.9
Platelets (× 1000/μL)	257 ± 99	294 ± 103	274 ± 102
Creatinine (mg/dL)	0.8 ± 0.4	0.8 ± 0.3	0.8 ± 0.3
CA 19-9 (IU/L) [median (range)]1	989 (2.9-65 920)	87.6 (9-11 641)	269 (2.9-65 920)

¹Data available for 29 patients;

^aP = 0.005; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CA 19-9: Carbohydrate antigen 19-9; γ-GT: γ-glutamyltranspeptidase; LDH: Lactate dehydrogenase.

Table 3 Analysis of predictive variables for resectable tumor

Variable	Univariate			Multivariate
	OR	95% CI	P	OR	95% CI	P
Age ≥ 73 yr	0.24	0.0-0.7	0.012	-
Distal location	5.27	1.6-17.1	0.004	-
CEA ≥ 5 IU/L	0.09	0.0-0.6	0.013	-
CA 19-9 ≥ 270 IU/L	0.05	0.0-0.5	0.003	0.07	0.0-0.7	0.026

CEA: Carcinoembrionary antigen; OR: Odds ratio.

Table 4 AJCC-TNM staging distribution

	Perihilar (n = 37)	Distal (n = 31)	Total (n = 68)
Tumor status
T1	3	3	6
T2	8	5	13
T3	16	9	25
T4	3	6	9
Unknown	7	8	15
Lymph node status
N0	27	19	46
N1	10	10	20
Unknown	1	1	2
Metastases status
M0	31	28	59
M1	6	3	9

AJCC: American Joint Committee on Cancer; TNM: Tumor, Node, Metastases.

Table 5 Univariate and multivariate analysis for prognostic survival variables

Variable (n)	Median survival (mo)	95% CI	P (univariate)	P (multivariate)	HR	95% CI
Age at diagnosis
< 73 yr (30)	4.7	0.7-8.7	0.054	-
≥ 73 yr (38)	2.2	0.7-3.8
History of weight loss
No (49)	3.6	0.9-6.2	0.085	-
Yes (19)	2.1	0.5-3.6
CCI score
0-1 (49)	4.7	3.1-6.3	0.017	0.045	3.36	1.0-10.9
≥ 2 (19)	1.4	0.4-2.3
Total bilirubin
< 10 mg/dL (23)	3.6	0.7-6.6	0.583	-
≥ 10 mg/dL (45)	2.3	0-0-4.6
Hemoglobin
≥ 12 g/dL (49)	3.6	1.4-5.7	0.097	-
< 12 g/dL (19)	2.2	0.1-4.4
CA 19-91
< 270 IU/L (15)	8.4	0.0-18.3	0.012	0.089	-	-
≥ 270 IU/L (14)	2.7	0.2-5.2
Primary location
Perihilar (37)	3.1	1.1-5.2	0.994	-
Distal (31)	2.5	0.0-6.3
Lymph node status2
No (46)	2.3	0.0-5.0	0.286	-
Yes (20)	3.6	1.5-5.8
Metastases
No (59)	3.6	1.3-6.1	0.068	-
Yes (9)	0.7	0.3-1.1
Tumor resection
No (49)	2.3	1.4-3.2	0.015	0.005	0.1	0.02-0.51
Yes (19)	8.7	0.0-19.8
Adjuvant therapy3
No (41)	2.1	1.0-3.1	0.129	-
Yes (8)	5.1	2.5-3.2

¹Data available for 29 patients;

²Data available for 66 patients;

³Denotes chemotherapy or brachy-radiotherapy in patients not receiving surgical resection; HR: Hazard ratio; CCI: Charlson comorbidity index.