Development of a model based on the age-adjusted Charlson comorbidity index to predict survival for resected perihilar cholangiocarcinoma

Table 1 Weighted index of comorbidities in the age-adjusted Charlson comorbidity index and patient distribution

Conditions	Training cohort (n = 244)	Validation cohort (n = 81)	Total patients (n = 325)
1 point per decade for age > 40 (0 to 4 points)
< 50	88 (36.1)	27 (33.3)	115 (35.4)
50-59	64 (26.2)	25 (30.9)	89 (27.4)
60-69	55 (22.5)	19 (23.5)	74 (22.8)
70-79	27 (11.1)	7 (8.6)	34 (10.5)
≥ 80	10 (4.1)	3 (3.7)	13 (4.0)
1 point
Mild liver disease	42 (17.2)	12 (14.8)	54 (16.6)
Peptic ulcer disease	11 (4.5)	4 (4.9)	15 (4.6)
Congestive heart failure	9 (3.6)	2 (2.4)	11 (3.4)
Peripheral vascular disease	9 (3.6)	5 (6.1)	14 (4.3)
Cerebrovascular disease	6 (2.4)	1 (1.2)	7 (2.2)
Chronic pulmonary disease	6 (2.4)	1 (1.2)	7 (2.2)
Connective tissue disease	4 (1.6)	3 (3.7)	7 (2.2)
Myocardial infarction	0 (0.0)	0 (0.0)	0 (0.0)
Dementia	0 (0.0)	0 (0.0)	0 (0.0)
Diabetes without end-organ damage	42 (17.2)	12 (14.8)	54 (16.6)
2 points
Diabetes with end-organ damage	10 (4.1)	4 (4.9)	14 (4.3)
Moderate/severe renal disease	8 (3.2)	1 (1.2)	9 (2.8)
Other tumor	0 (0.0)	0 (0.0)	0 (0.0)
Leukemia	0 (0.0)	0 (0.0)	0 (0.0)
Hemiplegia/paraplegia	0 (0.0)	0 (0.0)	0 (0.0)
Malignant lymphoma	0 (0.0)	0 (0.0)	0 (0.0)
3 points
Moderate/severe liver disease	3 (1.2)	0 (0.0)	3 (0.9)
6 points
Metastatic solid tumor	0 (0.0)	0 (0.0)	0 (0.0)
AIDS	0 (0.0)	0 (0.0)	0 (0.0)

AIDS: Acquired immune deficiency syndrome.

Table 2 Comparison of patient characteristics between the age-adjusted Charlson comorbidity index groups in the training cohort

Patient demographics	Total (n = 244)	ACCI = 0-1 (n = 116)	ACCI = 2-3 (n = 91)	ACCI ≥ 4 (n = 37)	P value
Sex, Female/Male	102/142 (41.8/58.2)	48/68 (41.4/58.6)	38/53 (41.8/58.2)	16/21 (43.2/56.8)	0.980
Age (years), ≤ 70/> 70	207/37 (84.8/15.2)	116/0 (100.0/0)	91/0 (100.0/0)	0/37 (0/100.0)	< 0.001
CCI, Low/High	96/148 (39.3/60.7)	57/59 (49.1/50.9)	34/57 (37.4/62.6)	5/22 (13.5/86.5)	0.001
Diabetes, No/Yes	224/20 (91.8/8.2)	106/10 (91.4/8.6)	85/6 (93.4/6.6)	33/4 (89.2/10.8)	0.714
Cirrhosis, No/Yes	222/22 (91.0/9.0)	109/7 (94.0/6.0)	82/9 (90.1/9.9)	31/6 (83.8/16.2)	0.159
ALT (U/L), ≤ 40/> 40	64/180 (26.2/73.8)	28/88 (24.1/75.9)	29/62 (31.9/68.1)	7/30 (18.9/81.1)	0.249
AST (U/L), ≤ 40/> 40	63/181 (25.8/74.2)	35/81 (30.2/69.8)	21/70 (23.1/76.9)	7/30 (18.9/81.1)	0.297
PLT (× 109/L), ≥ 100/< 100	11/233 (4.5/95.5)	6/110 (5.2/94.8)	4/87 (4.4/95.6)	1/36 (2.7/97.3)	0.818
ALB (g/L), ≥ 35/< 35	161/83 (66.0/34.0)	80/38 (69.0/31.0)	60/31 (65.9/34.1)	21/16 (56.8/43.2)	0.394
TB (mg/dL), ≤ 1/> 1	51/193 (20.9/79.1)	26/90 (22.4/77.6)	20/71 (22.0/78.0)	5/32 (13.5/86.5)	0.485
INR, ≤ 1.25/> 1.25	211/33 (86.5/13.5)	102/14 (87.9/12.1)	78/13 (85.7/14.3)	31/6 (83.8/16.2)	0.785
CA19-9 (U/L), ≤ 150/> 150	111/133 (45.5/54.5)	57/59 (49.1/50.9)	37/54 (40.7/59.3)	17/20 (45.9/54.1)	0.477
Preoperative PTCD, No/Yes	168/76 (68.9/31.1)	82/34 (70.7/29.3)	60/31 (65.9/34.1)	26/11 (70.3/29.7)	0.749
Maximum tumor size (cm), < 3/3-5/> 5	101/117/26 (41.4/48.0/10.7)	55/49/12 (47.4/42.2/10.3)	35/46/10 (38.5/50.5/11.0)	11/22/4 (29.7/59.5/10.8)	0.357
Macrovascular invasion, No/Yes	183/61 (75.0/25.0)	89/27 (76.7./23.3)	66/25 (72.5/27.5)	28/9 (75.7/24.3)	0.783
Microvascular invasion, No/Yes	199/45 (81.6/18.4)	99/17 (85.3/14.7)	69/22 (75.8/24.2)	31/6 (83.8/16.2)	0.200
Perineural infiltration, No/Yes	196/48 (80.3/19.7)	96/20 (82.8/17.2)	70/21 (76.9/23.1)	30/7 (81.1/18.9)	0.573
Tumor differentiation, well/(moderate/poor)	202/42 (82.8/17.2)	98/18 (84.5/15.5)	72/19 (79.1/20.9)	32/5 (86.5/13.5)	0.485
Extent of resection, Minor/Major	62/182 (25.4/74.6)	34/82 (29.3/70.7)	21/70 (23.1/76.9)	7/30 (18.9/81.1)	0.365
8th AJCC staging system, I-II/III/IV	134/99/11 (54.9/40.6/4.5)	67/45/4 (57.8/38.8/3.4)	52/35/4 (57.1/38.5/4.4)	15/19/3 (40.5/51.4/8.1)	0.373
Bismuth classification, I-II/III/IV	55/51/138 (22.5/20.9/56.6)	25/23/68 (21.6/19.8/58.6)	21/22/48 (23.1/24.2/52.7)	9/6/22 (24.3/16.2/59.5)	0.843
Lymphoid metastasis, No (ELN > 4)/No (ELN ≤ 4)/Yes	85/91/68 (34.8/37.3/27.9)	44/40/32 (37.9/34.5/27.6)	31/37/23 (34.1/40.7/25.3)	10/14/13 (27.0/37.8/35.1)	0.657
Intraoperative blood loss (mL), ≤ 500/> 500	91/153 (37.3/62.7)	42/74 (36.2/63.8)	37/54 (40.7/59.3)	12/25 (32.4/67.6)	0.646
Perioperative blood transfusion, No/Yes	85/159 (34.8/65.2)	42/74 (36.2/63.8)	30/61 (33.0/67.0)	13/24 (35.1/64.9)	0.888
Period of follow-up, months1	25.7 ± 22.7	32.7 ± 25.4	20.9 ± 18.9	15.7 ± 14.5	0.222
Recurrence during follow-up	183 (75.0)	81 (69.8)	69 (75.8)	33 (89.2)	0.059
Death during follow-up	166 (68.0)	69 (59.5)	66 (72.5)	31 (83.8)	0.011
OS, months2	23.0 (19.1-26.9)	34.0 (27.1-40.9)	18.0 (12.9-23.1)	11.0 (9.1-12.9)	< 0.001
1-yr OS rate, %	72.7	91.4	74.6	39.3
3-yr OS rate, %	32.4	45.6	19.8	14.6
5-yr OS rate, %	22.3	31.1	11.9	6.0

¹Values are the mean ± SD.

²Values are the median and 95% confidence interval.

ACCI: Age-adjusted Charlson comorbidity index; AJCC: American Joint Committee on Cancer; ALT: Alanine aminotransferase; ASA: American Society of Anesthesiologists; AST: Aspartate transaminase; CA19-9: Carbohydrate antigen 19-9; CCI: Charlson comorbidity index; INR: International normalized ratio; PLT: Platelet count; PTCD: Percutaneous transhepatic cholangial drainage; OS: Overall survival; ALB: Albumin; TB: Total bilirubin.

Table 3 Univariable and multivariable Cox regression analyses of overall survival in the training cohort

Variable	R comparison	Univariable Cox regression		Multivariable Cox regression
		HR (95%CI)	P value	HR (95%CI)	P value1
Age	> 70 vs ≤ 70 yr	1.793 (1.314-2.447)	< 0.001
Sex	Male vs Female	1.141 (0.838-1.555)	0.402
Diabetes	Yes vs No	1.203 (0.718-2.017)	0.482
Cirrhosis	Yes vs No	1.220 (0.738-2.016)	0.438
PLT	> 100 vs ≤ 100 × 109/L	1.538 (0.719-3.290)	0.267
Albumin	< 35 vs ≥ 35	1.131 (0.823-1.555)	0.447
ALT	> 40 vs ≤ 40 U/L	1.202 (0.848-1.704)	0.302
AST	> 40 vs ≤ 40 U/L	1.155 (0.815-1.638)	0.418
TB	> 1 vs ≤ 1 mg/dL	1.204 (0.813-1.785)	0.354
INR	> 1.25 vs ≤ 1.25	1.217 (0.795-1.863)	0.365
CA19-9	> 150 vs ≤ 150 U/L	1.768 (1.289-2.426)	< 0.001	1.471 (1.059-2.043)	0.021
Preoperative PTCD	Yes vs No	1.172 (0.848-1.620)	0.336
Maximum tumor size	3-5 vs < 3 cm	1.777 (1.269-2.488)	0.001	1.236 (0.858-1.779)	0.255
	> 5 vs < 3 cm	2.289 (1.377-3.803)	0.001	1.990 (1.166-3.396)	0.011
Macrovascular invasion	Yes vs No	2.165 (1.539-3.045)	< 0.001	1.700 (1.198-2.412)	0.003
Microvascular invasion	Yes vs No	2.212 (1.526-3.205)	< 0.001	1.752 (1.166-2.634)	0.007
Perineural infiltration	Yes vs No	1.267 (0.878-1.827)	0.205
Tumor differentiation	Poor vs Well/moderate	1.616 (1.102-2.369)	0.014	1.550 (1.042-2.305)	0.030
Extent of resection	Major vs Minor	1.348 (0.941-1.931)	0.104
Intraoperative blood loss	> 500 vs ≤ 500 mL	1.128 (0.821-1.550)	0.457
Perioperative blood transfusion	Yes vs No	1.069 (0.773-1.477)	0.688
Lymphoid metastasis	No (ELN ≤ 4) vs No (ELN > 4)	1.673 (1.146-2.441)	0.008	1.454 (0.987-2.141)	0.058
	Yes vs No (ELN > 4)	2.403 (1.618-3.567)	< 0.001	2.549 (1.684-3.859)	< 0.001
CCI	High vs Low	1.239 (0.901-1.703)	0.187
ACCI	Moderate vs Low	1.818 (1.292-2.558)	0.001	1.605 (1.133-2.273)	0.008
	High vs Low	2.791 (1.818-4.287)	< 0.001	2.498 (1.614-3.866)	< 0.001

¹Variables found significant at P < 0.10 in univariable analysis.

ACCI: Age-adjusted Charlson comorbidity index; ALT: Alanine aminotransferase; ASA: American Society of Anesthesiologists; AST: Aspartate transaminase; CA19-9: Carbohydrate antigen 19-9; CCI: Charlson comorbidity index; CI: Confidence interval; HR: Hazard ratio; INR: International normalized ratio; PLT: Platelet count; PTCD: Percutaneous transhepatic cholangial drainage; ALB: Albumin; TB: Total bilirubin.