Postoperative morbidity adversely impacts oncological prognosis after curative resection for hilar cholangiocarcinoma

Table 1 Postoperative outcomes of 239 patients who underwent curative resection for hilar cholangiocarcinoma

Postoperative outcomes (n = 239)	Patients (%)
Postoperative 30-d morbidity	146 (61.1)
Minor morbidity (Clavien-Dindo grade I-II)	78 (32.6)
Major morbidity (Clavien-Dindo grade III-IV)	68 (28.5)
Types of postoperative 30-d morbidity
PHLF	15 (6.3)
Blood infection	14 (5.9)
Lung infection	12 (5.0)
Bile leakage	32 (13.4)
Pleural effusion	24 (10.0)
Ascites	4 (1.7)
Intestines leak	9 (3.8)
Abdominal hemorrhage	10 (6.8)
Delayed gastric emptying	17 (7.1)
Surgical site infection	36 (15.1)
Others	11 (4.6)
Postoperative hospital stay, days1	19 (15, 26)

¹Values are median (interquartile range).

PHLF: Post-hepatectomy liver failure.

Table 2 Comparisons of patients’ clinicopathologic and operative variables between those with and without postoperative morbidity

Variables	Total (n = 239)	Without postoperative morbidity (n = 93)	With postoperative morbidity (n = 146)	P value
Age > 60 yr	54 (22.6)	22 (23.7)	32 (21.9)	0.754
Male sex	144 (60.3)	54 (58.1)	90 (61.6)	0.581
ASA score > 2	23 (9.6)	6 (6.5)	17 (11.6)	0.185
Obesity	28 (11.7)	4 (4.3)	24 (16.4)	0.004
Diabetes mellitus	24 (10.0)	4 (4.3)	20 (13.7)	0.018
Cirrhosis	39 (16.3)	8 (8.6)	31 (21.2)	0.010
Preoperative CA19-9 > 150 U/L	129 (54.0)	44 (47.3)	85 (58.2)	0.099
Maximum tumor size > 3 cm	68 (25.8)	21 (22.6)	47 (32.2)	0.108
Macrovascular invasion	144 (60.3)	55 (59.1)	89 (61.0)	0.779
Microvascular invasion	85 (35.6)	28 (30.1)	57 (39.0)	0.160
Peripheral nerve invasion	80 (33.5)	30 (32.3)	50 (34.2)	0.751
Poor tumor differentiation	77 (32.2)	29 (31.2)	48 (32.9)	0.785
Intraoperative blood transfusion	159 (66.5)	57 (61.3)	102 (69.9)	0.171
Intraoperative blood loss > 500 mL	185 (77.4)	65 (69.9)	120 (82.2)	0.027
Major hepatectomy	171 (71.5)	65 (69.9)	106 (72.6)	0.651
Hepatic artery reconstruction	12 (5.0)	5 (5.4)	7 (4.8)	0.841
Portal vein reconstruction	45 (19.6)	22 (23.7)	23 (15.8)	0.128
Pringle maneuver	175 (73.2)	73 (78.5)	102 (69.9)	0.142
Number of examined LNs > 4	125 (52.3)	52 (55.9)	73 (50.0)	0.372
LN metastasis	54 (22.6)	18 (19.4)	36 (24.7)	0.339
Bismuth type, III-IV	135 (56.5)	52 (55.9)	83 (56.8)	0.887
Preoperative drainage	71 (29.7)	28 (30.1)	43 (29.5)	0.914

ASA: American Society of Anesthesiologists; CA19-9: Carbohydrate antigen 19-9; LN: Lymph node.

Table 3 Univariable and multivariable logistic regression analyses of risk factors associated with postoperative morbidity following curative resection for hilar cholangiocarcinoma

Variables	Multivariable analyses1
	P value	OR (95%CI)
Obesity	0.023	3.694 (1.197-11.394)
Diabetes mellitus	0.036	3.395 (1.082-10.651)
Cirrhosis	0.017	2.867 (1.207-6.810)
Preoperative CA19-9 > 150 U/L	0.155	1.493 (0.859-2.593)
Intraoperative blood loss > 500 mL	0.016	2.240 (1.162-4.318)

¹Factors with P < 0.1 in Table 2 were applied to multiple logistic regression model.

CA19-9: Carbohydrate antigen 19-9; CI: Confidence interval; OR: Odds ratio.

Table 4 Comparisons of survival outcomes between patients with and without postoperative morbidity

Survival outcomes	Total (n = 239)	Without postoperative morbidity (n = 93)	With postoperative morbidity (n = 146)	P value
Period of follow-up, months1	19.0 (11.0, 34.0)	15.0 (23.0, 41.0)	16.0 (9.8, 30.0)	0.001
Death during the follow-up	160 (66.9)	55 (59.1)	105 (71.9)	0.041
Recurrence during the follow-up	172 (72.0)	60 (64.5)	112 (76.7)	0.041
OS, months2	23.0 (20.0-26.0)	31.0 (22.4-39.6)	18.0 (13.0-23.0)	0.003
1-yr OS rate, %	73.4	83.8	66.7
3-yr OS rate, %	34.0	45.5	26.7
5-yr OS rate, %	22.9	31.7	17.0
RFS, month2	19.0 (16.1-21.9)	26.0 (14.1-37.9)	16.0 (12.2-19.8)	0.002
1-yr RFS rate, %	64.6	75.1	54.3
3-yr RFS rate, %	28.7	40.8	22.4
5-yr RFS rate, %	18.2	30.4	13.3

¹Values are median (interquartile range).

²Values are median and 95% confidence interval.

OS: Overall survival; RFS: Recurrence-free survival.

Table 5 Univariable and multivariable Cox regression analyses of risk factors associated with overall survival following curative resection for hilar cholangiocarcinoma

Variables	Univariable analyses		Multivariable analyses1
	P value	HR (95%CI)	P value	HR (95%CI)
Age > 60 yr	0.341	1.190 (0.832-1.730)
Male sex	0.754	1.052 (0.766-1.445)
ASA score > 2	0.333	1.282 (0.775-2.120)
Obesity	0.772	0.928 (0.561-1.536)
Diabetes mellitus	0.063	1.595 (0.975-2.609)	0.288	1.324 (0.789-2.224)
Cirrhosis	0.222	1.283 (0.861-1.912)
Preoperative CA19-9 > 150 U/L	0.009	1.522 (1.112-2.083)	0.015	1.485 (1.079-2.044)
Maximum tumor size > 3 cm	< 0.001	1.809 (1.296-2.525)	0.001	1.805 (1.290-2.526)
Macrovascular invasion	0.014	1.507 (1.088-2.087)	0.012	1.527 (1.099-2.122)
Microvascular invasion	0.005	1.588 (1.151-2.192)	0.102	1.324 (0.946-1.853)
Peripheral nerve invasion	0.663	1.075 (0.776-1.488)
Poor tumor differentiation	0.005	1.608 (1.158-2.231)	0.003	1.654 (1.188-2.302)
Intraoperative blood transfusion	0.316	1.186 (0.850-1.654)
Intraoperative blood loss > 500 mL	0.593	1.108 (0.761-1.612)
Major hepatectomy	0.634	1.087 (0.771-1.531)
LN metastasis	0.016	1.551 (1.086-2.215)	0.021	1.527 (1.067-2.186)
Bismuth type, III-IV	0.346	1.163 (0.849-1.593)
Preoperative drainage	0.721	0.939 (0.665-1.326)
Postoperative morbidity	0.003	1.635 (1.178-2.269)	0.009	1.557 (1.119-2.167)

¹Those variables found significant at P < 0.100 in univariable analyses were entered into multivariable Cox regression analyses.

ASA: American Society of Anesthesiologists; CA19-9: Carbohydrate antigen 19-9; CI: Confidence interval; HR: Hazard ratio; LN: Lymph node.

Table 6 Univariable and multivariable Cox regression analyses of risk factors associated with recurrence-free survival following curative resection for hilar cholangiocarcinoma

Variables	Univariable analyses		Multivariable analyses1
	P value	HR (95%CI)	P value	HR (95%CI)
Age > 60 yr	0.330	1.201 (0.850-1.696)
Male sex	0.998	1.002 (0.793-1.136)
ASA score > 2	0.457	1.210 (0.732-1.997)
Obesity	0.911	0.973 (0.604-1.568)
Diabetes mellitus	0.035	1.654 (1.036-2.264)	0.177	1.403 (0.858-2.295)
Cirrhosis	0.247	1.260 (0.852-1.863)
Preoperative CA19-9 > 150 U/L	0.002	1.617 (1.193-2.192)	0.012	1.487 (1.092-2.024)
Maximum tumor size > 3 cm	0.002	1.695 (1.223-2.351)	0.002	1.665 (1.198-2.314)
Macrovascular invasion	0.008	1.534 (1.120-2.100)	0.011	1.514 (1.101-2.081)
Microvascular invasion	0.009	1.524 (1.118-2.088)	0.121	1.295 (0.934-1.794)
Peripheral nerve invasion	0.683	1.068 (0.780-1.462)
Poor tumor differentiation	0.007	1.547 (1.124-2.129)	0.006	1.575 (1.141-2.173)
Intraoperative blood transfusion	0.251	1.208 (0.875-1.668)
Intraoperative blood loss > 500 mL	0.819	1.043 (0.729-1.490)
Major hepatectomy	0.978	0.995 (0.718-1.379)
LN metastasis	0.010	1.573 (1.114-2.220)	0.017	1.528 (1.080-2.157)
Bismuth type, III-IV	0.788	1.042 (0.771-1.410)
Preoperative drainage	0.517	0.895 (0.640-1.252)
Postoperative morbidity	0.003	1.169 (1.180-2.220)	0.008	1.535 (1.117-2.108)

¹Those variables found significant at P < 0.100 in univariable analyses were entered into multivariable Cox regression analyses.

ASA: American Society of Anesthesiologists; CA19-9: Carbohydrate antigen 19-9; CI: Confidence interval; HR: Hazard ratio; LN: Lymph node.