Combined vascular resection and reconstruction for locally advanced perihilar cholangiocarcinoma: A multicenter study

Table 1 Baseline clinical characteristics of patients with perihilar cholangiocarcinoma stratified by vascular resection type, n (%)/median (range)

Variables	Non-VR (n = 204)	PVR (n = 51)	HAR (n = 65)	P value (PVR vs HAR)	P value (non-VR vs VR)
Age (year)	63 (34-80)	68 (31-81)	67 (35-79)	0.896	< 0.001
Body mass index (kg/m2)	21.5 (18.0-33.0)	22.1 (18.6-28.0)	22.3 (18.0-27.0)	0.397	0.141
Sex				0.728	0.158
Female	72 (35)	21 (41)	30 (46)
Male	132 (65)	30 (59)	35 (54)
Hypertension	69 (34)	21 (41)	29 (45)	0.855	0.126
Diabetes	83 (41)	25 (49)	32 (49)	1.000	0.178
CEA (ng/mL)	3 (1-135)	3 (1-42)	4 (2-80)	0.008	< 0.001
CA19-9 (U/mL)	143 (1-12000)	135 (10-27852)	150 (11-27563)	0.343	< 0.001
ASA score				0.798	0.772
1-2	140 (69)	35 (69)	42 (65)
3-4	64 (31)	16 (31)	23 (35)
Bismuth type				0.002	< 0.001
1-3	150 (74)	28 (55)	16 (25)
4	54 (26)	23 (45)	49 (75)
Preoperative biliary drainage	149 (73)	49 (96)	63 (97)	1.000	< 0.001
Preoperative portal vein embolization	15 (7.4)	3 (5.9)	5 (7.7)	1.000	1.000
Type of hepatectomy				< 0.001	< 0.001
S1234	70 (34)	11 (22)	18 (28)
S1458	3 (1.5)	1 (2.0)	1 (1.5)
S15678	71 (35)	20 (39)	12 (18)
S123458	39 (19)	7 (14)	33 (51)
S145678	7 (3.4)	12 (24)	1 (1.5)
Limited liver resection	9 (4.4)	0	0
Bile duct resection	5 (2.5)	0	0
Combined pancreatoduodenectomy	25 (12)	4 (7.8)	5 (7.7)	1.000	0.286
Longitudinal tumor invasion length (cm)	NA			0.608	NA
≤ 3	NA	21 (41)	31 (48)
> 3	NA	30 (59)	34 (52)
Pathologic nerve invasion				0.385	< 0.001
Yes	33 (16)	24 (47)	37 (57)
No	171 (84)	27 (53)	28 (43)
Pathologic vascular invasion				0.060	< 0.001
Yes	66 (32)	35 (69)	32 (49)
No	138 (68)	16 (31)	33 (51)
T stage				0.009	< 0.001
T1, T2, T3	182 (89)	14 (27)	5 (7.7)
T4	22 (11)	37 (73)	60 (92)
N stage				0.434	0.376
N0	126 (62)	26 (51)	39 (60)
N1-2	78 (38)	25 (49)	26 (40)
Distant metastasis	5 (2.5)	3 (5.9)	6 (9.2)	0.729	0.052
Postoperative adjuvant chemotherapy	22 (11)	22 (43)	32 (49)	0.642	< 0.001

VR: Vascular resection; Non-VR: Non-vascular resection; PVR: Portal vein resection; HAR: Hepatic artery resection; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; ASA: American Society of Anesthesiologists; S: Hepatic segment; NA: Not applicable.

Table 2 Perioperative outcomes and complications stratified by vascular resection type, n (%)/median (range)

Variables	Non-VR (n = 204)	PVR (n = 51)	HAR (n = 65)	P value (PVR vs HAR)	P value (non-VR vs VR)
Operation time (minutes)	314 (230-588)	425 (270-775)	496 (326-835)	0.002	< 0.001
Operative blood loss (mL)	600 (200-3000)	900 (220-4000)	900 (250-2400)	0.532	< 0.001
Blood transfusion	29 (14)	20 (40)	24 (39)	0.916	< 0.001
Liver failure ISGLS grade				0.939	0.005
Grade B	23 (11)	12 (24)	14 (22)
Grade C	3 (1.5)	2 (3.9)	3 (4.6)
Second operation	9 (4.4)	3 (5.9)	3 (4.6)	1.000	0.973
Clavien-Dindo				0.915	0.013
Grade 3	69 (34)	19 (37)	23 (35)
Grade 4	4 (2)	3 (5.9)	3 (4.6)
Grade 5 (death)	0 (0.0)	1 (2.0)	3 (4.6)
Bile leakage ISGLS grade ≥ B	50 (25)	13 (25)	18 (28)	0.761	0.686
Pancreatic fistula ISGPS grade ≥ B	39 (19)	10 (20)	12 (18)	0.729	0.696
Intraperitoneal abscess	15 (7.4)	3 (5.9)	4 (6.2)	1.000	0.827
Pleural effusion	17 (8.3)	5 (9.8)	9 (14)	0.707	0.374
Ascites	4 (2.0)	4 (7.8)	5 (7.7)	1.000	0.809
HA-associated complication				0.032	0.001
Thrombosis	0 (0)	0 (0)	3 (4.6)
Bleeding	3 (1.5)	1 (2.0)	2 (3.1)
Liver abscess	4 (2.0)	1 (2.0)	2 (3.1)
Liver infarction	1 (0.5)	1 (2.0)	6 (9.2)
PV thrombosis	3 (1.5)	4 (7.8)	3 (4.6)	0.698	0.040

VR: Vascular resection; Non-VR: Non-vascular resection; PVR: Portal vein resection; HAR: Hepatic artery resection; ISGLS: International Study Group of Liver Surgery; ISGPS: International Study Group of Pancreatic Surgery; HA: Hepatic artery; PV: Portal vein.

Table 3 Univariable and multivariable Cox proportional hazards analyses for overall survival in the vascular resection cohort

Variable	Univariable		Multivariable
	HR (95%CI)	P value	HR (95%CI)	P value
Age
> 70	1.49 (0.95-2.33)	0.079	1.67 (1.01-2.76)	0.047
≤ 70
Sex
Male	1.18 (0.77-1.80)	0.461	NA	NA
Female
Bismuth type
4	3.37 (2.09-5.43)	< 0.001	1.23 (0.69-2.19)	0.476
1, 2, 3
Combined PD
Yes	2.03 (0.88-4.68)	0.096	NA	NA
No
CA19-9
≤ 100	3.43 (2.10-5.59)	< 0.001	0.65 (0.35-1.23)	0.189
> 100
T stage
T4	2.45 (1.31-4.59)	0.005	3.47 (1.71-7.05)	0.001
T1, T2, T3
Lymph node metastasis
N1-2	5.80 (3.64-9.25)	< 0.001	2.56 (1.19-5.52)	0.016
N0
Distant metastasis
M1	34.46 (12.30-96.90)	< 0.001	9.04 (3.11-26.32)	< 0.001
M0
Histologic grade
G1, G2	0.18 (0.09-0.35)	< 0.001	0.33 (0.15-0.73)	0.006
G3
Postoperative adjuvant chemotherapy
Yes	0.51 (0.33-0.78)	0.002	0.86 (0.53-1.40)	0.547
No
Pathologic vascular invasion
Yes	2.99 (1.90-4.70)	< 0.001	1.91 (1.14-3.20)	0.013
No
Pathologic nerve invasion
Yes	4.24 (2.68-6.69)	< 0.001	1.52 (0.85-2.72)	0.162
No
Surgery type
HAR	1.01 (0.66-1.54)	0.962	NA	NA
PVR
Longitudinal tumor invasion length (cm)	11.87 (5.94-23.70)	< 0.001	3.40 (1.41-8.19)	0.007
≤ 3
> 3
NLR	1.60 (1.37-1.87)	< 0.001	1.00 (0.81-1.28)	0.883
PLR (per 20 unit)	2.19 (1.81-2.65)	< 0.001	1.45 (1.12-1.88)	0.004
CEA	1.00 (0.98-1.02)	0.982	NA	NA
ALB	0.92 (0.86-0.99)	0.019	1.05 (0.97-1.15)	0.196

HR: Hazard ratio; CI: Confidence intervals; PD: Pancreatoduodenectomy; CA19-9: Carbohydrate antigen 19-9; PVR: Portal vein resection; HAR: Hepatic artery resection; NLR: Neutrophil-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; CEA: Carcinoembryonic antigen; ALB: Albumin; NA: Not applicable.