Pattern and risk factors for postoperative recurrence in borderline resectable pancreatic cancer after upfront surgery

Table 1 Baseline characters of included patients, n (%)

Variables	Results
Sex
Male	116 (53.7)
Female	100 (46.3)
Age (year), mean ± SD	61.3 ± 9.8
Smoking
Yes	59 (27.3)
No	157 (72.7)
Surgical procedure
Pancreaticoduodenectomy	132 (61.1)
Distal pancreatectomy	10 (4.6)
Total pancreaticoduodenectomy	74 (34.3)
Vascular reconstruction procedure
End-to-end anastomosis	59 (31.9)
Allogeneic vascular graft	147 (68.1)
Pathological diagnosis
Adenocarcinoma	190 (88.0)
Adenosquamous carcinoma	23 (10.6)
Mucinous adenocarcinoma	2 (0.9)
Sarcomatoid carcinoma	1 (0.5)
Postoperative adjuvant chemotherapy	118 (54.6)

Table 2 Result of univariate Cox regression and Fine-Gray competing risk analysis for postoperative disease-free survival

Variables	Cox regression			Fine-Gray competing risks model
	HR	95%CI	P value	sHR	95%CI	P value
Age (years)	1.016	0.999-1.032	0.058	1.011	0.996-1.027	0.154
Sex
Male	Reference	-	-	Reference	-	-
Female	1.005	0.770-1.445	0.738	0.952	0.706-1.284	0.748
Smoking history
No	Reference	-	-	Reference	-	-
Yes	1.113	0.783-1.583	0.550	1.013	0.726-1.416	0.937
Diabetes
No	Reference	-	-	Reference	-	-
Yes	0.938	0.665-1.322	0.714	0.936	0.672-1.304	0.697
BMI (kg/m2)	1.011	0.969-1.056	0.606	1.015	0.975-1.056	0.472
WBC count (× 109/L)	1.045	0.977-1.118	0.199	1.057	1.004-1.112	0.034a
NEUT count (× 109/L)	1.043	0.972-1.119	0.244	1.052	1.000-1.106	0.049a
LYM count (× 109/L)	1.162	0.855-1.578	0.338	1.222	0.914-1.634	0.176
Hemoglobin (g/L)	1.004	0.994-1.013	0.429	1.001	0.992-1.010	0.833
Platelet count (× 109/L)	1.000	0.998-1.002	0.989	1.000	0.999-1.003	0.566
Serum albumin (g/L)	0.992	0.957-1.029	0.682	0.995	0.960-1.031	0.764
Serum ALT (U/L)	1.000	0.998-1.001	0.965	1.000	0.999-1.002	0.803
Serum total bilirubin (μmol/L)	1.001	0.999-1.003	0.232	1.001	0.999-1.003	0.179
Serum CEA (ng/mL)	1.029	1.012-1.047	0.001a	1.031	1.020-1.041	< 0.001a
Serum CA19-9 (U/mL)	1.203	1.100-1.317	< 0.001a	1.150	1.039-1.272	0.007a
Biliary drainage
No	Reference	-	-	Reference	-	-
Yes	1.082	0.726-1.611	0.700	1.108	0.763-1.608	0.591
Arterial invasion
No	Reference	-	-	Reference	-	-
Yes	1.090	0.693-1.713	0.710	0.976	0.590-1.614	0.924
Vascular invasion site
PV	Reference	-	-	Reference	-	-
Confluence of PV and SMV	1.077	0.697-1.662	0.739	0.875	0.592-1.293	0.502
SMV	0.910	0.571-1.448	0.690	0.763	0.503-1.157	0.202
Imaging vascular morphology changes
No	Reference	-	-	Reference	-	-
Yes	1.463	1.066-2.009	0.018a	1.429	1.054-1.936	0.022a
Length of vascular invasion (cm)	1.114	1.013-1.226	0.026a	1.104	1.005-1.213	0.039a
Angle of vascular invasion
≤ 180	Reference	-	-	Reference	-	-
> 180	1.005	0.718-1.407	0.976	1.030	0.743-1.427	0.862
Surgical procedure
Pancreaticoduodenectomy	Reference	-	-	Reference	-	-
Distal pancreatectomy	1.297	0.627-2.680	0.483	1.137	0.571-2.265	0.716
Total pancreaticoduodenectomy	1.058	0.746-1.500	0.751	0.933	0.664-1.311	0.690
Vascular reconstruction procedure
End-to-end anastomosis	Reference	-	-	Reference	-	-
Allogeneic vascular graft	1.335	0.949-1.877	0.097	1.254	0.922-1.704	0.149
Operation time (hours)	1.025	0.973-1.080	0.350	1.008	0.957-1.061	0.773
Intraoperative blood loss (mL)	1.000	1.000-1.000	0.398	1.000	0.999-1.000	0.800
Intraoperative blood transfusion
No	Reference	-	-	Reference	-	-
Yes	1.087	0.793-1.489	0.604	1.034	0.768-1.391	0.827
Tumor site
Pancreatic head and uncinate process	Reference	-	-	Reference	-	-
Pancreatic neck	1.089	0.794-1.559	0.642	0.966	0.704-2.169	0.462
Pancreatic body and tail	1.340	0.715-2.511	0.361	1.235	0.681-1.371	0.848
Tumor differentiation
Low	Reference	-	-	Reference	-	-
Moderate and high	0.605	0.437-0.838	0.003a	0.704	0.505-0.981	0.038a
Tumor diameter (cm)	1.159	1.069-1.256	< 0.001a	1.146	1.074-1.223	< 0.001a
Lymph node metastasis
No	Reference	-	-	Reference	-	-
Yes	1.702	1.176-2.463	0.005a	1.430	1.015-2.014	0.041a
Postoperative adjuvant chemotherapy
No	Reference	-	-	Reference	-	-
Yes	0.735	0.536-1.007	0.055	0.876	0.645-1.189	0.396

^aP < 0.05.

HR: Hazard risk; sHR: Subdistribution hazard ratio; CI: Confidence interval; BMI: Body mass index; WBC: White blood cell; NEUT: Neutrophil; LYM: Lymphocyte; ALT: Alanine transaminase; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; PV: Portal vein; SMV: Superior mesenteric vein.

Table 3 Comparison of general data of patients that developed tumor recurrence within and after postoperative 1-year, n (%)

Variables	Early recurrence group (n = 114)	Late recurrence group (n = 102)	P value
Age (years), median (Q1, Q3)	63.00 (57.00, 68.75)	60.50 (53.25, 66.75)	0.054
Sex			0.302
Male	65 (57.02)	51 (50.00)
Female	49 (42.98)	51 (50.00)
Smoking history			0.966
Yes	31 (27.19)	28 (27.45)
No	83 (72.81)	74 (72.55)
Diabetes			0.423
Yes	37 (32.46)	28 (27.45)
No	77 (67.54)	74 (72.55)
BMI (kg/m2), median (Q1, Q3)	23.14 (20.77, 24.97)	22.74 (20.82, 24.46)	0.529
WBC count (× 109/L), median (Q1, Q3)	5.80 (4.82, 7.07)	5.40 (4.37, 6.30)	0.024a
NEUT count (× 109/L), median (Q1, Q3)	3.62 (2.87, 4.65)	3.15 (2.59, 4.20)	0.023a
LYM count (× 109/L), median (Q1, Q3)	1.51 (1.17, 1.90)	1.39 (1.08, 1.80)	0.209
Hemoglobin (g/L), mean ± SD	123.47 ± 16.25	122.77 ± 16.68	0.756
Platelet count (× 109/L), median (Q1, Q3)	192.00 (164.00, 235.50)	190.00 (143.25, 248.75)	0.498
Serum albumin (g/L), mean ± SD	38.11 ± 4.31	38.77 ± 4.20	0.260
Serum ALT (U/L), median (Q1, Q3)	32.50 (16.00, 84.00)	40.00 (19.25, 97.00)	0.193
Serum total bilirubin (μmol/L), median (Q1, Q3)	15.85 (10.22, 111.20)	15.55 (9.62, 79.90)	0.597
Serum CEA (ng/mL), median (Q1, Q3)	3.25 (1.70, 5.80)	2.07 (1.40, 3.76)	0.003a
Serum CA19-9 (U/mL), median (Q1, Q3)	250.25 (39.23, 1000.73)	113.10 (28.63, 565.90)	0.020a
Biliary drainage			0.392
Yes	23 (20.18)	16 (15.69)
No	91 (79.82)	86 (84.31)
Vascular invasion site			0.961
PV	17 (14.91)	16 (15.69)
Confluence of PV and SMV	57 (50.00)	52 (50.98)
SMV	40 (35.09)	34 (33.33)
Imaging vascular morphology changes			0.014a
Yes	66 (57.89)	42 (41.18)
No	48 (42.11)	60 (58.82)
Length of vascular invasion (cm), median (Q1, Q3)	2.75 (2.15, 3.88)	2.40 (1.80, 3.27)	0.009a
Extent of vascular invasion			0.679
≤ 180	79 (69.30)	68 (66.67)
> 180	35 (30.70)	34 (33.33)
Arterial invasion			0.983
Yes	18 (15.79)	16 (15.69)
No	96 (84.21)	86 (84.31)
Surgical procedure			0.895
Pancreaticoduodenectomy	69 (60.53)	63 (61.76)
Distal pancreatectomy	6 (5.26)	4 (3.92)
Total Pancreaticoduodenectomy	39 (34.21)	35 (34.31)
Vascular reconstruction procedure			0.197
End-to-end anastomosis	32 (28.07)	37 (36.27)
Allogeneic vascular graft	82 (71.93)	65 (63.73)
Operation time (hours), median (Q1, Q3)	12.00 (11.00, 14.75)	13.00 (11.00, 15.00)	0.719
Intraoperative blood loss (mL), median (Q1, Q3)	750.00 (500.00, 1000.00)	600.00 (400.00, 1000.00)	0.372
Intraoperative blood transfusion			0.158
Yes	69 (60.53)	52 (50.98)
No	45 (39.47)	50 (49.02)
Tumor site			0.939
Pancreatic head and unicorn process	70 (61.40)	65 (63.73)
Pancreatic neck	37 (32.46)	31 (30.39)
Pancreatic body and tail	7 (6.14)	6 (5.88)
Tumor differentiation			0.003a
Low	54 (47.37)	28 (27.45)
Moderate and high	60 (52.63)	74 (72.55)
Tumor diameter (cm), median (Q1, Q3)	4.00 (3.00, 5.00)	3.00 (2.50, 4.00)	0.002a
Lymph node metastasis			0.001a
Yes	94 (82.46)	64 (62.75)
No	20 (17.54)	38 (37.25)
Postoperative adjuvant chemotherapy			0.242
Yes	58 (50.88)	60 (58.82)
No	56 (49.12)	42 (41.18)

^aP < 0.05.

BMI: Body mass index; WBC: White blood cell; NEUT: Neutrophil; LYM: Lymphocyte; ALT: Alanine transaminase; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; PV: Portal vein; SMV: Superior mesenteric vein.