Novel risk scoring system for prediction of pancreatic fistula after pancreaticoduodenectomy

Table 1 Demographic and clinical characteristics of the study and validation groups, n (%)

Variable	Study group (n = 189)	Validation group (n = 109)	P-value
POPF			0.976
No POPF	117 (61.9)	68 (62.4)
Grade A (BL)	34 (18.0)	18 (16.5)
Grade B	32 (16.9)	20 (18.3)
Grade C	6 (3.2)	3 (2.8)
Age (yr)	61.8 ± 9.9	62.4 ± 10.3	0.650
Sex			0.284
Male	116 (61.4)	60 (55.0)
Female	73 (38.6)	49 (45.0)
Surgery			0.595
PD	98 (51.9)	60 (55.0)
PPPD	91 (48.1)	49 (45.0)
BMI (kg/m2)	22.1 ± 2.9	22.4 ± 2.9	0.431
Diabetes mellitus			0.164
Yes	31 (16.4)	25 (22.9)
No	158 (83.6)	84 (77.1)
Location of tumor			0.493
Pancreas	105 (55.6)	65 (59.6)
Non-pancreas	84 (44.4)	44 (40.4)
Pathologic type			0.834
Benign	11 (5.8)	7 (6.4)
Pancreatic myxoid cystadenoma	7 (3.7)	5 (4.6)
Pancreatic serous cystadenoma	4 (2.1)	2 (1.8)
Malignant	178 (94.2)	102 (93.6)
Pancreatic cancer	92 (48.7)	56 (51.4)
Biliary duct cancer	29 (15.3)	21 (19.3)
Ampullary cancer	33 (17.5)	16 (14.7)
Duodenal cancer	24 (12.7)	9 (8.3)
Preoperative STB (μmol/L)	111.4 ± 120.4	116.0 ± 144.9	0.767
Preoperative pre-albumin (mg/L)	141.2 ± 57.1	142.4 ± 56.8	0.861
Preoperative serum albumin (g/L)	38.4 ± 5.7	37.5 ± 4.7	0.137
Preoperative serum globulin (g/L)	26.9 ± 4.2	27.2 ± 4.9	0.606
Preoperative hemoglobin (g/L)	121.4 ± 19.9	119.9 ± 19.5	0.533
Preoperative white blood cells (109/L)	7.0 ± 8.1	6.4 ± 2.6	0.465
Preoperative platelets (109/L)	233.7 ± 78.5	237.6 ± 73.7	0.671
Pancreatic texture			0.725
Soft	81 (42.9)	49 (45.0)
Hard	108 (57.1)	60 (55.0)
Main pancreatic duct diameter (mm)	3.1 ± 1.0	3.2 ± 1.1	0.496
Biliary tract compression	23 (12.2%)	15 (13.8)	0.691
Pancreaticojejunostomy anastomosis			0.061
Duct-to-mucosa	153 (81.0)	78 (71.6)
Dunking method	36 (19.0)	31 (28.4)
Pancreatic duct stent			0.735
Internal stent	85 (45.0)	50 (45.9)
External stent	68 (36.0)	35 (32.1)
None	36 (19.0)	24 (22.0)
Vascular invasion			0.483
Yes	32 (16.9)	22 (20.2)
No	157 (83.1)	87 (79.8)
Operative time (min)	269.5 ± 70.3	255.4 ± 64.7	0.088
Estimated blood loss (mL)	320.3 ± 269.3	326.6 ± 267.5	0.846
Serum albumin POD 1 (g/L)	33.01 ± 5.4	33.4 ± 5.7	0.623
Serum globulin on POD 1 (g/L)	23.4 ± 10.9	26.1 ± 27.2	0.233
Hemoglobin on POD 1 (g/L)	112.0 ± 16.8	112.4 ± 15.8	0.849

POPF: Postoperative pancreatic fistula; BL: Biochemical leak; BMI: Body mass index; PD: Pancreaticoduodenectomy; PPPD: Pylorus-preserving pancreaticoduodenectomy; POD: Postoperative day; STB: Serum total bilirubin.

Table 2 Demographic and clinical characteristics of the clinically relevant postoperative pancreatic fistula and non-clinically relevant postoperative pancreatic fistula groups, n (%)

Variable	non-CR-POPF (n = 237)	CR-POPF (n = 61)	P-value
Age (yr)	61.8 ± 10.1	62.2 ± 9.4	0.804
Sex			0.095
Male	135 (57.0)	41 (67.2)
Female	102 (43.0)	20 (32.8)
Surgery			0.445
PD	123 (51.9)	35 (57.4)
PPPD	114 (48.1)	26 (42.6)
BMI (kg/m2)	22.0 ± 2.9	22.5 ± 2.8	0.352
Diabetes mellitus			0.351
Yes	42 (17.7)	14 (23.0)
No	195 (82.3)	47 (77.0)
Location of tumor			0.131
Pancreas	130 (54.9)	40 (65.6)
Non-pancreas	107 (45.1)	21 (34.4)
Pathologic type			0.428
Benign	13 (5.5)	5 (8.2)
Malignant	224 (94.5)	56 (91.8)
Preoperative STB (μmol/L)	106.0 ± 120.0	132.8 ± 120.9	0.221
Preoperative pre-albumin (mg/L)	143.1 ± 56.2	133.7 ± 60.7	0.364
Preoperative serum albumin (g/L)	39.1 ± 5.4	35.9 ± 6.3	0.002
Preoperative serum globulin (g/L)	26.9 ± 4.3	27.2 ± 3.3	0.675
Preoperative hemoglobin (g/L)	122.1 ± 18.3	118.6 ± 25.2	0.339
Preoperative white blood cells (109/L)	7.0 ± 8.9	6.7 ± 2.1	0.833
Preoperative platelets (109/L)	236.3 ± 83.5	223.2 ± 54.1	0.358
Pancreatic texture			< 0.001
Soft	80 (33.8)	50 (82.0)
Hard	157 (66.2)	11 (18.0)
Main pancreatic duct diameter (mm)	3.2 ± 1.0	2.6±0.7	0.001
Biliary tract compression	31 (13.1)	7 (11.5)	0.738
Pancreaticojejunostomy anastomosis			0.201
Duct-to-mucosa	180 (75.9)	51 (83.6)
Dunking method	57 (24.1)	10 (16.4)
Pancreatic duct stent			0.052
Internal stent	99 (41.8)	36 (59.0)
External stent	88 (37.1)	15 (24.6)
None	50 (21.1)	10 (16.4)
Vascular invasion			0.272
Yes	40 (16.9)	14 (23.0)
No	197 (83.1)	47 (77.0)
Operative time (min)	267.9 ± 68.7	275.9 ± 76.9	0.531
Estimated blood loss (mL)	287.4 ± 229.3	451.3 ± 365.1	0.001
Serum albumin POD 1 (g/L)	33.03 ± 5.2	32.9 ± 5.9	0.918
Serum globulin on POD 1 (g/L)	23.5 ± 11.9	23.0 ± 4.9	0.832
Hemoglobin on POD 1 (g/L)	111.2 ± 17.3	114.9 ± 14.3	0.236

CR-POPF: Clinically relevant postoperative pancreatic fistula; BMI: Body mass index; PD: Pan-creaticoduodenectomy; PPPD: Pylorus-preserving pancreaticoduodenectomy; POD: Postoperative day; STB: Serum total bilirubin.

Table 3 Univariate and multivariate analyses of predictive factors for clinically relevant pancreatic fistula in the study group (n = 189)

Factor	Univariate analysis			Multivariate analysis
	OR	95%CI	P-value	OR	95%CI	P-value
Patient characteristics
Age (≥ 65 yr/< 65 yr)	1.07	0.52-2.21	0.848
Sex (male/female)	0.58	0.27-1.14	0.107
BMI (≥ 24/< 24 kg/m2)	0.99	0.44-2.22	0.983
Diabetes mellitus (yes/no)	0.73	0.26-2.04	0.546
Preoperative status
Location of tumor (pancreas/non-pancreas)	0.66	0.32-1.35	0.256
Preoperative STB (≥ 22 μmol/L vs < 22 μmol/L)	1.07	0.50-2.30	0.857
Preoperative pre-albumin (≥ 170 mg/L vs < 170 mg/L)	0.84	0.38-1.88	0.672
Preoperative serum albumin (≥ 35 g/L vs < 35 g/L)	0.19	0.09-0.40	< 0.001	0.92	0.85-0.99	0.032
Preoperative serum globulin (≥ 22 g/L vs < 22 g/L)	2.59	0.58-11.65	0.201
Preoperative hemoglobin (≥ 110 g/L vs < 110 g/L)	0.61	0.27-1.40	0.241
Preoperative WBC (≥ 3.5 × 109/L vs < 3.5 × 109/L)	0.75	0.14-3.85	0.725
Preoperative PLT (≥ 150 × 109/L vs < 150 × 109/L)	1.08	0.74-3.41	0.898
Intraoperative status
Pancreatic texture (hard/soft)	0.05	0.02-0.12	< 0.001	0.25	0.10-0.64	0.004
Surgery (PD/PPPD)	1.04	0.51-2.12	0.914
Pathologic type (benign/malignant)	2.42	0.67-8.74	0.166
Main pancreatic duct diameter (≥ 3 mm vs < 3 mm)	0.26	0.12-0.54	< 0.001	0.50	0.27-0.93	0.029
Pancreaticojejunostomy anastomosis (duct-to-mucosa/dunking method)	0.58	0.25-1.34	0.202
Pancreatic duct stent (yes/no)	1.71	0.62-4.73	0.301
Vascular invasion (yes/no)	0.90	0.34-2.38	0.834
Operative time (≥ 300 min vs < 300 min)	0.74	0.36-1.65	0.466
Estimated blood loss (≥ 500 mL vs < 500 mL)	3.63	1.65-7.98	0.001	1.002	1.001-1.003	0.006
Postoperative status
Serum albumin POD 1 (≥ 35 g/L vs < 35 g/L)	0.74	0.34-1.65	0.466
Serum globulin POD 1 (≥ 22 g/L vs < 22 g/L)	0.93	0.46-1.91	0.851
Hemoglobin POD 1 (≥ 110 g/L vs < 110 g/L)	2.07	0.96-4.46	0.062

BMI: Body mass index; PD: Pancreaticoduodenectomy; PPPD: Pylorus-preserving pancreaticoduodenectomy; POD: Postoperative day; WBC: White blood cells; PLT: Platelets; STB: Serum total bilirubin; OR: Odds ratio; CI: Confidence interval.

Table 4 Risk scoring system for clinical relevant pancreatic fistula

Risk factor	Points contributed
Texture of pancreas (3 points)
Hard	0 points
Soft	3 points
Main pancreatic duct diameter (2 points)
≥ 3 mm	0 points
< 3 mm	2 points
Preoperative serum albumin (2 points)
≥ 35 g/L	0 points
30-35 g/L	1 point
< 30 g/L	2 points
Estimated blood loss (3 points)
< 500 mL	0 points
500-1000 mL	1 point
≥ 1000 mL	3 points
Sun score	10 points
High-risk score	4-10 points
Low-risk score	0-3 points

Table 5 Correlation between risk score and postoperative pancreatic fistula

	Study group (n = 189)		Validation group (n = 109)		All (n = 298)
	Risk score		Risk score		Risk score
POPF grade	Low	High	Low	High	Low	High
No POPF	97	20	60	8	157	28
Grade A (BL)	18	16	11	7	29	23
Grade B	7	25	5	15	12	40
Grade C	0	6	0	3	0	9
CR-POPF rate	5.7%	46.3%	6.6%	54.6%	6.1%	49.0%
	r = 0.542		r = 0.586		r = 0.557
	P < 0.001		P < 0.001		P < 0.001

POPF: Postoperative pancreatic fistula; CR: Clinically relevant; BL: Biochemical leak.

Table 6 Relationship between postoperative drain amylase levels and clinically relevant postoperative pancreatic fistula

	Low risk group			High risk group
	P-value	AUC	Cut-off value	P-value	AUC	Cut-off value
POD 1	> 0.05	--	--	0.001	0.850	921.7 U/L
POD 3	0.003	0.859	4021.5 U/L	0.05	--	--
POD 5	0.042	0.748	4533.5 U/L	0.05	--	--

P-value: Grade B/C postoperative pancreatic fistula vs none/biochemical leak. AUC: Area under the curve; POD: Postoperative day.