Preoperative interleukin-17a as a predictor of acute pancreatitis after pancreaticoduodenectomy

Table 1 Comparison of patient characteristics and postoperative complications

Variables	No PPAP (n = 105)	PPAP (n = 45)	P value
Age [median (IQR)], years	63 (55-70)	63 (56.5–70)	0.549
Sex, n (%), male	230 (59.7%)	42 (51.2%)	0.155
Total bilirubin level (μmol/L)	12.0 (7.8-20.0)	19.5 (12.6-35.0)	0.04
Incidence of soft pancreatic texture (%)	61.0	34.0	< 0.001
Incidence of MPD ≤ 3 mm (%)	81.0	60.0	0.012
Incidence of PDAC or CP (%)	26.7	58.7	0.001
FRS risk area	Higher	Lower	< 0.001
Incidence of POPF (%)	55.6	7.4	< 0.001
Incidence of bile leak (%)	9.1	2.1	0.006
Incidence of intra-abdominal infection (%)	26.7	9.5	0.001
Incidence of major complications (%)	17A.2	3.8	0.001
Incidence of interventional drainage (%)	12.2	1.4	< 0.001
Incidence of reoperation (%)	5.6	0.7	0.021
Postoperative hospital stay (days)	28 (21-35)	14 (10-20)	< 0.001

PDAC: Pancreatic ductal adenocarcinoma; PPAP: Postpancreatectomy acute pancreatitis; MPD: Main pancreatic duct; CP: Chronic pancreatitis; FRS: Fistula risk score; POPF: Postoperative pancreatic fistula.

Table 2 Inflammatory marker profiles before surgery in relation to postpancreatectomy acute pancreatitis development

Variables	No PPAP (n = 105)	PPAP (n = 45)	P value
CRP [median (IQR)], mg/L	2.11 (1.12–7.92)	2.12 (1.13–5.24)	0.214
IFN-α [median (IQR)], pg/mL	0.2 (0.2–0.2)	0.2 (0.2–0.2)	0.472
IFN-γ [median (IQR)], pg/mL	3.6 (0.1–6.9)	3.4 (0.1–6.2)	0.578
IL-2 [median (IQR)], pg/mL	0.2 (0.2–0.2)	0.2 (0.2–0.2)	0.467
IL-4 [median (IQR)], pg/mL	0.2 (0.2–0.2)	0.2 (0.2–0.2)	0.401
IL-5 [median (IQR)], pg/mL	0.2 (0.4–3.6)	0.2 (0.1–3.6)	0.469
IL-17a [median (IQR)], pg/mL	12.5 (5.8–28.7)	3.5 (1.5–8.0)	< 0.001
WBC [median (IQR)], × 109/L	5.66 (4.64–6.67)	5.96 (5.06–7.42)	0.070
Fluid load [median (IQR)], mL/day	600 (500-700)	800(700-900)	< 0.001

CRP: C-reactive protein; WBC: White blood cell; PPAP: Post pancreatectomy acute pancreatitis; IL-17a: Interleukin-17A.

Table 3 Associations between preoperative interleukin-17A levels, standard inflammatory indicators, and postoperative complications, n (%)

Variables	IL-17a ≥ 4.5 pg/mL (n = 65)	IL-17a < 4.5 pg/mL (n = 84)	P value
CRP > 5 mg/L	43.5	30.0	0.053
CRP [median (IQR)], mg/L	3.50(1.50-10.5)	1.75 (1.00-4.5)	< 0.001
WBC > 10 × 109/L	10.0	12.0	0.765
WBC [median (IQR)], × 109/L	6.20 (5.10-7.80)	5.30 (4.40-6.20)	0.002
NE > 7 × 109/L	5.0	6.0	0.924
NE [median (IQR)], × 109/L	4.00 (3.20-5.10)	3.20 (2.60-4.10)	0.002
PPAP	31.3	7.5	< 0.001
POPF	29.8	12.9	< 0.001
Biliary leak	4 (6.5)	3 (4.5)	0.678
PPH	10 (15.0)	12 (18.0)	0.543
Intra-abdominal infections	18 (27.0)	20 (30.0)	0.789
DGE	6 (9.0)	8 (12.0)	0.654
Chyle leak	2 (3.0)	4 (6.0)	0.567
Interventional drains	12 (18.0)	15 (22.5)	0.456
Major complications	25 (37.5)	28 (42.0)	0.784
Relaparotomy	8 (12.0)	10 (15.0)	0.679
90-day mortality	3 (4.5)	5 (7.5)	0.564
Postoperative hospital stays, days	18 (15-22)	20 (17-25)	0.453

CRP: C-reactive protein; WBC: White blood cell; NE: Neutrophils; PPAP: Post pancreatectomy acute pancreatitis; IL-17a: Interleukin-17A; POPF: Postoperative pancreatic fistula; DGE: Delayed gastric emptying.

Table 4 Risk factor assessment for post pancreatectomy acute pancreatitis: A two-tiered statistical evaluation

Risk factors	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
IL-17a ≥ 4.5 pg/mL	3.85 (2.14-6.91)	< 0.001	4.67 (2.49-8.72)	< 0.001
WBC > 10 × 109/L	1.86 (0.64-5.36)	0.252
NE > 7 × 109/L	2.12 (0.82-5.12)	0.148
Age, years	1.11 (0.99-1.02)	0.382
Sex, male vs female	0.70 (0.43-1.13)	0.168
BMI, kg/m2	1.06 (0.97-1.03)	0.194
ASA ≥ III	0.75 (0.45-1.19)	0.268
Total bilirubin ≥ 24 μmol/L	0.64 (0.38-1.04)	0.068
Venous resection, yes vs no	1.34 (0.74-2.36)	0.384
Surgical procedure, RPD vs OPD	0.96 (0.55-1.69)	0.889
Operative time > 300 minutes	1.36 (0.84-2.26)	0.265
Estimated blood loss > 200 mL	1.38 (0.86-2.22)	0.247
Pathology (not PDAC/CP)	2.08 (1.26-3.44)	0.004	1.89 (1.08-3.30)	0.025

PDAC: Pancreatic ductal adenocarcinoma; CP: Chronic pancreatitis; WBC: White blood cell; NE: Neutrophils; IL-17a: Interleukin-17A; BMI: Body mass index; RPD: Robotic pancreaticoduodenectomy; OPD: Open pancreaticoduodenectomy.

Table 5 Subgroup analyses of risk factors for post pancreatectomy acute pancreatitis-associated postoperative pancreatic fistula

Risk factors	Univariate analysis		Multivariate analysis
	OR (95%CI)	P value	OR (95%CI)	P value
CRP, mg/L	0.85 (0.72-1.34)	0.17A9
IFN-α, pg/mL	3.84(2.25-6.84)	0.164
IFN-γ, pg/mL	1.86 (0.64-5.36)	0.252
IL-2, pg/mL	2.12 (0.82-5.12)	0.148
IL-17a, pg/mL	1.24 (1.12-1.36)	< 0.001	1.12 (1.11-1.16)	< 0.001
Age, years	0.75 (0.45-1.19)	0.268
Sex, male vs female	0.64 (0.38-1.04)	0.068
BMI, kg/m2	1.06 (0.58-2.17)	0.896
Albumin < 35 g/L	2.56 (1.37-4.77)	0.002
PBD, yes vs no	1.34 (0.74-2.36)	0.384
Pancreatic texture, soft vs firm	0.96 (0.55-1.69)	0.889
MPD ≤ 3 mm	1.36 (0.84-2.26)	0.265
Venous resection, yes vs no	1.38 (0.86-2.22)	0.247
Surgical procedure, RPD vs OPD	2.08 (1.26-3.44)	0.004
Operative time > 300 minutes	1.19 (0.65-1.86)	0.782
Estimated blood loss > 200 mL	2.78 (1.51-5.12)	0.001

PBD: Pancreatic biliary drainage; BMI: Body mass index; IL-17a: Interleukin-17A; CRP: C-reactive protein; RPD: Robotic pancreaticoduodenectomy; OPD: Open pancreaticoduodenectomy; POPF: Postoperative pancreatic fistula.