Novel diagnostics for aggravating pancreatic fistulas at the acute phase after pancreatectomy

Table 1 Demographics and clinical characteristics of 153 patients n (%)

Characteristic	Value
Age (yr), mean (range)	65.2 (28-89)
Male/female	101/52
Preoperative symptom(s)	37 (24)
Diabetes mellitus (preoperative )	39 (25)
History of pancreatitis	20 (13)
Body mass index, mean ± SD	22.5 ± 3.5
Procedure
Pancreatoduodenectomy	103
Distal pancreatectomy	50
Resection of the portal vein	21 (14)
Pathological diagnosis
Invasive carcinoma of the pancreas	68
Intraductal papillary mucinous neoplasm	35
Carcinoma of the ampulla	13
Cholangiocarcinoma	10
Pancreatic neuroendocrine tumor	8
Other	19
Grade of postoperative pancreatic fistula1
A	76
B	70
C	7

¹Defined according to the International Study Group on Pancreatic Fistula Definition.

Table 2 Inflammatory markers for clinically relevant postoperative pancreatic fistulas

Marker	POD 1		POD 3			POD 5		Change from POD 1 to 3			Change from POD 3 to 5
	AUC	P value	AUC	P value	Cutoff	AUC	P value	AUC	P value	Cutoff	AUC	P value
White blood cell count (/mm3)	0.545	0.343	0.524	0.615	11400	0.588	0.067	0.504	0.939	600	0.557	0.242
Neutrophil count (/mm3)	0.560	0.198	0.532	0.495	8200	0.591	0.060	0.506	0.898	-3300	0.560	0.215
Total lymphocyte count (/mm3)	0.524	0.604	0.577	0.097	600	0.541	0.397	0.550	0.285	0	0.518	0.708
Platelet count (/mm3)	0.540	0.399	0.615	0.014	164000	0.580	0.098	0.603	0.028	-24000	0.549	0.310
Serum amylase (IU/mL)	0.504	0.935	0.580	0.087	136	0.600	0.039	0.502	0.966	-69	0.522	0.643
C-reactive protein (mg/L)	0.534	0.532	0.688	< 0.001	158	0.684	< 0.001	0.767	< 0.001	28.4	0.565	0.200
Procalcitonin (ng/mL)	-	-	0.584	0.451	0.3	-	-	-	-	-	-	-
Neutrophil-to-lymphocyte ratio	0.532	0.497	0.579	0.092	9.6	0.590	0.061	0.537	0.433	-0.3	0.558	0.420
Platelet to lymphocyte ratio	0.517	0.718	0.529	0.557	231	0.557	0.243	0.508	0.858	67	0.539	0.231

P values were of the comparison between grade A and grade B/C as calculated by the Mann–Whitney U test. Cutoff values were determined by receiver operating characteristic curve analyses. POD: Postoperative day; AUC: Area under the curve.

Table 3 Diagnostic value of clinical factors for clinically relevant postoperative pancreatic fistula

Variable	Univariate			Multivariable
	Odds ratio	95%CI	P value	Odds ratio	95%CI	P value
Age (≥ 65 yr)	1.16	0.61-2.23	0.654
Gender (male)	1.29	0.66-2.53	0.459
Diabetes mellitus	1.39	0.67-2.92	0.378
History of pancreatitis	0.62	0.23-1.59	0.321
Body mass index (≥ 22)	1.48	0.79-2.82	0.226
Operative procedure (DP)	1.65	0.83-3.28	0.151
Invasive carcinoma of the pancreas	2.31	1.21-4.47	0.011	2.94	1.08-8.55	0.035
Operative time (≥ 360 min)	1.33	0.71-2.53	0.376
Blood loss (≥ 600 mL)	1.83	0.97-3.51	0.063	1.73	0.62-4.86	0.297
Intraoperative transfusion	1.45	0.48-4.59	0.511
Pancreas texture (soft)	1.46	0.69-3.10	0.322
Main pancreatic duct (< 4 mm)	1.36	0.70-2.65	0.366
Persistence of high fever (≥ 38 °C, ≥ 3 d)	1.10	0.57-2.14	0.781
Persistence of SIRS (≥ 3 d)	1.68	0.88-3.23	0.116
Usage of catecholamines	1.73	0.68-4.62	0.251
Total lymphocyte count (< 600/mm3, POD 3)	1.73	0.74-4.23	0.201
Platelet count (< 164000/mm3, POD 3)	2.28	1.20-4.39	0.012	1.28	0.44-3.64	0.646
CRP (≥ 158 mg/L, POD 3)	4.82	2.37-10.2	< 0.001	2.39	0.73-8.03	0.150
Neutrophil-to-lymphocyte ratio (≥ 9.6, POD 3)	1.84	0.97-3.52	0.061	1.56	0.55-4.40	0.401
CRP elevation (≥ 28.4 mg/L, POD 1 to 3)	11.4	4.35-34.3	< 0.001	4.82	1.25-20.2	0.022
Drain amylase (≥ 1918 IU/mL, POD 3)	3.00	1.57-5.86	0.001	1.50	0.55-4.08	0.423
Drain fluid bacterial culture (positive, POD 3)	1.62	0.68-3.87	0.278

Analyzed by binomial logistic analyses. DP: Distal pancreatectomy; SIRS: Systemic inflammatory response syndrome; CRP: C-reactive protein; POD: Postoperative day.

Table 4 Comparison of diagnostic performance of potent factors for clinically relevant postoperative pancreatic fistula

	Odds ratio	95%CI	P value	Sensitivity	Specificity	Positive predictive value	Negative predictive value	Likelihood ratio of positive result	Likelihood ratio of negative result
CRP ≥ 158 mg/L1	4.82	2.37-10.2	< 0.001	0.594	0.767	0.707	0.667	2.552	0.529
CRP elevation ≥ 28.4 mg/L2	11.4	4.35-34.3	< 0.001	0.864	0.643	0.655	0.857	2.418	0.212
Drain amylase ≥ 1918 IU/mL1	3.00	1.57-5.86	0.001	0.636	0.632	0.636	0.632	1.727	0.576
Risk score ≥ 8	12.9	5.13-35.4	< 0.001	0.795	0.768	0.729	0.827	3.427	0.266

¹Values on postoperative day (POD) 3;

²Change from POD 1 to POD 3. P values were analyzed by binomial logistic analyses. CRP: C-reactive protein.