Drain fluid biomarkers for prediction and diagnosis of clinically relevant postoperative pancreatic fistula: A narrative review

Table 1 Drain amylase accuracy evaluated beyond sensitivity and specificity

Ref.	Cut-off (U/L)	Predictive	Evaluated (POD)	Patients	Surgery	CR-POPF (%)	Study design	Publication
		Performance		n
Giovinazzo et al[48], 2018	350	AUC = 0.92	1	568	PD	NS	R	Abstract
Partelli et al[49], 2017	500	AUC = 0.881, OR = 21.72	1	463	PD	13.82	R	Abstract
Kerem et al[50], 2018	1363	AUC = 0.91	1	135	PD	13.33	R	Abstract
Kawai et al[51], 2009	5000	P = 0.1002 (univariate)	1	244	PD	28	R	Full paper
Teixeira et al[52], 2018	< 270	Higher median values statistically predicted CR-POPF	1	102	PD	25.5	P	Full paper
	271-5000
	> 5000
Mimura et al[53], 2012	2000	AUC = 0.81	1	240	PD	23.4	R	Abstract
Mimura et al[53], 2012	100	AUC = 0.86	5	240	PD	23.4	R	Abstract
Kawaida et al[54], 2018	860	P = 0.002 (univariate)	3	75	DP	9.3	P	Full paper
Recreo Baquedano et al[55], 2019	< 400	NPV = 0.968	3	278	PD	14	P	Abstract
Newhook et al[56], 2020	49	Sensitivity = 1	1	45	DP	24	P	Full paper
Newhook et al[56], 2020	26	Sensitivity = 1	3	45	DP	24	P	Full paper
van Dongen et al[57], 2021	100	Sensitivity = 1	2	285	PD	18.24	R	Abstract

POD: Postoperative day; AUC: Area under the receiver operating characteristic curve; OR: Odds ratio; CR-POPF: Clinically relevant postoperative pancreatic fistula; PD: Pancreatoduodenectomy; DP: Distal pancreatectomy; P: Prospective; R: Retrospective; NS: Not stated; NPV: Negative predictive value.

Table 2 Investigations of drain culture across different pancreatic surgery cohorts

Clinical condition	Pancreatoduodenectomy patients	Distal pancreatectomy patients
Present in CR-POPF patients	Fungi, gram-positive bacteria, Acinetobacter, Stenotrophomonas, Citrobacter spp, Staphylococcus, Enterococcus, Enterococcus faecalis Candida spp., Klebsiella, Klebsiella pneumoniae, Pseudomonas, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae	Fungi, Staphylococcus, Enterococcus, Pseudomonas, Acinetobacter, Stenotrophomonas, Escherichia coli and Klebsiella spp
Predictor of CR-POPF	Polymicrobial infections, Candida
Predictor of grade C	Gram-negative rods, Candida

CR-POPF: Clinically relevant postoperative pancreatic fistula.

Table 3 Recommendations for future research

Drain biomarker	To investigate	To confirm
Amylase	Accuracy of intraoperative predictive cut-offs in pancreatoduodenectomy patients	Diagnostic accuracy of proposed cut-offs
	Accuracy of POD2 cut-offs in distal pancreatectomy patients	The change in postoperative drain amylase required to be predictive of CR-POPF in pancreatoduodenectomy patients
	Accuracy of POD4 cut-offs in surgery specific cohorts	If a persistently high value for drain amylase x drain volume postoperatively is predictive of CR-POPF
	Accuracy of risk-stratified cut-offs in distal pancreatectomy patients
	The change in postoperative drain amylase required to be predictive of CR-POPF in distal pancreatectomy patients
	When drain amylase has the highest predictive accuracy
Lipase	The change in postoperative drain lipase required to be predictive of CR-POPF in surgery specific cohorts and its accuracy	Diagnostic accuracy of proposed cut-offs
	The accuracy of predictive cut-offs before POD3 in surgery specific cohorts	Diagnostic value of drain lipase in multi-factorial predictive models
	Accuracy of risk-stratified cut-offs in surgery specific cohorts	When drain amylase has the highest predictive accuracy
Drain culture	Bacteria within polymicrobial drain fluid samples which predict grade B and C POPF in surgery specific cohorts	Clinical relevance of Enterobacter, Enterococcus and Staphylococcus to CR-POPF risk in pancreatoduodenectomy patients
	When particular microorganisms are most predictive of CR-POPF
	The concentrations of high-risk bacteria that accurately predict CR-POPF in surgery specific cohorts
Other biomolecules	Accuracy of predictive cut-offs for each biomarker in surgery specific cohorts
	Accuracy of novel enzymes compared to drain amylase and lipase in matched surgical cohorts and PODs
Fluid appearance	Accuracy on specific days before POD3

POD: Postoperative day; CR-POPF: Clinically relevant postoperative pancreatic fistula.