Usefulness of urinary trypsinogen-2 and trypsinogen activation peptide in acute pancreatitis: A multicenter study in Japan

Table 1 The severity scoring system of acute pancreatitis of the Japanese Ministry of Health, Labour and Welfare (2008)[15]

Prognostic factors (1 point for each factor)
Base excess ≤ 3 mEq/L or shock (systolic blood pressure < 80 mmHg)
PaO2 ≤ 60 mmHg (room air) or respiratory failure (respirator management is needed)
BUN ≥ 40 mg/dL (or Cr ≥ 2.0 mg/dL) or oliguria (daily urine output <400 mL even after fluid replacement)
LDH ≥ 2 times of upper limit of normal
Platelet count ≤ 100000/mm3
Serum Ca ≤ 7.5 mg/dL
CRP ≥ 15 mg/dL
Number of positive measures in SIRS criteria ≥3
Age ≥ 70 yr
CT Grade by CECT
Extra-pancreatic progression of inflammation
Anterior pararenal space	0 point
Root of mesocolon	1 point
Beyond lower pole of kidney	2 points
Hypo-enhanced lesion of the pancreas
The pancreas is conveniently divided into three segments (head, body, and tail).
Localized in each segment or only surrounding the pancreas	0 point
Covers 2 segments	1 point
Occupies entire 2 segments or more	2 points
1 + 2 = total scores
Total score = 0 or 1	Grade 1
Total score = 2	Grade 2
Total score = 3 or more	Grade 3
Assessment of severity
(1) If prognostic factors are scored as 3 points or more, or (2) If CT Grade grade is judged as Grade grade 2 or more, the severity grading is evaluated to be as ‘‘severe’’.
Measures in SIRS diagnostic criteria: (1) Temperature > 38 °C or < 36 °C; (2) Heart rate > 90 beats/min; (3) Respiratory rate > 20 breaths/min or PaCO2 < 32 torr; and (4) WBC > 12000 cells/mm3, < 4000 cells/mm3, or > 10% immature (band) forms.

WBC: White blood cell; CT: Computed tomography; LDH: lactate dehydrogenase; CRP: C-reaction protein.

Table 2 The characteristics of patients at enrollment

	Acute pancreatitis (n = 78)	Other disease (n = 16)
Age, median (IQR), yr	57 (28)	61 (26)
Sex, n: male/female	50/26	9/7
Etiology of acute pancreatitis, n (%)
Alcohol	26 (33.3)
Gallstones	13 (16.7)
Idiopathic	12 (15.4)
Post-ERCP	5 (6.4)
Others	22 (28.2)
Prognostic factor score by JMHLW (2008) criteria (n = 78)
Mean (SD)	0.9 (1.2)
Severe acute pancreatitis (≥ 3), n (%)	9 (11.5)
Score of CT Grade by JMHLW (2008) criteria (n = 70)
Mean (SD)	1.0 (1.2)
Severe acute pancreatitis (Score ≥ 2), n (%)	28 (40)

Table 3 Urinary marker levels at enrollment in patients with severe and mild pancreatitis by prognostic factors according to the Japanese Ministry of Health, Labour and Welfare criteria (2008)[15]

	Severity by prognostic factors
	Severe		Mild
No. cases	9		69
Prognostic factors: mean (SD)	2.89	(1.83)	0.57	(0.69)
Age: median (LQ, UQ), yr	48.5	(45, 69.75)	58	(44, 72)
Sex: male/female	5/2		45/24
	Median (LQ, UQ)				AUC
Urinary trypsinogen-2, mg/dL	6.49	(2.41, 208.76)	2.87	(0.22, 19.98)	0.704
Urinary trypsinogen-2/cre	11.2	(2.43, 214.05)	6.36	(0.31, 33.02)	0.592
Urinary TAP, ng/mL	2.68	(2.07, 5.22)	2.79	(1.25, 5.53)	0.458
Urinary TAP/cre, × 0.0001	6.7	(2.40, 11.50)	4.1	(2.25, 7.20)	0.631
Urinary amylase, × 1000 U/L	1.42	(0.50, 3.16)	1.01	(0.40, 2.68)	0.563
Urinary amylase/cre, U/mg	3.65	(0.38, 8.47)	2.22	(0.81, 4.00)	0.58
Urinary creatinine, × 10 mg/dL	3.63	(3.16, 8.65)	6.09	(3.89, 10.24)	0.599
Serum amylase, × 100 U/L	11.37	(2.44, 23.37)	6.38	(3.46, 11.72)	0.581
Serum lipase, × 100 U/L	5.85	(4.41, 13.57)	6.95	(2.46, 16.71)	0.508
Serum creatinine, × 0.1mg/dL	9.7	(5.95, 19.65)	6.75	(5.83, 8.55)	0.676

Their area under the curve scores were calculated between severe and mild pancreatitis groups by logistic regression analysis. The cases with no available data were excluded from analysis. All data were showed by median, lower quartile, and upper quartile. AUC: Area under the curve; LQ: Lower quartile; UQ: Upper quartile; TAP: Trypsinogen activation peptide.

Table 4 Urinary marker levels at enrollment between patients with severe and mild pancreatitis by computed tomography Grade according to the Japanese Ministry of Health, Labour and Welfare criteria (2008)[15]

	Severity by CT Grade
	Severe		Mild
No. cases	28		42
Score of CT Grade: mean (SD)	2.37 (0.69)		0.17 (0.38)
Extra-pancreatic progression of inflammation (Score 0/1/2)	0/1/27		35/7/0
Hypo-enhanced lesion of the pancreas (Score 0/1/2)	19/3/4		42/0/0
Age: median (LQ, UQ), yr	53 (44, 67)		61 (47.5, 73.25)
Sex: male/female, n	20/6		24/18
	Median (LQ, UQ)				AUC
Urinary trypsinogen-2, mg/dL	14.68	(2.10, 66.90)	2.69	(0.20, 17.11)	0.701
Urinary trypsinogen-2/cre	14.40	(4.29, 104.03)	6.36	(0.32, 17.94)	0.678
Urinary TAP, ng/mL	3.98	(2.20, 7.81)	2.07	(0.96, 3.87)	0.692
Urinary TAP/cre, × 0.0001	6.70	(4.15, 10.90)	3.10	(2.20, 6.00)	0.727
Urinary amylase, × 1000 U/L	1.94	(0.64, 3.62)	0.97	(0.47, 2.29)	0.615
Urinary amylase/cre, U/mg	3.54	(0.63, 5.88)	2.23	(0.88, 3.65)	0.588
Urinary creatinine, × 10 mg/dL	6.55	(3.54, 9.24)	5.54	(3.49, 10.47)	0.472
Serum amylase, × 100 U/L	9.28	(2.88, 15.22)	6.28	(3.91, 11.74)	0.588
Serum lipase, × 100 U/L	8.10	(1.82, 18.49)	6.95	(4.32, 15.73)	0.521
Serum creatinine, × 0.1 mg/dL	7.25	(5.40, 8.90)	6.90	(5.75, 7.95)	0.574

Their area under the curve scores were calculated between severe and mild pancreatitis groups by logistic regression analysis. The cases with no available data were excluded from analysis. All data were showed by median, lower quartile, and upper quartile. AUC: Area under the curve; LQ: Lower quartile; UQ: Upper quartile; CT: Computed tomography; TAP: Trypsinogen activation peptide.

Table 5 Urinary marker levels at enrollment according to the score of computed tomography Grade by the Japanese Ministry of Health, Labour and Welfare criteria (2008)[15]

Extra-pancreatic progression of inflammation
Score of CT Grade		0	1	2	P value
n		32	8	24
Urinary trypsinogen-2 (mg/dL)	Median	1.26	27.65	16.98	0.001a
	(LQ, UQ)	(0.15, 11.20)	(2.67, 91.61)	(3.04, 71.25)
Urinary trypsinogen-2/cre	Median	3.11	28.5	15.77	0.046a
	(LQ, UQ)	(0.31, 13.17)	(6.70, 130.83)	(3.76, 106.64)
Urinary TAP (ng/mL)	Median	1.97	2.7	4.19	0.001a
	(LQ, UQ)	(0.95, 3.79)	(1.15, 4.73)	(2.55, 8.06)
Urinary TAP/cre (× 0.0001)	Median	2.75	3.65	6.95	0.003a
	(LQ, UQ)	(2.03, 6.53)	(3.10, 4.73)	(4.63, 11.20)
Urinary amylase (× 1000 U/L)	Median	0.94	1.44	2.11	0.06
	(LQ, UQ)	(4.63, 17.14)	(3.13, 41.84)	(8.25, 36.65)
Urinary amylase/cre (U/mg)	Median	2.22	2.02	3.72	0.22
	(LQ, UQ)	(0.85, 3.54)	(0.56, 4.36)	(0.91, 6.15)
Urinary creatinine (× 10 mg/dL)	Median	4.68	6.5	6.7	0.94
	(LQ, UQ)	(3.48, 10.20)	(3.24, 10.14)	(3.95, 9.57)
Serum creatinine (× 0.1 mg/dL)	Median	6.75	6.6	7.5	0.042a
	(LQ, UQ)	(5.88, 8.33)	(4.95, 7.20)	(5.20, 9.00)
Hypo-enhanced lesion of the pancreas
Score of CT Grade		0	1	2	P value
n		55	3	4
Urinary trypsinogen-2 (mg/dL)	Median	4.51	44.33	6.77	0.63
	(LQ, UQ)	(0.47, 30.35)	(1.78, 100.99)	(2.45, 14.81)
Urinary trypsinogen-2/cre	Median	8.37	148.96	9.07	0.84
	(LQ, UQ)	(0.53, 40.84)	(2.27, 179.09)	(6.54, 15.45)
Urinary TAP (ng/mL)	Median	2.61	3.07	5.88	0.45
	(LQ, UQ)	(1.33, 5.63)	(2.79, 5.22)	(1.04, 12.48)
Urinary TAP/cre (× 0.0001)	Median	4.1	6.7	6.85	0.65
	(LQ, UQ)	(2.30, 7.20)	(4.90, 10.30)	(3.25, 11.80)
Urinary amylase (× 1000 U/L)	Median	1.24	1.01	2.22	0.83
	(LQ, UQ)	(4.95, 28.55)	(7.87, 22.70)	(2.94, 35.16)
Urinary amylase/cre (U/mg)	Median	2.59	3.39	2.21	0.72
	(LQ, UQ)	(0.88, 4.56)	(1.00, 4.03)	(0.46, 6.13)
Urinary creatinine (× 10 mg/dL)	Median	6.37	5.64	7.47	0.56
	(LQ, UQ)	(3.70, 10.45)	(2.98, 7.85)	(3.11, 10.53)
Serum creatinine (× 0.1 mg/dL)	Median	6.95	7.8	6.25	0.3
	(LQ, UQ)	(5.83, 8.60)	(4.90, 8.60)	(4.70, 7.88)

Extra-pancreatic progression of inflammation: 0 = anterior pararenal space, 1 = root of mesocolon, 2 = beyond the lower pole of the kidney. Hypoenhanced lesion of the pancreas: The pancreas was divided into three segments. 0 = signal was localized in each segment or only the surrounding pancreas, 1 = covers two segments, 2 = entirely covered two or more segments. Data are expressed as the median (lower quartile, and upper quartile). Statistical significance is expressed as

^aP < 0.05 among the three groups by ordinal logistic regression analysis. LQ: Lower quartile; UQ: Upper quartile; CT: Computed tomography; TAP: Trypsinogen activation peptide.