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Three Part Question

In [adult patients with abdominal pain], can [urinary trypsinogen] be used to [diagnose acute pancreatitis]?

Clinical Scenario

A 44 year old man presents to the emergency department with severe epigastric pain. With a working diagnosis of acute pancreatitis, the result of serum amylase were inconclusive. As urinary trypsinogen have been recommended as an adjunct in supporting the diagnosis of pancreatitis, you wonder if it would be worthwhile performing a urine dipstick for this purpose.

Search Strategy

EMBASE 1974 to 2012 July 06

[({abdominal pain.mp. OR exp Abdominal Pain/} OR {exp Pancreatitis, Acute Necrotizing/ OR exp Pancreatitis/ OR exp Pancreatitis, Chronic/ OR exp Pancreatitis, Alcoholic/ OR pancreatitis.mp.}) AND ({exp "Sensitivity and Specificity"/ OR sensitivity.mp. OR specificity.mp.} OR {diagnosis.mp. OR exp Diagnosis/}) AND ({exp trypsinogen activation peptide/ or exp trypsinogen/ or trypsinogen.mp. AND exp urine/ or urine.mp.} OR urinary trypsinogen.mp.)] LIMIT to Human AND English Language.

Search Outcome

66 papers were found of which 52 papers were irrelevant or unavailable. The other 14 available are as follows.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
P. Abraham APR 2011 India	Total of 124 patients with abdominal pain of which 69 were diagnosed with acute pancreatitis.	Prospective cohorts study comparing accuracy of UT with other methods at diagnosing acute pancreatitis.	Accuracy of UT	Sensitivity - 73.9% (95% CI 61.9% to 83.8%)	Criteria of urine collection was not monitored. Study performed in single specialist center. Amylase and lipase used to determine diagnosis was used to compare accuracy of UT
				Specificity - 94.6% (95% CI 84.9% to 98.9%)
				PPV - 94.4%
				NPV - 74.3%
F. Kurti et al FEB 2011 Albania	45 patient presenting with abdominal pain to the emergency unit; 18 cases of which were due to AP.	Prospective cohort study evaluating and comparing the values of UT with serum amylase and lipase.	Performance of UT	True positive: 16/18 (88.8)	Only journal abstract available. Aims of study were not met; results were not explored in detail and were not compared. Single center study with small sample. Conclusion was largely subjective
				False negative: 2/18 (11.2%)
				False positive: 3/27 (11.1%)
Y. Cevik et al MAR 2010 Turkey	Total of 87 patients with abdominal pain of which 32 were diagnosed with AP.	Prospective cohort study evaluating the role of UT in excluding differentials of AP during admission and comparing the results with other conventional methods	Predictive value of UT	Sensitivity - 64%; Specificity - 85%; PPV - 72%; NPV - 81%; p<0.01	Single center study with small sample.
E. Aysan et al. DEC 2008 Istanbul	Total of 99 patients of which 50 were diagnosed with AP through abdominal CT	Prospective cohort study evaluating and comparing the value of UT with other methods of diagnosing AP	Predictive value of UT	Sensitivity - 56%; Specificity - 90.9%	Only journal abstract available. Single center study.
K. Erdinc et al DEC 2007 Turkey	Total of 92 patients presenting with abdominal pain of which the 25 patients with non-pancreatic abdominal pain where considered the control group.	Prospective cohort study evaluating the use UT test for early diagnosis and prediction of severity in AP.	Predictive value of UT	Sensitivity - 91%; Specificity - 72%; PPV - 96.6%; NPV - 70.4%; PLR - 3.4; NLR - 0.1
T. Jang et al JAN 2007 United States	191 patients in total of which 17 patients were diagnosed with AP through an extensive inclusion criteria	Prospective cohort study evaluating the use UT test for early diagnosis of AP during admission with a 3 minute UT test.	Accuracy of UT	Sensitivity: 100% (95% CI 77%-100%); Specificity - 96% (95% CI 92%-98%)	Urine sample were collected by different research assistant. Non-conventional inclusion criteria due to varying definition of AP. Single center study. Urinary test were confirmed in the laboratory instead of at the emergency unit.
Saez J. et al DEC 2005 Spain	A total of 50 patients with abdominal pain of which 22 patients were extrapancreatic in origin.	Prospective cohort study assessing value of UT, urinary trypsinogen activation peptide (TAP), and serum and urine concentrations of the activation peptide of carboxypeptidase B (CAPAP) in the diagnosis of acute pancreatitis.	Accuracy of UT	Sensitivity: 68%; Specificity: 86.4%; PPV: 91.9%; NPV: 54.3%	Single center study.
Y. Chen et al APR 2005 Taipei	165 patients with acute abdominal pain of which 67 were diagnosed with AP and 98 with other acute abdominal diseases.	Prospective cohort study evaluating the diagnostic value of UT in AP, using a cut-off of 50mug/L, with comparisons with serum amylase and serum lipase.	Predictive value of UT	Sensitivity - 89.6%; Specificity - 85.7%; PPV - 81.1%; NPV - 92.3%	Operators were not blinded. Single center study with small sample.
ML. Kylänpää-Bäck et al AUG 2002 Finland	Total of 237 patient with abdominal pain admitted to emergency unit.	Prospective cohort study comparing accuracy of UT with serum amylase and lipase in diagnosing AP.	Predictive value of UT	Sensitivity - 93%; Specificity - 92%	Only journal abstract available. Small single center study with small sample.
R. Pezzilli et al MAR 2001 Italy	A total of 90 patients were involved: 30 patient diagnosed with AP 30 patient with abdominal of extrapancreatic causes 30 healthy patient as control	Prospective cohort study evaluating the value to UT in diagnosing AP according to admission dates in comparison to serum/urine amylase and serum lipase.	Predictive value of UT	Sensitivity: 53.3% (95% CI 34.3± 71.6%)	Single center study with smal sample. Researchers and patients were not blinded
J. Hedstorm et al MAY 1996 Finland	Total of 122 patient: 63 patients without abdominal diseases 59 patients with AP 42 with acute abdominal diseases of extrapancreatic origin	Diagnostic cohort study comparing the value of UT with serum trypsinogen and lipase and urinary amylase.	AUC of UT	0.978	Single center study with small cohort
J. Hedstom et al MAR 1996 Finland	57 patients with AP; 40 patients with extrapancreatic abdominal pain	Prospective cohort study comparing the accuracy of urinary and serum trypsinogen	Accuracy of UT	True Positives: 52; False Negative - 5; False Positives - 4	Single center study with small cohort
A.M. Andersen JAN 2010 Denmark	75 patients with AP; 35 patients with extrapancreatic abdominal pain as control	Prospective cohort study evaluating accuracy of UT.	Accuracy of UT	Sensitivity - 77% (95% CI 66-86%); Specificity of 97% (95% CI 84-99.9%).	Single center study with small cohort
E.A. Kemppainen et al JUN 1997 Finland	500 patients in total with abdominal pain at two emergency units.	Diagnostic study using the UT to identify patients with AP. Result were compared with serum amylase, lipase and trypsinogen and urinary amylase.	Accuracy of UT	Sensitivity - 94%; Specificity 95% (95% CI 66-86%); Specificity of 97% (95% CI 84-99.9%).

Comment(s)

Currently, laboratory marker available for the diagnosis of AP include serum amylase, lipase and trypsinogen and urinary amylase. It's always been recognised that urinary trypsinogen can supplement the diagnosis with a relatively accurate predictive value. Literatures have quoted sensitivities and a specificities ranging from 53.3%-96% and 85.7%-95%. With the added benefit of being quick and easy to use, it may replace the current dependency on serum amylase as the standard diagnostic procedure in determining patients with AP.

Clinical Bottom Line

UT should be implemented in the process of AP diagnosis this decision should be confirmed with other diagnostic technique.

References

1. P. Abraham Point-of-care Urine Trypsinogen-2 Test for Diagnosis of Acute Pancreatitis JAPI APR 2011; 59(4), 231-232
2. F. Kurti et al Urinary Trypsinogen Test in Diagnosing Acute Pancreatitis. Pancreatology FEB 2011, 11, 14
3. Y. Cevik et al The role of urine trypsinogen-2 test in the differential diagnosis of acute pancreatitis in the Emergency Department Ulus Travma Acil Cerrahi Derg MAR 2012;16(2):125-129
4. E. Aysan et al. Effectivity of qualitative urinary trypsinogen-2 measurement in the diagnosis of acute pancreatitis: a randomized, clinical study Acta Chirurgica Belgica DEC 2008; 108(6): 696-698
5. K. Erdinc et al Early diagnosis and prediction of severity in acute pancreatitis using the urine trypsinogen-2 dipstick test: A prospective study World J Gastroenterol DEC 2007; 13(46): 6208-6212
6. T. Jang et al Point-of-care Urine Trypsinogen Testing for the Diagnosis of Pancreatitis Acad Emerg Med JAN 207; 14(1):29-34
7. Saez J. et al Clinical value of rapid urine trypsinogen-2 test strip, urinary trypsinogen activation peptide, and serum and urinary activation peptide of carboxypeptidase B in acute pancreatitis World J Gastroenterol DEC 2005; 11(46):7261-7265
8. Y. Chen et al Rapid Urinary Trypsinogen-2 Test Strip in the Diagnosis of Acute Pancreatitis Pancreas 2005; 30:243–247
9. ML. Kylänpää-Bäck et al Comparison of urine trypsinogen-2 test strip with serum lipase in the diagnosis of acute pancreatitis. Hepatogastroenterology AUG 2002; 49(46):1130-1134
10. R. Pezzilli et al Time-course and clinical value of the urine trypsinogen-2 dipstick test in acute pancreatitis. Eur J Gastroenterol Hepatol MAR 2001; 13(3):269-274
11. J. Hedstorm et al Urine trypsinogen-2 as marker of acute pancreatitis Clin Chem MAY 1996; 42(5): 685-690
12. J. Hedstom et al Urinary trypsinogen-2 test strip for acute pancreatitis The Lancet MAR 1996; 347: 729-731
13. A.M. Andersen Urinary Trypsinogen-2 Dipstick in Acute Pancreatitis Pancreas JAN 2010; 39(1): 26-30
14. E.A. Kemppainen et al Rapid measurement of urinary trypsinogen-2 as a screening test for acute pancreatitis. New England Journal of Medicine 336 (25) (pp 1788-1793)