Faecal Elastase 1: a Novel, Highly Sensitive, and Specific Tubeless Pancreatic Function Test Gut: First Published As 10.1136/Gut.39.4.580 on 1 October 1996

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Faecal Elastase 1: a Novel, Highly Sensitive, and Specific Tubeless Pancreatic Function Test Gut: First Published As 10.1136/Gut.39.4.580 on 1 October 1996 580 Gut 1996; 39: 580-586 Faecal elastase 1: a novel, highly sensitive, and specific tubeless pancreatic function test Gut: first published as 10.1136/gut.39.4.580 on 1 October 1996. Downloaded from Chr Loser, A Mollgaard, U R Folsch Abstract variables. `- Direct pancreatic function tests Background-Indirect pancreatic func- such as the secretin-cholecystokinin or tion tests available today are unreliable for secretin-caerulein test have the highest clinical practice in early chronic pancrea- sensitivity and specificity for the detection of titis due to their low sensitivity in mild and exocrine pancreatic insufficiency and remain moderate exocrine pancreatic insuffi- the 'gold standard' for testing pancreatic ciency. function.3?6 Direct pancreatic function tests, Aim-To evaluate the sensitivity, specifi- however, have various practical disadvantages: city, and practicability of faecal elastase 1 they are time consuming, invasive, expensive, determination in patients with mild, uncomfortable, not standardised, and require moderate, and severe exocrine pancreatic fluoroscopic tube placement. Therefore the insufficiency categorised according to the secretin-caerulein test is unsuitable for routine secretin-caerulein test as 'gold standard'. application and is confined to a few academic Patients and methods-Faecal and duo- centres. denal elastase 1 concentration (commer- Several simple indirect pancreatic function cial enzyme linked immunosorbent assay tests for clinical practice, such as the (ELISA)), faecal chymotrypsin activity, fluorescein dilaurate test, NBT-PABA or faecal fat analysis, and the secretin- bentiromide test, faecal chymotrypsin de- caerulein test were performed on 44 termination, or different breath tests, have patients with mild (n=8), moderate been established.' 37 However, these proved (n=14), and severe (n=22) exocrine to have limited sensitivity in mild and pancreatic insufficiency and 35 patients moderate exocrine pancreatic insufficiency and with gastrointestinal diseases of non- are interfered with by some drugs, diarrhoea, pancreatic origin. Fifty healthy volunteers pH, and gastrointestinal operations, which http://gut.bmj.com/ were studied as normal controls. Morpho- lower their specificity. In general these indirect logical examinations were carried out to pancreatic function tests are unreliable for definitely confirm or exclude chronic clinical practice in early chronic pancrea- pancreatitis. titiSI-3 5 8 9 and the search continues for a sensi- Results-With a cut off of 200 ,ug elastase tive as well as a practical test to definitely prove llg stool the sensitivity was 63% for mild, or exclude exocrine pancreatic insufficiency. on September 24, 2021 by guest. Protected copyright. 100% for moderate, 100% for severe, and Recently pancreatic elastase 1 was isolated 93% for all patients with exocrine and further characterised as a human and pancreatic insufficiency, and specificity pancreas specific enzyme that is not degraded was 93%. Values for chymotrypsin were during intestinal transport and which is five to 64% (sensitivity) and 89% (specificity). sixfold enriched in faeces compared with Significant (p<0.001) correlations were duodenal juice.'"'2 Furthermore, a highly found for faecal and duodenal elastase sensitive enzyme linked immunosorbent assay with duodenal lipase, amylase, trypsin, (ELISA) for human faecal and duodenal volume, and bicarbonate output. Individ- elastase 1 determination using two specific ual day to day variations offaecal elastase monoclonal antibodies is commercially avail- 1 concentrations were very low (mean able.'0 1" Early clinical studies gave promising CV=15%) and sample storage at room results in patients with exocrine pancreatic temperature is possible for at least one insufficiency for determination of faecal week. elastase 1 concentration in comparison with Conclusions-Faecal elastase 1 determi- the fluorescein dilaurate test'3 14 and in a few Medical Department, nation proved to be a highly sensitive and patients compared with the secretin-caerulein Christian-Albrechts- specific tubeless pancreatic function test. test as well. 15 16 University of Kiel, Germany (Gut 1996; 39: 580-586) The aim of the present study was to evaluate Chr Loser (a) the sensitivity and specificity of faecal A Mollgaard Keywords: chronic pancreatitis, lipase, pancreatic elastase 1 determination in a sufficient number U R Folsch insufficiency, pancreatic function test, secretin- of patients with exocrine pancreatic in- Correspondence to: caerulein test. Priv-Doz Dr Chr LUser, sufficiency in comparison with the 'gold Medizinische standard' of pancreatic function testing, the Universitatsklinik, Christian-Albrechts- secretin-caerulein test; (b) to characterise the Universitat, The diagnosis of chronic pancreatitis is sensitivity of the test according to a sub- Schittenhelmstrasse 12, D-24105 Kiel. hampered by the absence of easily available classification of patients with mild, moderate, Accepted for publication histological confirmation and is therefore and severe exocrine pancreatic insufficiency; 28 May 1996 based on morphological and functional (c) to compare these results with the Faecal elastase in exocrine pancreatic insufficiency 581 determination of faecal chymotrypsin activity; SECRETIN-CAERULEIN TEST (d) to perform various correlation studies to After an overnight fast patients were intubated further characterise clinically important vari- in the morning at 8 am with a gastroduodenal ables; and (e) to determine the practicability tube, which was placed up to the ligament of and clinical handling of faecal elastase 1 ana- Treitz. After 15 minutes' collection of basal Gut: first published as 10.1136/gut.39.4.580 on 1 October 1996. Downloaded from lysis with regard to individual day to day secreted duodenal juice, 1 U secretin/kg bwt/h variations, problems of sample storage, and was continuously given intravenously for two temperature dependency of sample analysis. hours and 30 ng caerulein/kg bwt/h was simultaneously given intravenously during the second hour. Pancreatic juice was collected Methods in 15 minute aliquots, and volume, pH, bicarbonate, amylase, trypsin, lipase, and CLASSIFICATION OF PATIENTS elastase were measured by commercial test kits Seventy nine consecutive patients with (amylase, lipase, trypsin, from Boehringer/ clinically suspected chronic pancreatitis were Mannheim, Germany). The lower normal referred to our clinic for the secretin-caerulein limits are two SD below the mean values: test. Morphological criteria according to the volume <150 ml/first hour, bicarbonate <10 Cambridge classification7 18 were assessed by mmol/first hour, amylase <15X 103 U/second ultrasonography, abdominal computed tomog- hour, lipase <90X 103 U/second hour, trypsin raphy, or endoscopic retrograde pancreatog- <6X 103 U/second hour, and elastase < 16X 103 raphy (ERP) to confirm or exclude chronic jig/second hour. pancreatitis. Thirty five patients had a normal secretin- caerulein test and no morphological signs of FAECAL ELASTASE chronic pancreatitis. The following non- Faecal elastase was measured using two pancreatic gastrointestinal diseases were monoclonal antibodies specific for human confirmed by further diagnostic investigations: pancreatic elastase 1, which bind to two erosive gastroduodenitis or gastric or duodenal distinct epitopes of this enzyme'0 "1 (test kit ulcer (n= 15), coeliac disease (n=3), gastro- from Schebo Tech, 35435 Wettenberg, oesophageal reflux (n=2), Crohn's disease Germany). The lower detection limit of the (n=2), cholecystitis (n= 1), gastric cancer elastase 1 assay is below 1 ng/ml. l The (n= 1), and functional diarrhoea (n= 1 1). intraassay variance is 5.8%, and the interassay Forty four patients had a pathological variance is 7.7%.` Stool (100 mg) was finally secretin-caerulein test together with morpho- diluted 1:500 and faecal elastase 1 concentra- logical criteria as defined in the Cambridge tion (,ug/g stool) was calculated photometric- http://gut.bmj.com/ classification.'7 18 According to the results of ally (OD 405 mm) in comparison with a the secretin-caerulein test these patients with standard solution.'0 l l chronic pancreatitis were subclassified3 19 into mild (I; n=8) (pathological secretion of one to three enzymes, normal volume and bicarbon- FAECAL CHYMOTRYPSIN ate secretion, no steatorrhoea), moderate (II; Faecal chymotrypsin activity (U/g stool) was n= 14) (pathological secretion of enzymes as calculated by photometric estimation with on September 24, 2021 by guest. Protected copyright. well as pathological volume and bicarbonate, a test kit from Boehringer Mannheim no steatorrhoea), and severe (III) exocrine (Germany).2 Values were expressed as U/g pancreatic insufficiency (n=22) (as II plus ste- stool and values <3 U/g stool were regarded as atorrhoea >7 g/day). Subclassification was per- pathological. formed according to functional criteria of the secretin-caerulein test only; morphological data were not used for this categorisation. FAECAL FAT ANALYSIS Faecal elastase concentration and faecal Faecal fat excretion was measured by the chymotrypsin activity were determined in all established method of van de Kamer et aP2' 79 patients and furthermore in 50 healthy with the patients consuming 90 g fat per day controls with no pathological clinical and during the three day sample collection period. laboratory findings. Table I shows the patients' Steatorrhoea was defined as faecal fat excretion characteristics of the several groups investi-
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