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Review article: Pancreatic function testing.

Pancreatic function tests are most commonly used to diagnose chronic pancreatitis. These tests include tests which document exocrine or endocrine gland insufficiency and tests which instead measure gradations of decreased secretory capacity. The tests in the former category generally become abnormal when advanced, longstanding chronic pancreatitis is present. Tests in the latter category, however, have the potential to detect chronic pancreatitis at an earlier stage than other available diagnostic tests, including commonly used imaging tests such as computed tomography and endoscopic retrograde cholangiopancreatography. This potential advantage of diagnostic sensitivity is, however, counterweighed by the fact that these tests which measure stimulated secretory capacity are only available at a very few referral centres. This article will review the variety of pancreatic function tests and describe their rationale, accuracy, cost, and clinical usefulness.

4-Aminobenzoic Acid↗

Pancreatic cancer: diagnostic value of pancreatic function tests.

Pancreatic secretion is abnormal in at least 90% of patients with pancreatic cancer. Any of the standard tests of pancreatic function that employ an exogenous secretin or CCK-like stimulus effectively reveal those abnormalities. However, despite a high sensitivity, the tests lack the specificity necessary to distinguish reliably between pancreatic cancer and chronic pancreatitis. With the current practice of testing pancreatic function in symptomatic patients and in the absence of an identifiable high-risk group within the population, it is unlikely that the established pancreatic function tests will provide a means for the earlier detection of pancreatic cancer.

Animals↗

Endoscopy-based pancreatic function tests.

Direct pancreatic function tests have been the mainstay for the diagnosis of pancreatic exocrine insufficiency. Due to their cumbersome nature and limited availability there is a continuous search for a rapid and inexpensive test of pancreatic function. Endoscopic approaches to evaluate pancreatic function have been assessed. This article critically reviews the current evidence related to this novel approach, outlining some elements for further refinement.

Adult↗

Fecal elastase test: evaluation of a new noninvasive pancreatic function test.

OBJECTIVES: Pancreatic elastase is highly stable along the intestinal tract. A new ELISA is commercially available to measure human specific elastase-1 concentration in stool. We evaluated the behavior of this fecal elastase test (FET) compared with other indirect pancreatic function tests in patients with chronic pancreatitis (CP). METHODS: A total of 69 patients were included in the study, 20 of whom were diagnosed with CP according to the findings on ERP and CT; 13 patients had other pancreatic diseases, and the remaining 36 patients had gastrointestinal or hepatic disorders. All patients' elastase-1 concentrations and chymotrypsin activities [fecal chymotrypsin test (FCT)] were measured, and the serum pancreolauryl test (PLT) was performed. RESULTS: Similar to PLT, fecal elastase concentration was significantly decreased in patients with moderate and severe CP (assessed by ERP) compared with patients with extrapancreatic disorders. However, and contrarily to PLT, FET was not affected by gastric resection, malabsorption due to intestinal disease, or marked alteration of the gastric motility. The sensitivity of FET was 100% for moderate to severe CP but 0% for mild CP; the specificity was 83%. Compared with other indirect pancreatic function tests, FET appears to be as sensitive as PLT and as specific as FCT, and it is clearly more specific than PLT and more sensitive than FCT. Unlike FCT, FET was not affected by oral enzyme supplementation. CONCLUSION: FET is a simple and accurate functional test for CP, and it is hardly influenced by extrapancreatic disorders or therapy with exogenous enzymes.

Adolescent↗

[Comparison of three indirect pancreatic function tests in severe chronic pancreatitis--personal observations].

The aim of the presented study was a comparative evaluation of the three indirect pancreatic function tests: pancreolauryl-test (PLT), NBT-PABA test and faecal chymotrypsin (CH) efficacy in detecting pancreatic exocrine function impairment in advanced chronic pancreatitis (acp). 30 patients with severe chronic pancreatitis (marked structure changes in ultrasound and CT following Cambridge criteria) confirmed by abnormal secretin-cerulein test (SCT) and 10 healthy controls underwent PLT, NBT-PABA and CH tests. The degree of pancreatic function impairment in SCT was classified following Malfertheiner into 3 subgroups: 1-mild, 2-moderate and 3-severe. All the indirect pancreatic function test were performed using commercially available kits (Temmler-Werke for PLT, Hoffman-La Roche for NBT-PABA and Boehringer Mannheim for CH) according to manufacturer instructions. PLT revealed changes in 27 (0.9), NBT-PABA-in 25 (0.83) and CH-in 22 (0.73) patients with acp. On the other hand those test have shown normal pancreatic function: PLT-in 0.9, NBT-PABA-in 0.7 and CH-in 0.8 in control group. The sensitivity of those test was increased up to 0.94 (PLT and NBT-PABA) and up to 0.88 (CH) and in the subgroup of severely impaired pancreatic function test in SCT. The concomittant use of two indirect pancreatic function tests caused increase of sensitivity up to 0.93. Our results suggest that with PLT, NBT-PABA and CH impaired pancreatic function may be succesfully recognized in advanced chronic pancreatitis, in particular, when two of them are applied concomittantly.

4-Aminobenzoic Acid↗

Synthetic porcine secretin is highly accurate in pancreatic function testing in individuals with chronic pancreatitis.

The secretin stimulation test is the most sensitive and specific test for pancreatic function. It is usually performed using biologically derived porcine secretin. Several shortages of biologic porcine secretin have occurred in the past few years. The aim of this study was to compare synthetic porcine secretin to biologic porcine secretin in pancreatic function testing in subjects with chronic pancreatitis. Twelve patients with a previously abnormal secretin stimulation test were enrolled. After an overnight fast, each patient underwent a secretin stimulation test on 2 consecutive days using 1 CU/kg biologic porcine secretin or 0.2 [microg/kg synthetic porcine secretin in a randomized fashion. The peak bicarbonate concentration in duodenal juice was used as a measure of pancreatic function. The peak bicarbonate concentration (mean +/- SD) obtained by using biologic porcine secretin and synthetic porcine secretin were 70 +/- 25 mEq/L and 68 +/- 31 mEq/L, respectively (p = 0.58, paired t test; R = 0.964). The accuracy of synthetic porcine secretin in diagnosing pancreatic insufficiency was 100% when compared with biologic porcine secretin. We conclude that synthetic porcine secretin is highly accurate and safe in pancreatic function testing. The 100% purity, excellent diagnostic accuracy, and ready availability make synthetic porcine secretin an attractive choice for secretin stimulation testing.

Adolescent↗

Fluorescein dilaurate serum test: a rapid tubeless pancreatic function test.

The value of a modified fluorescein dilaurate (FDL) serum test for the detection of pancreatic exocrine insufficiency was investigated in 89 patients with and without pancreatic disease. This test modification with fluorescein serum determination following metoclopramide (10 mg) and secretin (1 U/kg) i.v. injection appeared efficacious in a pilot study in six healthy volunteers. Individual peak fluorescein serum concentration was achieved within 180 min after the test meal in 96% of all subjects studied. Peak fluorescein serum concentration within this time period allowed the best discrimination between normal and abnormal pancreatic function. Sensitivity in detection of chronic pancreatitis was 86% (38 of 44 patients) when the lower normal fluorescein serum concentration was considered 4.5 micrograms/ml (this value corresponds to mean - 2 SD). The specificity of this test in detecting chronic pancreatitis was 100% when healthy controls were considered, but fell to 78% when patients with different gastrointestinal disorders, including those with secondary pancreatic insufficiency, were included. The correlation between serum and urinary fluorescein determination was significant (r = 0.61; p less than 0.01). Duodenal bicarbonate output/h after secretin also showed a significant correlation with peak fluorescein serum concentration (r = 0.79; p less than 0.001).

Adolescent↗

Comparative diagnostic accuracy of four tubeless pancreatic function tests in chronic pancreatitis.

The comparative sensitivity of 4 tubeless pancreatic function tests was evaluated in 125 patients with proved chronic pancreatitis associated with various degrees of pancreatic insufficiency. NBT-PABA, immunoreactive trypsin (IRT), and pancreatic isoamylase (P-iso) were studied in relation to the fecal chymotrypsin test (FCT) and steatorrhea. In advanced insufficiency (steatorrhea or FCT less than 20 micrograms/g) PABA, IRT, and P-iso were pathologically low in only 70-85% of patients. In less severe pancreatic insufficiency (FCT 21-120 micrograms/g) these tests yielded pathological results in 35-53% of patients. Thus the sensitivity of the three tests was comparable and rather low. IRT values (and P-iso) were constantly low or progressively decreasing in 64% of patients (30/47) studied repeatedly over an average of 17 months. The serum enzyme tests seem, therefore, to be valuable for monitoring pancreatic insufficiency, like the FCT. This is particularly important for the differential diagnosis of acute (reversible) and chronic (progressive) pancreatitis.

4-Aminobenzoic Acid↗

Faecal elastase 1: a novel, highly sensitive, and specific tubeless pancreatic function test.

BACKGROUND: Indirect pancreatic function tests available today are unreliable for clinical practice in early chronic pancreatitis due to their low sensitivity in mild and moderate exocrine pancreatic insufficiency. AIM: To evaluate the sensitivity, specificity, and practicability of faecal elastase 1 determination in patients with mild, moderate, and severe exocrine pancreatic insufficiency categorised according to the secretin-caerulein test as "gold standard'. PATIENTS AND METHODS: Faecal and duodenal elastase 1 concentration (commercial enzyme linked immunosorbent assay (ELISA)), faecal chymotrypsin activity, faecal fat analysis, and the secretin-caerulein test were performed on 44 patients with mild (n = 8), moderate (n = 14), and severe (n = 22) exocrine pancreatic insufficiency and 35 patients with gastrointestinal diseases of non-pancreatic origin. Fifty healthy volunteers were studied as normal controls. Morphological examinations were carried out to definitely confirm or exclude chronic pancreatitis. RESULTS: With a cut off of 200 micrograms elastase 1/g stool the sensitivity was 63% for mild, 100% for moderate, 100% for severe, and 93% for all patients with exocrine pancreatic insufficiency, and specificity was 93%. Values for chymotrypsin were 64% (sensitivity) and 89% (specificity). Significant (p < 0.001) correlations were found for faecal and duodenal elastase with duodenal lipase, amylase, trypsin, volume, and bicarbonate output. Individual day to day variations of faecal elastase 1 concentrations were very low (mean CV = 15%) and sample storage at room temperature is possible for at least one week. CONCLUSIONS: Faecal elastase 1 determination proved to be a highly sensitive and specific tubeless pancreatic function test.

Adult↗

Improved diagnostic accuracy of a modified oral pancreatic function test.

The oral pancreatic function test (PFT) depends upon urinary recovery of p-aminobenzoic acid (PABA) released by chymotrypsin hydrolysis of orally administered N-benzoyl-L-tyrosyl-p-aminobenzoid acid. The diagnostic value of the test is limited because falsely abnormal results frequently occur in patients with bowel or liver disease in whom PABA recovery is impaired by abnormal absorption or hepatic conjugation, even though pancreatic function is normal. To overcome this problem, we have modified the oral PFT to correct for impaired PABA absorption and conjugation. Results of the oral PFT have been compared with urinary recovery of an equivalent dose of free PABA in order to derive a PABA excretion index (PEI). When the modified oral PFT is used, the PEI clearly distinguished patients with pancreatic disease from normal subjects. In patients with small-bowel or liver disease and normal exocrine pancreatic function, the PEI results were similar to those of normal subjects, although a previous oral PFT had been falsey abnormal. The modified test can therefore distinguish abnormal results due to pancreatic disease from the falsely abnormal results found in liver and small-bowel disease.

4-Aminobenzoic Acid↗

Pancreolauryl test. Evaluation of a tubeless pancreatic function test in comparison with other indirect and direct tests for exocrine pancreatic function.

The sensitivity and specificity of the pancreolauryl test was evaluated in comparison with the NBT-PABA test, the estimation of fecal chymotrypsin and fat, and the secretin-pancreozymin test in 168 patients with and without pancreatic disease. The overall sensitivity rate was as follows: pancreolauryl test 90%, NBT-PABA test 86%, fecal chymotrypsin 66%. In patients with pancreatic steatorrhea the sensitivity of the pancreolauryl test was 100%, the NBT-PABA test 97%, and the fecal chymotrypsin estimation 92%. The specificity of these tests was: pancreolauryl test 97.6%, fecal chymotrypsin 87%, and NBT-PABA test 81.8%. The pancreolauryl test may be recommended as a noninvasive easy-to-perform tubeless pancreatic function test with a sufficiently high sensitivity and specificity.

4-Aminobenzoic Acid↗

Fecal elastase-1 determination: 'gold standard' of indirect pancreatic function tests?

BACKGROUND: Tubeless pancreatic function tests measuring the content of elastase-1 and the activity of chymotrypsin in stool are used with different cut-off levels and with varying success in diagnosing functional impairment of the pancreas. The aim of our study was to re-evaluate the sensitivity and specificity of elastase-1 and chymotrypsin in stool in the assessment of exocrine pancreatic insufficiency. METHODS: In 127 patients displaying clinical signs of malassimilation, the secretin-caerulein test ('gold standard'), fecal fat analysis, fecal chymotrypsin activity and fecal elastase-1 concentration were performed. Exocrine pancreatic insufficiency was graded, according to the results of the secretin-caerulein test, into mild, moderate and severe. Chymotrypsin and elastase-1 in stool were estimated using two commercially available test kits. Fecal elastase-1 concentration of 200 and 100 microg/g stool and chymotrypsin activity of 6 and 3 U/g stool were used separately as cut-off levels for calculation. RESULTS: 1) In 65 patients, a normal pancreatic function was found using the secretin-caerulein test. In 62 patients, an exocrine pancreatic insufficiency was found and classified into severe (n = 25), moderate (n = 14) and mild (n = 23). 2) The correlation between fecal elastase-1 and chymotrypsin with duodenal enzyme outputs of amylase, lipase, trypsin, chymotrypsin and elastase-1 ranged between 33% and 55% and 25% and 38%, respectively. 3) Using a cut-off of 200 microg elastase-1/g, stool sensitivities of fecal elastase-1 and fecal chymotrypsin (cut-off: 6 U/g) were 100% and 76%, respectively (P < 0.0001 and P < 0.001 respectively) in severe exocrine pancreatic insufficiency, 89% and 47% respectively (P < 0.001; P = 0.34, respectively) in moderate and 65% for both in mild pancreatic insufficiency. Specificities of elastase-1 and chymotrypsin in stool were 55% and 47%, respectively. 4) Elastase-1 based diagnostic provided a positive predictive value of 50% using a cut-off' 200 microg/g stool in a representative group of consecutively recruited patients with gastroenterological disorders. CONCLUSION: Determination of fecal elastase-1 is highly sensitive in the diagnosis of severe and moderate exocrine pancreatic insufficiency and is of significantly higher sensitivity than fecal chymotrypsin estimation. Specificity for both stool tests is low. Correlation between elastase-1 and chymotrypsin in stool and duodenal enzyme outputs is moderate. Neither test is suitable for screening, as they provide a pathologic result in roughly half of 'non-pancreas' patients.

Biomarkers↗

The oral pancreatic function test with N-benzoyl-L-tyrosyl-p-aminobenzoic acid: acute toxicity and effects of renal function on this test.

The oral pancreatic function test with N-benzoyl-L-tyrosyl-p-aminobenzoic acid was performed on 24 healthy test subjects, and its toxicity was examined. Eight patients with restricted renal function and known renal disease were also investigated. The pancreatic function test and the same procedure using free p-amino-benzoic acid were performed at 2-3-day intervals. During all the investigations with the pancreatic function test, no clinical side effects were observed. All parameters investigated at all the test times fell within the normal range. No toxicity of N-benzoyl-L-tyrosyl-p-amino-benzoic acid could be found. The excretion of p-aminobenzoic acid after administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid ws greatly reduced in all patients with restricted renal function. Four of eight patients also showed essentially no increase in excretion rate when free p-aminobenzoic acid was given instead of the peptide. It is therefore not possible to correct the pancreatic function test results in patients with renal insufficiency by calculating the ratio of p-aminobenzoic acid excretion after peptide intake to that after free p-aminobenzoic acid ingestion. Adequate renal function is therefore a prerequisite for the pancreatic function test.

4-Aminobenzoic Acid↗

Reproducibility of the fluorescein dilaurate pancreatic function test.

The indirect pancreatic function test, the fluorescein dilaurate test, was performed twice on nine healthy volunteers. The test is based on the renal excretion of fluorescein liberated from an ingested fluorescein ester by pancreatic enzymes. As a control, fluorescein sodium was ingested under similar conditions. The results of the test are expressed as the ratio of the amount of fluorescein excreted in the test part and the control part, forming the test/control (T/C) ratio. The mean values of excreted fluorescein correlated well with those reported by other authors. The coefficient of variation was 35% in the repeated test and of the same order in the series of individuals. The test cannot be recommended as a quantitative test until further investigation has been performed. Its use as a screening test is found questionable.

Adult↗

The diagnostic value of the oral pancreatic function test.

An oral pancreatic function test (PFT) using the synthetic peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid can assess pancreatic exocrine function, since urinary recovery of the ingested dose is an indirect index of chymotryptic activity. We have studied 34 subjects using this oral PFT, which correctly distinguished the control group (8 subjects) from the pancreatitis group (10 patients), results correlating well with Lundh test findings. However, the test was falsely abnormal on 9 out of 16 occasions in patients with bowel or liver disease. We therefore conclude that the present test cannot distinguish small-bowel disease from pancreatic disease, which is often the diagnostic problem, and is also frequently falsely abnormal in the presence of chronic liver disease.

4-Aminobenzoic Acid↗