Test Of Exocrine Pancreatic Function Research Articles

Duodenum-preserving head resection in chronic pancreatitis changes the natural course of the disease: a single-center 26-year experience.

To present preoperative and early postoperative data for 504 patients who underwent duodenum-preserving pancreatic head resection (DPPHR) for severe chronic pancreatitis (CP). The pancreatic head is considered to be the pacemaker of the disease in alcohol-induced CP. Indications for surgery in CP are intractable pain and local complications. DPPHR offers the advantage of treating the complications related to the inflammatory process in the head, relieving the pain syndrome, and preserving the bilioduodenal anatomy, and it may have the potential to change the natural course of chronic pancreatitis. Between November 1972 and December 1998, 504 patients with chronic pancreatitis and an inflammatory mass in the pancreatic head were treated surgically after medical pain treatment for a median of 3.6 years. The procedure resulted in a hospital mortality rate of 0.8%. A continuous follow-up investigation lasting up to 26 years was conducted, during which the patients were reevaluated four times (1983, 1987, 1994, 1996). Between November 1982 and October 1996, 388 patients treated surgically were reinvestigated to evaluate the late outcome; the follow-up rate was 94% (25 patients were lost to follow-up). The reinvestigation evaluation included glucose tolerance test, exocrine pancreatic function test, pain status, physical status, professional and social rehabilitation, and quality of life. After an observation period of up to 14 years, 78.8% of the patients were completely pain-free and 12.5% had (yearly) pain. 91.3% were considered as pain-free; 8.7% had continuing abdominal pain; 12% had abdominal complaints. During the 14 years of follow-up, only 9% were admitted to the hospital for acute episodes of chronic pancreatitis. Endocrine function was improved in 11%; in 21%, diabetes developed de novo. The rate of hospital admission for acute episodes decreased from 69% before surgery to 9% after surgery. In the clinical management period of 9 years (median), the frequency of hospital admission dropped from 5.4 per patient before surgery to 2.7 after surgery. Fourteen years after surgery, 69% of the patients were professionally rehabilitated; in 72%, the quality of life index (Karnofsky criteria) was 90 to 100 and in 18%, it was <80. In patients with alcoholic chronic pancreatitis in whom an inflammatory mass has developed in the pancreatic head, DPPHR results in a change in the natural course of the disease in terms of pain status, frequency of acute episodes, need for further hospital admission, late death, and quality of life.

Exocrine Pancreatic Function Tests, 1999: Is the Best We Have Good Enough?

Exocrine Pancreatic Function Tests, 1999: Is the Best We Have Good Enough?

Pancreatic exocrine and endocrine function after pancreatectomy for persistent hyperinsulinaemic hypoglycaemia of infancy

AIMTo evaluate long term detailed pancreatic endocrine and exocrine function in children with persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) after 85–95% pancreatectomy.METHODSSix children with PHHI between 0.9 and 12.7 years...

Pancreatic Exocrine Function Tests

Pancreatic Exocrine Function Tests

Pancreatic Exocrine Function Tests

Pancreatic Exocrine Function Tests

Faecal elastase 1 in children with cystic fibrosis.

Recently, a new ELISA kit for determination of elastase 1 in faeces has become commercially available. Studies in patients with chronic pancreatitis have indicated that it is a simple and sensitive test of exocrine pancreatic function. The aim of this study was to assess the clinical value of this new test in cystic fibrosis. A total of 72 children were studied: 27 who were healthy, 22 with cystic fibrosis and 23 with non-pancreatic disorders. Oral pancreatic extracts were not discontinued in the children with cystic fibrosis. A small sample of faeces was collected from each subject for elastase 1 concentration and chymotrypsin activity determination. In all of the healthy children and most of those with non-pancreatic disorders (20/23), elastase 1 concentrations were greater than 500 microg/g; in contrast, the vast majority (20/22) of children with cystic fibrosis had very low values (less than 20 microg/g). The differences between children with cystic fibrosis and the other two groups were highly significant (P < 0.001). With a cut-off level of 132 microg/g, the sensitivity and specificity of faecal elastase 1 for the determination of exocrine pancreatic insufficiency were 96% and 100%, respectively. The specificity of faecal chymotrypsin was 96%, but its sensitivity was not calculated since the children with cystic fibrosis continued to take pancreatic extracts during the study. The determination of faecal elastase 1 concentration is a simple and reliable means of assessing exocrine pancreatic function in children with cystic fibrosis. Results are not influenced by non-pancreatic disorders or by enzyme supplementation.

DIAGNOSIS OF EXOCRINE PANCREATIC INSUFFICIENCY IN CHILDREN BY USE OF PANCREOLAURYL TEST

In adult studies, the urine pancreolauryl test (PLT) is used as an indirect measure of pancreatic exocrine function: the fluorescein dilaurate is cleaved by the pancreas specific cholesterol ester hydrolase and the liberated fluorescein is absorbed and excreted in the urine. Duodenal intubation and stimulation of pancreatic secretion is complicated and unpleasant in children. We present here a modified version of PLT based on plasmatic fluorescein concentration, previously validated in adult patients, in the aim to measure exocrine pancreatic insufficiency (EPI) in children. Methods: 2 capsules containing 174,5 mg of fluorescein dilaurate were ingested with a standard meal. Plasmatic fluorescein concentration was determined spectrophotometrically (492 nm) on blood samples collected through a small catheter at time 0 and every 30 mn during 6 hours. In our adult series PLT has been validated by comparison with the results of duodenal intubation after pancreatic stimulation; 58 patients have been studied: 10 healthy subjects, 7 with chronic digestive disease without pancreatic involvement, 18 patients with moderate EPI and 23 with severe EPI. Calculation of the experimental area under curve (AUC) in mg/ml-1/h showed statistically significant differences (< 0.0001) between controls (57,39 ± 15,67) and EPI (moderate = 19,24 ± 23,93 and severe = 8,05 ± 9,50) and also between digestive diseases (35,75 ± 36,62) and severe EPI. Choosing 30 mg/ml-1/h as the cut off limit: sensitivity was 72% for moderate EPI and specificity was 100% for severe EPI. The PLT was carried out on 18 children (5-16 years): 8 with cystic fibrosis (CF), 2 with Swachman's syndrome (SS). 2 with chronic pancreatitis (CP), 3with chronic diarrhoea (CD),1 with constipation, 1 with failure to thrive, and 1 with recurrent pneumonia. Results: 13 children presented severe EPI (AUC ranging from 0,02 to 0,11): 7 with CF, 2 with SS, 2 with CP and 2 with CD. Fat absorption coefficient was below 90% in 4 of the 9 children tested. The calculated AUC for the child with failure to thrive was 16,95 expressing a moderate EPI and 4 children had normal AUC ranging from 38,08 to 52,63. Conclusion: the modified PLT eliminates the need for timed urine collections. It provides a simple, reliable, and tubeless test of exocrine pancreatic function, more sensitive than the fat absorption coefficient in children. PTL can be used as a diagnostic test to distinguish infants and children with EPI from normal children and those with other causes of diarrhoea and failure to thrive.

Determination of the exocrine pancreatic function with the NBT-PABA test using a novel dual isotope technique and gas chromatography-mass spectrometry

Larsen B, Ekelund S, Jørgensen L, Bremmelgaard A. Determination of the exocrine pancreatic function with the NBT-PAB A test using a novel dual isotope technique and gas chromatography-mass spectrometry. Scand J Clin Lab Invest 1997; 57: 159-166.We describe a tubeless test of exocrine pancreatic function based on a new dual isotope technique, using N-benzoyl-L-tyrosyl-p-aminobenzoic acid (NBT-PABA) as a substrate for intestinal chymotrypsin activity and the stable isotope, 13C-PABA as marker. Gas chromatography-mass spectrometry (GC-MS) was used for the quantification of PABA and 13C-PABA in blood. The method involves hydrolysis, extractions, separation by HPLC, and methyl ester formation of the test substances before GC-MS analysis.The test is precise and shows good separation of healthy volunteers from patients with pancreatic insufficiency. The PABA/13C-PABA ratios in serum after 1.5 h were 2.64±0.14 (mean±SEM) in 10 healthy volunteers and 1.26±0.22 in 10 patients with exocrine pancreatic insufficiency. We present a sensitive and specific assay, which is free of analytical interference and radiation hazards and, additionally, it illuminates extrapancreatic pharmacokinetic conditions. This test can eliminate the need for duodenal intubation, which makes it very acceptable to the patients.

Pancreatic exocrine function during acute exacerbation in WBN/Kob rats with spontaneous chronic pancreatitis.

Pancreatic exocrine hypofunction is markedly deteriorated during acute exacerbation in a rat model with chronic pancreatitis. Little is known about pancreatic exocrine function during acute exacerbation in patients with chronic pancreatitis. We investigated changes in pancreatic exocrine function after inducing acute pancreatitis in an animal model of spontaneous chronic pancreatitis. WBN/Kob rats with chronic pancreatitis sequentially underwent pancreatic exocrine function test 1-6 d after surgical preparation with external pancreatic fistula. We induced acute pancreatitis in another WBN/Kob rats by i.v. administration of cerulein at a rate of 10 micrograms/kg/h for 4 h 4 d after surgical preparation. Pancreatic exocrine function test was undertaken in a conscious state 1 d before and after cerulein administration. In WBN/Kob rats not given cerulein, pancreatic exocrine function remained almost constant at 3-6 d after surgery. Marked hyperamylasemia developed immediately after cerulein administration. After its administration, the pancreas microscopically showed prominent interstitial edema and intracellular vacuolization of acinar cells in addition to the finding of pre-existing chronic pancreatitis. Basal and cholecystokinin-stimulated flow rate, bicarbonate output, and protein output, which were substantially impaired 1 d before cerulein administration, were further reduced 1 d after its administration.

Clinical evaluation of the faecal elastase test in the diagnosis and staging of chronic pancreatitis.

To test the diagnostic accuracy of faecal elastase (FE), a new test of exocrine pancreatic function, in a large prospective population of patients with abdominal complaints. Between January 1994 and December 1995, 131 patients (age range 17-82 years) were submitted for exocrine pancreatic function testing. Sixty-three patients had a firm diagnosis of chronic pancreatitis (CP) at stage I-III according to endoscopic retrograde cholangiopancreatography (ERCP). Twenty patients suffered from other pancreatic diseases (PD), and 48 patients had various other gastrointestinal diseases (GD). Fifty-seven healthy controls (HC) were also investigated. Stool specimens were analysed for FE by enzyme-linked immunosorbent assay (ELISA) and for faecal chymotrypsin (FC). The pancreolauryl serum test (PLT) was also performed in 97 patients and 23 healthy controls. FE was 200; 45-500 micrograms/g (median; range) in CP-I (n = 19), 94; 0-400 micrograms/g in CP-II (n = 14) and 38; 0-135 micrograms/g in CP-III patients (n = 30). With a cutoff of 200 micrograms/g, abnormal test results were found in 47% of CP-I, 79% of CP-II and 100% of CP-III patients; in 30% of PD patients, in 38% of GD patients and in 7% of HC. Sensitivity of abnormal FE in diagnosing CP was 79% (FC: 48%; PLT: 71%). The specificity of only 62% (FC: 73%; PLT: 67%) in the GD group increased to 78% (FC: 81%; PLT: 77%) when patients with small bowel diseases and diarrhoea (n = 22) were excluded. Faecal elastase is more sensitive than chymotrypsin and comparable to the pancreolauryl test in the diagnosis of chronic pancreatitis. Indirect exocrine pancreatic function tests are not helpful to differentiate between pancreatic and small bowel diseases in a prospective population of patients with abdominal complaints.

Secretin-induced plasma bicarbonate decrease as a simple indicator of exocrine pancreatic function.

During a secretin-cerulein test for exocrine pancreatic function, venous acid-base analysis was performed before and 30 and 45 min after the intravenous injection of secretin (1 clinical unit/kg body weight). A decrease in plasma bicarbonate was observed in persons with normal exocrine pancreatic function as defined by normal bicarbonate and enzyme secretion in the secretin-cerulein test (n = 39). Bicarbonate values were 94.8 +/- 3.6% (mean +/- SD) of the initial concentration after 30 min and 92.9 +/- 3.9% after 45 min. In contrast, there was no statistically significant decrease in plasma bicarbonate in patients with global pancreatic exocrine deficiency (n = 15). In normal exocrine pancreatic function, the maximal plasma bicarbonate decrease was 2.17 +/- 1.12 mM (mean +/- SD; n = 39). In patients with global exocrine deficiency, however, a maximal plasma bicarbonate decrease of 0.54 +/- 0.68 mM (n = 15) was obtained. The difference was highly significant (p < 0.001). In patients with partial exocrine deficiency (isolated decrease in bicarbonate secretion or reduced excretion of a single enzyme), values were also significantly lower (1.44 +/- 1.40 mM; n = 14; p < 0.05). The maximal plasma bicarbonate decrease correlated with the bicarbonate secretion into the duodenal juice (r = 0.62, p < 0.001). If a maximal plasma bicarbonate decrease > or = 0.9 mM was considered normal, determination of plasma bicarbonate following secretin administration allowed us to detect the presence of global exocrine deficiency with a sensitivity of 87% and a specificity of 87%. The secretin-induced plasma bicarbonate decrease may therefore be used as a new simple tubeless test to evaluate exocrine pancreatic function.

Usefulness of caerulein stimulated plasma amino acids consumption test as tubeless pancreatic exocrine function test

Usefulness of caerulein stimulated plasma amino acids consumption test as tubeless pancreatic exocrine function test

Tests of exocrine pancreatic function.

Pancreatic disease is broadly categorized into acute and chronic forms. Acute pancreatitis is a potentially life-threatening disorder characterized by the autodigestion of the pancreas by its own enzymes, accompanied by local or generalized peritonitis. Exocrine and endocrine dysfunction during acute pancreatitis is usually transient and reversible, and if patients survive an acute episode the recovery of the pancreas is usually complete; the development of chronic pancreatitis is an unusual complication. Chronic disorders of the pancreas may affect both the endocrine and exocrine functions of this organ. In this review, tests of exocrine function are evaluated as to their usefulness in the investigation of chronic exocrine pancreatic diseases, where damage to the acinar cells impairs the release of digestive enzymes, bicarbonate and fluid into the duodenum in response to a meal. This can eventually progress to 'pancreatic malabsorption' characterized by an inability to digest proteins and lipids. Some patients with chronic pancreatic exocrine disease will also develop diabetes mellitus as the damage extends to the {j-islet cells. Diseases associated with exocrine pancreatic dysfunction are relatively uncommon (Table I), and present with various symptoms which influence the choice and order of investigations. Pancreatic disorders can be explored by looking for both structural abnormalities and exocrine dysfunction and several techniques, often used in combination, are available to investigate putative disease. Imaging methods visualize the anatomy and structure of the gland, and difficulties in interpretation do not occur in advanced disease:

Is the plasma amino acid consumption test an accurate test of exocrine pancreatic insufficiency?

Background/Aims: The amino acid consumption test has been proposed as an accurate test of exocrine pancreatic function. The diagnostic accuracy of this test was determined by simultaneously measuring plasma amino acids and enzyme secretion during stimulation of the pancreas with cholecystokinin octapeptide (CCK-OP) in 60 consecutive patients suspected of having pancreatic insufficiency. Methods: All patients underwent duodenal intubation and intravenous infusion of CCK-OP (40 ng·kg −1 ·h−1). Pancreatic enzyme (lipase and trypsin) outputs and plasma amino acids were measured for a period of 1 hour. Total and individual plasma amino acids were quantitated by ion-exchange chromatography. The severity of pancreatic insufficiency was graded on the basis of enzyme output during CCK-OP infusion. Results: There was no relationship between pancreatic enzyme output and plasma concentrations of individual or total amino acids before or during CCK-OP stimulation. Using a total amino acid decrease of 12% as the cutoff, the amino acid consumption test was 91% sensitive, but very nonspecific (21% specificity) for detection of pancreatic insufficiency. Conclusions: The amino acid consumption test with CCK-OP stimulation does not discriminate between patients with normal and impaired exocrine pancreatic secretion.

Standards for the diagnosis of chronic pancreatitis and for the evaluation of treatment.

The diagnosis of chronic pancreatitis should be based on the characteristic case history and a combination of exocrine pancreatic function tests and morphological examinations. For diagnostic purposes, an indirect pancreatic function test may be sufficient when direct tests are not available. Otherwise, and especially for scientific evaluation of chronic pancreatitis, a direct pancreatic function test is necessary. In each patient, an ultrasound examination of the pancreas should be performed and, if inconclusive, also computed tomography. In a symptomatic patient, that is, a patient suffering from relapsing pain attacks, an ERCP examination is indicated. A score for the severity of chronic pancreatitis using symptoms, results of function tests, and morphological examinations should be developed for a world-wide comparison of studies. Treatment results should be reported not earlier than 2 yr after the initiation of conservative treatment or surgery. The evaluation of treatment should be based on a score (also to be developed) making use of symptoms.

Idiopathic chronic calcifying pancreatitis with diabetes mellitus

We present a case of a 27-year-old female suffering from chronic calcifying pancreatitis with diabetes mellitus. Radiographic examinations and exocrine pancreatic function tests revealed considerable dilatation of pancreatic ducts with large intraductal calculi and exocrine pancreatic insufficiency, respectively. Recent literature indicates that a decrease in the activity of pancreatic stone protein (PSP), which inhibits CaCO3 crystal formation in pancreatic juice, is closely related to the development of chronic calcifying pancreatitis. The patient had no apparent cause or family history of pancreatitis. We therefore investigated the possibility that alterations in the PSP gene might explain the chronic pancreatitis seen in this patient. Six exons of the PSP gene amplified by polymerase chain reaction were directly sequenced, but there was no apparent base mutation observed. Furthermore, Southern blot analysis revealed neither rearrangement nor deletion of the PSP gene in the genomic DNA of this case. However, this genetic approach will be useful for future study of the etiology of hereditary pancreatitis.

Natural course in chronic pancreatitis. Pain, exocrine and endocrine pancreatic insufficiency and prognosis of the disease.

The natural course of the classical symptoms of chronic pancreatitis, i.e. pain, exocrine and endocrine pancreatic insufficiency, was followed up in 335 patients over a median of 9.8 years (mean 11.3 +/- 8.3 years). Pain relief was not obtained in the majority of patients, even after a long-term observation of > 10 years, and severe exocrine/endocrine insufficiency, severe duct abnormalities and pancreatic calcifications developed. Alcohol abstinence failed to have a significant beneficial effect on pain. Pancreatic surgery led to pain relief immediately after operation, but later on the pain course between operated and nonoperated patients was not significantly different. Repeated exocrine pancreatic function tests in 143 patients showed that functional exocrine impairment came to a standstill (46%), or improved (11%). At the end of observation, 22% of 335 patients still had normal endocrine function and only 40% required insulin treatment. Alcohol abstinence had a significant beneficial effect on endocrine, but not on exocrine pancreatic insufficiency. Chronic pancreatitis led to a sharp increase in unemployment and retirement. Pancreatic carcinoma occurred in 3% and extrapancreatic carcinoma in 4%. The mortality rate within the observation period was 22%, pancreatitis-induced complications accounted for 13% of these deaths.

The BT-PABA/PAS test in tropical diabetes

A ‘screening’ test is needed to identify patients with chronic pancreatitis among diabetics in tropical field surveys. We have examined the potential diagnostic yield of the BT-PABA/PAS test of exocrine pancreatic function in this setting. The recoveries of both PABA and PAS in eight healthy controls from Madras, south India, were lower than in controls from Manchester, north west England (mean ± S.D., 51 ± 11 vs. 79 ± 7%, P < 0.001 for PABA; 52 ± 11% vs. 81 ± 7%, P < 0.001 for PAS) but the % PABA/PAS excretion index (PEI) was similar (0.96 ± 0.14 vs. 0.96 ± 0.06). Using a cut-off value of 0.75 for the PEI in a study group including eight patients with chronic pancreatitis and 26 with primary forms of diabetes, test sensitivity was 75%, specificity 92%, positive predictive value 75%, negative predictive value 92% and efficiency 88%.

Measuring total plasma amino acid concentrations as a test of exocrine pancreatic function.

Endogenous and exogenous stimulation of the pancreas was studied to determine whether changes in protein output could be linked to decreased total plasma amino acid concentrations. In fasted rats, diversion of pancreatic juice resulted in a transient increase in protein output and a linked fall in total plasma amino acid. In fed animals, however, diversion of juice did not result in any change in protein output or total plasma amino acid concentrations, although protein output was two-fold greater than in fasted animals. Similarly, after atropine treatment, diversion of juice failed to result in any change in protein output or total plasma amino acid in either fed or fasted animals. Stimulation of the gland with increasing doses of cholecystokinin ranging from 1.25 to 10.00 Crick Harper Raper Units, resulted in dose response increases in protein output and corresponding dose response falls in total plasma amino acid concentrations. Maximum decrease in total plasma amino acid concentrations was seen at 50% from the baseline with 5.00 Crick Harper Raper Units of cholecystokinin. These results show that with exogenous and endogenous stimulation in fasted animals, a highly significant, inverse relationship exists between protein output and total plasma amino acid. This relationship is the basis for a reliable, non-invasive test of pancreatic function that allows free mobility, although a period of fasting is required in order to increase the sensitivity of the test.

Spectrofluorimetric determination of urinary p-aminobenzoic and p-aminosalicylic acids in the BT-PABA/PAS test of pancreatic function

Spectrofluorimetry was investigated as an alternative to HPLC for determining p-aminobenzoic acid and p-aminosalicylic acid in the N-benzoyl- L-tyrosyl- p-aminobenzoic acid/ p-aminosalicylic acid test of pancreatic exocrine function. Urine specimens were hydrolysed for 30 min in 4 M NaOH at 100 ° C. The fluorescence of p-aminobenzoic acid was measured in dimethyl sulphoxide solution ( λ ex = 300 nm, λ em = 340 nm) and that of p-aminosalicylic acid in sodium acetate buffer, pH 4.0 ( λ ex = 297 nm, λ em = 394 nm). The linear range was 0.038−8 mM for p-aminobenzoic acid and 0.051−12 mM for p-aminosalicylic acid, withinbatch precision was 2.2% and 5.5%, respectively, and the entire analysis could be completed within 40 min. Although not eliminated, drug interference was greatly reduced in comparison with colorimetry. In 23 consecutive pancreatic function tests there was an excellent correlation between the p-aminobenzoic acid/ p-aminosalicylic acid excretion index obtained by fluorimetry and the results from HPLC analysis ( y = 0.914 x + 0.070, r = 0.987, p < 0.001). The method is simple, cost-effective and may be particularly valuable in developing countries having a high incidence of chronic pancreatitis.