Indirect Pancreatic Function Tests Research Articles

Pancreatic exocrine insufficiency and pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer: A systematic review and meta-analysis.

Pancreatic cancer is the fourth leading cause of cancer mortality. Most patients are diagnosed with advanced pancreatic cancer, either at locally advanced or metastatic stages, and have a high rate of malnutrition and weight loss which are associated with poor outcomes. Pancreatic exocrine insufficiency is one of the causes of malnutrition and weight loss in these patients. The prevalence and clinical consequences of pancreatic exocrine insufficiency in advanced pancreatic cancer are poorly investigated with heterogeneous results. We sought to determine the prevalence and clinical consequences of pancreatic exocrine insufficiency and the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer by systematic review and meta-analysis. Scopus, Medline, and Embase were searched for cohort studies or randomised clinical trials reporting pancreatic exocrine insufficiency and/or the effect of pancreatic enzyme replacement therapy in patients with advanced pancreatic cancer. We considered pancreatic exocrine insufficiency as an abnormal result on direct and/or indirect pancreatic exocrine function tests. Pancreatic enzyme replacement therapy was evaluated by its effect on survival and quality of life in patients with advanced pancreatic cancer. A total of 11 studies were included; seven studies reported the prevalence of pancreatic exocrine insufficiency and seven the effect of pancreatic enzyme replacement therapy in advanced pancreatic cancer. The pooled prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer was 72% (95% confidence interval: 55-86%), being significantly higher when tumours were located in the pancreatic head (relative risk = 3.36, 1.07-10.54; p = 0.04) six studies investigated the impact of pancreatic enzyme replacement therapy on survival/quality of life. Pancreatic enzyme replacement therapy was associated with 3.8 months (95% confidence interval: 1.37-6.19) survival benefit. Patients receiving pancreatic enzyme replacement therapy had a trend towards a better quality of life.Conclusions The prevalence of pancreatic exocrine insufficiency in advanced pancreatic cancer is substantial and its treatment can improve the outcomes of these patients.

Method Performance of Bicarbonate and Electrolytes by Use of Duodenal Fluid for Assessment of Exocrine Pancreatic Function.

Evaluation of exocrine pancreatic insufficiency is challenging for both clinicians and laboratories. Indirect pancreatic function tests such as serum trypsinogen, fecal elastase, and fecal fat measurements are moderately sensitive for diagnosis of advanced chronic pancreatitis but show reduced sensitivity and specificity for diagnosis of early disease. An alternative is the endoscopic pancreatic function test, which uses duodenal secretions after administration of IV secretin. Samples are collected at various times via the endoscopic tube and then analyzed for bicarbonate, sodium, potassium, and chloride. Precision, linearity, method comparison, and stability studies were performed on the Beckman Coulter AU5822 chemistry analyzer with duodenal fluid. Comparison with the Vitros 4600 dry slide chemistry instrument was used to interrogate differences between methods. All assays produced a CV <2% without any measurable effects from the endoscopy fluid matrix and showed acceptable imprecision near the limit of detection (CV < 5%). All analytes showed linear dilution across the analytical measuring range. All the calculated error biases from dilutions were within 50% of the CLIA-allowable error for serum for each of the respective analytes. The calculated slopes ranged from 0.841 to 1.274 when compared to the Vitros 4600. Stability studies demonstrated that sodium, potassium, chloride, and bicarbonate remained stable after storage at -20 °C and after multiple freeze-thaw cycles. The percent change for all analytes was <5% mmol/L. The AU5800 series demonstrated adequate performance for the analysis of bicarbonate in duodenal fluid and therefore can be used for assessment of exocrine pancreatic function. However, notable discrepancies were observed for sodium, potassium, and chloride between the AU5800 series and the Vitros 4600.

13C-Mixed Triglyceride Breath Test and Fecal Elastase as an Indirect Pancreatic Function Test in Cystic Fibrosis Infants.

The 'gold standard' test for the indirect determination of pancreatic function status in infants with cystic fibrosis (CF), the 72-hour fecal fat excretion test, is likely to become obsolete in the near future. Alternative indirect pancreatic function tests with sufficient sensitivity and specificity to determine pancreatic phenotype need further evaluation in CF infants. Evaluation of the clinical utility of both the noninvasive, nonradioactive C-mixed triglyceride (MTG) breath test and fecal elastase-1 (FE1) in comparison with the 72-hour fecal fat assessment in infants with CF. C-MTG breath test and the monoclonal and polyclonal FE1 assessment in stool was compared with the 72-hour fecal fat assessment in 24 infants with CF. Oral pancreatic enzyme substitution (PERT; if already commenced) was stopped before the tests. Sensitivity rates between 82% and 100% for CF patients with pancreatic insufficiency assessed by both the C-MTG breath test and the FE1 tests proved to be high and promising. The C-MTG breath test (31%-38%) as well as both FE1 tests assessed by the monoclonal (46%-54%) and the polyclonal (45%) ELISA kits, however, showed unacceptably low-sensitivity rates for the detection of pancreatic-sufficient CF patients in the present study. The C-MTG breath test with nondispersive infrared spectroscopy (NDIRS) technique, as well as both FE1 tests, are not alternatives to the fecal fat balance test for the evaluation of pancreatic function in CF infants during the first year of life.

PTU-174 Low Faecal Elastase is not always Due to Pancreatic Insufficiency

IntroductionFaecal elastase-1(FE-1) is a widely available, simple, cheap indirect pancreatic function test used in patients in whom pancreatic exocrine insufficiency (PEI) is suspected. Sensitivity is 73–100% for moderate to severe,...

Diagnostic value of direct and indirect pancreatic function tests in chronic pancreatitis

Diagnostic value of direct and indirect pancreatic function tests in chronic pancreatitis

Indirect Pancreatic Function Tests in Children

Indirect Pancreatic Function Tests in Children

Indirect Pancreatic Function Tests in Children

Indirect Pancreatic Function Tests in Children

Vegetarian Diet and Exocrine Pancreatic Function Using Fecal Tests: The Authors’ Reply

In our preliminary study (1), we demonstrated that vegetarian diet alters the assessment of exocrine pancreatic function by tests of chymotrypsin activity and elastase-1 concentration, with a decreased specificity for both tests. Possible explanations for these findings have been discussed including the higher fiber intake. In addition, these indirect pancreatic function tests offer the most interesting possibility for the assessment of pancreatic adaptation to human nutrition that we are continuing to study with a more detailed analysis of the food components. The influence of soybean trypsin inhibitors has been studied both in animal and human models. Raw soybean flour containing trypsin inhibitors caused pronounced growth of the pancreas and stimulated pancreatic enzyme secretion (2). Intraduodenal instillation of raw soybeans almost abolished chymotrypsin and severely reduced (50%) tryptic activity. However, immunoreactive tryptic and chymotryptic material was increased (3). In our study (1), fecal chymotrypsin was measured by the colorimetric method (4), while pancreatic elastase-1 was determined by an immunoenzymatic assay (5). Application of soybean trypsin inhibitors therefore could influence colorimetric measurement of chymotrypsin resulting in reduced chymotrypsin activity. The immunoenzymatic assessment of fecal elastase-1, however, should not be influenced. In the case of a soy-based vegetarian diet, we would rather expect an increase of fecal elastase-1 concentration than a decrease. Dietary fiber has been shown to affect pancreatic enzyme activity in vivo and in vitro (6,7). However, the immunoenzymatic method determines fecal elastase-1 concentrations and not activity. A modified colonic microflora could produce a higher breakdown of chymotrypsin (8). Fecal chymotrypsin activity in randomly collected stool specimen of cystic fibrosis patients poorly correlates to pancreatic output measured by direct stimulation by secretin-pancreozymin test (9). In contrast, a high correlation between direct pancreatic function tests and fecal elastase-1 concentrations were found in cystic fibrosis patients and healthy subjects (10,11). The enzyme is highly specific for the pancreas and is not degraded during the intestinal passage like chymotrypsin (12). Moreover, the enzyme is stable in room temperature for 1 week (10). Therefore, bacterial degradation of pancreatic elastase-1 is rather unlikely. Selenium is an essential trace element in humans and animals, and the importance to human health is undebated (13). In severe deficiency in animals, reproductive impairment, growth depression, myopathy of heart and skeletal muscle and even pancreatic atrophy have been observed. Intake varies considerably between European countries (from 70 μg per day in Switzerland to 11 μg in Poland). Healthy Swedish vegetarians, and especially vegans, have a lower dietary selenium intake 10 to 12 μg compared to 27 to 40 μg in age-matched healthy omnivores (14). Possible involvement of selenoproteins in the human pancreatic secretory process cannot be excluded but has also not been documented. In addition, the functional consequence of a reduced intake is unclear (15). Jaroslaw Walkowiak Karl-Heinz Herzig *Poznan University of Medical Sciences †Agricultural University of Poznan, Poznan, Poland ‡A.I. Virtanen Institute for Molecular Sciences, Kuopio, Finland

Now that fecal elastase is available in the United States, should clinicians start using it?

Fecal elastase-1 estimation is an alternative fecal enzyme test for the detection of exocrine pancreatic insufficiency, which, in contrast to chymotrypsin estimation, uses monoclonal antibodies against human pancreatic elastase and is thus unaffected by simultaneous pancreatic enzyme replacement therapy. Similar to other indirect pancreatic function tests, it has a high sensitivity rate for detecting severe functional impairment of the gland. However, the two major problems for the clinician--namely diagnosing mild to moderate exocrine pancreatic insufficiency or chronic pancreatitis and differentiating pancreatic from nonpancreatic steatorrhea or diarrhea--cannot be solved by pancreatic elastase-1 determination. The test cannot be used in non-formed stool (ie, diarrhea) unless the stool is lyophilized. All in all, this new test does not seem to be the gold standard for pancreatic function that we have been waiting for.

Endoscopic ultrasonography (EUS) and fine-needle aspiration (FNA) cytology for diagnosis of chronic pancreatitis.

Previous studies have shown that endoscopic ultrasonography (EUS) sensitively detects morphologic abnormalities due to chronic pancreatitis. However, morphologic EUS findings have limited specificity, particularly at the early stages of chronic pancreatitis. Our aims were to study pancreatic morphology and inflammation in patients with chronic pancreatitis, using EUS and fine-needle aspiration cytology (EUS-FNA), and to compare the results with those of endoscopic retrograde cholangiopancreatography (ERCP) and pancreatic function tests. 37 patients (48 +/- 13 years) with clinical symptoms and laboratory test findings suggestive of chronic pancreatitis were prospectively studied. Patients with malignancy or major concomitant disorders were excluded. Clinical evaluation included indirect pancreatic function tests. Morphologic criteria for chronic pancreatitis included echo-intense septae/echo-reduced foci (i. e. pseudolobularity), ductal irregularities, and calcifications. EUS-FNA was performed in 27/37 patients, by means of the Hitachi FG34-UX echo endoscope and a 22-gauge needle, and tissue specimens were submitted for standard cytological evaluation. ERCP served as reference in all patients, using the Cambridge classification. 31 patients had chronic pancreatitis while six had normal findings at ERCP. EUS showed morphologic abnormalities of the pancreas in 33 patients. Morphologic abnormalities alone reached a sensitivity of 97 % for chronic pancreatitis with a specificity of only 60 %, while the positive predictive value (PPV) was 94 %, and the negative predictive value (NPV) was 75 %. EUS-FNA increased the negative predictive value to 100 % and the specificity to 67 %. On average, 2.3 needle passes were necessary to obtain sufficient amounts of tissue. The correlation of EUS findings with pancreatic function tests was poor. EUS results were in agreement with regard to the severity of chronic pancreatitis in 5/8 patients with grade I disease, in 11/13 patients with grade II, and in 10/10 patients with grade III disease. Minor complications occurred in two patients (7 %). EUS is as sensitive and effective as ERCP in the detection of chronic pancreatitis, particularly when only mild disease is present. However, EUS findings have limited specificity, particularly in patients with mild disease. EUS-FNA with cytology is safe and improves the negative predictive value. Negative EUS-FNA findings rule out chronic pancreatitis, but cytological investigation alone does not improve the specificity of EUS findings, suggesting that further improvements in tissue sampling and analysis are necessary to support routine use of FNA in patients with chronic pancreatitis.

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 secretincaerulein 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 µg/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 µg 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 µg/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.

Preoperative laboratory diagnosis in pancreatic surgery--what is necessary?

Some aspects of preoperative laboratory investigations are discussed in pancreatic surgery. Diagnosis of acute pancreatitis is not a major diagnostic problem with pancreatic enzyme measurement and with further regard to medical history and clinical presentation. However, early assessment of the prognosis of acute pancreatitis still remains a clinical challenge. The determination of C-reactive protein (CRP) and lactate dehydrogenase (LDH) is used successfully in clinical practice. The values of different serum markers are described in prognostic evaluation of acute pancreatitis, and some direct and indirect pancreatic-function tests are compared in preoperative management of patients with chronic pancreatitis. The most sensitive direct pancreatic-function test is the secretin-pancreozymin test (SP-test), among the indirect function tests estimation of faecal elastase 1 is superior. The significance of tumor marker measurement is described in pancreatic cancer.

13C-egg white breath test: a non-invasive test of pancreatic trypsin activity in the small intestine

BACKGROUNDThe recent availability of egg white protein highly enriched with 13C has allowed breath test technology to be adapted for the study of protein digestion and absorption. Pancreatic trypsin is...

Comparative Clinical Evaluation of the 13C-Mixed Triglyceride Breath Test as an Indirect Pancreatic Function Test

Background: Breath tests using stable isotopes of carbon or hydrogen are increasingly becoming established for the evaluation of various gastrointestinal functions, including measurement of exocrine pancreatic insufficiency. We wanted to evaluate the clinical relevance of the non-invasive, non-radioactive 13C-mixed triglyceride breath test in comparison with the secretin-caerulein test as the 'gold standard' of pancreatic function testing and with faecal chymotrypsin and elastase 1 in patients with mild and severe exocrine pancreatic insufficiency. Methods: The secretin-caerulein test, faecal fat analysis, 13C-mixed triglyceride breath test, faecal elastase 1, and chymotrypsin and various morphologic investigations were done in 26 patients with mild (n = 13) or severe (n = 13) exocrine pancreatic insufficiency and 25 patients with gastrointestinal diseases of non-pancreatic origin. Twenty-seven healthy volunteers served as normal controls. After a 12-h fast 200 mg mixed triglyceride (1,3-distearyl,2(carboxyl-13C)octanoyl glycerol) were orally administered with a test meal, and breath samples were taken before and at 30-min intervals for 5 h thereafter, and the increase in 13C/12C isotopic ratio in breath was analysed by mass spectrometry. Various modifications of the test procedure were investigated. Results: Specificity for impaired pancreatic function was higher for faecal elastase (90%) and equal for faecal chymotrypsin (82%) as compared with the various variables of the 13C-mixed triglyceride breath test (69-85%). The sensitivity of the 13C-mixed triglyceride breath test for total and separately for mild and severe exocrine pancreatic insufficiency was higher (total, 69-81%) than that of faecal chymotrypsin (total, 56%) but lower than faecal elastase (total, 92%). Conclusion: The 13C-mixed triglyceride breath test very sensitively reflects severe exocrine pancreatic insufficiency (steatorrhoea) but has limited sensitivity for the detection of mild cases. With regard to the higher sensitivity and specificity, the higher practicability, and the much lower cost, determination of faecal elastase 1 concentrations is superior to the 13C-mixed triglyceride breath test and therefore remains the most reliable indirect pancreatic function test available today.

Diagnostic value of indirect pancreatic function test in serum of anuric patients with chronic renal failure

Diagnostic value of indirect pancreatic function test in serum of anuric patients with chronic renal failure

Diagnostic value of indirect pancreatic function test in serum of anuric patients with chronic renal failure.

Although patients with chronic renal failure have a high incidence of chronic pancreatic disease, the condition is frequently overlooked. We have modified the pancreolauryl test--an indirect pancreatic function test--for anuric patients. The test permitted good discrimination between patients with chronic pancreatic disease and those with a normal pancreas when serum levels of fluorescein were measured 10 h after administration with a standard meal. The sensitivity at this time interval was 80% and the specificity 83%. We conclude that the pancreolauryl test with serum measurements provides a simple, noninvasive, and reliable diagnostic test for chronic pancreatic disease in anuric patients with chronic renal failure.

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.

Function tests in the diagnosis of chronic pancreatitis. Critical evaluation.

Direct pancreatic function tests, such as the secretin-pancreozymin test and the Lundh test, are--by direct measurement of the contents of duodenal secretion following exogenous (hormonal) or endogenous (test meal) stimulation--the best way to assess exocrine pancreatic function. However, these tests are time-consuming, invasive, and expensive, and therefore their use is limited to specialized centers only. Several studies have shown that indirect pancreatic function tests are a practicable alternative to direct pancreatic function tests for diagnosing exocrine pancreatic insufficiency. They allow staging of the disease and thereby facilitate comparison of different studies. They are also useful in some cases for determining whether pancreatic enzyme replacement therapy is necessary or not. In contrast to morphological procedures, they involve neither side effects, risks for the patient, nor complications for patients, investigators, and laboratory staff alike. The procedures being standardized, the test results depend to a lesser extent on the experience of the investigator, and more on the selection of and the instructions to the patient, and to some extent, on the severity of the exocrine pancreatic insufficiency. Like all pancreatic function tests, the indirect tests do not give a clue to etiology nor help investigators to differentiate between pancreatic insufficiency owing to chronic pancreatitis and that owing to pancreatic cancer. The role of pancreatic function tests in diagnosing early chronic pancreatitis in comparison to morphological examinations remains to be established.

Exocrine pancreatic function after gastrectomy: Specificity of indirect tests

We compared intraindividually the specificity of indirect pancreatic function tests before and after total (n = 4; Roux-en-Y) or subtotal (n = 6; Billroth II) gastrectomy. Before gastrectomy only 1 patient showed a falsely pathological result with the pancreolauryl test (90% specificity), while the results of all the other tests were correctly normal (100% specificity using the usual cutoff limits). After gastrectomy the respective specificities were as follows: pancreolauryl test 10%, bentiromide test 70%, fecal chymotrypsin 70%, and plasma amino acid consumption test 100%. There was no obvious difference in the reduction of specificity between subtotal and total gastrectomy. The respective preoperative to postoperative changes in the median test data were as follows: plasma amino acid consumption test +21%, bentiromide test −12%, fecal chymotrypsin −51%, and pancreolauryl test −53%. It is concluded that after gastrectomy only the plasma amino acid consumption test is unaffected by postoperative anatomic alterations.

The fecal chymotrypsin photometric assay in the evaluation of exocrine pancreatic capacity. Comparison with other direct and indirect pancreatic function tests.

Fecal chymotrypsin (FCT) has been measured by a new photometric method (Monotest Chymotrypsin; Boehringer, Mannheim) in 78 patients: 44 with chronic pancreatitis and 34 not affected by any pancreatic disease. The results were compared with those from other tests of pancreatic secretory (secretin-cerulein test) and digestive [serum and urinary p-aminobenzoic acid (PABA) and pancreolauryl] capacity. When FCT values were severely reduced (below 6.7 U/g), from 90 to 100% of the patients also presented abnormal pancreatic secretory and digestive capacity. On the other hand, 87% of the patients with normal FCT (above 20 U/g) presented normal secretory and digestive capacity. Patients with intermediate FCT values (between 6.7 and 20 U/g) showed normal or abnormal pancreatic secretory and digestive capacity with the same probability. Therefore, FCT, carried out as a first test, seems to identify subjects that need no further pancreatic function tests (normal and severely impaired FCT) and patients who need other more complex functional investigations (intermediate FCT values).