Prospective Assessment of Normal Pancreatic Secretory Function Measured by MRI in a Cohort of Healthy Children.

OBJECTIVES: Magnetic resonance imaging (MRI) with secretin stimulation promises to allow non-invasive testing for exocrine pancreatic insufficiency but normal data do not exist for children. The purpose of this study was to define, in healthy children, normal pancreatic secreted fluid volume and secretion rate, measured by MRI, in response to secretin. METHODS: In this Institutional Review Board-approved, prospective, cross-sectional study, 50 healthy children ages 6 to <16 years underwent MRI with secretin stimulation. Images were obtained before and at 1, 5, 10 and 15 min after secretin administration to calculate total secreted fluid volume and secretion rate based on image segmentation. Regression was used to define the relationship between secretory function and participant size measures, and linear quantile regression was used to define normal secretory values based on size measures. RESULTS: Median total secreted fluid volume post secretin was 79 mL (range: 32-162 mL; 5th and 95th percentiles: 43 and 123 mL) and median secretion rate was 5.1 mL/min (range: 2-9.4 mL/min; 5th and 95th percentiles: 2.3 and 7.7 mL/min). Secreted volume and secretion rate had the strongest correlation with body surface area (BSA) (r = 0.54 and 0.59, respectively) and multiple regression defined BSA as the only significant predictor of secretory function. Each 1 m2 increase in BSA was associated with a 38 mL increase in secreted fluid volume. CONCLUSIONS: In children, pancreatic secretory response to secretin, measured by MRI, depends on participant size, particularly BSA. Secreted volume <43 mL or a secretion rate <2.3 mL/min (5th percentile values) can be considered abnormal for children.

English language version of the S3-consensus guidelines on chronic pancreatitis: Definition, aetiology, diagnostic examinations, medical, endoscopic and surgical management of chronic pancreatitis.

Chronic pancreatitis is a disease of the pancreas in which recurrent inflammatory episodes result in replacement of pancreatic parenchyma by fibrous connective tissue. This fibrotic reorganization of the pancreas leads to a progressive exocrine and endocrine pancreatic insufficiency. In addition, characteristic complications arise, such as pseudocysts, pancreatic duct obstructions, duodenal obstruction, vascular complications, obstruction of the bile ducts, malnutrition and pain syndrome. Pain presents as the main symptom of patients with chronic pancreatitis. Chronic pancreatitis is a risk factor for pancreatic carcinoma. Chronic pancreatitis significantly reduces the quality of life and the life expectancy of affected patients. These guidelines were researched and compiled by 74 representatives from 11 learned societies and their intention is to serve evidence-based professional training as well as continuing education. On this basis they shall improve the medical care of affected patients in both the inpatient and outpatient sector. Chronic pancreatitis requires an adequate diagnostic workup and systematic management, given its severity, frequency, chronicity, and negative impact on the quality of life and life expectancy.

European guideline on indications, performance and clinical impact of 13 C-breath tests in adult and pediatric patients: An EAGEN, ESNM, and ESPGHAN consensus, supported by EPC.

INTRODUCTION: 13 C-breath tests are valuable, noninvasive diagnostic tests that can be widely applied for the assessment of gastroenterological symptoms and diseases. Currently, the potential of these tests is compromised by a lack of standardization regarding performance and interpretation among expert centers. METHODS: This consensus-based clinical practice guideline defines the clinical indications, performance, and interpretation of 13 C-breath tests in adult and pediatric patients. A balance between scientific evidence and clinical experience was achieved by a Delphi consensus that involved 43 experts from 18 European countries. Consensus on individual statements and recommendations was established if ≥ 80% of reviewers agreed and <10% disagreed. RESULTS: The guideline gives an overview over general methodology of 13 C-breath testing and provides recommendations for the use of 13 C-breath tests to diagnose Helicobacter pylori infection, measure gastric emptying time, and monitor pancreatic exocrine and liver function in adult and pediatric patients. Other potential applications of 13 C-breath testing are summarized briefly. The recommendations specifically detail when and how individual 13 C-breath tests should be performed including examples for well-established test protocols, patient preparation, and reporting of test results. CONCLUSION: This clinical practice guideline should improve pan-European harmonization of diagnostic approaches to symptoms and disorders, which are very common in specialist and primary care gastroenterology practice, both in adult and pediatric patients. In addition, this guideline identifies areas of future clinical research involving the use of 13 C-breath tests.

Chronic pancreatitis: A diagnostic dilemma.

Typical clinical symptoms of chronic pancreatitis are vague and non-specific and therefore diagnostic tests are required, none of which provide absolute diagnostic certainly, especially in the early stages of disease. Recently-published guidelines bring much needed structure to the diagnostic work-up of patients with suspected chronic pancreatitis. In addition, novel diagnostic modalities bring promise for the future. The assessment and diagnosis of pancreatic exocrine insufficiency remains challenging and this review contests the accepted perspective that steatorrhea only occurs with > 90% destruction of the gland.

Romanian guidelines on the diagnosis and treatment of exocrine pancreatic insufficiency.

In assessing exocrine pancreatic insufficiency (EPI), its diverse etiologies and the heterogeneous population affected should be considered. Diagnosing this condition remains a challenge in clinical practice especially for mild-to-moderate EPI, with the support of the time-consuming breath test or the coefficient of fat absorption. The fecal elastase-1 test, less precise for the diagnosis, cannot be useful for assessing treatment efficacy. Pancreatic enzyme replacement therapy (PERT) is the mainstay of treatment, whereby enteric-coated mini-microspheres are taken with every meal, in progressive doses based on an individual's weight and clinical symptoms. The main indication for PERT is chronic pancreatitis, in patients who have clinically relevant steatorrhea, abnormal pancreatic function test or abnormal function tests associated with symptoms of malabsorption such as weight loss or meteorism. While enzyme replacement therapy is not recommended in the initial stages of acute pancreatitis, pancreatic exocrine function should be monitored for at least 6-18 months. In the case of unresectable pancreatic cancer, replacement enzyme therapy helps to maintain weight and improve overall quality of life. It is also indicated in patients with celiac disease, who have chronic diarrhea (in spite of gluten-free diet), and in patients with cystic fibrosis with proven EPI.

Exocrine pancreatic insufficiency in adults: a shared position statement of the Italian Association for the Study of the Pancreas.

This is a medical position statement developed by the Exocrine Pancreatic Insufficiency collaborative group which is a part of the Italian Association for the Study of the Pancreas (AISP). We covered the main diseases associated with exocrine pancreatic insufficiency (EPI) which are of common interest to internists/gastroenterologists, oncologists and surgeons, fully aware that EPI may also occur together with many other diseases, but less frequently. A preliminary manuscript based on an extended literature search (Medline/PubMed, Cochrane Library and Google Scholar) of published reports was prepared, and key recommendations were proposed. The evidence was discussed at a dedicated meeting in Bologna during the National Meeting of the Association in October 2012. Each of the proposed recommendations and algorithms was discussed and an initial consensus was reached. The final draft of the manuscript was then sent to the AISP Council for approval and/or modification. All concerned parties approved the final version of the manuscript in June 2013.

[The diagnostic validity of non-invasive pancreatic function tests--a meta-analysis]. / Die diagnostische Validität nichtinvasiver Pankreasfunktionstests -- Eine Metaanalyse.

BACKGROUND: The paper discusses the non-invasive (tubeless) pancreatic function tests used to diagnose exocrine pancreatic insufficiency (EI). Studies evaluating the diagnostic validity of these tests are integrated into a meta-analysis, provided that they comply with the following criteria: The sensitivity (Ss) of a test has to be calculated by comparing it with an invasive function test which is accepted as the gold standard of pancreatic function diagnostics. Furthermore, the test must differentiate between slight (sl), moderate (md) and severe (sv) EI. For assessment of the specificity (Sp), the control group should not contain healthy persons but rather patients with other gastrointestinal diseases and a normal pancreatic function. In the statistical evaluation, each study was weighted according to the number of persons included. RESULTS: Tests (n = sum of persons included in all analysed studies): Fecal chymotrypsin: Ss (n = 169) 54 % (sl EI), 53 % (md EI), 89 % (sv EI), Sp (n = 202) 74 %. NBT-PABA test: Ss (n = 394) 49 % (sl EI), 64 % (md EI), 72 % (sv EI), Sp (n = 218) 83 %. Pancreolauryl test: Ss (n = 320) 63 % (sl EI), 76 % (md EI), 94 % (sv EI), Sp (n = 171) 85 %. Fecal elastase-1: Ss (n = 307) 54 % (sl EI), 75 % (md EI), 95 % (sv EI), Sp (n = 347) 79 %. Additional tests discussed but not included in the meta-analysis were fecal fat, (13)C breath tests, amino acid consumption test, serum tests. CONCLUSION: None of the non-invasive pancreatic function tests is sensitive enough to diagnose reliably a slight to moderate exocrine pancreatic insufficiency.

Pancreolauryl and NBT-PABA tests. Are serum tests more practicable alternatives to urine tests in the diagnosis of exocrine pancreatic insufficiency?

Serum fluorescein and p-aminobenzoic acid were measured during a urine pancreolauryl and an N-benzoyl-l-tyrosyl-p-aminobenzoic acid (NBT-PABA) test in 22 healthy controls, 17 patients with gastrointestinal nonpancreatic diseases (normal secretin-pancreozymin test), and 31 patients with abnormal exocrine pancreatic function due to chronic pancreatitis. The optimal cutoff point for separating normal from abnormal pancreatic function was after 210 min in the pancreolauryl test and after 150 min in the NBT-PABA test. The latter test was slightly less sensitive and specific than the pancreolauryl test. Serum tests seem to offer a practicable alternative to the established indirect pancreatic function tests in urine and may be used in the elderly and severely ill, as well as in outpatients in whom correct collection of the urine may be difficult.

A new direct pancreatic function test in pediatrics.

Traditional methods for collecting duodenal fluid are time consuming and technically difficult. A simple endoscopic method is proposed in this report as a means of collecting duodenal fluid to perform exocrine pancreatic function tests. Thirty-five patients between 24 and 36 months of age were studied for pancreatic exocrine function. Twenty-seven presented with chronic diarrhea and 8 with failure to thrive. In 20 patients (group 1), duodenal fluid was collected by means of a double-lumen tube and sequential administration of pancreozymin (PZN) and secretin (SEC). The rest (group 2) had duodenal aspiration from the level of the papilla of Vater through a fiberoptic endoscope following administration of SEC only. The procedure took approximately 3 h in group 1 and 45 min in group 2. Secretin administration produced comparable levels of enzymes in both groups. Pancreozymin produced the highest enzyme levels, but this was only significantly higher than SEC-induced levels in the case of lipase. Endoscopic collection of duodenal fluid following SEC administration is a safe, quick, and reliable method of collecting pancreatic secretion.

[Current techniques for investigating exocrine pancreatic function in children]. / Techniques actuelles d'exploration de la fonction pancréatique exocrine chez l'enfant.

The exocrine pancreas produces many of the enzymes responsible for the digestion of food. Severe alterations in exocrine pancreas function cause malabsorption which predominantly affects fats. Unfortunately, because it is a deep organ the pancreas is a difficult target for investigations. A large number of diagnostic tests have been developed to gather information on pancreatic function with minimal invasiveness. Although helpful in everyday practice, each of these methods investigates only one of the multiple components of pancreatic secretory function and all are relatively insensitive, i.e., detect only severe secretion deficiencies. Furthermore, none of these tests can evaluate water and electrolyte secretion. Consequently, invasive duodenal juice studies with stimulation remain the "gold standard" for evaluating exocrine pancreas function.

[Comparison of faecal lipase test and faecal elastase-1 test in the assessment of exocrine pancreatic function in cystic fibrosis]. / Porównanie przydatnosci oznaczania elastazy-1 i lipazy w stolcu w ocenie funkcji zewnatrzwydzielniczej trzustki u chorych na muskowiscydoze.

OBJECTIVE: In pediatric patients, indirect tests are preferred because of their less invasive character. Among those, faecal elastase-1 test has so far been shown been shown to have the highest sensitivity and specificity. However, the role of the faecal lipase test in the diagnostic work up for pancreatic insufficiency in cystic fibrosis (CF) patients has not been defined. Therefore, the aim of the present study was to compare the sensitivity and the specificity of faecal lipase test to the faecal elastase-1 test in the assessment of exocrine pancreatic function. MATERIAL AND METHODS: 63 CF patients and 95 healthy subjects (HS) were evaluated. In all subjects, faecal elastase-1 concentration (ELISA) and lipase activity (ELISA) were measured. In 50 HS, sample-to-sample (n=3) variation from the same stool and day-to-day variation from three consecutive stools were determined twice. The presence of pancreatic insufficiency patients was documented in 55 pancreatic insufficient CF patients by the determination of faecal fat excretion and in 12 pancreatic sufficient patients by the direct test. The sensitivity and specificity of the faecal elastase-1 test and faecal lipase test were compared. RESULTS: The sample-to-sample variation (mean + SEM: 13.2+1.2% vs. 23.4+2.2%) and day-to-day variation (mean + SEM: 16.3+1.2% vs. 32.5+2.6%) were significantly lower (p<0.0001) for elastase-1 determinations than for lipase measurements. With the cut-off levels giving the same specificity for both tests (95.8%), the sensitivity of faecal elastase-1 test (87.3%) was significantly higher (p<0.04) than that of faecal lipase test (77.8%). IN CONCLUSION: Faecal lipase test is less useful in the assessment of exocrine pancreatic function sensitive than faecal elastase-1 test.

Faecal elastase-1: lyophilization of stool samples prevents false low results in diarrhoea.

BACKGROUND: In patients with diarrhoea, faecal elastase-1 is used to detect exocrine pancreatic insufficiency. Diarrhoea is defined as >85% stool water content. METHODS: We analysed elastase-1 in 519 stool samples from 310 patients unprocessed as well as after lyophilization in a standard laboratory lyophilizator. Stool water content was calculated by weight difference before and after lyophilization. RESULTS: 151 stool samples were classified as 'diarrhoea' (mean stool water content 88.8%); all others had a mean water content of 75.4%. In the 'diarrhoea' samples, elastase-1 levels were considerably higher after lyophilization--with a calculated normal water content of 75% (606 +/- 359 microg/g, mean +/- s)--compared to measurement when unprocessed (279 +/- 151 microg/g; P < 0.0001). In 16 of the 151 cases (11%), the abnormally low elastase-1 level below 200 microg/g found in unprocessed stools proved normal (>200 microg/g) after lyophilization and correction for stool water content. CONCLUSION: Diarrhoea can result in falsely decreased elastase-1 levels in a number of patients with non-pancreatogenic diarrhoea. Lyophilization is a simple measure by which to determine elastase-1 independently of stool water content. Lyophilization of stool samples can therefore help to prevent wrong positive elastase-1 test results.

Detection and follow up of exocrine pancreatic insufficiency in cystic fibrosis: a review.

UNLABELLED: Pancreatic function testing is particularly difficult when the degree of remaining function has to be quantified. Detection of pancreatic insufficiency can suggest the diagnosis of cystic fibrosis (CF). It is, however, also important to follow the degree of pancreatic insufficiency in CF since its function can decline with age. Adaptation of pancreatic enzyme replacement therapy on residual function is necessary. Different tests with their advantages and disadvantages are critically reviewed in this article with respect to specificity, sensitivity, performance and cost-effectiveness. CONCLUSION: Elastase-1 detection in faeces is probably the easiest test for the detection of pancreatic insufficiency in cystic fibrosis. For clinical follow-up tests, measuring the fat assimilation such as steatocrit and breath tests are more suited.