Exocrine pancreatic insufficiency (EPI) is a condition caused by a deficiency of exocrine pancreatic enzymes, resulting in malabsorption of nutrients. Clinical manifestations of EPI may include steatorrhea, weight loss, diarrhea, and abdominal pain. Although direct testing is the most sensitive and specific for EPI, these tests are invasive, time consuming, expensive, and not well standardized. Fecal elastase (FE-1) has been shown to be an indirect marker of the exocrine secretory capacity of the pancreas and has become the most commonly employed indirect test for diagnosis of EPI. Measurement of fecal elastase consists of two main phases, a preanalytical phase and analytical phase. The preanalytical phase involves stool collection, storage and handling. The second phase is the analytical phase, which includes the actual assay processes and products used to produce a result. For FE-1 this includes sample extraction and measurement on an immunoassay. Each step in the process can influence the result and contribute to heterogeneity in FE-1 measurement, potentially impacting clinical diagnosis and management. Thus, this paper provides an overview of the preanalytical and analytical factors that can affect measurement and interpretation of FE-1 results.

Pancreatic cancer is an aggressive malignancy and the seventh leading cause of global cancer deaths in industrialised countries. More than 80% of patients suffer from significant weight loss at diagnosis and over time tend to develop severe cachexia. A major cause of weight loss is malnutrition. Patients may experience pancreatic exocrine insufficiency (PEI) before diagnosis, during nonsurgical treatment, and/or following surgery. PEI is difficult to diagnose because testing is cumbersome. Consequently, PEI is often detected clinically, especially in non-specialised centres, and treated empirically. In this position paper, we review the current literature on nutritional support and pancreatic enzyme replacement therapy (PERT) in patients with operable and non-operable pancreatic cancer. To increase awareness on the importance of PERT in pancreatic patients, we provide recommendations based on literature evidence, and when data were lacking, based on our own clinical experience.

Exocrine pancreatic insufficiency (EPI) is a condition caused by reduced or inappropriate secretion or activity of pancreatic juice and its digestive enzymes, pancreatic lipase in particular. EPI can result in clinical manifestation and biochemical alterations causing reduced quality of life and life-threating complications. EPI is common in pancreatic disorders, where it should be suspected and actively investigated, and in many extrapancreatic conditions. There are various tests available to diagnose EPI, with indirect, noninvasive ones, such as concentration of fecal elastase being more commonly employed. Administration of pancreatic enzymes replacement therapy remains the mainstay of EPI treatment. The present review article will discuss current evidence regarding the prevalence of EPI, the available tests to diagnose it and its treatment.

Tests to quantify fecal levels of chymotrypsin like elastase family member 3 (CELA3 or elastase-1) in feces are widely used to identify patients with exocrine pancreatic insufficiency (EPI). However, the diagnostic accuracy of this test, an ELISA, is not clear. We performed a systematic review and meta-analysis to determine the accuracy of measurement of fecal elastase-1 in detection of EPI.

We searched PubMed, Embase, and reference lists for articles through November 2016 describing studies that compared fecal level of elastase-1 with results from a reference standard, direct method (secretin stimulation test), or indirect method (measurement of fecal fat) for detection of EPI. Sensitivity and specificity values were pooled statistically using bivariate diagnostic meta-analysis.

We included total of 428 cases of EPI and 673 individuals without EPI (controls), from 14 studies, in the meta-analysis. The assay for elastase-1, compared to secretin stimulation test, identified patients with pancreatic insufficiency with a pooled sensitivity value of 0.77 (95% CI, 0.58-0.89) and specificity value of 0.88 (95% CI, 0.78-0.93). In an analysis of 345 cases of EPI and 312 controls, from 6 studies, the fecal elastase-1 assay identified patients with EPI with a pooled sensitivity value of 0.96 (95% CI, 0.79-0.99) and specificity value of 0.88 (95% CI, 0.59-0.97), compared to quantitative fecal fat estimation. In patients with low pre-test probability of EPI (5%), the fecal elastase-1 assay would have a false-negative rate of 1.1% and a false-positive rate of 11%, indicating a high yield in ruling out EPI but not in detection of EPI. In contrast, in patients with high pre-test probability of EPI (40%), approximately 10% of patients with EPI would be missed (false negatives).

In a systematic review and meta-analysis of studies that compared fecal level of elastase-1 for detection of EPI, we found that normal level of elastase-1 (above 200 mcg/g) can rule out EPI in patients with a low probability of this disorder (such as those with irritable bowel syndrome with diarrhea). However, in these patients, an abnormal level of elastase-1 (below 200 mcg/g) has a high false-positive rate.

Pancreatic exocrine insufficiency (PEI) results in maldigestion due to inadequate activity of pancreatic enzymes in the small bowel. PEI can arise from a variety of medical conditions that reduce enzyme synthesis within the pancreatic parenchyma or from secondary factors that may occur despite optimal parenchymal function, such as pancreatic duct obstruction or impaired or poorly synchronized enzyme release.

To provide practical guidance for primary care physicians managing patients who are at risk of PEI or who present with symptoms of PEI.

For each of six key clinical questions identified by the authors, PubMed searches were conducted to identify key English-language papers up to April 2017. Forward and backward searches on key articles were conducted using Web of Science. Clinical recommendations proposed by the co-chairs (P.D. and C.T.) were vetted and approved based on the authors?

The most characteristic symptom of PEI is steatorrhea ? voluminous, lipid-rich stools; other common signs and symptoms include unexplained weight loss and deficiencies of fat-soluble vitamins and other micronutrients. Pancreatic enzyme replacement therapy (PERT) can relieve symptoms and long-term sequelae of PEI. Diagnosis of PEI and initiation of PERT are usually the responsibility of gastroenterology specialists. However, primary care physicians (PCPs) are well positioned to identify potential cases of PEI and to participate in the collaborative, long-term management of patients already seen by a specialist.

In this document, a panel of Canadian gastroenterologists has conducted a critical review of the literature on PEI and PERT and has developed practical diagnostic and treatment recommendations for PCPs. These recommendations provide guidance on identifying patients at risk of PEI, the triggers for PEI testing and referral, and best practices for co-managing patients with confirmed PEI.

Fecal calprotectin determination has been demonstrated to be useful in diagnosing various inflammatory diseases of the gastrointestinal tract; however, data available for patients with pancreatic diseases are scarce. Our aim was to assess fecal calprotectin in order to evaluate the presence of intestinal inflammation in patients with pancreatic disease.

Eligible patients with suspected pancreatic illness were enrolled, and in all of them fecal calprotectin and elastase-1, as well as serum amylase and lipase activities, were assayed using commercially available kits.

A total of 90 subjects (47 men, 43 women, mean age 58.6 +/- 14.9 years) were enrolled: 20 (22.2%) had chronic pancreatitis; 15 (16.7%) had pancreatic cancer; six (6.7%) had chronic nonpathological pancreatic hyperenzymemia; 16 (17.8%) had nonpancreatic diseases; and 23 (25.6%) had no detectable diseases. Diarrhea was present in 19 patients (21.1%). In univariate analyses, the presence of diarrhea and low fecal elastase-1 concentrations were significantly associated (P = 0.019 and P = 0.002, respectively) with abnormally high fecal calprotectin concentration, and the multivariate analysis demonstrated that low fecal elastase-1 concentration was the only variable independently associated with a high fecal calprotectin concentration.

Pancreatic insufficiency may cause intestinal inflammation, probably because of a modification of the intestinal ecology.

Two enzyme-linked immunosorbent assay methodologies are used to detect pancreatic insufficiency: monoclonal and polyclonal. We sought to compare these assays in patients with cystic fibrosis and to correlate these with the coefficient of fat absorption (CFA).

As part of a larger study, subjects had stool elastase measured by both methods while taking exogenous enzymes. Subjects subsequently stopped enzymes and had a fecal fat balance study performed; the CFA was then calculated.

One hundred twenty-four subjects participated in this substudy. The median values for the monoclonal and polyclonal assays were 0.3 and 22.75 microg/g, respectively. The correlation coefficient between the 2 tests was 0.86 (P < 0.0001). The correlation coefficients between CFA and the monoclonal and polyclonal assays were 0.24 (P = 0.006) and 0.10 (P = 0.27), respectively. If the criterion standard definition of pancreatic insufficiency was set at a CFA < 90% and the test definition of pancreatic insufficiency was set at <100 microg/g, then the monoclonal and polyclonal assay positive predictive values were 97.6% (120 of 123) and 97.4% (111 of 114), respectively.

The positive predictive value of both monoclonal and polyclonal fecal elastase in patients with cystic fibrosis is extremely good; however, correlation of either test with CFA was poor. The median value for the polyclonal elastase assay is higher than for the monoclonal assay, which could potentially lead to lower sensitivity of the polyclonal assay at lower cutpoints for the monoclonal assay is used.

A primary function of the pancreas is to produce digestive enzymes that are delivered to the small intestine for the hydrolysis of complex nutrients. Much of our understanding of digestive enzymes comes from studies in animals. New technologies and the availability of the sequence of the human genome allow for a critical review of older reports and assumptions based on animal studies. This report updates our understanding of human pancreatic digestive enzymes with a focus on new insights into the biology of human proteases, lipases and amylases.

Early detection and management of pancreatic insufficiency is essential to optimize health and outcomes in cystic fibrosis patients. The gold standard measures for assessment of pancreatic function are direct pancreatic stimulation tests, which have numerous limitations. Estimation of fecal elastase-1 level to determine pancreatic function is an attractive alternative as the test is simple, rapid, cost-effective and easy to perform even in children. This review summarizes the data from studies reflecting the validity, limitation and advantages of fecal elastase-1 in assessing pancreatic function in cystic fibrosis patients.