Fecal elastase-1 as a test for pancreatic function: a review.

Pancreatic elastase-1 is a specific human protease synthetized by the acinar cells. Immunoreactive elastase-1 cannot be detected in either porcine or bovine pancreatic enzyme preparations. It is very stable and, in contrast to fecal chymotrypsin, elastase is unaffected by exogenous pancreatic enzyme treatment, and correlates well with exocrine pancreatic function tests. The measurement of this proteolytic enzyme in stool by means of an enzyme-linked immunosorbent assay (ELISA) is a sensitive, specific, and relatively inexpensive non-invasive test. It is an accurate function test for patients with chronic pancreatitis confirmed by endoscopic retrograde cholangiopancreatography and computerized axial tomography. It shows higher sensitivity and specificity for exocrine pancreatic insufficiency than fecal chymotrypsin determination and is comparable to oral pancreatic function tests such as the pancreolauryl test.     

Fecal chymotrypsin and elastase-1 determination on one single stool collected at random: diagnostic value for exocrine pancreatic status

OBJECTIVE: The secretin-cholecystokinin test is the "gold standard" to evaluate exocrine pancreatic function. But this direct duodenal intubation test is invasive, particularly in children, time-consuming, and expensive. For several years, indirect noninvasive tests of pancreatic insufficiency have been developed, such as fecal chymotrypsin (FChT) and fecal elastase-1 (FEL-1) measurements. Generally, elastase-1 is truly admitted to be the most relevant test of exocrine pancreatic status. However, so far, no consensus for stool collection protocol exists. The aim of our study was to investigate the diagnostic advantage from measuring fecal proteases in stool samples collected for two or three consecutive days in comparison to one single stool sample collected at random. DESIGN: A total of 69 children were divided into group A (stool samples collected for three consecutive days) and group B (stool samples collected for two consecutive days). These two groups included pancreatic-sufficient patients (PS) and severe pancreatic-insufficient patients (PI). One single determination of fecal chymotrypsin activity and of fecal elastase-1 concentration was realized on each stool. RESULTS: The same relatively important intraindividual variability of fecal proteases was observed in group A and B (mean coefficients of variation (CVs) 36% vs. 40.2% for chymotrypsin, 22.2% vs. 26.8% for elastase-1). No significant PS or severe PI diagnostic discordance was observed between 1, 2, or 3 days of stool collections. CONCLUSION: Our study clearly shows that the determination of fecal proteases on one single stool collected at random is sufficient to evaluate pancreatic exocrine status for PS and severe PI.     

Validation of fecal elastase-1 determination using immunoenzymatic assay in HIV-infected patients

Pancreatic elastase-1 is a proteolytic enzyme exclusively produced in the pancreas, is stable when passing through the bowel, and its determination is associated with chronic pancreatitis. The clinical diagnosis of pancreatitis is based on anamnesis, physical examination, radiological, sonographic, endoscopic, and laboratory findings. Nowadays, there is a test for the determination of fecal elastase-1, by enzymatic reaction (enzyme-linked immunosorbent assay, ELISA), which specifically determines human elastase-1, promoting the pancreatic function evaluation. Parameters such as linearity, calibration curve, sensitivity, specificity, precision, accuracy, recovery, and receiver operator characteristic (ROC) curve are used to evaluate the test. The aim of this study was the validation of the immunoenzymatic assay (ELISA) and the use of its results in patients with HIV, alcoholics, and under antiretroviral therapy. The study involved 157 patients, 95 of them were HIV-infected, and 62 were completely healthy. The elastase-1 ELISA kit from Bioserv was used, and we noted that the obtained results were linear, sensitive, precise, and accurate. Moreover, our results suggest that this test can be a laboratory evaluation to determine the relationship of pancreatitis with alcohol use, but not its association with antiretroviral use in HIV patients (P=0.424). This test is useful to diagnose pathologies related to pancreatic insufficiency.     

Pancreatic function after endoscopic and surgical occlusion of the pancreatic duct in patients with chronic pancreatitis

Complex monitoring of pancreatic function was done after 18 endoscopic or surgical occlusions of the pancreatic duct in 15 patients with chronic pancreatitis. The indirect function tests (starch tolerance test, Lipiodol test and fat loading) as well as the direct tests (secretin-pancreozymin and Lundh tests) demonstrated only moderate pancreatic insufficiency. Overall values of the Lundh test performed before and after the treatment in 10 cases did not change significantly. The surgical procedure decreased pancreatic function somewhat more effectively, but the symptom-free "burned-out" state was only rarely achieved. Even glucose tolerance slightly diminished after treatment. The uneven results of obstruction therapy were attributed to the recovered exocrine function of the pancreas. Patients with severe pancreatic insufficiency or proximal resection of the pancreas seem to be better candidates for such treatments.     

Update of exocrine functional diagnostics in chronic pancreatitis

Diagnostics of pancreatic insufficiency rely mainly on tests of pancreatic exocrine function based on either measurement of pancreatic secretion or the secondary effects resulting from lack of digestive enzymes or imaging modalities. These methods have been developing rapidly over the last decades, and the aims of this review were to describe exocrine functional testing and imaging of the pancreas in chronic pancreatitis..     

Clinical significance of serum pancreatic enzymes in the quiescent phase of chronic pancreatitis

The most commonly used serum enzymes in pancreatic diseases are total amylase, pancreatic isoamylase, lipase and trypsin. To determine which of these enzymes is the most useful in the diagnosis of clinically quiescent chronic pancreatitis and which enzyme best reflects exocrine functional reserve, we studied 22 healthy control subjects, 44 patients with gastrointestinal, liver and biliary tract diseases, and 25 patients with chronic pancreatitis. On the basis of duodenal intubation, the latter were divided into two subgroups: one group of 13 patients with slight to moderate secretion deficiency and another of 12 patients with severe exocrine insufficiency. Of the enzymes studied, lipase, trypsin and pancreatic isoamylase are equally suitable for the evaluation of function in severe chronic pancreatitis, but not for the early diagnosis of the disease. Results for total amylase are not reliable so that its use in the study of chronic pancreatitis is not advisable.     

Chronic Pancreatitis: Ultrasound, Computed Tomography, and Magnetic Resonance Imaging Features

Chronic pancreatitis is a progressive, irreversible inflammatory and fibrosing disease of the pancreas with clinical manifestations of chronic abdominal pain, weight loss, and permanent pancreatic exocrine and endocrine insufficiency. In the United States, a long history of heavy alcohol consumption is the most common cause of chronic pancreatitis. This review discusses the different modalities such as computed tomography, transabdominal and endoscopic ultrasound, magnetic resonance imaging/magnetic resonance cholangiopancreatography, and endoscopic retrograde cholangiopancreatography available to image chronic pancreatitis, along with their advantages and limitations. In addition, topics such as groove pancreatitis and autoimmune pancreatitis are examined, along with a discussion of distinguishing chronic pancreatitis from pancreatic adenocarcinoma.     

Elevated fasting cholecystokinin levels in pancreatic exocrine impairment: evidence to support feedback regulation

Previous studies have suggested that intraduodenal protease suppression of pancreatic exocrine secretion may be mediated through cholecystokinin (CCK) release. Our study compares basal plasma immunoreactive CCK concentrations in normal human subjects with those obtained in patients with chronic pancreatitis. Fasting plasma samples were collected from 18 normal subjects and from 18 patients with chronic pancreatitis. Eight patients had mild to moderate pancreatic exocrine impairment, and 10 had severe exocrine insufficiency. Venous plasma immunoreactive CCK concentrations were measured with two distinct peptide region-specific antibodies. Basal plasma CCK concentration in controls was 14.3 +/- 1.3 fmol/ml (mean +/- SEM), a value significantly less than that obtained in all patients with chronic pancreatitis, 30.1 +/- 4.0 fmol/ml (p less than 0.001). Patients with mild to moderate impairment had a fasting plasma CCK concentration of 32.8 +/- 7.9 fmol/ml (vs. control p less than 0.01), and those with severe disease 27.9 +/- 3.6 fmol/ml (vs. control p less than 0.001). In five patients with mild to moderate impairment of exocrine function and pancreatic extract-responsive abdominal pain, there was a 39 +/- 11% decrease in basal CCK levels during extract therapy (p less than 0.05). Results of this study indicate that pancreatic exocrine impairment is associated with elevated basal CCK levels, which may reflect a failure to provide feedback downmodulation of CCK release.     

Serum vitamin E,lipid peroxide and glutathione peroxidase in patients with chronic pancreatitis

It has been reported that lipid peroxidation increases in patients with antioxidant deficiencies, such as vitamin E and glutathione peroxidase. The relationships between serum lipid peroxide and vitamin E on the one hand and glutathione peroxidase on the other were examined in 22 patients with chronic pancreatitis, often accompanied by malabsorption of fats and fat-soluble vitamins due to the impaired exocrine pancreatic function.Both serum vitamin E concentrations and glutathione peroxidase activities were depressed, especially in patients with chronic calcifying pancreatitis. On the other hand, serum lipid peroxide levels were elevated. A significant negative correlation was found between the serum lipid peroxide levels and vitamin E concentration.These findings suggest that an elevation of the serum lipid peroxide level may be due to the lack of an antioxidative defense mechanism, such as vitamin E, against lipid peroxide.     

Proteases in the evaluation of pancreatic function and pancreatic disease

This paper reviews the role of pancreatic proteases (focusing upon trypsin, chymotrypsin and elastase) in the diagnosis and management of chronic pancreatic insufficiency (CPI), emphasizing advances over the last 5 years. Some important novel aspects of these enzymes in acute pancreatitis are also described, including their role in diagnosis and their interaction with cholecystokinin in the pathogenesis of the disease. The recent interest in these enzymes as agents promoting the spread of cancer in animals and human subjects is also described. A hierarchical approach has been taken to explore the advantages and limitations of tests in different source materials: serum, feces, duodenal aspirate, and non-invasive pancreatic function tests. The practical usefulness of fecal elastase-1 and of fecal chymotrypsin concentrations in diagnosis and management of CPI, respectively, is one of the major lessons to be learned from analysis of the recent literature, and forms the principal message of this review.     

Predictive factors for pancreatic cancer in patients with chronic pancreatitis in association with K-ras gene mutation

BACKGROUND AND STUDY AIMS: Chronic pancreatitis is considered to be a predisposing factor for pancreatic ductal adenocarcinoma (PAC). The purpose of this study was to examine the prognostic value of a finding of mutated (K- ras) gene in predicting the development of PAC in patients with chronic pancreatitis. PATIENTS AND METHODS: The pancreatic duct brushings of 146 patients with chronic pancreatitis were examined in order to identify K- ras gene mutations. A total of 112 patients were followed up (median duration 42 months) using clinical evaluation, serum CA19 - 9 levels, and imaging studies. RESULTS: One or more K- ras mutations were found in 57 of the 146 patients with chronic pancreatitis (39 %). Patients harboring K- ras mutations had a higher incidence of persistent alcohol consumption ( P = 0.041) and of prior rupture of the main pancreatic duct ( P = 0.040). A finding of nuclear atypia in brushing cytology was also more common in patients with K- ras mutation ( P = 0.048). Out of the 112 patients who were followed up, PAC occurred in four of the 44 patients who had a K- ras mutation, but in none of the 68 patients with the wild genotype ( P = 0.022). PAC occurred in three of the 25 patients who did not have pancreatic calcifications ( P = 0.034) and in four of the 54 patients who had demonstrated exocrine insufficiency, but in none of the 58 patients with preserved exocrine function ( P = 0.051). Using stepwise logistic regression, the absence of calcifications, the presence of exocrine insufficiency, and the presence of K- ras mutation were identified as independent predictive factors for cancer development in all patients with chronic pancreatitis. CONCLUSIONS: K- ras gene mutations occur in chronic pancreatitis and are associated with evolution towards PAC. The absence of pancreatic calcifications and the presence of exocrine insufficiency were identified as additional predictive factors for the development of PAC.     

口服胰功肽测定胰腺外分泌功能在消化系疾病的应用

本文通过对30例正常人,110例消化系疾病患者口服一定量的 N—苯甲酰—L—酪氨酰—对氨基苯甲酸(下称 BT—PABA)做胰腺外分泌功能试验.发现肝硬化、慢性肝炎、慢性胃炎及消化系溃疡患者的 BT—PABA 排出率与正常人比较无显著差异.肝硬变并肾功能损害者、胰腺癌及急、慢性胰腺炎患者的 PABA 排出率低于正常人。此实验对鉴别急、慢性胰腺炎及胰腺炎恢复过程的动态观察有一定价值。     

Fecal elastase-1 is decreased in villous atrophy regardless of the underlying disease

BACKGROUND: Fecal elastase-1 (E1) is a sensitive and reliable test in the assessment of exocrine pancreatic function in cystic fibrosis (CF). In patients with celiac disease (CD), different E1 values have been reported. E1 levels in other malabsorption conditions are unknown. Therefore, the aim of the present study was to evaluate E1 concentrations in various malabsorption syndromes. MATERIAL AND METHODS: The study was carried out in 54 patients, selected from patients referred with suspicion of CF, who had been diagnosed as celiac disease (CD; n = 16), secondary malabsorption syndrome (SMS, giardiasis- or cow milk-related enteropathy; n = 18) and food allergy (FA; n = 20). 70 age-matched healthy children (HC) and 131 cystic fibrosis (CF) patients served as control groups. In CD and SMS patients, a gluten-free diet was introduced. In addition, SMS patients were treated appropriately to underlying disease. In all subjects, E1 concentrations were measured. In CD and SMS patients, E1 concentrations were repeatedly measured after one year of the treatment. RESULTS: With a cut-off level of 200 microg g-1, abnormal E1 concentrations were found in 87.2% of the CF group and in 56.2% and 50.0% of the CD and SMS subgroups, respectively. In none of FA patients, were E1 values below the normal range. After mucosal recovery, E1 concentrations in patients with CD and SMS increased, suggesting that villous atrophy can diminish exocrine pancreatic secretion. In 18 out of 19 CD and SMS patients with abnormal E1 concentrations, monitored for at least 12 months of a gluten-free diet, abnormal E1 concentrations increased above the cut-off value to normal range. Two out of the 54 referred patients were finally diagnosed as having CF, one with stable low E1 levels and the second with finally normal values. CONCLUSIONS: The exocrine pancreatic function is decreased in villous atrophy regardless of underlying disease. The specificity of the fecal elastase-1 test in the differentiation between 'primary' exocrine pancreatic insufficiency and intestinal malabsorption with mucosal atrophy is low. After mucosal regeneration, fecal elastase-1 specificity is high.     

Symptomatic diabetes mellitus in patients with chronic recurrent pancreatitis

Out of 279 patients with chronic recurrent cholepancreatitis 34 (12.2%) developed secondary diabetes mellitus. The secondary genesis of the diabetes was suggested in view of its origin in the presence of chronic pancreatitis and absence of hereditary predisposition, concomitant diseases promoting diabetes onset. The frequency of pancreatitis exacerbations and the degree of pancreatic exocrine insufficiency correlate with the occurrence of symptomatic diabetes. Diminished blood levels of insulin and C-peptide, inhibited response to pancreozymin registered in the patients may be indicative of symptomatic diabetes onset. Ketoacidosis was recorded in 9 patients, diabetic retinopathy in no patients. Ten patients out of 34 patients with chronic pancreatitis with secondary diabetes, 9 of which had episodes of ketoacidosis, received insulin. The sequence chronic cholecystitis-pancreatitis-diabetes was discussed in detail.     

Chemical pancreatectomy treats chronic pancreatitis while preserving endocrine function in preclinical models

Chronic pancreatitis affects over 250,000 people in the US and millions worldwide. It is associated with chronic debilitating pain, pancreatic exocrine failure, and high risk of pancreatic cancer and usually progresses to diabetes. Treatment options are limited and ineffective. We developed a new potential therapy, wherein a pancreatic ductal infusion of 1%–2% acetic acid in mice and nonhuman primates resulted in a nonregenerative, near-complete ablation of the exocrine pancreas, with complete preservation of the islets. Pancreatic ductal infusion of acetic acid in a mouse model of chronic pancreatitis led to resolution of chronic inflammation and pancreatitis-associated pain. Furthermore, acetic acid–treated animals showed improved glucose tolerance and insulin secretion. The loss of exocrine tissue in this procedure would not typically require further management in patients with chronic pancreatitis because they usually have pancreatic exocrine failure requiring dietary enzyme supplements. Thus, this procedure, which should be readily translatable to humans through an endoscopic retrograde cholangiopancreatography (ERCP), may offer a potential innovative nonsurgical therapy for chronic pancreatitis that relieves pain and prevents the progression of pancreatic diabetes.     

Cationic trypsinogen mutations and pancreatitis

The discovery of PRSS 1 mutations in hereditary pancreatitis and analysis of how the genotype affects the presentation and progression of hereditary pancreatitis has led to a better understanding of the pathophysiology of the disease. Patients with hereditary pancreatitis present with symptoms at an early age and have a significant lifetime risk for the development of endocrine and exocrine insufficiency, albeit at a later stage than patients with either idiopathic or alcoholic chronic pancreatitis. There are distinct phenotypic differences between hereditary pancreatitis and with other types of pancreatitis. As many as 80% of patients with symptomatic hereditary pancreatitis have an underlying causative PRSS1 mutation; there are, however, few significant phenotypic differences between these PRSS1 mutations. TheR122H mutation is the most common PRSS1 mutation observed, and patients with the R122H mutation present earlier. This, however, does not necessarily translate into a more aggressive disease with respect to complications of chronic pancreatitis. Indeed, the age of presentation of symptoms may be a poor surrogate for predicting outcome, as inherited disorders of trypsinogen may cause subclinical attacks of pancreatitis, which ultimately lead to pancreatic destruction and dysfunction. All patients, irrespective of whether they carry a PRSS1 mutation, are at significant risk of developing pancreatic ductal adenocarcinoma. The risk appears to be insignificant below the age of 40 years, but it increases incrementally thereafter. Significantly, the risk of pancreatic cancer is not related to PRSS1 mutation type and does not appear to be related to the mode of inheritance. The role of SPINK1 mutations in modifying the expression of PRSS1mutations is unclear but appears to be of clinical importance. It is unlikely that they act as causative mutations per se, at least in the Western form of the disease. Additionally, they do not appear to have an impact on the penetrance of PRSS1 gene mutations in hereditary pancreatitis.     

Analysis of exocrine pancreatic function in cystic fibrosis: one mild CFTR mutation does not exclude pancreatic insufficiency

BACKGROUND: Cystic fibrosis (CF) is the most common cause of exocrine pancreatic insufficiency in childhood. The aim of the present study is to evaluate the correlation between genotype and exocrine pancreatic insufficiency in CF patients. The special emphasis was put on the analysis of mild CFTR mutations. DESIGN: The study comprised 394 CF patients and 105 healthy subjects (HS). Elastase-1 concentrations were measured in all subjects. RESULTS: Severe pancreatic insufficiency was associated with the presence of two CFTR gene mutations (DeltaF508, N1303K, CFTR dele 2,3 (21kb), G542X, 1717-1G-A, R533X, W1282X, 621GT, 2183AAG, R560T, 2184insA and DeltaI507, G551D, 895T) and mild insufficiency with the presence of at least one mutation (R117H, 3171insC, A155P2, 138insL, 296 + 1G-A, E92GK, E217G, 2789 + 5G-A. 3849 + 1kbC-T/3849 + 1kbC-T) genotype resulted in high elastase-1-values. However, in case of patients with genotype DeltaF508/3849 + 10kbC-T, 1717-1GA/3849 + 10kbC-T as well as with DeltaF508/R334W, both high and low elastase-1 concentrations were found. Low E1 values were found in a patient with DeltaF508/R347P genotype. CONCLUSION: Patients who carry two 'severe' mutations develop pancreatic insufficiency, whereas those who carry at least one 'mild' usually remain pancreatic sufficient. However, the presence of one mild mutation does not exclude pancreatic insufficiency.     

The prognostic value of immunologic indices in chronic pancreatitis]

Analysis of clinical and immunologic parallels in 200 patients with chronic pancreatitis has revealed that lymphocyte autosensitization to pancreatic tissue in the lymphocyte blastogenesis test (LBGT) is in high correlation with the frequency of the disease recurrences, and the severity of pancreatic exocrine insufficiency with the immune complex level. This permits recommending LBGT with pancreatic tissue antigen for the prediction of the condition recurrences, and measurements of the immune complexes level for the prediction of the developing exocrine pancreatic insufficiency.     

Tumor-associated focal chronic pancreatitis from invasion of the pancreatic duct by common bile duct carcinoma: radiologic-pathologic correlation

We report a case of tumor-associated focal chronic pancreatitis of the uncinate process of the pancreas. The chronic pancreatitis was secondary to stenosis of the main pancreatic duct from invasion by a common bile duct carcinoma. A feature distinguishing the chronic pancreatitis from pancreatic carcinoma was the localized dilatation of pancreatic duct branches evident in the focal lesion of the uncinate process.     

Tumor-associated focal chronic pancreatitis from invasion of the pancreatic duct by common bile duct carcinoma: radiologic–pathologic correlation

We report a case of tumor-associated focal chronic pancreatitis of the uncinate process of the pancreas. The chronic pancreatitis was secondary to stenosis of the main pancreatic duct from invasion by a common bile duct carcinoma. A feature distinguishing the chronic pancreatitis from pancreatic carcinoma was the localized dilatation of pancreatic duct branches evident in the focal lesion of the uncinate process.