Apolipoprotein A2 isoforms associated with exocrine pancreatic insufficiency in early chronic pancreatitis.

BACKGROUND AND AIM: Apolipoprotein A2 (apoA2) isoforms have been reported to undergo the aberrant processing in pancreatic cancer and pancreatic risk populations compared with that in healthy subjects. This study aimed to clarify whether apoA2 isoforms were as useful as N-benzoyl-p-aminobenzoic acid (BT-PABA) test for exocrine pancreatic dysfunction markers in patients with early chronic pancreatitis (ECP). METHODS: Fifty consecutive patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) (n = 18), with ECP (n = 20), and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 12) based on the Rome IV classification and the Japan Pancreatic Association were enrolled in this study. The enrolled patients were evaluated using endoscopic ultrasonography and endoscopic ultrasonography elastography. Five pancreatic enzymes were estimated. Pancreatic exocrine function was analyzed using the BT-PABA test. Lighter and heavier apoA2 isoforms, AT and ATQ levels were measured by enzyme-linked immunosorbent assay methods. RESULTS: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption and smoking among patients with AP-P, FD-P, and ECP. The BT-PABA test and lighter apoA2 isoform, AT level in the enrolled patients had a significant correlation (P < 0.01). The BT-PABA test in patients with ECP was significantly lower (P = 0.04) than that in AP-P. ApoA2-AT level in patients with ECP was lower than that in AP-P, albeit, insignificantly. Interestingly, apo A2-AT level was significantly (P = 0.041) associated with exocrine pancreatic insufficiency by multiple logistic regression analysis. CONCLUSIONS: ApoA2-AT level is a useful tool to evaluate exocrine pancreatic insufficiency in the early stage of chronic pancreatitis.

A systematic review and meta-analysis of the accuracy and methodology of the 13C mixed triglyceride breath test for the evaluation of pancreatic function.

INTRODUCTION: The diagnosis of pancreatic exocrine insufficiency (PEI) is challenging. The 13C mixed triglyceride breath test (13C MTGT) has emerged as a promising diagnostic method. However, there is need to assimilate high quality evidence to understand its accuracy and address variation in the conduct of the test. This systematic review aims to appraise the existing literature on the methodology and accuracy of the 13C MTGT. METHODS: A systematic literature search of PUBMED, MEDLINE, and EMBASE databases identified articles describing the use of the 13C MTGT in the analysis of pancreatic function in adults. Data extraction addressed each methodological step in detail. These were combined in a narrative synthesis. For quantitative analysis, those studies within this search that assessed the accuracy of the 13C MTGT were selected. RESULTS: 37 studies were included for qualitative review, 6 assessed sensitivity and specificity of the 13C MTGT against another measure of PEI and were included in quantitative synthesis. Areas with a majority consensus were pre-test overnight fasting, a test meal with a lipid load of at least 10 g, within-test control of exercise and dietary intake, breath sampling every 30 min and the preference of isotope ratio mass spectrometry (IRMS) for analysis. Good evidence suggests there is no benefit to extend the total timeframe of breath sampling beyond 6 h. Areas of uncertainty are a) Duration of PERT cessation b) the addition of metoclopramide, c) the ideal test meal and d) if the time frame can be shortened. Quantitative analysis among 6 studies demonstrated a pooled sensitivity and specificity of the 13C MTGT for diagnosing PEI of 0.84 (95% CI: 0.73-0.91) and 0.87 (95% CI: 0.79-0.93) respectively. CONCLUSION: There is yet to emerge a clear standard of breath test methodology that is validated for all causes of PEI and suitable for routine use. The accuracy of the 13C MTGT for diagnosing PEI is encouraging when compared to other measures. We present a suggested set protocol based on the current literature and identify areas that need further, high quality evidence. With refinement, the 13C MTGT could become a valuable, non-invasive PEI diagnostic tool that could be used outside of specialist centres.

Combination of high-density cholesterol level, elastic score, and severity of exocrine pancreatic dysfunction may be useful for a predictive factor for patients with early chronic pancreatitis.

BACKGROUND: This study aimed to clarify whether any risk factors including clinical characteristics, endosonographic features, and exocrine pancreatic dysfunction may be useful for a predictive factor for patients with early chronic pancreatitis. METHODS: A total of 163 consecutive patients that presented with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) (n = 46), early chronic pancreatitis (ECP) (n = 47), and asymptomatic patients with pancreatic enzyme abnormalities (AP-P) (n = 70) based on the Rome III classification and the Japan Pancreatic Association were included in this study. The enrolled patients were evaluated using endosonography (EUS) and EUS elastography. The levels of the five pancreatic enzymes were measured. Pancreatic exocrine function was analyzed using N-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA). RESULTS: There were no significant differences in clinical characteristics such as age, gender, body mass index, alcohol consumption, and smoking among patients with AP-P, FD-P, and ECP. The ratio of BT-PABA test less than 35% in patients with ECP was significantly (P = 0.043) higher than in AP-P patients. Elastic score was a useful tool to differentiate the FD-P group from the ECP group. The high-density cholesterol levels in patients with ECP were significantly lower than those in AP-P. In addition, the combination of total and high-density cholesterol levels, BT-PABA test, and elastic score has a higher area under the curve value (0.708) of patients with ECP than in the other groups. CONCLUSIONS: The combination of high-density cholesterol levels, elastic score, and severity of exocrine pancreatic dysfunction may be useful for a predictive factor for patients with ECP.

Pancreatic Elastography Predicts Endoscopic Secretin-Pancreatic Function Test Result in Patients With Early Changes of Chronic Pancreatitis: A Prospective, Cross-Sectional, Observational Study.

INTRODUCTION: The endoscopic pancreatic function test (ePFT) has been proposed for the evaluation of patients with suspected early chronic pancreatitis (CP) in the appropriate clinical context, but the cost and duration of the test limit its clinical applicability. Pancreatic secretion decreases as pancreatic fibrosis develops in CP. Pancreatic fibrosis can be quantified by endoscopic ultrasound-elastography (EUS-E). We aim at evaluating whether EUS-E correlates with and could replace ePFT for the evaluation of patients with suspected CP. METHODS: A prospective, cross-sectional, and observational study of patients with clinical suspicion of CP and inconclusive EUS findings was conducted. EUS-E and ePFT were performed. Diagnosis of CP was supported if the ePFT result (bicarbonate peak) was abnormally low (<80 mEq/L). Correlation between EUS-E (strain ratio [SR]) and ePFT results was analyzed by linear regression. Diagnostic accuracy of EUS-E for CP was calculated using ePFT as a reference method. RESULTS: Sixty-one patients were included and analyzed. The mean peak bicarbonate concentration at the ePFT was 63.8 ± 23.6 mEq/L, and it was abnormally low in 50 patients (82.0%). The mean SR was 3.85 ± 1.24. Correlation between SR and bicarbonate secretion was highly significant ( r = 0.715, P < 0.0001). Diagnostic accuracy of EUS-E for CP was 93.4%. DISCUSSION: The degree of pancreatic fibrosis as evaluated by EUS-E correlates significantly with the secretin-stimulated pancreatic secretion of bicarbonate in patients with clinical suspicion of CP and inconclusive EUS findings of the disease. EUS-E could replace ePFT for the evaluation of these patients in clinical practice.

Minimal Change Patients Versus Obvious Chronic Pancreatitis: A Comparison of Classical Secretin Stimulation Testing Results.

OBJECTIVES: The objective was to assess if the peak bicarbonate level during secretin stimulation testing (SST) differs between patients with minimal change (or small duct) chronic pancreatitis (CP) versus those with obvious CP (or large duct) versus those without CP. METHODS: Two hundred nineteen patient records at the University of Florida who had been referred for SST were analyzed for peak bicarbonate, total volume of juice collected, age, sex, and clinical presentation. RESULTS: Fifty-one patients with minimal change CP were identified. Thirty-three patients were felt to have advanced CP, and 135 patients did not have CP by clinical criteria. The peak bicarbonate and total volume of pancreatic juice collected was significantly different (P < 0.001) between all 3 groups by multiple comparison testing. The peak bicarbonate of advanced CP and minimal change groups was less than controls (P < 0.001). There was a significant difference (P < 0.05) on direct testing between peak bicarbonate in advanced CP and minimal change CP. CONCLUSIONS: The peak bicarbonate and volume measured during SST differs among patients with minimal change CP, advanced CP and in disease controls. These results could be useful in diagnosing minimal change/early CP.

Evaluation of pancreatic functions in cases of primary and secondary malnutrition.

BACKGROUND: This study assessed pancreatic functions by investigating fecal elastase-1 (FE-1) levels in stool specimens in children with primary and secondary malnutrition. METHODS: A total of 139 malnourished children who were hospitalized and followed up at a tertiary care pediatrics clinic and 23 healthy children with no known systemic disease or malnutrition were included in this study. Malnourished patients were divided into four groups according to underlying diagnosis including primary malnutrition (N.=51), cystic fibrosis (N.=44), celiac disease (N.=12) and secondary malnutrition (N.=32; remaining patients with various diagnoses). Patient's demographic characteristics and laboratory data were investigated. FE-1 levels of the patients and healthy subjects were evaluated. RESULTS: FE-1 levels in patients with cystic fibrosis, primary malnutrition, and celiac disease, and other patients with secondary malnutrition were significantly lower than those in the control group. CONCLUSIONS: Pancreatic enzymes are used due to pancreatic failure in cases of cystic fibrosis, and patients benefit considerably from treatment. This study shows that pancreatic failure may also occur in cases of primary and secondary malnutrition apart from cystic fibrosis, emphasizing the likelihood of pancreatic enzyme support to be useful in terms of pancreatic failure developing secondarily in cases of primary malnutrition.

Chronic pancreatitis for the clinician. Part 1: Etiology and diagnosis. Interdisciplinary position paper of the Societat Catalana de Digestologia and the Societat Catalana de Pàncrees. / Pancreatitis crónica para el clínico. Parte 1: etiología y diagnóstico. Documento de posicionamiento interdisciplinar de la Societat Catalana de Digestologia y la Societat Catalana de Pàncrees.

Chronic pancreatitis is a chronic fibroinflammatory disease of the pancreas with prevalence around 50 cases per 100,000 inhabitants. It appears to originate from diverse and yet mixed etiological factors. It shows highly variable presenting features, complication types and disease progression rates. Treatment options are as wide as the multiple personalized scenarios the disease might exhibit at a given time point. Some medical societies have developed guidelines for diagnosis and treatment based on scientific evidence. Although these efforts are to be acknowledged, the gathered level of evidence for any topic is usually low and, therefore, recommendations tend to be vague or weak. In the present series of position papers on chronic pancreatitis from the Societat Catalana de Digestologia and the Societat Catalana de Pàncrees we aimed at providing defined position statements for the clinician based on updated review of published literature and on interdisciplinary expert agreement. The final goal is to propose the use of common terminology and rational diagnostic/therapeutic circuits based on current knowledge. To this end 51 sections related to chronic pancreatitis were reviewed by 21 specialists from 6 different fields to generate 88 statements altogether. Statements were designed to harmonize concepts or delineate recommendations. Part 1 of this paper series discusses topics on aetiology and diagnosis of chronic pancreatitis. Main clinical features are abdominal pain, exocrine and endocrine insufficiency and symptoms derived from complications. Some patients remain symptom-free. Diagnosis (definitive, probable or uncertain) should be based on objective data obtained from imaging, histology, or functional tests.

Staging exocrine pancreatic dysfunction.

Digestive capacity of the gastrointestinal tract, largely but not wholly, depends on exocrine pancreatic function to achieve near complete digestion and absorption of ingested food. Coefficient of fat absorption (CFA), the proportion of ingested fat absorbed (normal >93%), reflects digestive capacity. Exocrine pancreatic insufficiency (EPI) is the state of insufficient digestive capacity (CFA <93%) caused by severe loss of pancreatic exocrine function despite variable compensation by upregulation of extra-pancreatic lipolysis. Fecal elastase 1 (FE1) level is the most widely used, though imperfect, non-invasive test of pancreatic enzyme output. Decline in pancreas enzyme output, or pancreatic exocrine dysfunction (EPD), has a variable correlation with measurable decline in CFA. EPI results in steatorrhea, weight loss and nutrient deficiency, which are mitigated by pancreatic enzyme replacement therapy (PERT). We propose a staging system for EPD, based on measurement of fecal elastase (FE1) and, if necessary, CFA and serum fat-soluble vitamin levels. In Stage I (Mild) EPD, FE1 is 100-200 mcg/gm; if steatorrhea is present, non-pancreatic causes are likely. In Stage II (Moderate) EPD), FE1 is < 100 mcg/gm without clinical and/or laboratory evidence of steatorrhea. In Stage III, there are marked reductions in FE1 and CFA, but vitamin levels remain normal (Severe EPD or EPI without nutritional deficiency). In Stage IV all parameters are abnormal (Severe EPD or EPI with nutritional deficiency). EPD stages I and II are pancreas sufficient and PERT may not be the best or first approach in management of early-stage disease; it needs further study to determine clinical utility. The term EPI refers strictly to EPD Stages III and IV which should be treated with PERT, with Stage IV requiring micronutrient supplementation as well.

Outcomes of Cystic Fibrosis Screening-Positive Infants With Inconclusive Diagnosis at School Age.

BACKGROUND AND OBJECTIVES: Cystic fibrosis (CF) screen-positive infants with an inconclusive diagnosis (CFSPID) are infants in whom sweat testing and genetic analysis does not resolve a CF diagnosis. Lack of knowledge about the health outcome of these children who require clinical follow-up challenges effective consultation. Early predictive biomarkers to delineate the CF risk would allow a more targeted approach to these children. METHODS: Prospective, longitudinal, multicenter, Canada-wide cohort study of CF positive-screened newborns with 1 to 2 cystic fibrosis transmembrane conductance regulator gene variants, of which at least 1 is not known to be CF-causing and/or a sweat chloride between 30 and 59 mmol/L. These were monitored for conversion to a CF diagnosis, pulmonary, and nutritional outcomes. RESULTS: The mean observation period was 7.7 (95% confidence interval 7.1 to 8.4) years. A CF diagnosis was established for 24 of the 115 children with CFSPID (21%) either because of reinterpretation of the cystic fibrosis transmembrane conductance regulator genotype or because of increase in sweat chloride concentration ≥60 mmol/L. An initial sweat chloride of ≥40 mmol/l predicted conversion to CF on the basis of sweat testing. The 91 remaining children with CFSPID were pancreatic sufficient and showed normal growth until school age. Pulmonary function as well as lung clearance index in a subgroup of children with CFSPID were similar to that of healthy controls. CONCLUSIONS: Children with CFSPID have good nutritional and pulmonary outcomes at school age, but rates of reclassifying the diagnosis are high. The initial sweat chloride test can be used as a biomarker to predict the risk for CF in CFSPID.

Laboratory Tests in the Patient with Abdominal Pain.

Abdominal pain is one of the most common presenting complaints to the emergency department (ED). More often than not, some degree of laboratory testing is used to narrow the differential diagnosis based on the patient's history and examination. Ordering practices are often guided by evidence, habit, consulting services, and institutional/regional culture. This review highlights relevant laboratory studies that may be ordered in the ED, as well as commentary on indications and diagnostic value of these tests.

Pancreatic lipase: why laboratory community does not take enough care of this clinically important test?

Although being the recommended laboratory test to diagnose acute pancreatitis, serum pancreatic lipase (LIP) is among the poorly standardized laboratory tests, and laboratory stakeholders often appear to not take enough care of the quality of its measurements. Here we discuss some important issues that, if not correctly managed and solved, make misdiagnosis of acute pancreatitis by using serum LIP a real possibility. First, the current unavailability of a suitable higher-order reference material to be used as common calibrator should be filled up to definitively improve the inter-method bias. Second, knowledge of the analytical characteristics that may explain the defective performance of LIP assays should be deepened. IVD manufacturers should be more explicit in providing this information, including description of their internal protocol for transferring LIP values from internal references to commercial calibrators. Third, recommended models for accurately estimating measurement uncertainty and reliably defining analytical performance specifications for LIP measurements should be applied. Finally, investments considering alternative options for measuring LIP (e.g., targeted to the development of automated LIP immunoassays) should be warranted. All involved stakeholders (standardization bodies, higher-order reference providers, in vitro diagnostics manufacturers, and laboratory professionals) should contribute to fill the existing gap.

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.

Endoscopic Pancreatic Drainage Improves Exocrine Pancreatic Function in Patients With Unresectable Pancreatic Cancer: A Double-Blind, Prospective, Randomized, Single-Center, Interventional Study.

OBJECTIVES: Exocrine pancreatic insufficiency is a frequent and clinically relevant complication of pancreatic cancer probably secondary to pancreatic duct obstruction. We aimed at evaluating the impact of endoscopic pancreatic drainage on pancreatic function in patients with unresectable pancreatic cancer. METHODS: A double-blind, prospective, randomized, single-center, interventional study was designed. Patients undergoing endoscopic retrograde cholangiopancreatography for jaundice secondary to unresectable pancreatic cancer were randomized to biliary drainage (group A) or biliopancreatic drainage (group B). Pancreatic function was evaluated by 13C-mixed triglyceride breath test before and 2 weeks after endoscopic retrograde cholangiopancreatography. Breath test result is expressed as 13C-cumulative recovery rate. Abdominal symptoms and nutritional markers were evaluated as secondary outcomes. RESULTS: Twenty patients were included. Sixteen patients had exocrine pancreatic insufficiency, and 13 completed the study (7 in group A and 6 in group B). The median absolute improvement of 13C-cumulative recovery rate was of 23.75% (interquartile range, 9.62-31.74) after biliopancreatic drainage compared with -1.92% (interquartile range, -4.17 to 13.92) after biliary drainage (P = 0.015). Nutritional markers improved after biliopancreatic drainage, but not after biliary drainage. CONCLUSIONS: Biliopancreatic and not biliary endoscopic drainage is associated with a significant improvement of exocrine pancreatic function in patients with unresectable pancreatic cancer.

Impaired exocrine pancreatic function in different stages of type 1 diabetes.

INTRODUCTION: Aim of this study was to investigate the pancreatic exocrine function in patients with type 1 diabetes (T1D) by multiple non-invasive tests. RESEARCH DESIGN AND METHODS: The study is a single-center, cross-sectional study of pancreatic exocrine function in adult patients with new-onset or long-standing T1D and healthy controls. RESULTS: Healthy controls, new-onset T1D, and long-standing T1D were similar for age at the time of the study, gender and body mass index (BMI) categories. Age of onset of T1D patients with long-standing disease was younger than that of patients with new-onset T1D (p<0.001). As expected, the three groups differed for C-peptide and hemoglobin A1c (HbA1c) levels. Lipase activity measured by 13C-mixed triglyceride breath test was reduced progressively, although not significantly, from controls to recent-onset T1D and long-standing T1D participants. Fecal elastase-1 was significantly lower in participants with T1D, either new onset or long standing. Pancreatic amylase, lipase, retinol binding protein and prealbumin were significantly different across the groups, with a significant trend toward lower values in long-standing T1D and intermediate values in new-onset T1D, while no differences were observed for total amylase. The markers of impaired exocrine function tests (fecal elastase-1, serum pancreatic amylase and lipase) and of nutritional status (retinol binding protein and prealbumin levels) correlated with the reduction of fasting and urinary C-peptide. CONCLUSIONS: Our results confirm that exocrine pancreatic impairment is a feature of T1D, with low fecal elastase-1, serum pancreatic amylase and lipase as specific markers, associated with reduced levels of nutritional indexes. Moreover, the evidence of more advanced insufficiency in long-standing disease reflects the chronic nature of this process, and its correlation with the residual ß-cell function suggests parallel pathways for the impairment of the endocrine and exocrine pancreatic function.

Glucose Metabolism After Pancreatectomy: Opposite Extremes Between Pancreaticoduodenectomy and Distal Pancreatectomy.

CONTEXT: The rate of glucose metabolism changes drastically after partial pancreatectomy. OBJECTIVE: This work aims to analyze changes in patients' glucose metabolism and endocrine and exocrine function before and after partial pancreatectomy relative to different resection types (Kindai Prospective Study on Metabolism and Endocrinology after Pancreatectomy: KIP-MEP study). METHODS: A series of 278 consecutive patients with scheduled pancreatectomy were enrolled into our prospective study. Of them, 109 individuals without diabetes, who underwent partial pancreatectomy, were investigated. Data were compared between patients with pancreaticoduodenectomy (PD, n = 73) and those with distal pancreatectomy (DP, n = 36). RESULTS: Blood glucose levels during the 75-g oral glucose tolerance test (75gOGTT) significantly decreased after pancreatectomy in the PD group (area under the curve [AUC] -9.3%, P < .01), and significantly increased in the DP population (AUC + 16.8%, P < .01). Insulin secretion rate during the 75gOGTT and glucagon stimulation test significantly decreased after pancreatectomy both in the PD and DP groups (P < .001). Both groups showed similar homeostasis model assessment of insulin resistance (HOMA-IR) values after pancreatectomy. Decrease in exocrine function quality after pancreatectomy was more marked in association with PD than DP (P < .01). Multiple regression analysis indicated that resection type and preoperative HOMA-IR independently influenced glucose tolerance-related postoperative outcomes. CONCLUSIONS: Blood glucose levels after the OGTT differed markedly between PD and DP populations. The observed differences between PD and DP suggest the importance of individualization in the management of metabolism and nutrition after partial pancreatectomy.

Pancreatic atrophy and exocrine insufficiency associate with the presence of diabetes in chronic pancreatitis patients, but additional mediators are operative.

OBJECTIVES: Diabetes mellitus is a frequent complication of chronic pancreatitis (CP) and has traditionally been considered to develop as a consequence of pancreatic islet cell loss. However, additional mechanisms may be operative including accumulation of pancreatic fat and fibrosis. We used advanced magnetic resonance imaging (MRI) to study pancreatic morphology and exocrine function in a reference population and in CP patients with and without diabetes. METHODS: This was a cross-sectional mono centre study. All subjects underwent advanced MRI including assessment of pancreatic ductal parameters (Cambridge classification and main pancreatic duct diameter), parenchymal parameters (DIXON technique and diffusion weighted imaging as proxies for pancreatic fat content and fibrosis, as well as pancreatic volume segmentation). Pancreatic exocrine function was determined as duodenal secretion following secretin stimulation and by the faecal elastase test. RESULTS: The study included 76 patients with definite CP of whom 23 (30.1%) had diabetes and 23 sex- and age matched healthy volunteers. Compared to their non-diabetic counterparts, diabetic patients were characterised by a low pancreatic volume (20 vs. 36 ml; p = .02) and impaired pancreatic exocrine function (faecal elastase 19 vs. 48 µg/g; p = .008), while no difference between patients with and without diabetes were seen in relation to MRI derived proxies for fibrosis and pancreatic fat accumulation and pancreatic duct parameters. A large proportion of non-diabetic patients (49%) had similar morphological and functional characteristics as patients with diabetes. CONCLUSION: Pancreatic atrophy and exocrine insufficiency are present in most CP patients with diabetes, but additional mediators seem to be operative in post pancreatitis diabetes mellitus.

Delayed Processing of Secretin-Induced Pancreas Fluid Influences the Quality and Integrity of Proteins and Nucleic Acids.

OBJECTIVES: Endoscopic pancreatic function tests are used to diagnose pancreatic diseases and are a viable source for the discovery of biomarkers to better characterize pancreatic disorders. However, pancreatic fluid (PF) contains active enzymes that degrade biomolecules. Therefore, we tested how preservation methods and time to storage influence the integrity and quality of proteins and nucleic acids. METHODS: We obtained PF from 9 subjects who underwent an endoscopic pancreatic function test. Samples were snap frozen at the time of collection; after 1, 2, and 4 hours on ice; or after storage overnight at 4°C with or without RNase or protease inhibitors (PIs). Electrophoresis and mass spectrometry analysis determined protein abundance and quality, whereas nucleic acid integrity values determined DNA and RNA degradation. RESULTS: Protein degradation increased after 4 hours on ice and DNA degradation after 2 hours on ice. Adding PIs delayed degradation. RNA was significantly degraded under all conditions compared with the snap frozen samples. Isolated RNA from PF-derived exosomes exhibited similar poor quality as RNA isolated from matched PF samples. CONCLUSIONS: Adding PIs immediately after collecting PF and processing the fluid within 4 hours of collection maintains the protein and nucleic acid integrity for use in downstream molecular analyses.

EUS pancreatic function testing and dynamic pancreatic duct evaluation for the diagnosis of exocrine pancreatic insufficiency and chronic pancreatitis.

BACKGROUND AND AIMS: EUS and endoscopic pancreatic function tests (ePFTs) may be used to diagnose minimal-change chronic pancreatitis (MCCP). The impact of evaluation for exocrine pancreatic insufficiency (EPI) and real-time assessment of EUS changes after intravenous secretin on the clinical diagnosis of MCCP is unknown. METHODS: Patients with suspected MCCP underwent baseline EUS assessment of the pancreatic parenchyma and measurement of the main pancreatic duct (B-MPD) in the head, body, and tail. Human secretin 0.2 µg/kg was given intravenously followed 4, 8, and 12 minutes later by repeat MPD (S-MPD) measurements. Duodenal samples at 15, 30, and 45 minutes were aspirated to assess bicarbonate concentration. Endoscopists rated the percentage clinical likelihood of chronic pancreatitis (1) before secretin; (2) after secretin but before aspiration; and (3) after bicarbonate results. RESULTS: A total of 145 consecutive patients (mean age, 44±13 years; 98 females) were diagnosed with EPI (n = 32; 22%) or normal exocrine pancreatic function (n = 131, 78%). S-MPD/B-MPD ratios in the tail 4 and 8 minutes after secretin were higher in the group with normal exocrine function. Ratios at other times, locations, and duodenal fluid volumes were similar between the 2 groups. A statistically significant change in the median percentage likelihood of chronic pancreatitis was noted after secretin in all groups. The sensitivity and specificity of EPI for the EUS diagnosis of chronic pancreatitis (≥5 criteria) were 23.4% (95% confidence interval, 12.3-38.0) and 78.6% (95% confidence interval, 69.1-86.2), respectively. CONCLUSION: Real-time EUS findings and ePFTs have a significant impact on the clinical assessment of MCCP. The diagnosis of EPI shows poor correlation with the EUS diagnosis of MCCP. (Clinical trial registration number: NCT01997476.).