Diagnosis Of Exocrine Pancreatic Insufficiency Research Articles

Exocrine pancreatic insufficiency as a possible predictor of pancreatic cancer development.

679 Background: Chronic and acute pancreatitis are established risk factors for pancreatic cancer. Chronic pancreatitis and pancreatic cancer are also common causes of exocrine pancreatic insufficiency (EPI), which is characterized by inadequate pancreatic secretion of exocrine digestive enzymes. Although the association between EPI and pancreatic cancer has been thought to be linked by preceding chronic pancreatitis, it is unclear if EPI, regardless of etiology, is a risk factor or early marker for pancreatic cancer or cancer in general. Methods: This is a retrospective observational study utilizing the electronic health records of Ochsner Health System, Louisiana, over a 3-year period from January 2017 to January 2020 to identify patients with a diagnosis of EPI by ICD-10 codes. Two cohorts were reviewed: patients with EPI (n=677) and patients with pancreatitis (n=1852). Both history of acute and/or chronic pancreatitis were included in the pancreatitis cohort. The cohorts were compared based on cancer prevalence at the start and end of the 3 year observation period. Results: In the EPI cohort, the cancer prevalence was 15.95% (108) at start, and 43.9% (297) at end, (p<0.05); and pancreatic cancer prevalence at start was 6.65% (123) and 29.8% (552) at end (p<0.05). In the pancreatitis cohort, the cancer prevalence was 5.4% (100) at start and 15.9% (294) at end (p<0.05); and pancreatic cancer 0.8% at start and 5% at end (p<0.05). Conclusions: Over a 3 year period, the rise in prevalence of general cancer and pancreatic cancer was higher in the EPI cohort compared to the pancreatitis cohort. Additionally, there was a statistically significant 2.8-fold increase in prevalence of cancer diagnosis and 4.5-fold increase in prevalence of pancreatic cancer diagnosis in the EPI cohort over the 3 year observation period. Though this is an observational study, it suggests the possibility that EPI, regardless of etiology, may be an independent predictor/risk factor for the development of future cancer in general and pancreatic cancer in particular. In addition it appears that this risk potential is substantively greater than that from a history of pancreatitis alone.

Prevalence of cancer and alcohol use in patients with exocrine pancreatic insufficiency compared to patients with cystic fibrosis.

680 Background: Cystic fibrosis (CF), the most prevalent genetic disorder among persons of European decent, is an autosomal recessive disorder due to CFTR gene mutations which lead to abnormally viscid exocrine secretions of the pancreas and other exocrine glands of the body. Exocrine pancreatic insufficiency (EPI) is a condition seen in ~85% of CF patients, in which the pancreas is unable to secrete adequate amounts of digestive enzymes. Although most patients with CF develop EPI, not all cases of EPI are caused by CF. Other risk factors for EPI include acute or chronic pancreatitis which may be triggered by alcohol, among other etiologies. Some studies suggest alcohol use as a possible independent risk factor for development of various cancers. Given these associations, we sought to characterize the prevalence of both alcohol use and cancer in patients with EPI vs patients with CF. Methods: A retrospective observational study was performed using electronic health records in Ochsner System, Louisiana, over a 3 year period: January 2017 to January 2020. Two cohorts were reviewed: patients with EPI excluding CF (n=596) and patients with CF (n=81). Results: While there was no significant difference in the prevalence of cancer at start vs end of the 3 year observation period in the CF cohort (4.1% at start, 7.2% at end), the prevalence of cancer was significantly greater among patients in the EPI cohort, both at start and end of the 3 year period: 15.95% at start, 43.9% at end (p <0.05). Also, while there was no significant change in alcohol use over the 3 year period for the CF cohort, the prevalence of alcohol use was significantly lower in CF cohort (0.45% at start, 2.2% at end) compared to EPI cohort which showed significant increase in alcohol use over the observation period: 7.7% at start vs 16% at end (p <0.05). Conclusions: There was a significantly higher prevalence of cancer in the EPI cohort compared to the CF cohort; while this may be due to higher prevalence of pancreatic cancer associated with EPI compared to CF, it does not explain the entirety of this observation. Not only was there a significantly higher prevalence of alcohol use in EPI cohort compared to CF cohort, but over the 3 year observation there was a 2-fold increase in prevalence of alcohol use within patients who already had a diagnosis of EPI. Within the EPI cohort, the observed increase in cancer prevalence and the increase in alcohol warrant further investigation into which factors unique to EPI patients without CF may modulate these social and health risk indices.

Diagnostic accuracy of faecal elastase-1 test for the diagnosis of pancreatic exocrine insufficiency: A systematic review and meta-analysis

Diagnostic accuracy of faecal elastase-1 test for the diagnosis of pancreatic exocrine insufficiency: A systematic review and meta-analysis

Diagnostic accuracy of faecal elastase-1 test for the diagnosis of pancreatic exocrine insufficiency: a systematic review and meta-analysis

Diagnostic accuracy of faecal elastase-1 test for the diagnosis of pancreatic exocrine insufficiency: a systematic review and meta-analysis

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

IntroductionThe 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. MethodsA 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. Results37 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. ConclusionThere 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.

The clinical and laboratory impact of reporting faecal elastase-1 in watery stool samples.

Low faecal elastase-1 (FE-1) results are suggestive of pancreatic insufficiency, but watery diarrhoea may lead to falsely low results. FE-1 results reported on watery samples over a three-year period were reviewed. Results in watery samples were compared to those from a formed sample. The follow-up of patients in whom an FE-1 result ≤199 ug/g stool (Schebo ELISA) was reported on a watery sample was also reviewed. In total, 288 watery samples were identified. All results (19/19) ≥200 ug/g in watery samples were also ≥200 ug/g when measured in a formed sample from the same patient. There were 41 results ≤199 ug/g in watery samples, of which 29 (71%) were ≥200 ug/g when measured in a formed sample. Thirty-seven patients with a single FE-1 value ≤199 ug/g from a watery sample were followed up. Pancreatic Enzyme Replacement Therapy (PERT) was commenced in 15 patients. This was inappropriate in at least one patient. Reporting practice was subsequently changed to not report FE-1 values ≤199 ug/g in watery samples. This change was assessed after 12 months. Repeat samples were received from 15/56 (27%) of patients. Overall, 10/15 (67%) of samples were ≥200 ug/g on repeat. PERT was not commenced inappropriately in any of these patients. There is value in measuring FE-1 in watery samples, as 144/288 (50%) of watery samples analysed were ≥200 ug/g, enabling a diagnosis of exocrine pancreatic insufficiency to be excluded. Not reporting FE-1 values ≤199 ug/g in a first-time watery stool samples appears clinically safe and has potentially reduced inappropriate diagnoses and prescribing.

Psychosomatic disorders in chronic pancreatitis

Diagnosis of pancreatic exocrine insufficiency (PEI) is hindered by methodological difficulties of pancreatic function tests. The probability of PEI in chronic pancreatitis (CP) increases as pancreatic fibrosis develops. Pancreatic fibrosis in CP may be quantified by EUS elastography.To evaluate whether EUS-elastography can predict PEI in patients with CP.Prospective, observational study.Department of Gastroenterology, University Hospital of Santiago de Compostela, Spain.Patients diagnosed with CP based on EUS and magnetic resonance imaging and MRCP findings.Diagnosis of PEI was based on the 13C-mixed triglyceride breath test. EUS-elastography was performed with PENTAX echoendoscopes and Hitachi-Preirus US platform. Two areas were selected for elastographic evaluation: area A corresponds to the pancreatic parenchyma and area B to a soft peripancreatic reference area. The quotient B/A (strain ratio [SR]) was considered the elastographic result.Pancreatic SR in CP patients with and without PEI.A total of 115 patients with CP (mean age, 50.2 years, range, 21-81; 92 male) of different etiologies were included; 35 patients (30.4%) had PEI. Pancreatic SR was higher in patients with PEI (4.89; 95% confidence interval, 4.36-5.41) than in those with a normal breath test result (2.99; 95% confidence interval, 2.82-3.16) (P < .001). A direct relationship was found between the SR and the probability of PEI, which increases from 4.2% in patients with an SR less than 2.5 to 92.8% in those with an SR greater than >5.5.Single-center study.The degree of pancreatic fibrosis as measured by EUS-guided elastography allows quantification of the probability of PEI in patients with CP.

Changes of oral and duodenal microbiota in patients with pancreatic cancer are possible diagnostic and prognostic biomarkers

Diagnosis of pancreatic exocrine insufficiency (PEI) is hindered by methodological difficulties of pancreatic function tests. The probability of PEI in chronic pancreatitis (CP) increases as pancreatic fibrosis develops. Pancreatic fibrosis in CP may be quantified by EUS elastography.To evaluate whether EUS-elastography can predict PEI in patients with CP.Prospective, observational study.Department of Gastroenterology, University Hospital of Santiago de Compostela, Spain.Patients diagnosed with CP based on EUS and magnetic resonance imaging and MRCP findings.Diagnosis of PEI was based on the 13C-mixed triglyceride breath test. EUS-elastography was performed with PENTAX echoendoscopes and Hitachi-Preirus US platform. Two areas were selected for elastographic evaluation: area A corresponds to the pancreatic parenchyma and area B to a soft peripancreatic reference area. The quotient B/A (strain ratio [SR]) was considered the elastographic result.Pancreatic SR in CP patients with and without PEI.A total of 115 patients with CP (mean age, 50.2 years, range, 21-81; 92 male) of different etiologies were included; 35 patients (30.4%) had PEI. Pancreatic SR was higher in patients with PEI (4.89; 95% confidence interval, 4.36-5.41) than in those with a normal breath test result (2.99; 95% confidence interval, 2.82-3.16) (P < .001). A direct relationship was found between the SR and the probability of PEI, which increases from 4.2% in patients with an SR less than 2.5 to 92.8% in those with an SR greater than >5.5.Single-center study.The degree of pancreatic fibrosis as measured by EUS-guided elastography allows quantification of the probability of PEI in patients with CP.

Faecal elastase testing and factors linked with development of pancreatic exocrine insufficiency in diabetes: the Belfast Trust experience

AbstractBackground: Pancreatic exocrine insufficiency (PEI) is characterised by inadequate secretion of pancreatic enzymes and can result in significant gastrointestinal symptoms, malabsorption and increased morbidity.Aims: To evaluate testing for PEI (with faecal elastase – FEL‐1) among patients with diabetes mellitus in the Belfast Trust, and to identify factors that were associated with the development of PEI.Methods: Clinical and laboratory data were obtained from electronic health care records. PEI was assessed by FEL‐1. Based on FEL‐1 levels (μg/g faeces), patients were categorised to have severe PEI (&lt;100), moderate PEI (100–200) and normal (&gt;200). A retrospective analysis of all FEL‐1 samples in patients with diabetes mellitus/pre‐diabetes between 1 February 2019 and 1 February 2020 was undertaken.Results: Of the 536 FEL‐1 samples analysed by the Belfast Trust over the 12‐month period, 162 (30%) were from diabetic or pre‐diabetic patients. A total of 128 (80%) had normal FEL‐1 results, nine (5%) moderate PEI, and 25 (15%) severe PEI. Of the 34 with PEI, 30/34 (88%) had gastrointestinal symptoms at diagnosis of PEI. For those with PEI, three had type 1 diabetes, 15 had type 2 diabetes, 16 had secondary diabetes mellitus; 28/34 (82%) were not on pancreatic enzyme replacement therapy previously. Source of testing for those confirmed with PEI included inpatients (n=12), general practice patients (n=5) and outpatients (n=17). PEI was associated more with male gender, those with type 3c diabetes (pancreatic diabetes) and worse glycaemic control.Summary: From our cohort, 1 in 4 FEL‐1 samples sent from patients with diabetes had PEI. There is potential for targeted screening for symptoms in this population which could increase diagnostic rates of PEI and subsequent treatment with pancreatic enzyme replacement therapy. Copyright © 2022 John Wiley &amp; Sons.

The pancreatic exocrine function in patients with pancreatic endocrine insufficiency: the evaluation with cine-dynamic magnetic resonance cholangiopancreatography using a spatially selective inversion-recovery pulse and T1 mapping

PurposeTo evaluate the association of the pancreatic exocrine function estimated by cine-dynamic magnetic resonance cholangiopancreatography (MRCP) using a spatially selective inversion-recovery (IR) pulse with the pancreatic endocrine function estimated by the T1 relaxation time of the pancreatic parenchyma and HbA1c values.Materials and methodsForty-three patients with suspected hepatobiliary or pancreatic diseases were included. Patients were classified into three groups: HbA1c < 5.7% (normal group), 5.7% ≤ HbA1c < 6.5% (prediabetes group), and HbA1c ≥ 6.5% (diabetes group). The frequency of the secretory flow of the pancreatic juice was observed within the area of the IR pulse, and the moving distance (mean secretion grade) of the pancreatic juice inflow within the area of the IR pulse on cine-dynamic MRCP, and the T1 relaxation time of the pancreatic parenchyma on the T1 map images were assessed. The MR imaging measurements were compared using Spearman’s rank correlation coefficient analysis and the Kruskal–Wallis and Mann–Whitney U tests.ResultsBoth the mean secretion grade and frequency of the pancreatic secretory inflow had a significant negative correlation with the T1 relaxation time of the pancreatic parenchyma (r = − 0.335, p = 0.028 and r = − 0.305, p = 0.047, respectively) and HbA1c values (r = − 0.308, p = 0.044 and r = − 0.313, p = 0.041, respectively). Both the mean secretion grade and frequency of the pancreatic secretory inflow in the elevated HbA1c (prediabetes and diabetes) group were significantly lower than those in the normal group (p = 0.030 and p = 0.029, respectively).ConclusionThe pancreatic exocrine function estimated by cine-dynamic MRCP was significantly lower in patients with prediabetes and diabetes than in controls. Cine-dynamic MRCP with a spatially selective IR pulse may be useful for the early diagnosis of pancreatic exocrine insufficiency in patients with pancreatic endocrine insufficiency.

Serum feline pancreatic lipase immunoreactivity and trypsin-like immunoreactivity concentrations in cats with experimentally induced chronic kidney disease.

BackgroundSerum feline pancreatic lipase immunoreactivity (fPLI) and trypsin‐like immunoreactivity (fTLI) concentrations are commonly used in cats for the evaluation of pancreatic disease. The effect of kidney disease on these tests in cats are unknown.ObjectiveTo investigate the effect of experimentally induced chronic kidney disease (CKD) on serum fPLI and fTLI concentrations.AnimalsSurplus serum samples from 20 cats with CKD experimentally induced for an unrelated project and a group of healthy control cats.MethodsSerum fTLI and fPLI concentrations were compared between groups.ResultsMean (±SD) serum fTLI concentrations in 20 cats with CKD (117.8 ± 63.6 μg/L) were significantly higher than those in healthy cats (n = 32; 46.9 ± 17.5 μg/L; P < .0001). Serum fTLI concentrations in cats with CKD were above the upper limit of the reference interval in 13 of 20 cats (65%). Serum fPLI concentrations were not significantly different between cats with induced CKD (n = 18; 8.6 μg/L; range, 5.4‐9.9 μg/L) and healthy cats (n = 41; 7.4 μg/L; range, 5.0‐15.2 μg/L; P = .12). All cats with experimentally induced CKD had serum fPLI concentrations within the reference interval.Conclusions and Clinical ImportanceDecreased renal function has a clinically relevant impact on serum fTLI concentrations and potentially could interfere with a diagnosis of exocrine pancreatic insufficiency (EPI). Serum fPLI concentration was not affected by experimentally induced CKD and thus serum fPLI may be used for the diagnosis of pancreatitis in cats with kidney disease. Additional studies are needed to verify these results in cats with naturally occurring CKD.

Untargeted analysis of the serum metabolome in cats with exocrine pancreatic insufficiency.

Exocrine pancreatic insufficiency (EPI) causes chronic digestive dysfunction in cats, but its pathogenesis and pathophysiology are poorly understood. Untargeted metabolomics is a promising analytic methodology that can reveal novel metabolic features and biomarkers of clinical disease syndromes. The purpose of this preliminary study was to use untargeted analysis of the serum metabolome to discover novel aspects of the pathobiology of EPI in cats. Serum samples were collected from 5 cats with EPI and 8 healthy controls. The diagnosis of EPI was confirmed by measurement of subnormal serum feline trypsin-like immunoreactivity (fTLI). Untargeted quantification of serum metabolite utilized ultra-high-performance liquid chromatography-tandem mass spectroscopy. Cats with EPI had significantly increased serum quantities of long-chain fatty acids, polyunsaturated fatty acids, mevalonate pathway intermediates, and endocannabinoids compared with healthy controls. Diacylglycerols, phosphatidylethanolamines, amino acid derivatives, and microbial metabolites were significantly decreased in cats with EPI compared to healthy controls. Diacyclglycerols and amino acid metabolites were positively correlated, and sphingolipids and long-chain fatty acids were negatively correlated with serum fTLI, respectively. These results suggest that EPI in cats is associated with increased lipolysis of peripheral adipose stores, dysfunction of the mevalonate pathway, and altered amino acid metabolism. Differences in microbial metabolites indicate that feline EPI is also associated with enteric microbial dysbiosis. Targeted studies of the metabolome of cats with EPI are warranted to further elucidate the mechanisms of these metabolic derangements and their influence on the pathogenesis and pathophysiology of EPI in cats.

Untargeted Metabolomics for the Diagnosis of Exocrine Pancreatic Insufficiency in Chronic Pancreatitis.

Background and Objectives: The clinical manifestations and course of chronic pancreatitis (CP) are often nonspecific and variable, hampering diagnosis of the risk of exocrine pancreatic insufficiency (EPI). Development of new, reproducible, and non-invasive methods to diagnose EPI is therefore a major priority. The objective of this metabolomic study was to identify novel biomarkers associated with EPI. Materials and Methods: We analyzed 53 samples from patients with CP, 32 with and 21 without EPI, using an untargeted metabolomics workflow based on hydrophilic interaction chromatography coupled to high-resolution mass spectrometry. Principal component and partial least squares-discriminant analyses showed significant between-group differentiation, and univariate and multivariate analyses identified potential candidate metabolites that significantly differed between samples from CP patients with EPI and those without EPI. Results: Excellent results were obtained using a six-metabolic panel to diagnose the presence of EPI in CP patients (area under the ROC curve = 0.785). Conclusions: This study confirms the usefulness of metabolomics in this disease setting, allowing the identification of novel biomarkers to differentiate between the presence and absence of EPI in CP patients.

Breath testing for the diagnosis of pancreatic disease.

Pancreatic function tests are mainly used for the diagnosis of exocrine pancreatic insufficiency (EPI) in patients with pancreatic diseases or after pancreatic or gastric surgery. Breath tests evaluate not just pancreatic secretion but the digestion capacity of the pancreas. These tests are good candidates for the diagnosis of EPI as they are noninvasive, accurate and easy to apply to clinical practice. The C-labelled mixed triglyceride (MTG) breath test has been optimized and validated against adequate reference methods for the diagnosis of EPI in patients with chronic pancreatitis and for the evaluation of the efficacy of pancreatic enzyme replacement therapy (PERT). In addition, reported C-MTG breath test results in patients with other pancreatic diseases and after pancreatic and gastric surgery support the accuracy and clinical applicability of this test. The evidence of pancreatic function breath tests with other C-labelled substrates is limited. Increasing evidence supports the accuracy and clinical usefulness of the C-MTG breath test for the diagnosis of EPI and the evaluation of the efficacy of PERT in different clinical conditions. Commercial availability of this test is required for a wide clinical use. The use of optimized and validated breath test protocols is mandatory.

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

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. 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. 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. 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.).

1873-P: Glycemic Impact of Pancreatic Enzyme Replacement in Patients with Diabetes and Exocrine Pancreatic Insufficiency: A Case Series

Some patients with type 2 diabetes (T2DM) and/or pancreatogenous diabetes have exocrine pancreatic insufficiency (EPI). The impact of pancreatic enzyme replacement (PER) on diabetes (DM) control is largely undocumented and unknown. We present 4 cases suggesting PER may positively impact DM glycemic and lipids. Case 1 is a 46 yr Caucasian (C) man with T2DM and recurrent gall stone pancreatitis. Prior to onset his HBA1c was between 6.3-7.4 but with recurrent episodes reached peak of 10.8. He was diagnosed with chronic pancreatitis with EPI and commenced PER. After 3 mths on PER his HBA1c was 6.7 with resolution of hypertriglyceridemia (HTG) and improved total cholesterol (TC). Case 2 is a 57 yr old C man with T2DM and episodic HTG related pancreatitis. He had erratic medication access due to insurance limitations. He was recently diagnosed with EPI but initially could not afford PER. HBA1c at diagnosis of EPI was 9.7 with elevated TC and HTG. When he secured PER, within 8 wks of use HBA1c reduced to 7.6 with improved HTG and TC. Case 3 is a 24 yr old C man with known cystic fibrosis and cystic fibrosis related DM. Initial HBA1c was 8.6 and he had been of PER voluntarily for yrs. He had features of EPI and was urged to resume PER which he did. At 4 mth follow up after restarting PER his HBA1c was 6.4 with improvement in HTG. Case 4 is a 36 yr old C man with prior well controlled T2DM and known MEN-1. His prior mean HBA1c was 6.7. Due to recurrent bouts of severe hypoglycemia in the prior 2 yrs work up revealed multiple pancreatic insulinomas for which he had partial pancreatectomy. His DM control declined with peak HBA1c of 11.3. He developed symptoms of EPI and was commenced on PER. 3mths after starting PER his HBA1c was 7.1 with resolution of HTG and improved TC. Early recognition of EPI in patients with DM is important. Commencement of PER in such patients may positively impact glycemia and dyslipidemia especially HTG. Further study of the relationship of PER to DM metabolic control is warranted. Disclosure G.I. Uwaifo: None.

Secretin-Enhanced Magnetic Resonance Cholangiopancreatography - A Reliable Approach to Assess Exocrine Pancreatic Function?

Objectives: To investigate the relation between exocrine pancreatic function and secretin-stimulated magnetic resonance cholangiopancreatography (sMRCP) fluid volumes and its concordance to pancreatic elastase using a case-control approach. Methods: Navigator-triggered T2-weighted 3D-turbo-spin-echo sMRCP was performed on a 1·5-T-system in 977 subjects including volunteers without a history of pancreatitis (group: A n=917) and chronic pancreatic disorder patients without (group: B, n=32) and with diagnosis of exocrine pancreatic insufficiency (EPI) (group: C, n=28). After intravenous administration of 1 unit/kg secretin duodenal filling was graded (0-3) and quantified as sMRCP fluid volume. According to pancreatic elastase ELISA subjects were grouped as severe (<100 μg/g) and moderate (100-200 μg/g) pancreatic elastase insufficiency (PEI). Statistic evaluation comprised Kruskal-Wallis Test, multinomial logistic, linear regression and area-under-the-curve (AUC) analysis. Findings: sMRCP fluid volume was lower in patients with pancreatic disorders compared to controls (P=0·001), but independent of the presence of PEI. The odds ratio of a reduced grading of duodenal filling was higher in patients with EPI (group: C compared to controls) (P=0·001) but not significantly different between controls and patients without EPI (group: B P=0·911) or between both patient groups (group: B versus group: C P=0·059). There was only a small association of sMRCP fluid volume with pancreatic elastase (R2=0·04,P=0·001). AUCs of sMRCP fluid volume were 0·967 (95%CI 0·950-0·985) to detect EPI and 0·581 (95% CI 0·471-0·691) to detect severe PEI. Interpretation: Static sMRCP allows assessment of exocrine pancreatic function and can differentiate patients with diagnosis of EPI from volunteers, but is not suitable for screening of patients with PEI because of its discordance to pancreatic elastase. Funding Statement: The work is part of the Community Medicine Research net, which was funded by following institutions: Federal Ministry of Education and Research (grants 01ZZ9603, 01ZZ0103, 01ZZ0403, 01ZZ0701, 03ZIK012), Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, Federal Ministry of Nutrition, Agriculture and Consumer’s Safety (07HS003), German Research Foundation (projects Gr 1912/5-1, Ko 799/5-1, Vo 955/5-1, Vo 955/6-1, Vo 955/10-1), Competence Network Heart Failure (01GI0205), Competence Network Diabetes (01GI0855), German Asthma and COPD Network (COSYCONET; BMBF 01GI0883), Genopathomik (BMBF FZK 03138010), Alfried Krupp von Bohlen und Halbach Foundation, Alexander v. Humboldt Foundation, Leibniz Society, Siemens AG, Health Care Sector (Erlangen, Germany), Pfizer Pharma GmbH (SBU Endocrinology and Ophthalmology; Berlin Germany), Novo Nordisk (Mainz, Germany), Data Input GmbH (Darmstadt, Germany), GABA International AG (Therwil, Switzerland), Imedos Systems (Jena, Germany) and Heinen and Lowenstein (Bad Ems, Germany). Declaration of Interests: There are no conflicts of financial interest. Ethics Approval Statement: The local ethics committee approved the SHIP study, and written informed consent was obtained from all participating subjects before study inclusion.

Update on the diagnosis and management of exocrine pancreatic insufficiency.

Exocrine pancreatic insufficiency (EPI) is characterized by inadequate pancreatic enzyme delivery to the small intestine Exocrine pancreatic insufficiency (EPI) is characterized by inadequate pancreatic enzyme delivery to the small intestine, resulting in malabsorption. Clinical manifestations of EPI are often nonspecific and can lead to lack of timely recognition and diagnosis. Central to this clinical dilemma is the lack of highly accurate or specific testing which leads to misdiagnosis and suboptimal treatment. Identification of high-risk patients is key in the diagnosis of EPI and this includes patients with pancreatic parenchyma disorders such as chronic pancreatitis, pancreatic malignancy, cystic fibrosis, and those undergoing pancreatic resection for benign and malignant disease. Less recognized are the number of additional conditions which may also have EPI as a consequence. Owing to an increase in morbidity and impaired quality of life associated with this condition, goals of treatment have been aimed at repleting exocrine enzyme deficiency by oral pancreatic enzyme replacement therapy (PERT). The basis of PERT is to provide activated digestive enzymes to the small bowel during the prandial period, mainly, leading to sufficient absorption of fat and fat-soluble vitamins. The benefits of PERT have been shown to go beyond the improvement in signs and symptoms associated with EPI and include decreasing prevalence of osteopathy and improving survival outcomes in subsets of patients with this condition. However, despite the overall benefits in treatment, the diagnosis and management of EPI are suboptimal. Current literature suggests patients at high risk of developing EPI are not tested and those who are diagnosed are not treated with adequate dosages. In this review, we highlight patients who are at high risk for the development of EPI, analyze consequences and treatment of this disorder, review rationale for enzyme replacement therapy, and examine current evidence for treatment optimization.

Management of Exocrine Pancreatic Insufficiency in Children.

The diagnosis of exocrine pancreatic insufficiency (EPI) can be difficult, as symptoms may be nonspecific. A delayed diagnosis of EPI can negatively impact health through poor weight gain, impaired growth, and malabsorption of nutrients. Because of active growth and development, children are more vulnerable to the consequences of untreated EPI. Pancreatic enzyme replacement therapy is the cornerstone of management and offers both symptomatic relief and improvement in clinical outcomes. Additionally, a high-energy diet with unrestricted fat and supplementation with fat-soluble vitamins is often required to optimize growth and prevent nutrition deficiencies. Cystic fibrosis (CF) is the most common condition in children that causes EPI, and improvement in nutrition management is associated with improved pulmonary function and increased survival. Currently, the management of other conditions leading to EPI in children is not well studied, and inferences from the CF literature are often necessary in caring for these patients.

Pancreatogenic diabetes vice versa: exocrine pancreatic insufficiency against the background of diabetes mellitus

The analysis has been performed for the normal physiological interrelations of exocrine and endocrine pancreatic parenchyma. There were elucidated literature data regarding pathogenesis, clinical peculiarities, treatment of pancreatogenic diabetes mellitus and exocrine pancreatic insufficiency secondary to the diabetes mellitus. It has been established that fecal elastase‑1 is an ideal biomarker for the diagnosis of exocrine pancreatic insufficiency in patients with type‑2 diabetes mellitus. The study results have been demonstrated, testifying a strong association of diabetes with the low fecal elastase‑1 levels, as well as direct correlation between levels of fecal elastase‑1 and C-peptide, lipase, C-reactive protein levels, body mass index, total 25(OH) vitamin D. The authors presented data regarding the existence of two intra-pancreatic axes of interconnections: one is involved in the regulation of insulin-mediated enzyme production via insulin-acinar axis; and another provides insulin release on account of the pancreatic enzymes via acini-insular axis. The concept of acini-islet-acinar axis has been presented. Thus, the exocrine pancreatic insufficiency can be considered as s complication of diabetes mellitus. The pathogenetic ground has been provided for the expediency of Creon indication in type 3 diabetes mellitus and for the treatment of exocrine pancreatic insufficiency in patients with diabetes mellitus. The Pancreatin therapy has been proved as a safe treatment for the patients with diabetes mellitus and exocrine pancreatic dysfunction.