OBJECTIVE: Magnetic resonance (MR) imaging with secretin stimulation (MR-PFTs) is a non-invasive test for pancreatic exocrine function based on assessing the volume of secreted bowel fluid in vivo. Adoption of this methodology in clinical care and research is largely limited to qualitative assessment of secretion as current methods for secretory response quantification require manual thresholding and segmentation of MR images, which can be time-consuming and prone to interrater variability. We describe novel software (PFTquant) that preprocesses and thresholds MR images, performs heuristic detection of non-bowel fluid objects, and provides the user with intuitive semi-automated tools to segment and quantify bowel fluid in a fast and robust manner. We evaluate the performance of this software on a retrospective set of clinical MRIs.
METHODS: Twenty MRIs performed in children (< 18 years) were processed independently by two observers using a manual technique and using PFTquant. Interrater agreement in measured secreted fluid volume was compared using intraclass correlation coefficients, Bland-Altman difference analysis, and Dice similarity coefficients.
RESULTS: Interrater reliability of measured bowel fluid secretion using PFTquant was 0.90 (0.76-0.96 95% C.I.) with - 4.5 mL mean difference (-39.4-30.4 mL 95% limits of agreement) compared to 0.69 (0.36-0.86 95% C.I.) with - 0.9 mL mean difference (-77.3-75.5 mL 95% limits of agreement) for manual processing. Dice similarity coefficients were better using PFTquant (0.88 +/- 0.06) compared to manual processing (0.85 +/- 0.10) but not significantly (p = 0.11). Time to process was significantly (p < 0.001) faster using PFTquant (412 +/- 177 s) compared to manual processing (645 +/- 305 s).
CONCLUSIONS: Novel software provides fast, reliable quantification of secreted fluid volume in children undergoing MR-PFTs. Use of the novel software could facilitate wider adoption of quantitative MR-PFTs in clinical care and research.

Exocrine pancreatic insufficiency (EPI) is a disorder caused by the failure of the pancreas to deliver a minimum/threshold level of specific pancreatic digestive enzymes to the intestine, leading to the maldigestion of nutrients and macronutrients, resulting in their variable deficiencies. EPI is frequently underdiagnosed and, as a result, patients are often not treated appropriately. There is an urgent need to increase awareness of and treatment for this condition. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review was to provide Best Practice Advice on the epidemiology, evaluation, and management of EPI.
This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: EPI should be suspected in patients with high-risk clinical conditions, such as chronic pancreatitis, relapsing acute pancreatitis, pancreatic ductal adenocarcinoma, cystic fibrosis, and previous pancreatic surgery. BEST PRACTICE ADVICE 2: EPI should be considered in patients with moderate-risk clinical conditions, such as duodenal diseases, including celiac and Crohn\'s disease; previous intestinal surgery; longstanding diabetes mellitus; and hypersecretory states (eg, Zollinger-Ellison syndrome). BEST PRACTICE ADVICE 3: Clinical features of EPI include steatorrhea with or without diarrhea, weight loss, bloating, excessive flatulence, fat-soluble vitamin deficiencies, and protein-calorie malnutrition. BEST PRACTICE ADVICE 4: Fecal elastase test is the most appropriate initial test and must be performed on a semi-solid or solid stool specimen. A fecal elastase level <100 μg/g of stool provides good evidence of EPI, and levels of 100-200 μg/g are indeterminate for EPI. BEST PRACTICE ADVICE 5: Fecal elastase testing can be performed while on pancreatic enzyme replacement therapy. BEST PRACTICE ADVICE 6: Fecal fat testing is rarely needed and must be performed when on a high-fat diet. Quantitative testing is generally not practical for routine clinical use. BEST PRACTICE ADVICE 7: Response to a therapeutic trial of pancreatic enzymes is unreliable for EPI diagnosis. BEST PRACTICE ADVICE 8: Cross-sectional imaging methods (computed tomography scan, magnetic resonance imaging, and endoscopic ultrasound) cannot identify EPI, although they play an important role in the diagnosis of benign and malignant pancreatic disease. BEST PRACTICE ADVICE 9: Breath tests and direct pancreatic function tests hold promise, but are not widely available in the United States. BEST PRACTICE ADVICE 10: Once EPI is diagnosed, treatment with pancreatic enzyme replacement therapy (PERT) is required. If EPI is left untreated, it will result in complications related to fat malabsorption and malnutrition, having a negative impact on quality of life. BEST PRACTICE ADVICE 11: PERT formulations are all derived from porcine sources and are equally effective at equivalent doses. There is a need for H2 or proton pump inhibitor therapy with non-enteric-coated preparations. BEST PRACTICE ADVICE 12: PERT should be taken during the meal, with the initial treatment of at least 40,000 USP units of lipase during each meal in adults and one-half of that with snacks. The subsequent dosage can be adjusted based on the meal size and fat content. BEST PRACTICE ADVICE 13: Routine supplementation and monitoring of fat-soluble vitamin levels are appropriate. Dietary modifications include a low-moderate fat diet with frequent smaller meals and avoiding very-low-fat diets. BEST PRACTICE ADVICE 14: Measures of successful treatment with PERT include reduction in steatorrhea and associated gastrointestinal symptoms; a gain of weight, muscle mass, and muscle function; and improvement in fat-soluble vitamin levels. BEST PRACTICE ADVICE 15: EPI should be monitored and baseline measurements of nutritional status should be obtained (body mass index, quality-of-life measure, and fat-soluble vitamin levels). A baseline dual-energy x-ray absorptiometry scan should be obtained and repeated every 1-2 years.

OBJECTIVE: 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.

OBJECTIVE: We sought to evaluate associations between Magnetic Resonance Imaging (MRI) findings, exocrine pancreatic insufficiency (EPI) and endocrine insufficiency (prediabetes or diabetes) in children.
METHODS: This was a retrospective study that included patients<21 years of age who underwent MRI and endoscopic pancreatic function testing (ePFT; reference standard for pancreatic exocrine function) within 3 months. MRI variables included pancreas parenchymal volume, secreted fluid volume in response to secretin, and T1 relaxation time. Data were analyzed for the full sample as well as the subset without acute pancreatitis (AP) at the time of imaging.
RESULTS: Of 72 patients, 56% (40/72) were female with median age 11.4 years. A 5 mL decrease in pancreas parenchymal volume was associated with increased odds of exocrine pancreatic dysfunction by both ePFT (OR = 1.16, p = 0.02 full sample; OR = 1.29, p = 0.01 no-AP subset), and fecal elastase (OR = 1.16, p = 0.04 full sample; OR = 1.23, p = 0.02 no-AP subset). Pancreas parenchymal volume had an AUC 0.71 (95% CI: 0.59, 0.83) for predicting exocrine pancreatic dysfunction by ePFT and when combined with sex and presence of AP had an AUC of 0.82 (95% CI: 0.72, 0.92). Regarding endocrine function, decreased pancreas parenchymal volume was associated with increased odds of diabetes (OR = 1.16, p = 0.03), and T1 relaxation time predicted glycemic outcomes with an AUC 0.78 (95% CI: 0.55-1), 91% specificity and 73% sensitivity.
CONCLUSIONS: Pancreas parenchymal volume is an MRI marker of exocrine and endocrine pancreatic dysfunction in children. A model including sex, AP, and pancreas volume best predicted exocrine status. T1 relaxation time is also an MRI marker of endocrine insufficiency.

OBJECTIVE: To develop and validate a radiomics nomogram based on a fully automated pancreas segmentation to assess pancreatic exocrine function. Furthermore, we aimed to compare the performance of the radiomics nomogram with the pancreatic flow output rate (PFR) and conclude on the replacement of secretin-enhanced magnetic resonance cholangiopancreatography (S-MRCP) by the radiomics nomogram for pancreatic exocrine function assessment.
METHODS: All participants underwent S-MRCP between April 2011 and December 2014 in this retrospective study. PFR was quantified using S-MRCP. Participants were divided into normal and pancreatic exocrine insufficiency (PEI) groups using the cut-off of 200 µg/L of fecal elastase-1. Two prediction models were developed including the clinical and non-enhanced T1-weighted imaging radiomics model. A multivariate logistic regression analysis was conducted to develop the prediction models. The models\' performances were determined based on their discrimination, calibration, and clinical utility.
RESULTS: A total of 159 participants (mean age [Formula: see text] standard deviation, 45 years [Formula: see text] 14;119 men) included 85 normal and 74 PEI. All the participants were divided into a training set comprising 119 consecutive patients and an independent validation set comprising 40 consecutive patients. The radiomics score was an independent risk factor for PEI (odds ratio = 11.69; p < 0.001). In the validation set, the radiomics nomogram exhibited the highest performance (AUC, 0.92) in PEI prediction, whereas the clinical nomogram and PFR had AUCs of 0.79 and 0.78, respectively.
CONCLUSIONS: The radiomics nomogram accurately predicted pancreatic exocrine function and outperformed pancreatic flow output rate on S-MRCP in patients with chronic pancreatitis.
CONCLUSIONS: • The clinical nomogram exhibited moderate performance in diagnosing pancreatic exocrine insufficiency. • The radiomics score was an independent risk factor for pancreatic exocrine insufficiency, and every point rise in the rad-score was associated with an 11.69-fold increase in pancreatic exocrine insufficiency risk. • The radiomics nomogram accurately predicted pancreatic exocrine function and outperformed the clinical model and pancreatic flow output rate quantified by secretin-enhanced magnetic resonance cholangiopancreatography on MRI in patients with chronic pancreatitis.

BACKGROUND: 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.
CONCLUSIONS: 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.

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.

BACKGROUND: 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%.
CONCLUSIONS: 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.

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.
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.
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.
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.

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.