A short endoscopic Secretin test for the diagnosis of chronic pancreatitis

Background: The diagnosis of CP is not yet clearly defined. Many national guidelines exist, but - as in many other not clearly defined diseases - there is no worldwide consensus. In CP, evaluation of exocrine pancreatic function is crucial because symptoms are often diffuse and overlooked by the doctors. Additionally, early diagnosis of exocrine pancreatic failure is important as its consequence, malnutrition and commonly abdominal pain, leads to serious complications and reduced life expectancy. Direct pancreas function testing with analyses of enzymes in duodenal juice may give this information. Aims: The main aim was to develop and establish a multimodal algorithm for the diagnoses of CP, accurate and easy to handle in clinical practice. Secondary, we wanted to simplify direct pancreas function testing including a): the performance of a short endoscopic test (article I) and b): the analyses of ingredients in duodenal juice by automation: bicarbonate (article II), Amylase (article III) and Lipase (article IV). Materials and Methods: We examined consecutively healthy controls and patients referred to our outpatient clinic due to symptoms suspicious of CP. We assessed patients with a modified Layer (Mayo) score, which includes imaging, pancreas function testing and medical history. We established a short endoscopic secretin test and analysed bicarbonate, Amylase and Lipase in duodenal juice as markers for ductal and acinar exocrine pancreatic function. In article I, we determined sensitivity, specificity and accuracy of bicarbonate and faecal-elastase, using our modified secretin-stimulated upper endoscopy (short endoscopic secretin test, or EST). In article II, III, IV, we describe correlation between automation of analyses of Bicarbonate, Amylase and Lipase in duodenal juice to labour-intensive manual methods. Results: I. Short endoscopic secretin test: Fifty-two patients aged 19 to 67 years and 25 healthy controls aged 19 to 64 years were included. Twenty-four patients fulfilled the modified Layer score for CP or non-CP. The overall accuracy of the EST versus FE1 test was 85%/71%, with positive and negative predictive values of 100%/79% and 80%/69%, respectively. II. Automation of bicarbonate measurement: 177 samples from 71 patients were analysed. Correlation coefficient of all measurements was r = 0.98 (p < 0.001). Correlation coefficient of fresh versus frozen samples conducted with automatic spectrophotometry (n = 25): r = 0.96 (p < 0.001). III. Automation of amylase measurement: We analysed 52 samples for assay of amylase in pairs. Correlation between measurements with the two methods was r = 0.99 (p < 0.001). IV. Automation of lipase measurement: We tested stability of 54 samples from 21 patients. Diluting samples with MOPS buffer, added BSA gave stable results, and was superior to diluting samples in saline. We compared the two assays in 50 samples from 20 patients and found a good correlation between the two assays (r=0.91, p < 0.001). Conclusions: I: Short EST is rapid and easy to perform and can be incorporated in daily routine in every clinical endoscopic unit. EST is superior to FE1 in the assessment of pancreatic insufficiency, leading to earlier diagnosis of moderate and early or mild CP. II: The measurement of bicarbonate in fresh and thawed samples by automatic spectrophotometric analysis correlates excellent with the back-titration gold standard. III and IV: Quantification of duodenal amylase and lipase activity with automated spectrophotometry has excellent correlation to measurements made by the manual methods. Overall, Endoscopic secretin test is easy to perform, and can be incorporated in a diagnostic endoscopic examination. Automated measurement of bicarbonate, lipase and amylase in duodenal juice simplifies the analytical methods and shortens time from test to result substantially. Standardized, centre-independent analyses of duodenal juice with quantification of ductal and acinar function in any unit with basic endoscopic and laboratory services is within reach

Diagnostic accuracy of transabdominal ultrasound in chronic pancreatitis

The performance of transabdominal ultrasound (US) in chronic pancreatitis (CP) following the advances in US technology made during recent decades has not been explored. Our aim in this prospective study was to evaluate the diagnostic accuracy of modern abdominal US compared with the Mayo score in CP. One hundred thirty-four patients referred for suspected CP were included in the study. Fifty-four patients were assigned the diagnosis CP. After inclusion, transabdominal US was performed. Ductal features (calculi, dilations and caliber variations, side-branch dilations and hyper-echoic duct wall margins) and parenchymal features (calcifications, cysts, hyper-echoic foci, stranding, lobulation and honeycombing) were recorded. Features were counted and scored according to a weighting system defined at the international consensus meeting in Rosemont, Illinois (Rosemont score). Diagnostic performance indices (95% confidence interval) of US were calculated: The unweighted count of features had a sensitivity of 0.69 (0.54–0.80) and specificity of 0.97 (0.90–1). The Rosemont score had a sensitivity of 0.81 (0.69–0.91) and specificity of 0.97 (0.90–1). Exocrine pancreatic failure was most pronounced in Rosemont groups I and II (p < 0.001). We conclude that using both unweighted and weighted scores, the diagnostic accuracy of modern transabdominal US is good. The extent of pancreatic changes detected by the method is correlated with exocrine pancreatic function.publishedVersio

Effects of high intake of cod or salmon on gut microbiota profile, faecal output and serum concentrations of lipids and bile acids in overweight adults: a randomised clinical trial

Purpose To explore whether high intake of cod or salmon would affect gut microbiota profile, faecal output and serum concentrations of lipids and bile acids. Methods Seventy-six adults with overweight/obesity with no reported gastrointestinal disease were randomly assigned to consume 750 g/week of either cod or salmon, or to avoid fish intake (Control group) for 8 weeks. Fifteen participants from each group were randomly selected for 72 h faeces collection at baseline and end point for gut microbiota profile analyses using 54 bacterial DNA probes. Food intake was registered, and fasting serum and morning urine were collected at baseline and end point. Results Sixty-five participants were included in serum and urine analyses, and gut microbiota profile was analysed for 33 participants. Principal component analysis of gut microbiota showed an almost complete separation of the Salmon group from the Control group, with lower counts for bacteria in the Bacteroidetes phylum and the Clostridiales order of the Firmicutes phyla, and higher counts for bacteria in the Selenomonadales order of the Firmicutes phylum. The Cod group showed greater similarity to the Salmon group than to the Control group. Intake of fibres, proteins, fats and carbohydrates, faecal daily mass and output of fat, cholesterol and total bile acids, and serum concentrations of cholesterol, triacylglycerols, non-esterified fatty acids and total bile acids were not altered in the experimental groups. Conclusion A high intake of cod or salmon fillet modulated gut microbiota but did not affect faecal output or serum concentrations of lipids and total bile acids. Clinical trial registration This trial was registered at clinicaltrials.gov as NCT02350595.publishedVersio

Pancreatic enzyme treatment in chronic pancreatitis : Quality of management and adherence to guidelines–A cross-sectional observational study

Objectives: Pancreatic exocrine insufficiency (PEI) is a common complication in patients with chronic pancreatitis (CP), leading to increased morbidity and mortality if not treated adequately. Pancreatic enzyme replacement therapy|pancreas enzyme replacement therapy (PERT) is the cornerstone in treatment of patients with PEI. In the present study, we use data from the Scandinavian Baltic Pancreatic Club database to examine adherence of PERT according to United European Gastroenterology evidence-based guidelines treatment of CP. Patients and methods: Patients with definitive or probable CP according to M-ANNHEIM diagnostic criteria were included. We collected information on exposures, exocrine function, intake of pancreatic enzymes, and markers of nutrition. Fecal elastase <200 μg/g was defined as a marker for PEI. Enzyme replacement therapy of 100,000 lipase units or more was defined as adequate treatment. Results: We included 1006 patients from 8 centers in five countries. Sixty-four percent of the patients were correctly treated. Twenty-five per cent of PEI patients were not taking enzymes at all, and 20% of PEI patients were undertreated with insufficient PERT doses according to the guidelines. Fourteen percent of patients with sufficient pancreatic function were receiving enzymes despite normal exocrine pancreatic function. There were center differences. Current smoking was associated with lack of treatment and alcohol abuse was associated with under-treatment. There were no associations between “no treatment” or “under-treatment” for underweight or vitamin D deficiency. Conclusion: In our CP expert centers, the adherence to guidelines for enzyme treatment is insufficient. Both patient factors and center differences have influence on treatment adherence.publishedVersionPeer reviewe

A short endoscopic Secretin test for the diagnosis of chronic pancreatitis

Background: The diagnosis of CP is not yet clearly defined. Many national guidelines exist, but - as in many other not clearly defined diseases - there is no worldwide consensus. In CP, evaluation of exocrine pancreatic function is crucial because symptoms are often diffuse and overlooked by the doctors. Additionally, early diagnosis of exocrine pancreatic failure is important as its consequence, malnutrition and commonly abdominal pain, leads to serious complications and reduced life expectancy. Direct pancreas function testing with analyses of enzymes in duodenal juice may give this information. Aims: The main aim was to develop and establish a multimodal algorithm for the diagnoses of CP, accurate and easy to handle in clinical practice. Secondary, we wanted to simplify direct pancreas function testing including a): the performance of a short endoscopic test (article I) and b): the analyses of ingredients in duodenal juice by automation: bicarbonate (article II), Amylase (article III) and Lipase (article IV). Materials and Methods: We examined consecutively healthy controls and patients referred to our outpatient clinic due to symptoms suspicious of CP. We assessed patients with a modified Layer (Mayo) score, which includes imaging, pancreas function testing and medical history. We established a short endoscopic secretin test and analysed bicarbonate, Amylase and Lipase in duodenal juice as markers for ductal and acinar exocrine pancreatic function. In article I, we determined sensitivity, specificity and accuracy of bicarbonate and faecal-elastase, using our modified secretin-stimulated upper endoscopy (short endoscopic secretin test, or EST). In article II, III, IV, we describe correlation between automation of analyses of Bicarbonate, Amylase and Lipase in duodenal juice to labour-intensive manual methods. Results: I. Short endoscopic secretin test: Fifty-two patients aged 19 to 67 years and 25 healthy controls aged 19 to 64 years were included. Twenty-four patients fulfilled the modified Layer score for CP or non-CP. The overall accuracy of the EST versus FE1 test was 85%/71%, with positive and negative predictive values of 100%/79% and 80%/69%, respectively. II. Automation of bicarbonate measurement: 177 samples from 71 patients were analysed. Correlation coefficient of all measurements was r = 0.98 (p < 0.001). Correlation coefficient of fresh versus frozen samples conducted with automatic spectrophotometry (n = 25): r = 0.96 (p < 0.001). III. Automation of amylase measurement: We analysed 52 samples for assay of amylase in pairs. Correlation between measurements with the two methods was r = 0.99 (p < 0.001). IV. Automation of lipase measurement: We tested stability of 54 samples from 21 patients. Diluting samples with MOPS buffer, added BSA gave stable results, and was superior to diluting samples in saline. We compared the two assays in 50 samples from 20 patients and found a good correlation between the two assays (r=0.91, p < 0.001). Conclusions: I: Short EST is rapid and easy to perform and can be incorporated in daily routine in every clinical endoscopic unit. EST is superior to FE1 in the assessment of pancreatic insufficiency, leading to earlier diagnosis of moderate and early or mild CP. II: The measurement of bicarbonate in fresh and thawed samples by automatic spectrophotometric analysis correlates excellent with the back-titration gold standard. III and IV: Quantification of duodenal amylase and lipase activity with automated spectrophotometry has excellent correlation to measurements made by the manual methods. Overall, Endoscopic secretin test is easy to perform, and can be incorporated in a diagnostic endoscopic examination. Automated measurement of bicarbonate, lipase and amylase in duodenal juice simplifies the analytical methods and shortens time from test to result substantially. Standardized, centre-independent analyses of duodenal juice with quantification of ductal and acinar function in any unit with basic endoscopic and laboratory services is within reach

Ultrasound echo-intensity predicts severe Pancreatic affection in cystic fibrosis patients

Background: Pancreatic destruction affects the majority of patients with cystic fibrosis. We aimed to relate ultrasound findings to exocrine pancreatic function and cystic fibrosis genotype. Methods: Patients with cystic fibrosis and a matched group of healthy controls were included. We performed transabdominal ultrasound, and recorded echo intensities of the pancreas and parenchymal characteristics according to endoscopic ultrasound based Rosemont criteria. Results: We included 39 patients and 29 healthy controls. The cystic fibrosis patients were grouped according to exocrine pancreatic function; Cystic fibrosis, insufficient (n = 20) and sufficient (n = 19). Echo intensity measures and visual score demonstrated hyper-echogenicity in the pancreas insufficient group compared to the pancreas sufficient groups (p<0.001). Ductal and parenchymal changes were not prevalent in any of the groups. Conclusion: The hyper-echoic pancreas was the most frequent ultrasonographic finding in exocrine pancreas insufficient cystic fibrosis patients. Pancreatic echo levels correlated to pancreatic phenotype

Diagnostic accuracy of a short endoscopic secretin test in patients with cystic fibrosis

Objective: Short endoscopic secretin tests for exocrine pancreatic function are not properly evaluated in cystic fibrosis (CF). Methods: Patients with CF and healthy controls (HCs) underwent endoscopic collection of duodenal juice between 30 and 45 minutes after secretin stimulation. Duodenal juice was analyzed for HCO3- concentration and pancreatic enzyme activities. Stool was analyzed for fecal elastase. Results: Thirty-one patients with CF and 25 HCs were tested. Patients were classified as exocrine pancreatic sufficient (n = 13) or insufficient (n = 18). Both bicarbonate concentrations and enzyme activities in duodenal juice differentiated patients with CFI from patients with CFS and HC (P < 0.001). The population displays strong correlation between severe CF genotype in both alleles and pancreatic insufficient phenotype (P < 0.001). Conclusions: Pancreatic exocrine insufficient CF patients could be differentiated from exocrine sufficient patients and HCs using short endoscopic secretin test

Automated spectrophotometric bicarbonate analysis in duodenal juice compared to the back titration method

AbstractObjectivesWe have recently evaluated a short endoscopic secretin test for exocrine pancreatic function. Bicarbonate concentration in duodenal juice is an important parameter in this test. Measurement of bicarbonate by back titration as the gold standard method is time consuming, expensive and technically difficult, thus a simplified method is warranted. We aimed to evaluate an automated spectrophotometric method in samples spanning the effective range of bicarbonate concentrations in duodenal juice. We also evaluated if freezing of samples before analyses would affect its results.MethodsPatients routinely examined with short endoscopic secretin test suspected to have decreased pancreatic function of various reasons were included. Bicarbonate in duodenal juice was quantified by back titration and automatic spectrophotometry. Both fresh and thawed samples were analysed spectrophotometrically.Results177 samples from 71 patients were analysed. Correlation coefficient of all measurements was r = 0.98 (p < 0.001). Correlation coefficient of fresh versus frozen samples conducted with automatic spectrophotometry (n = 25): r = 0.96 (p < 0.001)ConclusionsThe measurement of bicarbonate in fresh and thawed samples by automatic spectrophotometrical analysis correlates excellent with the back titration gold standard. This is a major simplification of direct pancreas function testing, and allows a wider distribution of bicarbonate testing in duodenal juice. Extreme values for Bicarbonate concentration achieved by the autoanalyser method have to be interpreted with caution

Secretin-stimulated ultrasound estimation of pancreatic secretion in cystic fibrosis validated by magnetic resonance imaging

Objectives: Secretin-stimulated magnetic resonance imaging (s-MRI) is the best validated radiological modality assessing pancreatic secretion. The purpose of this study was to compare volume output measures from secretin-stimulated transabdominal ultrasonography (s-US) to s-MRI for the diagnosis of exocrine pancreatic failure in cystic fibrosis (CF). Methods: We performed transabdominal ultrasonography and MRI before and at timed intervals during 15 minutes after secretin stimulation in 21 CF patients and 13 healthy controls. To clearly identify the subjects with reduced exocrine pancreatic function, we classified CF patients as pancreas-sufficient or -insufficient by secretin-stimulated endoscopic short test and faecal elastase. Results: Pancreas-insufficient CF patients had reduced pancreatic secretions compared to pancreas-sufficient subjects based on both imaging modalities (p < 0.001). Volume output estimates assessed by s-US correlated to that of s-MRI (r = 0.56–0.62; p < 0.001). Both s-US (AUC: 0.88) and s-MRI (AUC: 0.99) demonstrated good diagnostic accuracy for exocrine pancreatic failure. Conclusions: Pancreatic volume-output estimated by s-US corresponds well to exocrine pancreatic function in CF patients and yields comparable results to that of s-MRI. s-US provides a simple and feasible tool in the assessment of pancreatic secretion