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