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Background & Aims: Different mutations in the cystic fibrosis gene (CFTR) are associated with different functional status of the exocrine pancreas. We investigated whether CFTR genotypes determine the risk of pancreatitis in patients with cystic fibrosis (CF). Methods: Patients with pancreatic-sufficient CF were identified from 2 CF population-based databases (N = 277; 62 with pancreatitis and 215 without pancreatitis); patients'' genotypes and clinical characteristics were analyzed. The loss of pancreatic function associated with each CFTR genotype was determined based on the pancreatic insufficiency prevalence (PIP) score. Results: Patients with pancreatitis were more likely to have genotypes associated with mild (70%) than moderate-severe (30%) PIP scores (P = .004). The cumulative proportion of patients who developed pancreatitis through to the age of 50 years was significantly greater for genotypes associated with mild (50%) than moderate-severe (27%) PIP scores (P = .006). The genotype associated with mild PIP scores had a hazard ratio of 2.4 for pancreatitis (95% confidence interval, 1.3–4.5; P = .006). Patients with pancreatitis were diagnosed with CF at an older median age than those without pancreatitis (14.9 years [interquartile range, 9.5–27.7] vs 9.3 years [interquartile range, 1.5–21.4]; P = .003) and had lower mean levels of sweat chloride than patients without pancreatitis (74.5 ± 26.2 mmol/L vs 82.8 ± 25.2 mmol/L; P = .03). Conclusions: Specific CFTR genotypes are significantly associated with pancreatitis. Patients with genotypes associated with mild phenotypic effects have a greater risk of developing pancreatitis than patients with genotypes associated with moderate-severe phenotypes. This observation provides further insight into the complex pathogenesis of pancreatitis. [Copyright &y& Elsevier]

Background & Aims: Although pancreatic stimulation tests quantify acinar and ductal exocrine pancreatic function, no standard methodology exists. We evaluated the impact of several variables on test accuracy. Methods: We performed a retrospective analysis of pancreatic stimulation tests, which involved continuous stimulation with cholecystokinin and secretin, 3 sampling periods (20-min each), and perfusion markers to correct for intestinal losses. Results were recalculated using the following variables: no correction for losses; shortened sampling time (20-min); no correction and shortened sampling time; and enzyme concentration. We examined how these variables influenced measurements of pancreatic secretion and classification of pancreatic function status (sufficient or insufficient). Results: We analyzed 363 tests in control patients (20), and patients with cystic fibrosis (137), Shwachman-Diamond syndrome (40), or other pancreatic or intestinal disorders (166). Recovery of pancreatic juice varied markedly between tests (median, 59%; range, 4%–106%) and was significantly poorer during the first 20-minute period compared with the 2 subsequent periods (P < .01). Failure to correct for intestinal losses underestimated secretory capacity (median trypsin output reduced by >50%, P < .0001) and shortened sampling time increased test variability. Both variables together resulted in greater discrepancies. More than 25% of the pancreatic-sufficient patients with impaired pancreatic function were misclassified as pancreatic insufficient when uncorrected output plus a shortened sampling time or enzyme concentration were used to define categories. Conclusions: Pancreatic function tests using brief aspiration periods without marker perfusion or measures of concentration greatly underestimate pancreatic secretory capacity and misclassify the clinical status of an unacceptably large number of patients. [Copyright &y& Elsevier]