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Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07.

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Chronic pancreatitis (CP) is historically defined as an irreversible inflammatory condition of the pancreas leading to varying degrees of exocrine and endocrine dysfunction. Recently however, the paradigm for the diagnosis has changed in that it breaks with the traditional clinicopathologic-based definition of disease, focusing instead on diagnosing the underlying pathologic process early in the disease course and managing the syndrome more holistically to change the natural course of disease and minimize adverse disease effects. Currently, the most accepted mechanistically derived definition of CP is a pathologic fibroinflammatory syndrome of the pancreas in individuals with genetic, environmental, and/or other risk factors who develop persistent pathologic responses to parenchymal injury or stress. The most common symptom of CP is abdominal pain, with other symptoms such as exocrine pancreatic insufficiency and diabetes developing at highly variable rates. CP is most commonly caused by toxins such as alcohol or tobacco use, genetic polymorphisms, and recurrent attacks of acute pancreatitis, although no history of acute pancreatitis is seen in many patients. Diagnosis is made usually on cross-sectional imaging, with modalities such as endoscopic ultrasonography and pancreatic function tests playing a secondary role. Total pancreatectomy represents the only known cure for CP, although difficulty in patient selection and the complications inherent to this intervention make it usually an unattractive option. This guideline will provide an evidence-based practical approach to the diagnosis and management of CP for the general gastroenterologist.

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SUMMARYPancreatic function tests are most commonly used to diagnose chronic pancreatitis. These tests include tests which document exocrine or endocrine gland insufficiency and tests which instead measure gradations of decreased secretory capacity. The tests in the former category generally become abnormal when advanced, longstanding chronic pancreatitis is present. Tests in the latter category, however, have the potential to detect chronic pancreatitis at an earlier stage than other available diagnostic tests, including commonly used imaging tests such as computed tomography and endoscopic retrograde cholangiopancreatography. This potential advantage of diagnostic sensitivity is, however, counterweighed by the fact that these tests which measure stimulated secretory capacity are only available at a very few referral centres. This article will review the variety of pancreatic function tests and describe their rationale, accuracy, cost, and clinical usefulness.