Gastroenterology

Gastroenterology

Volume 132, Issue 4, April 2007, Pages 1557-1573
Gastroenterology

Review in basic and clinical Gastroenterology
Chronic Pancreatitis: Challenges and Advances in Pathogenesis, Genetics, Diagnosis, and Therapy

https://doi.org/10.1053/j.gastro.2007.03.001Get rights and content

Chronic pancreatitis (CP) is characterized by progressive pancreatic damage that eventually results in significant impairment of exocrine as well as endocrine functions of the gland. In Western societies, the commonest association of chronic pancreatitis is alcohol abuse. Our understanding of the pathogenesis of CP has improved in recent years, though important advances that have been made with respect to delineating the mechanisms responsible for the development of pancreatic fibrosis (a constant feature of CP) following repeated acute attacks of pancreatic necroinflammation (the necrosis-fibrosis concept). The pancreatic stellate cells (PSCs) are now established as key cells in fibrogenesis, particularly when activated either directly by toxic factors associated with pancreatitis (such as ethanol, its metabolites or oxidant stress) or by cytokines released during pancreatic necroinflammation. In recent years, research effort has also focused on the genetic abnormalities that may predispose to CP. Genes regulating trypsinogen activation/inactivation and cystic fibrosis transmembrane conductance regulator (CFTR) function have received particular attention. Mutations in these genes are now increasingly recognized for their potential ‘disease modifier’ role in distinct forms of CP including alcoholic, tropical, and idiopathic pancreatitis. Treatment of uncomplicated CP is usally conservative with the major aim being to effectively alleviate pain, maldigestion and diabetes, and consequently, to improve the patient’s quality of life. Surgical and endoscopic interventions are reserved for complications such as pseudocysts, abscess, and malignancy.

Section snippets

Clinical Features

The 3 major clinical features of CP are pain, maldigestion, and diabetes.

Natural History

The natural history of CP has been difficult to characterize because of the variability in presentation of the disease and the relative inaccessibility of the pancreas to histologic assessment. However, several studies involving large series of medical and surgical cases have provided some important insights in this area.5, 9, 10, 12, 13, 14

Alcohol-induced CP usually develops after a prolonged period (5–15 y) of heavy alcohol consumption and does not develop after an isolated bout of heavy

Pathogenesis of Chronic Pancreatitis

Research into the pathogenesis of CP was initially focused on large and small pancreatic ducts and then on the pancreatic parenchymal and nonparenchymal cells. In more recent times, the genetics of CP has attracted considerable attention and has revolutionized our knowledge of the possible mechanisms mediating pancreatic injury (this topic is discussed in more detail later in the section titled “Genetics of Chronic Pancreatitis”). The majority of studies related to the pathogenesis of CP have

Genetics of Chronic Pancreatitis

More than 50 years ago, it was recognized for the first time that CP may cluster in selected families, suggesting an inherited disease in these patients.75 The underlying genetic defect, however, remained obscure for more than 4 decades. As stated in this first report on inherited pancreatitis, “hereditary chronic relapsing pancreatitis does not present earmarks which distinguish it from nonhereditary chronic relapsing pancreatitis.”75 In 10%–30% of patients suffering from CP, no apparent

Diagnosis of Chronic Pancreatitis

The diagnosis of CP relies on relevant symptoms, imaging modalities to assess pancreatic structure, and assessment of pancreatic function. The diagnostic gold standard of early stage disease would be an adequate surgical biopsy, which is rarely available. However, because the primary lesions of early stage CP are usually focal, fine-needle biopsy examinations may yield false-negative results. In the absence of definite signs of CP, it often is difficult to differentiate early stage disease from

Treatment of Chronic Pancreatitis

The treatment of CP is mainly symptomatic and is directed toward the cardinal features of pain, and exocrine and endocrine insufficiency. A diagnosis of CP does not necessarily require treatment because patients may be asymptomatic. However, if a precipitating factor such as an anatomic anomaly or a metabolic disease can be identified, it may be treated by surgical or medical intervention. In general, the therapeutic strategies for CP include abstinence from alcohol and cigarette consumption,

Summary

In summary, CP is characterized by progressive and ultimately irreversible pancreatic injury that manifests clinically as maldigestion and diabetes. Alcohol abuse is the most common association of CP in the Western world. Important advances have been made in recent years with respect to our understanding of the pathogenesis of this disease, particularly related to the mechanisms responsible for the development of pancreatic fibrosis (a cardinal feature of CP) after repeated acute attacks of

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    1

    J.S.W. was the senior author

    2

    H.W., M.V.A., and V.K. contributed equally to this article as co–first authors.

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