Definition and classification of pancreatitis

Overview

Despite five international consensus meetings over the last 40 years, the definition and classification of pancreatitis (see Chapter 55, Chapter 56, Chapter 57, Chapter 58 ) continues to evolve. The main reason is the actual difficulty, in contrast to other common inflammatory diseases of the gastrointestinal (GI) tract, of obtaining pancreatic tissue specimens to define the diagnosis during the inflammatory process. As a consequence, classifications of pancreatitis are necessarily based on clinical, morphologic, and laboratory features.

The main historical landmark in defining and classifying pancreatitis was the development of the distinction between acute pancreatitis (AP) and chronic pancreatitis (CP; see Chapters 55 and 57 ), as first stated by Lagerlof in 1942. In more recent years, with an improved understanding of the clinical presentation of pancreatitis, an increase in the number of experimental trials, and improved accuracy of imaging studies—particularly magnetic resonance imaging (MRI) of the bile ducts and the duct of Wirsung (see Chapters 2 and 17 )—the classic distinction between AP and CP has undergone extensive revision.

The process leading to fibrotic changes in the glandular tissue usually begins with typical acute abdominal pain, with increased serum amylase and lipase and subsequent resolution. AP leads to CP because of episodes of obstruction secondary to edema or inflammation of the sphincter of Oddi. As in other inflammatory diseases, timing seems to play the main role in determining whether glandular inflammation leads to a chronic condition or self-limits with no further sequelae.

The most typical natural history regarding the correlation between AP and CP is what is known as recurrent pancreatitis. It is not possible to define this condition as acute or chronic, per se, and it represents the best example of the new understanding of the pathologic process. Nevertheless, distinguishing between AP and CP still represents a milestone in helping to develop further diagnostic and therapeutic algorithms.

History of the definition and classification of pancreatitis

Pancreatitis is an inflammation of glandular parenchyma, leading to injury or possibly irreversible destruction of acinar components. This inflammatory pathologic process could acutely result in either a self-limited disease with no sequelae or in catastrophic autodigestion with systemic cytotoxic effects and life-threatening complications. In the case of chronic inflammation, permanent fibrosis and calcification are the characteristic features of the disease.

The history of the definition and classification of pancreatitis is summarized in Table 54.1 . The first effort to classify and define pancreatitis by a worldwide group of experts led to the Marseille Consensus Meeting in 1963. In this initial effort at consensus, it was agreed that AP and CP were different diseases mainly because of their different morphologic patterns. Relapsing pancreatitis was defined as the presence of multiple episodes in a morphologic pattern of AP or CP. The distinctive features of the two diseases were the pathologic benign course of acute inflammation, with biologic restitution in the acute condition, and the progressively worsening parenchymal lesions in the chronic condition ( Table 54.2 ). This histology-based classification did not provide clinically useful definitions, making it impossible to compare different clinical experiences. From a clinical point of view, AP and CP show a similar pattern, at least in the early phases.

After the Cambridge meeting, the distinction between AP and CP was maintained, and the term relapsing pancreatitis was abandoned. The importance of the clinical impact of the different severity of systemic responses was emphasized ( Table 54.3 ), and the importance of defining a morphologic characterization of the inflammatory process was recognized, particularly for the AP group. The Cambridge group pointed out the relevant problem of etiology, and the role of imaging in CP was addressed.

Endoscopic retrograde cholangiopancreatography (ERCP) classification ( Box 54.1 ) is still in use in some centers. Several studies in the literature showed that ERCP findings are not pathognomonic of CP but could coexist with many clinical conditions. In particular, cholelithiasis and its complications (see Chapters 33 and 37 ) lead to demonstrable alterations in the morphology of the duct of Wirsung, as stated in the Cambridge classification, ^, and these morphologic changes could persist for many months. In biliary cirrhosis, Sjögren’s syndrome, and sclerosing cholangitis (see Chapter 41 ), pancreatic duct changes are commonly observed at ERCP. For all these reasons, the ERCP morphology of the duct of Wirsung is not a specific finding that allows for a diagnosis of CP. In addition, increasing use of MRI of the bile ducts and duct of Wirsung can provide excellent morphologic imaging of the main- and side-branch ducts so that many centers currently have completely replaced the routine use of ERCP with MRI cholangiopancreatography (see Chapter 17 ).

The increasing attention to duct morphology resulted in new terminology at the second Marseille meeting held in 1984. In addition to the classic distinction between AP and CP, a new entity was identified: obstructive chronic pancreatitis ( Table 54.4 ). The role of duct obstruction in the chronic inflammatory process was recognized as a distinctive pathway to developing pancreatitis. This new concept has gained importance over the years in distinguishing chronic calcifying pancreatitis in alcoholics from obstructive CP initially presenting as relapsing acute attacks because of strictures from different conditions, such as solid tumors, mucinous plugs typical of intraductal papillary mucinous neoplasms (IPMN; see Chapter 60 ), severe pancreatitis with duct disruption (see Chapters 55 and 56 ), and scar and inflammation of the sphincter of Oddi of biliary origin. Regarding AP, another hallmark was recognized by the second Marseille meeting: the absence of necrosis in mild pancreatitis. The recognition of the pivotal role of necrosis in severe pancreatitis opened the doors to studies on severity assessment and prevention of complications.

A new classification system was established after the Rome 1988 consensus ( Table 54.5 ). The main feature of the new classification concerned the reversibility of lesions observed in the course of AP; even the severe forms showed complete clinical response in almost half of severe pancreatitis patients. In contrast, in CP, some pathologic features were defined as permanent, and the condition was described as chronic inflammatory pancreatitis, morphologically characterized by loss of exocrine parenchyma and fibrosis with mononuclear cell infiltration. For the first time, etiology specifically was addressed, with pancreas divisum and alcohol as possible causes of AP (see Chapters 53 and 55 ).

The need for further effort to better define AP resulted from the observation that the terminology of the Rome meeting was conflicting and not widely applied worldwide. In 1992 40 pancreatologists met in Atlanta and developed a new classification system of AP ( Table 54.6 ). The clinical and morphologic features of pancreatitis were considered, resulting in a dynamic ongoing classification system better able to characterize the individual patient and predict disease severity.

The Zurich classification for alcoholic CP ( Table 54.7 ) specifically addresses the most common cause of the disease and gives less importance to other causes, which are sometimes difficult to diagnose, resulting in a quite complex classification system not widely adopted (see Chapter 57 ). In 1997 a new definition of CP was published, dividing definite from probable CP ( Table 54.8 ). This definition provided a list of radiologic and/or laboratory features in CP patients lacking etiologic and pathogenetic features. The TIGAR-O risk factor classification system ( t oxic-metabolic, i diopathic, g enetic, a utoimmune, r ecurrent severe, o bstructive; Table 54.9 ) provides a complete overview of the risk factors for CP development, with special attention to the relationship between acute and chronic disease. In recent years, two separate categorization systems have been proposed: the ABC system and the Manchester classification ( Box 54.2 ). The aim of these systems is to provide an accurate description of CP while underlining various therapeutic approaches and prognoses depending on disease stage. The ABC system divides patients into grades depending on the presence or absence of abdominal pain, complications, and deficiency in pancreatic function. The Manchester classification uses the terms mild, moderate, and end stage to represent disease progression, allowing comparison between patient groups.