Overview

Despite four international consensus meetings over 40 years, the issue of definition and classification of pancreatitis (see Chapters 53 to 55) is still under critical revision. The main reason is the difficulty, in contrast to other common inflammatory gastroenterologic diseases, to obtain pancreatic tissue specimens to define the diagnosis better during the inflammatory process. Any classification of pancreatitis must be based on clinical, morphologic, and laboratory features.

The history of the definition and classification of pancreatitis is characterized mainly by the distinction between acute and chronic pancreatitis as stated by Lagerlof in 1942. These two clinical conditions seemed to be two different and separate pathologic processes. In recent years, with the widening of clinical observation and improved accuracy of imaging studies, particularly magnetic resonance imaging (MRI) of the bile ducts and duct of Wirsung, the classic distinction between acute and chronic pancreatitis is under critical revision.

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

The most typical natural history regarding the correlation between acute and chronic pancreatitis is so-called 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 comprehension of the pathologic process. Nevertheless, today we must keep in mind a classification of acute and chronic pancreatitis to help in developing diagnostic and therapeutic algorithms.

History of the Definition and Classification of Pancreatitis

Pancreatitis is an inflammation of glandular parenchyma lead to injury or destruction of acinar components. The pathologic process could result in a self-limited disease with no sequelae or in catastrophic autodigestion activity with systemic cytotoxic effects and life-threatening complications in the acute form. In the case of chronic inflammation, fibrosis and calcification are the main features of the disease.

The history of the definition and classification of pancreatitis shows the progressive awareness of experts that acute and chronic inflammation should be defined by different pathologic, clinical, and etiogenetic perspectives (Table 52.1). The different points of view correlate with each other and together provide the best comprehension of the inflammatory process. Consequently, the clinical management of an individual patient can be improved only by considering all the features of pancreatitis.

Table 52.1 A Synopsis of Pancreatitis Classification from 1946 to 2011

US, ultrasound; CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography

The first effort to classify and define pancreatitis by a worldwide group of experts led to the Marseille Consensus Meeting in 1963 (Sarles, 1965). The panel of pancreatologists agreed that acute and chronic pancreatitis were different diseases mainly because of different morphologic patterns. Relapsing pancreatitis was characterized by the presence of multiple episodes in a morphologic pattern of acute or chronic processes. 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 52.2). The present histology-based classification does not provide clinically useful definitions, making it impossible to compare different experiences. From the clinical point of view, acute and chronic pancreatitis show a similar pattern, at least in the earlier phases.

Table 52.2 Marseille Classification of Pancreatitis

Modified from Sarles H, 1965: Proposal adopted unanimously by the participants of the symposium of acute pancreatitis in Marseille, 1963. Bibl Gastroenterol 7:7-8.

Progress in the comprehension of pancreatitis and its classification resulted from the Cambridge meeting (Sarner & Cotton, 1984). The distinction between acute and chronic pancreatitis was confirmed, and the term relapsing pancreatitis was avoided in the chosen terminology. The importance of the clinical impact of different severity systemic responses was emphasized (Table 52.3), and the importance of definition of a morphologic characterization of the inflammatory process was recognized, particularly for the acute pancreatitis group. The Cambridge group pointed out the relevant problem of etiology, and the role of imaging in chronic pancreatitis was addressed.

Endoscopic retrograde cholangiopancreatography (ERCP) classification (Table 52.4) is still in use in some centers. Several studies in the literature showed that ERCP findings are not pathognomonic of chronic pancreatitis but could coexist with many clinical conditions. In particular, cholelithiasis and its complications lead to demonstrable alterations in the morphology of the duct of Wirsung, as stated in the Cambridge classification (Buchler et al, 1987; Misra et al, 1990), and these morphologic changes could persist for many months. In biliary cirrhosis, Sjögren syndrome, and sclerosing cholangitis, pancreatic duct changes are commonly observed at ERCP (Bastid et al, 1990; Epstein et al, 1982; Lindstrom et al, 1991). For all these reasons, the ERCP morphology of the duct of Wirsung is not mandatory to diagnose chronic disease. In addition, increasing use of MRI of the bile ducts and duct of Wirsung provides excellent morphologic imaging of the main and side branch ducts.

Table 52.4 Grading of Chronic Pancreatitis by Endoscopic Retrograde Cholangiopancreatography

CT, Computed tomography

Modified from Sarner M, Cotton PB, 1984: Classification of pancreatitis. Gut 25:756-759.

The increasing attention to duct morphology and consequently to the cause-and-effect relationship of obstruction resulted in new terminology at the second Marseille meeting held in 1984 (Singer et al, 1985). In addition to the classic distinction between acute and chronic disease, a new entity was identified: obstructive chronic pancreatitis (Table 52.5). 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 chronic pancreatitis initially presenting as relapsing acute attacks owing to strictures resulting from different conditions, such as solid tumors, mucinous plugs typical of intraductal papillary mucinous tumors, severe pancreatitis with duct disruption, and scar and inflammation of the sphincter of Oddi of biliary origin. Regarding acute pancreatitis, another hallmark was recognized by the second Marseille meeting: The rule in mild pancreatitis is the absence of necrosis. The recognition of a dramatic and central role of necrosis in severe pancreatitis opened the doors to wide-ranging and fundamental studies on severity assessment and complication prevention; increasing use of CT scan in staging of the disease also contributed (Beger et al, 1985).

A panel of experts met in Rome in 1988 to integrate the second Marseille classification into use (Table 52.6). The main feature of the new classification (Sarles et al, 1989) was the statement about the reversibility of the lesions observed in the course of acute pancreatitis; even the severe forms responded to clinical observation in almost half of severe pancreatitis patients. In contrast, in chronic pancreatitis, 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 acute pancreatitis.

The need for further effort to better define acute pancreatitis resulted from the observation that the terminology of the Rome meeting was conflicting and not widely applied all over the world (Lumsden & Bradley, 1990). In 1992, 40 pancreatologists met in Atlanta and developed a new, reliable classification system of acute pancreatitis (Table 52.7; Bradley, 1993). 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 chronic pancreatitis (Table 52.8; Amman, 1997) 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. In 1997, a new definition of chronic pancreatitis was published, dividing definite from probable chronic pancreatitis (Table 52.9; Homma et al, 1997). This definition provided a list of radiologic or laboratory features in chronic pancreatitis patients lacking etiologic and pathogenetic features. The TIGAR-O risk factor classification system (toxic-metabolic, idiopathic, genetic, autoimmune, recurrent severe, obstructive) (Table 52.10), provides a complete overview of the risk factors for chronic pancreatitis development with special attention to the relationship between acute and chronic disease (Etemad & Whitcomb, 2001). In recent years, two main three-stage categorization systems have been mainly proposed: the ABC system (Ramesh, 2002) and the Manchester classification (Table 52.11; Bagul & Siriwardena, 2006). The aim of these systems is to provide an accurate description of chronic pancreatitis, underlining different 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.

Table 52.8 Zurich Classification for Alcoholic Chronic Pancreatitis

* These diagnostic definitions also may be used for nonalcoholic chronic pancreatitis.

From Amman RW, 1997: A clinically based classification system for alcoholic chronic pancreatitis: summary of an international workshop on chronic pancreatitis. Pancreas 14:215-221.

Table 52.9 Diagnostic Criteria for Chronic Pancreatitis from the Japan Pancreas Society

CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography

Modified from Homma T, et al, 1997: Diagnostic criteria for chronic pancreatitis by the Japan Pancreas Society. Pancreas 15:14-15.

Table 52.11 Manchester Classification System for Chronic Pancreatitis

Note that abdominal pain may or may not be present.

ERP, endoscopic retrograde pancreatography; MRP, magnetic resonance pancreatography; CT, computed tomography

Modified from Bagul A, Siriwardena AK, 2006: Evaluation of the Manchester Classification System for Chronic Pancreatitis. J Pancreas (Online) 7(4):390-396.

The most recent classification attempt is represented by the M-ANNHEIM multiple risk factor system (Table 52.12), aimed to provide a standardized method for the clinical diagnosis of chronic pancreatitis according to etiology, clinical stage, and severity of disease and to direct clinical practice (Schneider et al, 2007).

Table 52.12 The M-ANNHEIM Multiple Risk Factor Classification System

Modified from Schneider A, Lohr JM, Singer MV, 2007: The M-ANNHEIM classification of chronic pancreatitis: introduction of a unifying classification system based on a review of previous classification of the disease. J Gastroenterol 42:101-119.

It is therefore evident how all these more recent advances in the “definition dilemma” abandoned the mere clinical purpose of a classification to better investigate different specific features of this complex disease. The classification systems will likely come full circle with the recognition of the deep but still controversial correlation between acute and chronic inflammation.

Future Perspectives

The history of every patient must be carefully considered to identify risk factors that may include alcohol abuse, obstruction, genetics, and autoimmune disease. The clinical evidence of pancreas-related abdominal pain associated with alterations of serum amylase and lipase led to the term pancreatitis. The ongoing clinical observations obtained with imaging studies that include ultrasound, CT, and especially MRI of the bile ducts and duct of Wirsung should address the required treatment patient by patient. The early stage is the most difficult to diagnose, but it is also important to give the right medical or surgical option. Only the dynamic observation of patients with controlled follow-up enables us to classify pancreatitis and to define the disease better, assigning the definitive labels supported by the biochemical and radiologic sources well characterized by the different classification systems available. The clinician should recognize pancreatitis at an early stage but avoid assigning a definitive classification immediately, instead investigating all the factors available to determine whether a first acute attack could lead to chronic changes with fibrosis, permanent disruptions, and exocrine endocrine insufficiency.