Elsevier

The Lancet

Volume 377, Issue 9772, 2–8 April 2011, Pages 1184-1197
The Lancet

Seminar
Chronic pancreatitis

https://doi.org/10.1016/S0140-6736(10)61852-1Get rights and content

Summary

Chronic pancreatitis is a progressive fibroinflammatory disease that exists in large-duct (often with intraductal calculi) or small-duct form. In many patients this disease results from a complex mix of environmental (eg, alcohol, cigarettes, and occupational chemicals) and genetic factors (eg, mutation in a trypsin-controlling gene or the cystic fibrosis transmembrane conductance regulator); a few patients have hereditary or autoimmune disease. Pain in the form of recurrent attacks of pancreatitis (representing paralysis of apical exocytosis in acinar cells) or constant and disabling pain is usually the main symptom. Management of the pain is mainly empirical, involving potent analgesics, duct drainage by endoscopic or surgical means, and partial or total pancreatectomy. However, steroids rapidly reduce symptoms in patients with autoimmune pancreatitis, and micronutrient therapy to correct electrophilic stress is emerging as a promising treatment in the other patients. Steatorrhoea, diabetes, local complications, and psychosocial issues associated with the disease are additional therapeutic challenges.

Introduction

Chronic pancreatitis is a progressive inflammatory disorder in which pancreatic secretory parenchyma is destroyed and replaced by fibrous tissue, eventually leading to malnutrition and diabetes. Two forms are recognised—a large-duct calcifying type1 and a small-duct variant.2, 3, 4 The disease is uncommon in Europe and the USA; its prevalence in France is 26 per 100 000 people.5 This prevalence is not dissimilar to the middle of three estimates from Japan,6, 7 but considerably lower than the figure of 114–200 per 100 000 in south India.7

The main symptom of chronic pancreatitis is usually pain, which occurs as attacks that mimic acute pancreatitis or as constant and disabling pain. Despite decades of research, treatment of chronic pancreatitis remains mostly empirical, and thus patients are repeatedly admitted to hospital and have interventional procedures, which strains medical resources.8 This absence of progress in treatment is a sign of uncertainty about how the identified causative factors lead to the disease. Therefore, in this Seminar we focus on the pathophysiology and pathology of chronic pancreatitis before describing clinical management.

Section snippets

Definition

Traditionally, chronic pancreatitis has been classed as fundamentally different from acute pancreatitis—the latter is usually characterised by restoration of normal pancreatic histology after full clinical recovery.1 However, acute, recurrent acute, and chronic pancreatitis are now regarded as a disease continuum.9, 10 There are several reasons for this change: recurrent acute pancreatitis can develop into chronic pancreatitis;10, 11, 12 there is an overlap in causative factors, both genetic

Pathophysiology and pathology

Experimental studies since the 1950s have shown that an attack of pancreatitis begins as pancreastasis,13 prevention of apical exocytosis in the pancreatic acinar cell (figure 1).15 The acinar cell quickly releases newly synthesised enzyme via the basolateral membrane into lymphatics, by way of the interstitium, and directly into the bloodstream.16 Some zymogen granules also release their stored enzyme basolaterally.15 These events result in inflammation.17 Findings from prospective clinical

Causes

Panel 1 lists causative factors of chronic pancreatitis. In adults, excluding those with cystic fibrosis, 90–95% of patients are regarded as having alcoholic or idiopathic disease. Infective causes are rare.52 The connection between chronic pancreatitis and drugs (eg, valproate) is mostly anecdotal. Studies from Italy,53 China, and Japan54 report an association with gallstones in about 30% of patients.

Pathogenesis

There is no agreement as to how these diverse causative factors lead to chronic pancreatitis. There are many hypotheses about the pathogenesis of the disease,43 which fall into five main categories.

Clinical features

Alcoholic chronic pancreatitis presents in the fourth or fifth decade of life and mainly affects men.86 Idiopathic disease has early-onset (second decade) and late-onset (sixth decade) forms, which have equal gender distribution.12, 86 Hereditary disease manifests at around 10 years87 and tropical pancreatitis at between 20 and 30 years,65 whereas the more common type-1 form of autoimmune disease affects men in the sixth decade.51

Presenting features of chronic pancreatitis usually fall into one

Diagnosis

Routine laboratory tests might reveal incipient diabetes, type-1 hyperlipidaemia, or hypercalcaemia in patients with suspected chronic pancreatitis. If type-1 autoimmune disease is a possibility, serology will show raised concentrations of γ-globulin, IgG (IgG4 predominantly), and various antibodies, including anti-lactoferrin, anti-carbonic anhydrase, rheumatoid factor, and anti-nuclear antibody.50, 51 An abnormal liver function profile suggests alcoholic liver disease, non-alcoholic

Treatment goals

The goals of treatment for chronic pancreatitis are to relieve acute or chronic pain, calm the disease process to prevent recurrent attacks, correct metabolic consequences such as diabetes or malnutrition, manage complications when they arise, and address psychosocial problems. Endoscopic treatment, surgery, or both, are only needed when optimum medical treatment fails to relieve pain (figure 8) and to deal with specific complications (figure 3). A detailed discussion of complications is beyond

Conclusions

Chronic pancreatitis remains a challenging disease. Resective surgery continues to be the definitive treatment for persistent pain, but is not ideal in a chronic inflammatory process. Micronutrient treatment might offer a viable alternative.

Search strategy and selection criteria

We searched PubMed and the Cochrane library (to August, 2010) for reviews on chronic pancreatitis. We used Google scholar for specific searches, with “chronic pancreatitis” as the key phrase combined with “epidemiology”, “pathology”, “aetiology”, “gene mutations”, “pathogenesis”, “classification”, “diagnosis”, “pancreatic function tests”, “pancreatic imaging tests”, “treatment of pain”, “pancreatic enzyme therapy”, “micronutrient therapy”, “antioxidant therapy”, “endoscopic treatment”, or

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