Pancreatitis

Seminar

Chronic pancreatitis
Joan M Braganza, Stephen H Lee, Rory F McCloy, Michael J McMahon
Lancet 2011; 377: 1184–97 Published Online March 11, 2011 DOI:10.1016/S01406736(10)61852-1 Department of Gastroenterology (J M Braganza DSc) and Department of Radiology (S H Lee FRCR), Manchester Royal Infirmary, Manchester, UK; Department of Education, Lancashire Teaching Hospitals, Preston, UK (RF McCloy FRCS); and University of Leeds and Nuffield Hospital, Leeds, UK (Prof M J McMahon FRCS) Correspondence to: Dr Joan M Braganza, c/o Mrs Jenny Parr, Core Technology Facility, 3rd Floor, Grafton Street, Manchester M13 9NT, UK jenny.parr@manchester.ac.uk

Chronic pancreatitis is a progressive fibroinflammatory disease that exists in large-duct (often with intraductal calculi) or small-ductform. 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 apicalexocytosis 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 asa 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. Twoforms are recognised—a large-duct calcifying type1 and a small-duct variant.2–4 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, whichoccurs 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 causativefactors lead to the disease. Therefore, in this Seminar we focus on the pathophysiology and pathology of chronic pancreatitis before describing clinical management.

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;10–12 there is an overlap in causative factors, both genetic and environmental;10,13 experimental protocols can be modified to induce each condition;14 and the pancreatitis attack is stereotyped—patients have severe abdominal pain and increased blood amylase, lipase, and trypsinogen.

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...