Chronic pancreatitis is due to persistent progressive inflammation of the pancreas resulting in loss of exocrine function, and frequently in diabetes. Alcohol abuse accounts for about 75% of cases, although only about 5% of those with alcohol problems develop pancreatitis. Other known causes include tropical pancreatitis, cystic fibrosis and genetic syndromes such as hereditary pancreatitis, which between them account for about 5% of cases. About 20% of cases develop for reasons that are unknown. Chronic pancreatitis may develop silently, but usually presents with recurrent painful episodes, and is associated with chronic pain and cachexia due to loss of exocrine function. Diabetes develops in some 50–70% of cases, typically presenting about 5 years after the diagnosis of pancreatitis. Recurrent acute pancreatitis predisposes to the development of chronic pancreatitis, and chronic pancreatitis, whether hereditary or alcohol-related, predisposes to carcinoma of the pancreas. Diagnosis is by contrast-enhanced computerised tomography (CT). Treatment is symptomatic, with avoidance of predisposing factors such as alcohol, pancreatic enzymes taken by mouth to combat malabsorption, and control of diabetes, for which insulin is often needed. Intractable pain may lead to narcotic addiction; surgical treatment with pancreatic resection can be helpful.
Chronic pancreatitis arises from recurrent or persistent inflammation of the pancreas, resulting in permanent damage to the organ. It is difficult to diagnose in its early stages, and its true incidence is unknown. The incidence of chronic pancreatitis has increased fourfold over the past 30 years, but this is probably due to greater awareness and improved diagnostic procedures, and it is likely that a high proportion of cases are subclinical or undiagnosed, particularly in those who do not experience pain. The true prevalence is therefore unknown.
The majority of cases present at 35–55 years old with recurrent episodes of acute abdominal pain or pancreatitis, progressing to chronic intractable pain. The pain is typically epigastric, radiating to the back, and brought on by food; it is sometime relieved by leaning forward or sitting upright. About 10–20% of cases present without pain.
Other presenting features include weight loss, steatorrhoea, malabsorption or vitamin deficiency; diabetes usually presents late in the disease course.
The likely pathophysiology includes activation of trypsinogen with local release of the digestive enzyme trypsin. Trypsinogen and other precursors of digestive enzymes are contained within zymogen granules located within the acinar cells of the pancreas, and these granules release their contents into the pancreatic ducts and thence into the small intestine as a result of food ingestion. Aberrant release may produce autodigestion of the surrounding pancreatic tissue, and the resulting inflammatory response will in turn promote local scarring and fibrosis.
The acute response is usually self-limiting, but chronic changes may result from recurrent episodes of pancreatic inflammation. Inflammation followed by cell death results in the 'necrosis-fibrosis sequence', and ongoing fibrosis leads to loss of pancreatic acinar cells and the development of exocrine deficiency. Beyond a certain point, and for reasons which are still unknown, these changes become self-sustaining and progress toward total destruction of the organ. Persistent inflammation may also lead to DNA damage, accumulation of harmful mutations and the development of pancreatic a
Role of the pancreatic stellate celldenocarcinoma.
The pancreatic stellate cell is a myofibroblast-like cell resident in the inter-acinar spaces, and it has been postulated that activation of this cell type may play a key role in the onset and progression of pancreatic fibrosis.
The TIGAR-O classification of risk factors associated with chronic pancreatitis id as follows:
Toxic: alcohol, chronic renal failure, drugs
Idiopathic: unknown causes, tropical pancreatis
Recurrent: recurrent acute pancreatitis, post-irradiation
Obstructive: obstruction for any cause, pancreas divisum
The incidence typically ranges between 3 and 10 per 100,000 around the world. Chronic pancreatitis carries a mortality 3.6 times higher than in individuals without pancreatitis, in large part due to the lifestyle and extensive co-morbidity that are associated with the condition.
Chronic pancreatitis may present silently or in the context of recurrent episodes of acute pancreatitis, observed in about 50% of patients. Pancreatic pain, whose origin remains uncertain, may affect up to 75% of those affected, and is sometimes highly debilitating. Steatorrhea and other manifestations of exocrine pancreatic deficiency are common, and diabetes is also commonly present.
Carcinoma of the pancreas
Alcoholic chronic pancreatitis is associated with a lifestyle and life expectancy that limit the possibilities of long-term surveillance, but the risk of progression to pancreatic adenocarcinoma has been estimated at 1.8% after 10 years and 4% after 20 years, with a relative risk of about 14.
The relationship between pancreatitis and adenocarcinoma has been most clearly defined for hereditary pancreatitis, a rare condition characterised by recurrent episodes of acute pancreatitis beginning in childhood or adolescence, with almost inevitable progression to chronic pancreatitis. In this condition the risk of pancreatic cancer is increased 50-fold, to the extent that 40% of individuals are affected by the age of 70 years.
The relationship between chronic pancreatitis and carcinoma of the pancreas might potentially be explained on the basis that shared genes or genetic mutations are responsible for both conditions. On present evidence, the hypothesis of genetic predestination appears unlikely, since environmental agents undoubtedly play a major role. Cigarette smoking is for example strongly linked to the development of pancreatic cancer, to the extent that individuals with hereditary pancreatitis who smoke develop the cancer at a median age 20 years below that of non-smokers. On the basis of this and allied evidence, Whitcomb concludes that pancreatic adenocarcinoma, like almost all the other common cancers, is a complex trait disorder resulting from the interaction of multiple genes and environmental exposures.