Clinical review

Chronic pancreatitis

P C Bornman, I J Beckingham. 

Chronic pancreatitis has an annual incidence of about one person per 100 000 in the United Kingdom and a prevalence of 3/100 000. In temperate areas alcohol misuse accounts for most cases, and it mainly affects men aged 40-50 years. There is no uniform threshold for alcohol toxicity, but the quantity and duration of alcohol consumption correlates with the development of chronic pancreatitis. Little evidence exists, however, that either the type of alcohol or pattern of consumption is important. Interestingly, despite the common aetiology, concomitant cirrhosis and chronic pancreatitis is rare.

In a few tropical areas, most notably Kerala in southern India, malnutrition and ingestion of large quantities of cassava root are implicated in the aetiology. The disease affects men and women equally, with an incidence of up to 50/1000 population.

View larger version (139K): [in this window] [in a new window]   Endoscopic retrograde cholangiopancreatogram showing dilated common bile duct (thick arrow) and main pancreatic ducts (thin arrow) in patient with advanced chronic pancreatitis

	Natural course

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Alcohol induced chronic pancreatitis usually follows a predictable course. In most cases the patient has been drinking heavily (150-200 mg alcohol/day) for over 10 years before symptoms develop. The first acute attack usually follows an episode of binge drinking, and with time these attacks may become more frequent until the pain becomes more persistent and severe. Pancreatic calcification occurs about 8-10 years after the first clinical presentation. Endocrine and exocrine dysfunction may also develop during this time, resulting in diabetes and steatorrhoea. There is an appreciable morbidity and mortality due to continued alcoholism and other diseases that are associated with poor living standards (carcinoma of the bronchus, tuberculosis, and suicide), and patients have an increased risk of developing pancreatic carcinoma. Overall, the life expectancy of patients with advanced disease is typically shortened by 10-20 years.

	Symptoms and signs

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The predominant symptom is severe dull epigastric pain radiating to the back, which may be partly relieved by leaning forward. The pain is often associated with nausea and vomiting, and epigastric tenderness is common. Patients often avoid eating because it precipitates pain. This leads to severe weight loss, particularly if patients have steatorrhoea.

View larger version (80K): [in this window] [in a new window]   Computed tomogram showing dilated pancreatic duct with multiple calcified stones

Steatorrhoea presents as pale, loose, offensive stools that are difficult to flush away and, when severe, may cause incontinence. It occurs when over 90% of the functioning exocrine tissue is destroyed, resulting in low pancreatic lipase activity, malabsorption of fat, and excessive lipids in the stools.

One third of patients will develop overt diabetes mellitus, which is usually mild. Ketoacidosis is rare, but the diabetes is often "brittle," with patients having a tendency to develop hypoglycaemia due to a lack of glucagon. Hypoglycaemic coma is a common cause of death in patients who continue to drink or have had pancreatic resection.

View larger version (131K): [in this window] [in a new window]   Plain abdominal radiograph showing multiple calcified stones within the pancreatic duct

	Diagnosis

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Early diagnosis of chronic pancreatitis is usually difficult. There are no reliable biochemical markers, and early parenchymal and ductal morphological changes may be hard to detect. The earliest signs (stubby changes of the side ducts) are usually seen on endoscopic retrograde cholangiopancreatography, but a normal appearance does not rule out the diagnosis. Tests of pancreatic function are cumbersome and seldom used to confirm the diagnosis. Thus, early diagnosis is often made by exclusion based on typical symptoms and a history of alcohol misuse.

In patients with more advanced disease, computed tomography shows an enlarged and irregular pancreas, dilated main pancreatic duct, intrapancreatic cysts, and calcification. Calcification may also be visible in plain abdominal radiographs. The classic changes seen on endoscopic retrograde cholangiopancreatography are irregular dilatation of the pancreatic duct with or without strictures, intrapancreatic stones, filling of cysts, and smooth common bile duct stricture.

	Treatment

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Treatment is focused on the management of acute attacks of pain and, in the long term, control of pain and the metabolic complications of diabetes mellitus and fat malabsorption. It is important to persuade the patient to abstain completely from alcohol. A team approach is essential for the successful long term management of complex cases.

Pain
Persistent or virtually permanent pain is the most difficult aspect of management and is often intractable. The cause of the pain is unknown. Free radical damage has been suggested as a cause, and treatment with micronutrient antioxidants (selenium,  carotene, methionine, and vitamins C and E) produces remission in some patients. However, further randomised trials are required to confirm the efficacy of this approach. In the later stages of disease pain may be caused by increased pancreatic ductal pressure due to obstruction, or by fibrosis trapping or damaging the nerves supplying the pancreas.

View larger version (78K): [in this window] [in a new window]   Patient using hot water bottle to relieve back pain due to chronic pancreatitis

Steatorrhoea
Steatorrhoea is treated with pancreatic replacements with the aim of controlling the loose stools and increasing the patient's weight. Pancreatic enzyme supplements are rapidly inactivated below pH5, and the most useful supplements are high concentration, enteric coated microspheres that prevent deactivation in the stomachfor example, Creon or Pancrease. A few patients also require H₂ receptor antagonists or dietary fat restriction.

Diabetes mellitus
The treatment of diabetes is influenced by the relative rarity of ketosis and angiopathy and by the hazards of potentially lethal insulin induced hypoglycaemia in patients who continue to drink alcohol or have had major pancreatic resection. It is thus important to undertreat rather than overtreat diabetes in these patients, and they should be referred to a diabetologist when early symptoms develop. Oral hypoglycaemic drugs should be used for as long as possible. Major pancreatic resection invariably results in the development of insulin dependent diabetes.

View larger version (43K): [in this window] [in a new window]   Duodenal preserving resection of the pancreatic head (Beger procedure). Top: pancreatic head resected. Bottom: reconstruction with jejunal Roux loop

	Endoscopic procedures

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Endoscopic procedures to remove pancreatic duct stones, with or without extracorporeal lithotripsy and stenting of strictures, are useful both as a form of treatment and to help select patients suitable for surgical drainage of the pancreatic duct. However, few patients are suitable for these procedures, and they are available only in highly specialised centres.

	Surgery

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Surgery should be considered only after all forms of conservative treatment have been exhausted and when it is clear that the patient is at risk of becoming addicted to narcotics. Unless complications are present, the decision to operate is rarely easy, especially in patients who have already become dependent on narcotic analgesics.

View larger version (116K): [in this window] [in a new window]   Large pseudocyst in patient with chronic pancreatitis. The cyst is thin walled and bulging into the stomach and is ideal for endoscopic drainage

The surgical strategy is largely governed by morphological changes to parenchymal and pancreatic ductal tissue. As much as possible of the normal upper gastrointestinal anatomy and pancreatic parenchyma should be preserved to avoid problems with diabetes mellitus and malabsorption of fat. The currently favoured operations are duodenal preserving resection of the pancreatic head (Beger procedure) and extended lateral pancreaticojejunostomy (Frey's procedure). More extensive resections such as Whipple's pancreatoduodenectomy and total pancreatectomy are occasionally required. The results of surgery are variable; most series report a beneficial outcome in 60-70% of cases at five years, but the benefits are often not sustainable in the long term. It is often difficult to determine whether failures are surgically related or due to narcotic addiction.

	Complications of chronic pancreatitis

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Pseudocysts
Pancreatic pseudocysts are localised collections of pancreatic fluid resulting from disruption of the duct or acinus. About 25% of patients with chronic pancreatitis will develop a pseudocyst. Pseudocysts in patients with chronic pancreatitis are less likely to resolve spontaneously than those developing after an acute attack, and patients will require some form of drainage procedure. Simple aspiration guided by ultrasonography is rarely successful in the long term, and most patients require internal drainage. Thin walled pseudocysts bulging into the stomach or duodenum can be drained endoscopically, with surgical drainage reserved for thick walled cysts and those not bulging into the bowel on endoscopy. Occasionally, rupture into the peritoneal cavity causes severe gross ascites or, via pleuroperitoneal connections, a pleural effusion.

View larger version (126K): [in this window] [in a new window]   Endoscopic drainage of pseudocyst: sphincterotome is cutting a hole between stomach and pseudocyst wall

Biliary stricture
Stenosis of the bile duct resulting in persistent jaundice (more than a few weeks) is uncommon and usually secondary to pancreatic fibrosis. The duct should be drained surgically, and this is often done as part of surgery for associated pain or duodenal obstruction. Endoscopic stenting is not a long term solution, and is indicated only for relief of symptoms in high risk cases.

Gastroduodenal obstruction
Gastroduodenal obstruction is rare (1%) and usually due to pancreatic fibrosis in the second part of the duodenum. It is best treated by gastrojejunostomy.

	Splenic vein thrombosis

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Venous obstruction due to splenic vein thrombosis (segmental or sinistral hypertension) may cause splenomegaly and gastric varices. Most thrombi are asymptomatic but pose a severe risk if surgery is planned. Splenectomy is the best treatment for symptomatic cases.

Gastrointestinal bleeding
Gastrointestinal bleeding may be due to gastric varices, coexisting gastroduodenal disease, or pseudoaneurysms of the splenic artery, which occur in association with pseudocysts. Endoscopy is mandatory in these patients. Pseudoaneurysms are best treated by arterial embolisation or surgical ligation.

	Footnotes

P C Bornman is professor of surgery, University of Cape Town, South Africa.

The ABC of diseases of liver, pancreas, and biliary system is edited by I J Beckingham, consultant hepatobiliary and laparoscopic surgeon, department of surgery, Queen's Medical Centre, Nottingham (Ian.Beckingham{at}nottingham.ac.uk). The series will be published as a book later this year.