Chronic pancreatitis

Published on 09/04/2015 by admin

Filed under Gastroenterology and Hepatology

Last modified 22/04/2025

Print this page

This article have been viewed 1352 times

Chapter 12 CHRONIC PANCREATITIS

• Chronic pancreatitis, chronic inflammation of the pancreas, is characterised by progressive irreversible loss of pancreatic exocrine and endocrine function.

• Chronic pancreatits manifests with chronic abdominal pain, maldigestion and secondary diabetes mellitus.

• The most common cause in Western nations is alcohol abuse.

• Autoimmune pancreatitis can present as a mass masquerading as a pancreatic malignancy.

AETIOLOGY AND PATHOGENESIS

The most common cause of chronic pancreatitis in Western nations is alcohol abuse (Table 12.1).

TABLE 12.1 Causes of chronic pancreatitis

• Chronic alcohol abuse

• Idiopathic

• Hypercalcaemia

• Hypertriglyceridaemia

• Trauma

• Hereditary

• Cystic fibrosis

• Tropical pancreatitis

• Autoimmune

• Obstruction, e.g. pancreas divisum, tumour, calculi

Alcohol

Alcohol accounts for 70%–90% of all cases of chronic pancreatitis in Western societies. The onset of alcoholic pancreatitis usually occurs in the fourth decade, and the majority of patients are males consuming alcohol in the order of 100–150 g/day (i.e. 10–15 standard drinks/day) in the 5–15 years prior to initial presentation. Typically, the initial clinical presentation of alcohol-mediated pancreatic injury is acute pancreatitis. However, the characteristic histological and radiological features of chronicity (atrophy, fibrosis and calcification) are already evident in a large proportion of these patients on initial presentation.

Idiopathic chronic pancreatitis

This condition has a bimodal distribution with an earlier median peak at 19 years and a late median peak at 56 years of age. This condition also presents initially as clinical recurrent acute pancreatitis manifesting chronic features over time. Several genetic defects have been linked to the development of idiopathic chronic pancreatitis. A less severe phenotype of idiopathic chronic pancreatitis in the absence of the classic full cystic fibrosis syndrome can be caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7q31.2. Inappropriate activation of the cationic trypsinogen gene (PRSS1), and mutations of the serine protease inhibitor Kazal type 1 (SPINK1), a potent natural inhibitor of pancreatic trypsin activity, may also result in chronic pancreatitis.

Hereditary pancreatitis

This inherited form of pancreatitis caused by mutations of the cationic trypsinogen gene (PRSS1) on chromosome 7q35 is autosomal dominant with 80% penetrance. Trypsin activation is central to the activation of the other digestive pancreatic proenzymes. The onset of this condition is in childhood, with progression to chronic pancreatitis as early as the late teens. There is an increased risk of pancreatic cancer: 40% of patients will have cancer by age 70. Mutation of the SPINK1 gene has been implicated in hereditary pancreatitis. Other inherited disorders that may cause pancreatitis are cystic fibrosis (see below), familial hyperparathyroidism with hypercalcaemia, familial hyperlipidaemia due to lipoprotein lipase deficiency and apolipoprotein C-II deficiency.

Cystic fibrosis

There is a correlation between the degree of abnormal CFTR function and severity of cystic fibrosis. Exocrine pancreatic insufficiency occurs in approximately 85% of patients with cystic fibrosis due to defective secretory capacity of bicarbonate and digestive enzymes. Chronic pancreatitis and pancreatic atrophy arises from inspissated protein-rich acinar secretions that obstruct the ducts resulting in cellular destruction and fibrosis.

Tropical pancreatitis

This form of pancreatitis is restricted to areas within 30 degrees of latitude from the equator and is associated with protein–calorie malnutrition. The pathogenesis of this condition has not been clarified.

Autoimmune pancreatitis

Autoimmune pancreatitis is characterised by the presence of autoantibodies and elevated immunoglobulins (elevated IgG4) in the serum, and lymphocytic infiltration of the pancreas. It may masquerade as pancreatitis or as a pancreatic mass mistaken for cancer. Corticosteroids are the mainstay of therapy for this condition.

Obstructive pancreatitis

Obstruction of the pancreatic duct by tumours, papillary stenosis, cysts and strictures may cause pancreatitis. In pancreas divisum, the dorsal pancreatic duct is drained by the minor papilla. Inadequacy of drainage may, in a small minority of cases of pancreas divisum, result in acute or chronic pancreatitis.

ASSESSMENT

The diagnosis of chronic pancreatitis is clinical, based on symptomatology, known risk factors and investigatory evidence.

History and examination

Investigations

Serum pancreatic enzymes

The diagnosis of acute pancreatitis is made clinically and confirmed by an elevated serum amylase and/or lipase greater than three times the upper limit of normal. However, in chronic pancreatitis, the levels of these enzymes may be normal or below the normal range.

Pancreatic imaging

Abdominal X-ray, ultrasonography

Plain abdominal X-ray and ultrasound may detect the pancreatic calcification of chronic pancreatitis.

Computed tomography, magnetic resonance imaging

Computed tomography (CT) with intravenous contrast is useful for diagnosing pancreatitis, pancreatic necrosis (non-contrast enhancing segments of pancreas) and the development of fluid collections. Magnetic resonance imaging (MRI) can provide images of the pancreatic parenchyma.

Endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography

Endoscopic retrograde cholangiopancreatography (ERCP) defines abnormalities of pancreatic ducts in chronic pancreatitis. However, ERCP is invasive and can cause complications including inducing acute pancreatitis, duodenal perforation, sepsis and haemorrhage. Magnetic resonance cholangiopancreatography (MRCP) is non-invasive and can demonstrate ductal anatomy with accuracy comparable to that of ERCP.

Endoscopic ultrasonography

Endoscopic ultrasonography (EUS) of the pancreas produces high-resolution imaging of both duct and parenchyma and can aid biopsy of areas of interest. Although it shows promise, the full role of EUS in the diagnosis of chronic pancreatitis is yet to be defined.

Pancreatic function tests

Secretin/CCK/meal stimulation tests (tube tests of pancreatic function)

These tests involve the collection of pancreatic juice to measure enzyme, volume or bicarbonate output via duodenal intubation and are performed following stimulation of the pancreas by a secretagogue such as secretin or cholecystokinin (CCK) or a test meal (Lundh test). Pancreatic insufficiency is diagnosed by a low flow rate of pancreatic juice and/or decreased enzyme and bicarbonate levels in the juice. These tests are available in only a few specialised units worldwide.

Indirect tests of pancreatic function

These tests are of limited value because they miss less severe cases of chronic pancreatitis. Indirect tests of exocrine pancreatic function include the ¹³C-/¹⁴C-triolein breath test, measurement of faecal chymotrypsin and elastase, the N-benzoyl-L-tyrosyl-para-aminobenzoic acid (bentiromide; NBT-PABA) test, the pancreolauryl test and the fluorescein dilaurate test.

Faecal fat analysis

Quantitative fat analysis

The van de Kamer method is considered the gold standard test of steatorrhoea and measures the grams of faecal fat output per day. Faecal fat excretion of <7 g/day on a 100 g/day fat diet is considered normal. However the test is cumbersome and unpleasant, and requires laboratory handling of 72-hour stool collection.

Qualitative faecal fat analysis

A microscopic examination of random stool using glacial acetic acid and Sudan III stain for orange fat globules is a simple test for steatorrhoea. However, the test has only 78% sensitivity and 70% specificity.

Differential diagnosis of chronic upper abdominal pain

Peptic ulcer disease

Peptic ulcer pain is typically central epigastric, intermittent and burning in quality. Classical teaching distinguishes duodenal ulcer (DU) pain from the gastric ulcer (GU) pain by its relation to food. The pain of DU occurs in the evening and early morning and wakes the patient up from sleep between 12 am and 3 am, corresponding to times of high duodenal acid load. Hunger pains and pain relieved by food and weight gain are other features. In contrast, GU pain is aggravated rather than relieved by food and is more associated with nausea or anorexia. Patients who suffer from GU tend to be older than patients with DU and are more likely to be consuming aspirin or NSAIDs. Importantly, patients taking NSAIDs presenting with complicated ulcers often do not have antecedent abdominal pain, possibly due to the analgesic effect from the drug. Conversely, many patients who have typical ulcer-like pain turn out to have non-ulcer dyspepsia. Thus the sensitivity and specificity of typical dyspepsia for the diagnosis of peptic ulcers are low.

Less common causes of ulcers in the upper gastrointestinal tract that can present with pain are Crohn’s disease, viral infections, Behçet’s disease and Zollinger-Ellison syndrome.

Non-ulcer (functional) dyspepsia

Dyspepsia refers to recurrent chronic epigastric pain or meal-related discomfort. The pain of non-ulcer dyspepsia (NUD) is caused by a combination of visceral hypersensitivity and dysmotility, with possible psychosocial influences.

Malignancy

Cancers of the stomach, pancreas, colon and lymphomas may localise pain to the upper abdomen. New-onset pain in the elderly is particularly suspicious and warrants further investigation.

Biliary causes

Biliary colic is typically visceral, sudden in onset and localised in the epigastrium. Movement does not aggravate pain. Common bile duct stones may also cause jaundice, cholestasis (pale stools with dark urine) and cholangitis (fever, rigors). Cholecystitis causes a peritoneal type of pain and tenderness localised at the right upper quadrant. Sphincter of Oddi dysfunction also presents with recurrent biliary pain.

Neuropathic causes

Neuropathic pain may arise from intercostal nerve neuralgia such as from herpes zoster.

Other causes

Mesenteric ischaemia may cause epigastric or periumbilical pain made worse by eating, leading to sitophobia and weight loss. Uncommon causes of abdominal pain include poorly controlled or new onset diabetes mellitus, hypercalcaemia, porphyria and lead poisoning.

MANAGEMENT OF CHRONIC PANCREATITIS

Diet, nutrition and antioxidants

A low to moderate fat diet (30%–40% of total calories) helps reduce steatorrhoea and stimulation of pancreatic secretion. Supplementation of fat-soluble and other vitamins are indicated in deficient states. Medium-chain triglycerides, which are directly absorbed into the portal vein and do not require digestion, are rarely required. Protein intake should average 1.0–1.5 g/kg/day. Abstinence from alcohol is absolutely essential in alcoholic pancreatitis. Oxidative stress has been proposed as a mechanism in chronic pancreatitis. Whether antioxidants are useful in the treatment of chronic pancreatitis is unclear.

Treatment of pain

Appropriate and adequate treatment of the abdominal pain of chronic pancreatitis can be a challenge. In some situations, a team effort involving a gastroenterologist, surgeon, pain specialist, psychiatrist/psychologist and social worker may be required. Drug and alcohol dependence requires treatment by specialists in this field.

Analgesics

Analgesics, including non-steroidal antiinflammatory agents, paracetamol and tramadol, should be tried initially. Non-opioid analgesics, however, are often insufficient in managing pain and patients frequently require preparations that include codeine, dextropropoxyphene, oxycodone or morphine. Long-acting agents are more effective (e.g. transdermal fentanyl). A common dilemma is differentiating between narcotic addiction and pancreatic pain as the major driving force behind the patient’s presentation.

Pancreatic enzymes

Exogenous pancreatic enzymes, when administered in sufficient quantities with meals, reduce the secretion of endogenous enzymes from the pancreas through a negative feedback mechanism. This, in turn, may reduce pancreatic intraductal and interstitial pressure and provide pain relief.

Octreotide

Octreotide (300 μg/day by subcutaneous injection) can significantly reduce pancreatic secretion as measured by faecal chymotrypsin. However, pain scores and consumption of analgesics were not reduced compared to controls in a short-term trial.

Treatment of pancreatic exocrine insufficiency

For treating exocrine insufficiency, adequate amounts of pancreatic enzymes need to be taken; the treatment aims are weight stabilisation, improvement of diarrhoea and reduction in faecal fat excretion. Refractory steatorrhoea is treated with dose increase of pancreatic enzymes, use of an enteric coated formulation and introduction of acid suppression with a proton pump inhibitor (to reduce enzyme degradation in the stomach).

Treating diabetes mellitus

Achieving glucose homeostasis can be difficult in patients with secondary diabetes because of the increased potential for hypoglycaemia due to malabsorption, irregular caloric intake and impaired glucagon secretion (‘brittle diabetes’). Insulin therapy should be avoided in those who continue to abuse alcohol.

Endoscopic interventional therapies

These procedures have been designed to clear the ducts of calculi (often with the aid of extracorporeal shock wave lithotripsy), relieve duct obstruction due to strictures (by stenting) or divide the pancreatic duct sphincter, with the rationale that pain from chronic pancreatitis partly originates from raised intraductal and/or interstitial pressure. As yet these procedures have not been subjected to high-quality randomised controlled trials.

Surgery

The rationale for surgical treatment of chronic pancreatitis is to decompress the pancreatic duct and interstitium or to resect diseased tissue causing pain. Surgical treatments comprise pancreatic drainage procedures or pancreatic resection. Currently, surgery is considered for intractable pain that substantially interferes with the patient’s quality of life and that cannot be controlled by medical therapy.

Pancreatic duct drainage

The Puestow procedure (lateral pancreaticojejunostomy) is performed when the main pancreatic duct in the head and body of the pancreas dilates to at least 7 mm. The rationale for this operation is to reduce intraductal pressure. This procedure has the advantage of preserving pancreatic tissue with low morbidity and mortality. In terms of pain reduction, surgery is superior to endoscopic treatment in those with a dilated pancreatic duct.

Pancreatic resection

Pancreatic resection is considered when the main duct is not dilated. Distal pancreatectomy is undertaken for disease confined to the body and tail of the gland. A pylorus-preserving Whipple procedure or duodenal-preserving resection of the pancreatic head is performed for more diffuse disease.

Coeliac plexus neurolysis

Percutaneous or EUS-guided coeliac plexus neurolysis using alcohol may provide temporary relief.

COMPLICATIONS OF CHRONIC PANCREATITIS

Pancreatic pseudocyst

Pseudocysts can occur in approximately 25% of patients with chronic pancreatitis. They present with pain, local pressure symptoms caused by mass effect, bleeding or sepsis. Symptomatic longstanding pseudocysts that are greater than 6 cm and with mature walls are usually treated. Drainage of the cyst can be percutaneous, EUS-guided, or surgical (cystogastrostomy, cystoenterostomy).

Bleeding

Gastrointestinal haemorrhage associated with pancreatitis may be from several causes. Isolated gastric varices may develop as a result of portal hypertension due to splenic vein thrombosis. Pseudoaneurysms may develop as a result of enzymatic or pressure erosion of an artery by a pseudocyst and may subsequently rupture into the peritoneal cavity or gastrointestinal tract.

Pancreatic fistula

Fistulae develop when pancreatic juice leaks from disrupted pancreatic ducts. An external fistula results from tracking of the pancreatic juice along a surgical or percutaneous tract. Internal fistulae develop following rupture of a pseudocyst (communicating with the pancreatic duct) into the peritoneal cavity, pleural cavity and other spaces. Treatment includes octreotide to reduce pancreatic secretion, endoscopic stenting of pancreatic duct obstruction downstream from the site of the leak and possibly surgery.

Pancreatic cancer

Chronic pancreatitis is associated with an increased risk of pancreatic cancer, with a cumulative risk of 1.8% (95% confidence interval [CI]: 1.0 to 2.6) for subjects followed for 10 years and 4% (95% CI: 2.0 to 5.9) for those followed for 20 years. Imaging techniques often cannot distinguish between cancer and focal pancreatitis. Screening may be appropriate in patients with hereditary pancreatitis who have a very high risk of developing cancer.

SUMMARY

Up to 50% of patients with chronic pancreatitis develop diabetes mellitus. Pancreatic imaging is a vital part of the investigation of chronic pancreatitis (see Figure 12.1). Tests include abdominal X-ray and ultrasonography to detect calcification. CT scan and MRI can detect pancreatic necrosis and fluid collections. MRCP can demonstrate ductal anatomy. EUS assesses parenchyma and duct and can biopsy suspicious lesions.

FIGURE 12.1 Chronic pancreatitis.

Quantitative or qualitative faecal fat analysis may assist in the diagnosis of chronic pancreatitis.

Management focuses on alcohol abstinence, improving nutrition and treatment of pain. Non-opioid analgesics may help, but patients often require narcotic preparations. Exogenous pancreatic enzymes are the cornerstone of therapy.

Endoscopic interventional therapies have been used to clear the ducts of calculi, relieve duct obstruction due to strictures or to divide the pancreatic duct sphincter. Surgery may be indicated to decompress the pancreatic duct and is more effective than endoscopic trans-ampullary drainage.

Major complications of chronic pancreatitis are pancreatic pseudocyst, gastrointestinal haemorrhage, pancreatic fistula (internal or external) and an increased risk of pancreatic cancer.

Recent Posts

Meta

Categories

Search Engine

Chronic pancreatitis

Share this:

Related

Related posts: