4.2.1 CLINICAL MANIFESTATIONS 

Pain from acute pancreatitis is a knife-like, steady, sharp pain that starts suddenly and reaches its zenith rapidly. It is commonly localized to the epigastric area and may radiate directly to the back. It improves on leaning forward and is frequently associated with nausea or vomiting. Depending on the location of the inflammation, the pain may be referred to either the left upper quadrant or the right upper quadrant. When the pancreatitis is severe, it may result in shock and may lead to death. Frequently the pain is dyspeptic in quality and aggravated by food. This is due partially to the fact that eating stimulates secretion. Classically the pain lasts between three and four days. When the pancreatitis is severe, it may result in peripheral circulatory failure; under these conditions, the mortality rate approaches 60%.

Recurrent nausea and vomiting may be due to a reflex mechanism secondary to pain and occurs in over 90% of the cases. Other causes include pseudo-obstruction secondary to ileus and distention or obstruction secondary to a pancreatic mass or pseudocyst. Since the common bile duct traverses the pancreatic head before entering the duodenum, jaundice may occur, often transiently.

Depending on the severity of pancreatitis, the patient may appear in distress or be in shock. Jaundice may be caused by edema of the head of the pancreas or by an obstructing stone. Tachycardia could be secondary to pain, volume depletion or the inflammatory process. Low-grade fever could be secondary to the inflammation in the pancreas or result from such complications as abscess formation.

Abdominal examination may reveal epigastric and abdominal tenderness with guarding or rigidity. Bluish discoloration of the flanks (Grey Turner's sign) or of the periumbilical area (Cullen's sign) indicates that blood from hemorrhagic pancreatitis has entered the fascial planes. The signs are not specific and may occur in any condition that causes retroperitoneal hemorrhage. Tender red and painful nodules that mimic erythema nodosum may appear over the extremities. These are often due to circulating lipases.

Since the signs and symptoms of acute pancreatitis may mimic those of surgically correctable intra-abdominal disorders, the diagnosis of acute pancreatitis is often one of exclusion. Other diseases to be considered are a perforated peptic ulcer, mesenteric thrombosis, intestinal obstruction, dissecting aneurysm, peritonitis, acute cholecystitis and appendicitis. The diagnostic process is complicated by the fact that hyperamylasemia can occur in disorders other than pancreatic inflammation (such as ectopic pregnancy, parotiditis, carcinoma of the lung, posterior penetrating ulcer, ruptured aortic aneurysm and opiate administration). Although amylase values greater than 1,000 units have been said to occur principally in conditions requiring surgery (e.g., biliary tract disease), this distinction is not absolute.

Local involvement of pancreatitis includes phlegmon (18%), pancreatic abscess (3%), pancreatic pseudocyst (10%) and thrombosis of the central portal system. Phlegmon is an area of edema, inflammation and necrosis without a definite structure (unlike an abscess). A phlegmon results from acute intrapancreatic inflammation with fat necrosis and pancreatic parenchymal and peripancreatic necrosis. This arises from the ischemic insult caused by decreased tissue perfusion and release of the digestive enzymes. When this damage is not cleared, further inflammation ensues, declaring itself by increased pain, fever and tenderness. In severe cases a secondary infection ensues, a process termed infected necrosis of the pancreas, which occurs within the first one to two weeks of the illness and carries a high mortality. This diagnosis can be made by computerized tomography (CT) and percutaneous aspiration of the area with subsequent bacterial staining and appropriate cultures. In 3% of acute pancreatitis an abscess develops, usually several weeks into the illness. An abscess is a well-defined collection of pus occurring after the acute inflammation has subsided.

A pseudocyst develops as a result of pancreatic necrosis and the escape of activated pancreatic secretions through pancreatic ducts. It contains blood and debris. This fluid coalesces and becomes encapsulated by an inflammatory reaction and fibrosis. These patients usually have pain and hyperamylasemia, but may be asymptomatic. They may present with an abdominal mass, causing compressive symptoms.

The aims of therapy of acute pancreatitis are (1) hemodynamic stabilization, (2) alleviation of pain, (3) stopping the progression of the damage, and (4) treatment of local and systemic complications. As yet there are no specific medical therapies capable of reducing or reversing the pancreatic inflammation. Hence therapeutic interventions are aimed at the complications of the disease.

Once the diagnosis is established with certainty, the patient's intravascular volume is replenished, and electrolytes, calcium, magnesium and blood sugar are closely monitored. Depending on the severity of the attack, an indwelling urinary catheter and close monitoring of urinary output may be necessary. Analgesics such as meperidine should be administered regularly during the first several days of the attack. This may alleviate the pain, decrease the patient's apprehension and improve respiration, thus preventing pulmonary complications such as atelectasis. The risk of narcotic addiction is minimal during the first days; most patients settle within 72 hours. The patient is kept off oral feeding; nasogastric suctioning is maintained if the disease is severe and complicated by vomiting and ileus. Mild cases with minimal symptoms may be managed without suctioning. The rationale behind nasogastric suctioning is to place the pancreas at rest by removing the acidic gastric juices. This suppresses secretin release and decreases pancreatic stimulation. The validity of this postulate has not been substantiated. Similarly, the use of acid-suppressive medications such as cimetidine has failed to show benefit in the treatment of acute pancreatitis. The use of enzyme inhibitors such as soybean trypsin inhibitor to prevent further damage is controversial, as is the use of prostaglandins and corticosteroids.

The routine administration of antibiotics does not improve the course of mild to moderate disease. However, when the development of pancreatic abscess is suspected from an increase in fever and abdominal pain, antibiotic therapy should be instituted using an aminoglycocide and cephalosporin.

Respiratory insufficiency may occur in up to 40% of the cases, usually in patients with severe or recurrent pancreatitis. In such patients, arterial oxygen saturation should be monitored and corrected. Fluid overload should be avoided. Intubation and ventilation may be required.

Peritoneal lavage has been advocated in patients with severe disease, such as those with marked hypovolemia or hypotension or those who continue to deteriorate despite appropriate medical therapy. Although this technique reduces the circulatory and renal complications, it does not seem to alter the local complications.

Intravenous hyperalimentation has been advocated in patients who continue to have pain and whose symptoms are aggravated postprandially. If during a trial of six weeks or longer, complications develop (such as an abscess or an enlargement of phlegmon), a surgical debridement may be warranted, albeit as a last resort.

Chronic pancreatitis is defined as a continued inflammation characterized by irreversible morphologic changes. These changes include fibrosis, ductal abnormality, calcification and cellular atrophy. Alcohol is the major etiologic factor, accounting for about 75% of the cases. Repeated attacks of gallstone-related pancreatitis rarely if ever result in chronic pancreatitis. Other causes include diabetes, protein-calorie malnutrition, hereditary pancreatitis, cystic fibrosis and idiopathic causes.

Alcohol presumably causes pancreatic injury by the intraductal formation of protein plugs secondary to increased protein concentration and precipitation, with or without calcification. These plugs lead to obstruction and secondary pancreatic damage caused by autodigestion. In developed countries chronic pancreatitis occurs after a long history (6 to 17 years) of alcohol ingestion of 150 to 170 g per day. Alcoholic pancreatitis is known to occur with much less consumption of alcohol, as low as 50 g per day. The mean age of a patient with new onset of disease is around 32 years, with a male predominance. Despite heavy drinking only a small number of alcoholics develop chronic pancreatitis, suggesting other factors that potentiate the injurious side effects of alcohol, including high-protein diet with either very high or very low fat content.

Chronic pancreatitis is characterized by irreversible injury to the pancreas and clinically by intractable abdominal pain and loss of exocrine and endocrine pancreatic function. The pain is localized to the upper abdomen, with radiation to subcostal regions and to the back. The pain is aggravated by meals and improves with fasting.

When more than 90% of exocrine pancreatic function is lost, maldigestion and malabsorption ensue. This is manifested by steatorrhea (fat malabsorption) associated with diarrhea and bloating, azotorrhea (protein malabsorption) and progressive weight loss. These patients frequently present with loss of adipose tissue, judged by hanging skin folds, and more objectively by demonstrating that the skin fold at the mid-triceps is less than 8 mm in males and less than 12 mm in females. In addition, patients manifest muscle wasting and edema, indicating protein deficiency. Latent fat-soluble vitamin deficiency (vitamins A, D, E and K) in addition to deficiencies of magnesium, calcium and essential fatty acids may occur and are closely related to dysfunction of fat digestion. Endocrine insufficiency presenting as diabetes mellitus may present at the same time as exocrine insufficiency or a few years later.

4.3.2 COMPLICATIONS

4.3.2.1 Pancreatic pseudocyst

Pancreatic pseudocyst is localized fluid collection occurring within a pancreatic mass or in the peripancreatic spaces following acute or chronic pancreatitis. The pseudocyst is usually surrounded by a non-epithelial-lined fibrous wall of granulation tissues. Its frequency varies from 10-50% of patients experiencing severe pancreatitis. When a pseudocyst is present for less than six weeks, it is considered acute; after that it becomes chronic. The pseudocyst may be asymptomatic or may present as an acute exacerbation of pancreatitis, with abdominal pain, nausea, vomiting and weight loss. These pseudocysts may obstruct intra-abdominal viscera, cause pancreatic ascites, rupture into viscera or the abdominal cavity, hemorrhage or become infected. Spontaneous resolution occurs in 20% of the cases within the first six weeks of the pseudocyst's development. Chronic pseudocysts or pseudocysts greater than 5 cm rarely improve. Asymptomatic patients with persistent psuedocysts should be observed and intervention may be considered if symptoms appear. Successful percutaneous catheter drainage may be accomplished by CT- or ultrasound-guided drainage techniques. The catheter may be required for up to six weeks and is frequently associated with infections. Surgical drainage is sometimes necessary for failed percutaneous drainage or for complicated pseudocysts. If the pseudocyst is in the head of the pancreas, drainage can be done via ERCP.

4.3.2.2 Pancreatic ascites

Pancreatic ascites results from the leakage of pancreatic juices into the peritoneal cavity through a fistula or ruptured pseudocyst. It presents with gradually increasing massive ascites, high levels of amylase, abdominal pain and weight loss. Painful areas of subcutaneous fat necrosis result from the high levels of circulating pancreatic lipase.

4.3.2.3 Common bile duct stricture

Common bile duct compression is another manifestation of chronic pancreatitis, but it rarely results in significant obstruction. As the distal common bile duct traverses the head of the pancreas, it may be narrowed secondary to inflammation, with edema or fibrosis of the gland.

Although pancreatic carcinoma was formerly thought to be increased in chronic pancreatitis, the incidence is now believed to be the same as in the general population. Pancreatic carcinoma may present as pancreatitis.

4.3.3 DIAGNOSTIC AND RADIOGRAPHIC EVALUATION

The ultimate goals of treatment in chronic pancreatitis are to alleviate pain, maintain adequate nutritional status, and reduce symptoms associated with steatorrhea such as abdominal pain, bloating and diarrhea.

The mechanism of pain in chronic pancreatitis is not known. Abstinence from alcohol may decrease the frequency and severity of painful attacks in patients with alcoholic pancreatitis. Large meals with foods rich in fat should be avoided. Analgesics should be given prior to meals, since the pain is maximal postprandially. The continuous use of narcotics often leads to drug addiction, which makes the management of pain more difficult. Large doses of pancreatic extracts may reduce the frequency and severity of the pain in patients with no demonstrable duct obstruction. These enzymes appear to suppress pancreatic exocrine output, thus putting the pancreas at rest and resulting in pain relief. Pancreatic replacement is given with meals and at bedtime. Patients who respond to this therapeutic regimen tend to be middle-aged women with idiopathic pancreatitis who suffer from mild or moderate disease. These patients tend to have a bicarbonate output greater than 55 mEq/L and normal fat absorption. Patients with more severe disease, whose peak bicarbonate output is less than 50 mEq/L, tend not to respond to this regimen.

Patients with intractable pain who fail to respond to medical therapy may benefit from surgical intervention. When there is a dilated pancreatic duct with obstructive areas, longitudinal pancreatojejunostomy (modified Pustow operation) may induce immediate pain relief. When the duct is small, partial surgical resection of the pancreas may control the pain in a certain percentage of patients. Although pain alleviation with surgery may be achieved in certain patients, its long-term benefit is limited since pain recurs in the majority of patients. An alternative to surgical drainage may be achieved by endoscopic insertion of an an endoprosthesis (stent) into the pancreatic duct. Although this approach is promising, its long-term benefit has not been proven.

Octreotide, a long-acting somatostatin analogue, appears to decrease the pain of chronic pancreatitis. Its action is mediated by suppressing pancreatic secretion, hence resting the pancreas. The role of octreotide remains uncertain.

Administration of high-potency, enteric-coated pancreatic enzymes remains the main therapy for the treatment of steatorrhea in the majority of patients with idiopathic and alcoholic pancreatitis. This will improve fat digestion, increase absorption and allow weight gain, although it will not correct the steatorrhea completely. Azotorrhea is more easily reversed than steatorrhea, since trypsin is more resistant to acid inactivation than lipases. It seems that the most important barrier preventing correction of steatorrhea is the destruction of enzymes in the stomach, which prevents the delivery of enough active enzyme into the duodenum.