The insidious nature of chronic pancreatitis delays the early diagnosis of this disorder in many patients. Patients usually come to medical attention after considerable damage has occurred to the gland. In most cases, it is difficult to differentiate acute relapsing pancreatitis, in which the permanent pancreatic damage is mild to moderate, from chronic relapsing pancreatitis.
Clinical presentations. Chronic pancreatitis is an insidious process of parenchymal damage with necrosis and fibrosis of the gland. Approximately one half of the patients present with episodes of acute pancreatitis superimposed onto the damaged organ. One third of the patients may present with only abdominal pain. Other patients may have jaundice, weight loss, malabsorption, steatorrhea, diabetes mellitus, or upper gastrointestinal bleeding. Ten percent of the patients never experience pain. The average age of the patient at initial diagnosis is 35 to 50 years.
Pain accompanying chronic pancreatitis is described as a steady boring, achy sensation usually associated with nausea with or without vomiting. It is commonly present in the mid epigastrium, but it may also be perceived in the right or left upper quadrant or periumbilical area. It usually radiates to the back, increases in the supine position, and decreases on sitting up and leaning forward. Most patients require analgesics and may become addicted to narcotics.
The course of the pain of chronic pancreatitis differs in different patient groups. In most patients, it is a constant experience in the first 5 years after its diagnosis. Thereafter, in about two thirds of the patients, it may resolve spontaneously or diminish in severity and frequency.
Pancreatic exocrine function steadily diminishes with chronic pancreatitis.
Fat and protein malabsorption becomes apparent after the loss of 90% of the pancreatic secretory capacity. Protein malabsorption may be compensated for with increased oral intake of protein without additional abdominal discomfort to the patient. However, increased fat intake results in more diarrhea and abdominal pain. The steatorrhea of chronic pancreatitis consists mainly of triglycerides (esterified fats) in contrast to steatorrhea of sprue, which contains free fatty acids: The esterified fats are hydrolyzed by pancreatic lipase to free fatty acids, but they are not absorbed by the diseased intestinal mucosa. Stool volume is also smaller in chronic pancreatitis, again due to the presence of esterified fats, because hydroxylated free fatty acids are the secretagogues of colonic chloride and water secretion.
Carbohydrate malabsorption is rare in chronic pancreatitis, because loss of 97% of amylase secretion is necessary for maldigestion of starch.
- Vitamin B12 malabsorption. Decreased pancreatic exocrine function does not affect the absorption of bile salts, water- or fat-soluble vitamins, iron, or calcium. However vitamin B12 malabsorption may occur in some patients due to diminished secretion of trypsin. As vitamin B12 is ingested, a nonspecific protein (R protein) found in the upper gastrointestinal secretions binds with it and does not allow it to bind intrinsic factor (intrinsic factor) from the stomach. Normally, trypsin in the second portion of the duodenum cleaves off the R protein and allows the association of vitamin B12 to intrinsic factor. The intrinsic factor-vitamin B12 complex is necessary for the active absorption of the vitamin B12 at the terminal ileum. In chronic pancreatitis with diminished levels of pancreatic proteases, especially trypsin, in the duodenal lumen, the R protein is not cleaved off vitamin B12 and intrinsic factor-vitamin B12 complex does not form, leading to vitamin B12 malabsorption.
- Diabetes mellitus. Along with exocrine insufficiency, endocrine insufficiency with diminished insulin and glucagon release develops in these patients. Seventy percent of the patients with pancreatic calcifications develop diabetes mellitus. Microangiopathy and nephropathy do not seem to complicate diabetes mellitus resulting from chronic pancreatitis. However, due to concomitant diminished glucagon secretion, these patients are very sensitive to exogenous insulin and may develop hypoglycemia even with low doses.
- Physical examination. There are no specific findings in chronic pancreatitis. Some patients have epigastric tenderness. A mass may be palpable if a palpable pseudocyst exists. Patients with malabsorption may have weight loss but do not present with signs of fat-soluble vitamin deficiency (vitamins A, D, E, and K) such as hypocalcemia, osteomalacia, and bleeding tendency. Jaundice may exist in patients with common bile duct obstruction due to scarring in the pancreatic head. In these patients, it may be difficult to differentiate pancreatic cancer from chronic pancreatitis.
Serum chemistry profile. There are no specific findings in the serum chemistry profile in patients with chronic pancreatitis. Even during acute attacks, the serum amylase or lipase level may not be elevated. The serum chemistry profile may reflect concomitant liver disease. With obstruction of the common bile duct, a cholestatic liver chemistry profile may emerge and should be confirmed by imaging techniques.
Stool fat. Steatorrhea is best confirmed by 72-hour stool collection for quantitative determination of fat. Most patients consuming 100 g of fat per day excrete more than 10 g of fat per day. In advanced pancreatic insufficiency, stool fat may reach 30 to 40 g per day.
Pancreatic calcifications are present on plain abdominal radiographs in one third of patients with chronic pancreatitis.
Ultrasound and, especially, computed tomography (computed tomography) scan provide for more sensitive detection of pancreatic calcifications. The presence of pseudocysts, ductal dilatation, and tumors can also be delineated.
When a tumor is suspected, angiography may be helpful in identifying neovascularity of the tumor, deviation of normal vascularity due to tumor, or the lack of vascularity of the cystic lesions. When splenic vein thrombosis has occurred, angiography demonstrates the site of occlusion and the presence of gastric or esophageal varices.
Endoscopic retrograde cholangiopancreatography. Pancreatic ductal anatomy is best delineated with endoscopic pancreatography: Dilatation, cystic changes, strictures, and calculi are demonstrated. Most patients with advanced chronic pancreatitis have a dilated common pancreatic duct with intermittent sites of narrowing, creating the «chain of lakes» appearance on the pancreatograms. The damage is also noted in the secondary ducts, with dilatation and blunting leading to loss of the fine «acinarization»
Endoscopic retrograde cholangiopancreatography may also be helpful in the differentiation of pancreatic cancer from chronic pancreatitis. In pancreatic cancer, only that part of the duct involved with the tumor is abnormal, in contrast to generalized abnormal changes seen with chronic pancreatitis.
Endoscopic ultrasonography may be used in instances of Chronic calcifying pancreatitis in which a tumor is suspected. The differentiation of sclerotic pancreatic cancer from atrophic and fibrotic pancreatic parenchyma may be difficult with this technique.
Tests of pancreatic exocrine function. Chronic pancreatitis or pancreatic insufficiency can be determined with certainty only by demonstrating diminished exocrine function during adequate stimulation of the pancreas. These tests may be necessary in situations in which no calcification is seen on radiographic studies and the ducts appear normal on endoscopic retrograde cholangiopancreatography.
Secretin stimulation test. In this test, the duodenum is intubated under fluoroscopy and the duodenal contents are aspirated, collected, and analyzed after the patient receives intravenous secretin (1 U/kg of body weight) to stimulate pancreatic water and bicarbonate secretion. The total output of bicarbonate correlates well with the extent of pancreatic damage.
The addition of cholecystokinin to secretin, to stimulate exocrine enzyme secretion (e.g., amylase or lipase), does not seem to increase the diagnostic accuracy. The secretin stimulation test is difficult to perform and requires technical expertise. It is reliably performed in specialized medical centers. The overall sensitivity is 74% to 90%.
The Lundh test meal provides for endogenous stimulation of pancreatic exocrine secretion. After the patient is given a standard test meal, the proximal jejunal fluid is aspirated for 2 hours and analyzed for trypsin. This test is not as sensitive as the secretin stimulation test (sensitivity, 60%-90%).
Patients ingest 500 mg of N-benzoyl-L-tyrosyl-p-aminobenzoic acid (bentiromide), a synthetic peptide, which is specially cleaved by chymotrypsin to liberate paraaminobenzoic acid in the proximal small intestine. Paraaminobenzoic acid is normally absorbed, conjugated in the liver, and excreted in the urine. Recovery of less than 60% of the liberated paraaminobenzoic acid from a 6-hour urine collection is considered to be abnormal and suggests pancreatic insufficiency with decreased chymotrypsin output.
False-positive results may be obtained in patients with diffuse intestinal disease resulting in diminished absorption of paraaminobenzoic acid, with chronic liver disease resulting in decreased conjugation of paraaminobenzoic acid, and with renal insufficiency with reduced urinary output of paraaminobenzoic acid. The accuracy of the test may be increased with a concomitant d-xylose test or by giving a small amount of carbon 14-labeled paraaminobenzoic acid along with the test dose of the peptide. The ratio of urinary paraaminobenzoic acid to 14C-paraaminobenzoic acid helps in differentiating false-positive results from pancreatic insufficiency.
Even though this test does not seem to be as sensitive as the secretin test in patients with mild pancreatic insufficiency, its ease of performance makes it a desirable alternative. Its overall sensitivity is 37% to 90%.