Wednesday, September 21, 2011

Laboratory Testing in Pancreatic Cancer Diagnosing and Monitoring


Lab Tests Overview

Early diagnosis of pancreatic cancer is difficult, even with recent advances in diagnostic methods. Symptoms develop gradually and steadily, and are often present for many months before diagnosis. Physicians typically use a range of imaging studies to confirm the diagnosis. Tumor markers (substances in the body that indicate the presence of tumors) do not permit early diagnosis of pancreatic cancer, but on follow-up are used to indicate the presence of tumors.

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The following tests are often used when pancreatic cancer development is suspected, or when the patient state is monitored before, during, and after cancer treating procedures:
  • Comprehensive metabolic panel: a group of tests that may be used to evaluate why someone is jaundiced, to detect elevated levels of bilirubin and liver enzymes, and to monitor liver and kidney function.
  • CA 19-9 (Cancer Antigen 19-9): a tumor marker for pancreatic cancer; it may be used to monitor for cancer recurrence but is not useful for detection or diagnosis.
  • CEA (Carcinoembryonic antigen): a tumor marker used as a monitoring tool.
  • Calcium: this is sometimes raised in pancreatic cancer (as in other cancers), producing symptoms such as weakness, nausea, abdominal pain and thirst. Raised calcium caused by cancer can be treated and the symptoms relieved.
  • Other tests, such as fecal fat, stool trypsin, trypsinogen, and lipase, may be ordered to help evaluate how well the pancreas is functioning and to determine whether pancreatic enzyme supplementation is necessary.

Some of the tests are reviewed below in more details.

CA 19-9

CA 19-9 (carbohydrate antigen 19-9) is not sensitive or specific enough to use as a screening test for cancer, and it is not diagnostic of a specific type of cancer. CA 19-9 is the mainstay tumor marker and is ordered when pancreatic cancer is suspected, particularly if the patient shows signs of jaundice (yellowing of the skin):
  • To help differentiate between cancer of the pancreas and other conditions, such as pancreatitis
  • To monitor a person's response to pancreatic cancer treatment and/or cancer progression at the course of the disease following surgery, chemotherapy, or radiotherapy, normalizing or decreasing soon after treatment.
  • To watch for pancreatic cancer recurrence.

Low amounts of CA 19-9 can be detected in healthy people, and many conditions that affect the liver or pancreas can cause temporary elevations. Moderate to high levels are found in pancreatic cancer, other cancers, and in several other diseases and conditions. The highest levels of CA 19-9 are seen in cancer of the exocrine pancreas. This cancer arises in the tissues that produce food-digesting enzymes and in the ducts that carry those enzymes into the small intestine. About 95% of pancreatic cancers are of this type.

Serial measurements of CA 19-9 may be useful during and following cancer treatment. Rising or falling levels may give the doctor important information about whether the treatment is working, whether all of the cancer was removed successfully during surgery, and whether the cancer is recurring. However, additional diagnostic methods are required because this test is only 70 percent sensitive and 87 percent specific for pancreatic cancer.

Serum Bilirubin

This test is a measure of the bilirubin in the blood.
Normal Value: total bilirubin = less than 1.5 mg/100ml
Clinical Implications: Bilirubin is present in blood at all times due to the breakdown of hemoglobin which occurs all the time. Normally, bilirubin is removed from the blood by the liver. Increased serum bilirubin levels indicate obstructive disease of the liver, hemolysis or actual liver cell damage.

CEA

CEA is used mainly to monitor the treatment of cancer patients, especially those with colon cancer. Following surgery, CEA values are helpful in monitoring the response to therapy and in determining whether the disease has recurred. CEA is also used as a marker for other forms of cancer, including cancers of the rectum, lung, breast, liver, pancreas, stomach, and ovary. Not all cancers produce CEA, and a positive CEA test is not always due to cancer. Therefore, CEA is not used for screening the general population.

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Assessment of pancreatic function

In pancreatic cancer, abnormal digestion associated with inadequate pancreatic enzymes and function (insufficiency) can occur. When pancreatic enzyme levels fall below 1 percent to 2 percent of normal, poor nutrient digestion and incorporation occur. Poor digestion can cause significant weight loss, nutritional deficiencies, and foul-smelling or greasy bowel movements. It is also associated with changes in gastrointestinal function, such as changes in acid-base balance, bile acid metabolism, stomach emptying, and motility of the intestine.

Tests for pancreatic enzyme function are sensitive for moderate-to-severe pancreatic insufficiency, but are of limited value in mild pancreatic impairment.
  • Bicarbonate secretion is probably the single most useful measure of pancreatic enzyme function. Indirect estimation can be done via the 72-hour fat balance test, which determines fat losses as a percentage of daily fat intake.
  • Measuring the activity of pancreatic chymotrypsin (a pancreatic enzyme).
  • A test in which oral fluorescein dilaurate is broken down by esterase, a pancreatic enzyme.
  • Fecal elastase-1 is a simple, non-invasive, and robust test of fat balance in the body.
  • Cholesteryl-[14C]octanoate breath test.

Testing Pancreatic Enzymes: Amylase

Amylase is an enzyme that is synthesized primarily in the pancreas and salivary glands. Amylase (alpha-amylase or AML) helps to digest starch and glycogen in the mouth, stomach, and intestine. In cases of suspected acute pancreatic disease, measurement of serum or urine AML is the most important laboratory test.

Normal serum amylase results: 25 to 160 U/L

**Please note: There are more than 20 different lab methods for determining the results of this test. Be sure to use the normal values at your facility. Be sure to withhold drugs that elevate AML levels such as aspirin, asparaginase, azathioprine, corticosteroids, cyprohepadine, narcotic analgesics, oral contraceptives, rifampin, sulfasalazine, and thiazide or loop diuretics. If they cannot be withheld, note them on the lab slip.

After the onset of acute pancreatitis, AML levels begin to rise within 2 hours, peak within 12 to 48 hours, and return to normal within 3 to 4 days. Determination of urine levels should follow normal serum AML results to rule out pancreatitis. Moderate serum elevations may accompany obstruction of the common bile duct, pancreatic duct, ampulla of Vater, pancreatic injury from a perforated peptic ulcer, pancreatic cancer, or acute salivary gland disease. Impaired kidney function may increase serum levels.

Testing Pancreatic Enzyme: Lipase

Lipase is produced by the pancreas and secreted into the duodenum, where it converts triglycerides and other fats into fatty acids and glycerol. The destruction of pancreatic cells, which occurs in acute pancreatitis, causes large amounts of lipase to be released into the blood. This test is used to measure serum lipase levels. It is most useful when performed with a serum or urine amylase test.

Normal value: 56 to 239 U/L (depending on method)

Prior to the test, withhold cholinergics, codeine, meperidine, and morphine. If these drugs cannot be withheld, note their use on the lab slip when the specimen is sent to the lab.

High lipase levels suggest acute pancreatitis or pancreatic duct obstruction. After an acute attack, levels remain elevated for up to 14 days. Lipase levels may also increase in other pancreatic injuries, such as perforated peptic ulcer with chemical pancreatitis due to gastric juices, and in patients with high intestinal obstruction, pancreatic cancer, or renal disease with impaired excretion.


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