Molecular marker from pancreatic ‘juices’ helps identify pancreatic cancer

Researchers at Mayo Clinic have developed a promising method to distinguish between pancreatic cancer and chronic pancreatitis - two disorders that are difficult to tell apart. A molecular marker obtained from pancreatic “juices” can identify almost all cases of pancreatic cancer, their study shows. The findings were being presented at Digestive Disease Week 2013 in Orlando, Fla.

“Many researchers have been working on such a diagnostic test for a long time - for me, it has been 20 years,” says lead investigator Massimo Raimondo, M.D., a gastroenterologist at Mayo Clinic in Florida. “But for the first time, we have found a very strong candidate molecular marker.

“We all want a foolproof method to detect pancreatic cancer in our patients so that we can deliver appropriate therapy, as soon as possible,” Dr. Raimondo adds. “While we know more research is needed, including validation of our findings, we can’t help but be excited about this advance.”

Pancreatic cancer and chronic pancreatitis both produce the same signs of disease in the pancreas, such as inflammation, but cancer in the organ is a life-threatening disorder that must be treated immediately and aggressively, Dr. Raimondo says.

The research team, which included investigators from Mayo Clinic in Rochester, Minn., tested a method that examined secretions from the pancreas during a routine upper endoscopy.

In patients suspected of having chronic pancreatitis or pancreatic cancer, physicians use a thin flexible scope to examine the upper digestive tract. In this study, during such routine endoscopies, physicians injected the substance secretin intravenously, to fool the pancreas into believing the stomach contains food that the pancreas needs to help digest. The organ then secreted juice rich in enzymes to help break down the food, along with exfoliated cells, and the researchers collected some of this fluid.

Molecular marker from pancreatic 'juices' helps identify PAncreatic Cancer
They examined the juice for markers that might distinguish the two disorders, and discovered that the altered gene CD1D, as a single marker, detected 75 percent of patients later diagnosed with pancreatic cancer, but was present in only 9 percent of patients with chronic pancreatitis.

“CD1D performed much better than any other pancreatic secretion marker previously tested in identifying pancreatic cancer,” Dr. Raimondo says.

The research team is working on further improving the accuracy of this promising molecular diagnostic approach.

Signs and symptoms of exocrine pancreatic cancer

Jaundice is yellowing of the eyes and skin caused by the buildup of bilirubin in the body Bilirubin is a dark yellow-brown substance that is made in the liver. Normally, the liver excretes bilirubin into bile. Bile goes through the common bile duct into the intestines, eventually leaving the body in the stool. When the common bile duct becomes blocked, bile can’t reach the intestines, and the level of bilirubin builds up. At least half of all people with pancreatic cancer and in all people with ampullary cancer have jaundice.

Cancers that begin in the head of the pancreas are near the common bile duct. These cancers can compress the duct while they are still fairly small. This can lead to jaundice, which may allow these tumors to be found in an early stage. But cancers that begin in the body or tail of the pancreas do not compress the duct until they have spread through the pancreas. By this time, the cancer may have also spread beyond the pancreas.

When pancreatic cancer spreads, it often goes to the liver. This can also lead to jaundice.

Sometimes, the first sign of jaundice is darkening of the urine from bilirubin. As bilirubin levels in the blood increase, the urine becomes brown in color.

If the bile duct is blocked, bile (and bilirubin) can’t get through to the bowel. When this happens, a person may notice their stools becoming lighter in color.

When bilirubin builds up in the skin, it turns yellow and starts to itch.

Cancer is not the most common cause of jaundice. Other causes, such as gallstones, hepatitis, and other liver diseases, are much more common.

Abdominal or back pain
Pain in the abdomen or back is common in advanced pancreatic cancer. Cancers that start in the body or tail of the pancreas may grow fairly large and start to compress other nearby organs, causing pain. The cancer may also spread to the nerves surrounding the pancreas, which often causes back pain. The pain may be constant or it may come and go. Of course, pancreatic cancer is not a common cause of pain in the abdomen or back. It is more often caused by a non-cancerous disease or even another type of cancer.

Weight loss and poor appetite
Unintended or unexpected weight loss is very common in patients with pancreatic cancer. These people also complain of being very tired and having little or no appetite.

Digestive problems
If cancer blocks the release of the pancreatic juice into the intestine, a person may not be able to digest fatty foods. The undigested fat may cause stools to be unusually pale, bulky, greasy, and to float in the toilet. The cancer may also wrap around the far end of the stomach and partly block it. This can cause nausea, vomiting, and pain that tend to be worse after eating.

Gallbladder enlargement
If the cancer blocks the bile duct, bile can build up in the gallbladder, which then becomes enlarged. This can sometimes be felt by a doctor during a physical exam. It can also be detected by imaging studies.

“These results on Dr. Raimondo’s carefully collected samples are really exciting and have clear practice-changing implications,” says co-author David Ahlquist, M.D., who led the collaborating laboratory team at Mayo Clinic in Rochester. Diagnostic accuracy well above 90 percent is possible, he says.

When such a biomarker test is perfected, it could be used not only to distinguish pancreatic cancer from chronic pancreatitis, but, potentially, as a screening test for patients at high risk for pancreatic cancer, Dr. Raimondo says.

The pancreas is an organ in the upper abdomen located beneath the stomach and adjacent to the first portion of the small intestine, called the duodenum. The pancreas is composed of glands that are responsible for a wide variety of tasks. The glandular functions of the pancreas can be divided into the following two categories:

  Exocrine: The exocrine glands secrete enzymes into ducts that eventually empty into the duodenum. These enzymes then help in the digestion of food as it moves through the intestines.
  Endocrine: The endocrine glands secrete hormones, including insulin, into the bloodstream. Insulin is carried by the blood throughout the rest of the body to assist in the process of using sugar as an energy source. Insulin also controls the levels of sugar in the blood.

The pancreas can be divided into the following four anatomical sections:

  Head - The rightmost portion that lies adjacent to the duodenum
  Uncinate process - An extension of the head of the pancreas
  Body - The middle portion of the pancreas
  Tail - The leftmost portion of the pancreas that lies adjacent to the spleen

Intraductal papillary mucinous neoplasia (IPMN) is a type of pancreatic cancer that is beginning to be recognized more frequently. This pancreatic cancer has a better prognosis than other types of pancreatic cancer. Intraductal papillary mucinous neoplasia is usually diagnosed endoscopically


The study was funded by grants from the Charles Oswald Foundation.

About Mayo Clinic Cancer Center
As a leading institution funded by the National Cancer Institute, Mayo Clinic Cancer Center conducts basic, clinical and population science research, translating discoveries into improved methods for prevention, diagnosis, prognosis and therapy. For information on cancer clinical trials, call 507-538-7623.

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Kevin Punsky
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Mayo Clinic

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