Pancreatic cancer leads to almost certain death
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BY MARK ANDERSEN/Lincoln Journal Star
Bobby stares out upon a world made cold by pancreatic cancer.
Appearing scared and confused, the 2-year-old stands small in a photo taken hours after his mother's funeral.
He can't possibly fathom that one day his sisters will struggle to describe their mother, her flowing black hair, her melodious giggle.
Today, 21 years later, Bobby can recall nothing about her.
Last year, his eldest sister, Christy, turned 37, the age at which their mother died in an ambulance outside their home, flashing red lights bathing the faces staring out of darkened windows.
"I'm so afraid," Sheila whispered as a pulmonary embolism, a side-effect of intensive chemotherapy, stole her final breaths.
From the beginning, hers had been no ordinary duel with cancer, not even the unfair fight many get.
Another sibling explained it to me as we traveled to a hospital a few weeks before her death those many years ago.
Among major cancers, pancreatic cancer is the least curable. Of the 30,000 Americans who get the bad news this year, a few hundred survive to celebrate the one-year anniversary of their diagnosis.
With this disease, you put your affairs in order.
That day, we watched Sheila, disheveled and in a hospital gown, escort her IV pole to a hospital bathroom, grimacing in pain.
In the years after her death, that pain would metastasize, spreading into the lives of some of her children.
Sister to nine, mother to four, wife to one, she was glue to all of them.
I never knew my sister was the touchstone for our large family until she was gone.
University of Nebraska Medical Center research scientists Tony Hollingsworth and Surinder Batra joined the effort to understand this relentless killer at Duke University in the 1980s, when research into pancreatic cancer was still rare.
Recently, they received a $3.3 million grant to look for better indicators of the disease. Omaha is among about 10 places in the country where uncovering the basic understanding of pancreatic cancer is a full-time job.
"We're probably as active as anywhere in the world," Hollingsworth said.
Their efforts could be a crucial step toward a breakthrough that so far has eluded pursuers.
The standard therapy for pancreatic cancer at present is a drug called gemcitabine. It often makes patients feel better but statistically it adds a matter of days to their lives — more for some and less for others.
There has been a lot of progress into understanding what causes the disease, Hollingsworth said.
"We're not as far as we'd like to be but we're farther than we were."
With pancreatic cancer, nothing comes easily.
Its symptoms of back pain and indigestion don't set it apart. About 50 million Americans have these. Pancreatic cancer is the cause in 0.06 percent of cases.
Located deep in the body behind other organs, the pancreas is also camera shy, even using the best medical imaging equipment.
Doctors typically don't know cancer is there until late in the disease, when it has spread throughout the abdominal area and along the nerves.
It's far easier to study many other cancers in their early stages, Hollingsworth said.
He suspects pancreatic cancer is a slow-growing, insidious disease that has lain undiscovered for possibly a decade before it makes its presence known.
That slow growth would explain why traditional cancer therapies, which target fast-growing cells, don't often work.
Sheila first mentioned her symptoms of back pain nine months before her death. She was hopeful that a shoe lift recommended by her chiropractor would eliminate it.
The next I heard about it was a phone call describing her discovery.
"You might want to come home," a brother said.
In the hospital, Sheila spoke of waves of unbearable pain, followed by a curious thought that it couldn't possibly have been that bad.
It seemed an apt comment for life at the time.
The pancreas is a 6-inch long, pear-shaped gland surrounded by the stomach, small intestine, liver and spleen. About 80 percent of its function is given to creating the enzymes of digestion. About 10 to 15 percent is dedicated to producing insulin, which regulates sugar.
Ductal cells, which form the tubes used to transport the enzymes, account for about 5 to 10 percent of the pancreas but 95 percent of pancreatic cancers and most of the worst ones.
Ductal cancers are subtyped by appearance. Does the tumor want to make ducts? Does it try but mostly fail?
Surprisingly, it isn't cancer cells that make up the bulk of these tumors. Often, there is a small nest of cancer cells surrounded by a huge growth of dense, fibrous stromal cells. These normally serve as scaffolding.
A cell doesn't just wake up one day and decide to be cancer. There has to be a mutation in its genetic code, the cell's key operating instructions. Mistakes occur infrequently, but with billions of cells reproducing, they occur, and sometimes in key areas. Much of the code is garbage, an evolutionary remnant.
Often, the coding most crucial to forming cancers are those involved in communicating information to other cells: Hey, divide, we need to heal this wound — so step on the gas. Or: Step on the brakes, we have enough.
In cancer cells, several mutations have permanently slammed the gas pedals to the floor and disabled the brakes.
"There are lots of gas pedals and lots of brakes," Hollingsworth said.
The variety of cancer subtypes and variability of appearance depends upon the particular combinations of mutations occurring.
With other cancers, the changed appearance of cells caused by the mutations serves as a warning. In the colon or cervix, for examples, cells transitioning into cancer but not yet there can be cut out and the cancer prevented.
Similar changes occur in the pancreas. Roughly 50 percent of those older than age 50 have one common precancerous pancreas lesion.
"It would be a waste of effort to look for these," Hollingsworth said, because so few of them advance to become cancers.
One strategy for finding cancers earlier is to look for abnormal levels of cell signals produced by the cancer cells. With pancreatic cancer, the relatively small number of cells at the center of each tumors means these tests must be highly sensitive.
The grant Hollingsworth and Batra received will fund experiments aimed at improving the CA19-9 radioimmunoassay blood test, which measures tumor-associated antigens. The marker also is affected by a benign liver disease.
Their search will look for ways to make the test more discriminating, better at catching cancers earlier.
"If we could catch it early, could we cure more individuals?" Hollingsworth asked himself. "Probably. Would it cure all? I doubt it."
It would still be necessary to find what kills it.
"But it would make a difference, Batra said. "It is a battle."
Nobody really knows the mechanisms of how cancer kills, Hollingsworth said. Physicians often talk about a lethal body mass of about 2 kilograms of tumors, but typically at that point the tumor hasn't compromised organ function. And by themselves, the tumors aren't large enough to drain sufficient energy from vital functions.
Somehow the tumor disrupts other cell signaling, causing functions to go haywire. A common effect is cachexia, muscle wasting, where certain muscles burn energy like Las Vegas burns electricity.
That's why a sudden, unexplained weight loss is a possible warning sign.
"Muscles and who knows what else are burning energy," Hollingsworth said.
The effectiveness of the chemotheraphy drug gemcitabine may result not from its ability to kill cancer, he said, but because it is disrupting some secondary effect of the cancer.
Millions of people die from cancer. Sheila was one.
Pancreatic cancer, however, tries to rob even the possibility of hope. In the broader picture of things, it's into this leaky dike that Hollingsworth and Batra have placed their fingers.
RISK FACTORS FOR PANCREATIC CANCER
Smoking
Smoking is the number one risk factor for pancreatic cancer. People who smoke cigarettes are two to three times more likely to develop pancreatic cancer than people who do not smoke.
Age
Most people diagnosed with pancreatic cancer are over the age of 60. The chance of developing pancreatic cancer increases with age.
Family history
If a person's mother, father, sister or brother had pancreatic cancer, then that person's risk for developing the disease at least doubles. Also, if there is a family history of ovarian cancer, colon cancer, familial melanoma or hereditary pancreatitis, the risk of pancreatic cancer increases.
Chronic pancreatitis
Those who have been diagnosed with chronic pancreatitis, particularly at a younger age, have an increased risk of developing pancreatic cancer. Chronic pancreatitis is usually diagnosed in individuals 35-45 years old.
Race (ethnicity)
People of African-American descent have a higher incidence of pancreatic cancer compared to people of Asian, Hispanic or Caucasian descent. There is also a higher incidence of pancreatic cancer among Ashkenazi Jews.
Gender
Slightly more men are diagnosed with pancreatic cancer than women. This may be linked to higher smoking rates in men.
Diabetes
Pancreatic cancer is twice as likely to occur in people who have diabetes than in people who do not have diabetes.
Diet
The association of diet and the development of pancreatic cancer is still inconclusive. A diet high in meats, fats and carbohydrates is thought to increase the risk of developing pancreatic cancer, while a diet high in fruits and vegetables decreases the risk. There may also be a risk associated with eating foods that are high in salt and refined sugar, or foods that have been smoked, dehydrated or fried.
Source: PanCan, the Pancreatic Cancer Action Network (www.pancan.org)
Reach Mark Andersen at 473-7238 or mandersen@journalstar.com
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