Pancreatic Cancer Deadly Inheritance, Desperate TradeOff

BALTIMORE - The room lights were dimmed, and all eyes turned to the grainy pictures on a pair of overhead monitors in a small room at Johns Hopkins Hospital.

When doctors found precancerous cysts, Nancy Platt chose to have her pancreas removed.

Mrs. Platt's daughter, Laura Train, and husband, Sam, were by her side at Johns Hopkins.

Nancy Platt lay on her side, sedated, while Dr. Marcia Canto eased a long, camera-tipped tube down her throat to her stomach and began capturing ultrasound images of her pancreas.

Here and there, dark spots blinked onto the screen. They were pancreatic cysts - an ominous sign in someone like Mrs. Platt, 66, who lost her mother and a daughter to cancer of the pancreas. The cysts were unlikely to be cancerous, but given her family history, the odds were high that some would turn malignant.

An earlier test had also found cysts, and Mrs. Platt had traveled to Hopkins from her home near Houston to have part of her pancreas removed. Now, the picture was turning out to be even worse than expected.

"She has them all over the place," said Dr. Canto, zeroing in on more cysts. Would she need to have her entire pancreas removed? asked a medical resident, eyeing the monitors. The pancreas makes insulin (and digestive enzymes), and removing it would cause severe diabetes that would require several insulin shots a day.

"It's a big decision, but I don't see how she can avoid it," Dr. Canto said.

Mrs. Platt is part of a study aimed at preventing pancreatic cancer in people who are at high risk for it, by finding precancerous growths and removing all or part of the pancreas to get rid of them. So far, about 20 people have had the preventive surgery at Johns Hopkins, and a small number of others have undergone it at other centers.

In essence, these patients are trading the risk of cancer for the reality of diabetes, and their willingness to do it is a measure of the fear and desperation that pancreatic cancer provokes.

"With pancreatic cancer you don't have much opportunity to save lives, and we are, with this approach," said Dr. Canto, the director of endoscopy at Johns Hopkins.

Her program is strictly limited to high-risk families. Many other people have pancreatic cysts that turn up as incidental findings when they have scans for other reasons, and doctors are divided about whether to remove them.

Pancreatic cancer is one of the deadliest and most painful types of cancer. Even though it is only the 11th most common cancer in the United States, with 37,170 new cases expected this year, it is the fourth-leading cause of cancer death, because nearly all the patients die. This year, pancreatic cancer is expected to kill 33,370 people.

Ninety-five percent die in less than five years. Family history is a strong risk factor, but most patients have no affected relatives. Smoking, being over 60 and having diabetes or chronic pancreatitis increase the risk; so does being a man or an African-American.

It is not uncommon to hear of patients dying less than a year after the diagnosis. Mrs. Platt's daughter, who was 37 and the mother of two young children, survived only three months.

The disease is so lethal partly because it is usually advanced by the time symptoms occur. The tumors cannot be felt during a physical exam because the pancreas lies deep in the abdomen, behind the stomach. And at every stage, the tumors resist chemotherapy and radiation.

"It is one of the most challenging human malignancies, for sure," said Dr. Eileen O'Reilly, an oncologist who specializes in the disease at Memorial Sloan-Kettering Cancer Center in New York. "I honestly can't think of a worse one."

Even half-inch tumors in the pancreas are often fatal, while growths that size in the breast or intestine have a good prognosis, said Dr. Scott E. Kern, a molecular biologist at Johns Hopkins.

"Why? We don't know," Dr. Kern said, adding that even a small pancreas tumor "has all the mutations it needs to kill the patient."

Scientists think that the many mutations, along with the tumors' tendency to encase themselves in a capsule of scarlike tissue, help them resist chemotherapy. The organ's natural ability to avoid being dissolved by its own digestive enzymes may also protect it from chemotherapy.

Researchers struggling to understand the disease are searching for genetic mutations that start cells down the path to cancer. They are also looking for biomarkers, molecules from abnormal cells that might be used for early detection, and they are studying the tumors themselves to find out what drives their growth, in hopes of blocking it. But many in the field say new ideas are badly needed.

Dr. Elizabeth M. Jaffee, who is trying to develop a vaccine against pancreatic cancer at Johns Hopkins, said, "I'm typically optimistic, but we are so far behind in this disease in understanding the biology, compared to breast or prostate cancer, that to expect therapies that will impact a good proportion of people who get this disease in the next few years, is very hard."

Financing has lagged behind that for other cancers, and researchers say it is partly because there are not enough survivors to march on Washington.

Dr. Robert J. Mayer, the director of gastrointestinal oncology at the Dana-Farber Cancer Institute in Boston, said he thought research in pancreatic cancer would eventually catch up.