Fatal Inheritance. By Scott Holter.

The author, UW Gastroenterologist Teri Brentnall, was not only researching the genetics of pancreatic cancer, she was also part of a new surveillance program for patients at high risk. Thanks to breakthroughs in molecular biology, researchers at the UW and other schools were developing early diagnostic tests for pancreatic cancer.

The UW's Surveillance Program started in 1994, the first of its kind in the world. In addition to Brentnall, the team includes Medicine Professor Michael Kimmey, head of GI endoscopy at the UW Medical Center; Pathology Professor Mary Bronner; and Surgery Professor David Byrd. The group has one important goal: identify affected patients before they develop invasive cancer but after "dysplasia" or pre-cancer has developed.

This vital organ can be a time bome for some families.

But the results of these tests can leave patients with an almost impossible choice: Continue living normally and hope the pre-cancer will not develop into the ravaging form of the disease, or let doctors remove the pancreas, becoming a full-fledged diabetic, forever dependent on insulin. While it is possible that the precancerous cells will not turn into cancer, it is a serious risk. Doctors can't be sure because there is no natural history data on cancer development in the pancreas.

Two months after her brother's death, Mayer, who was showing no symptoms and in seemingly perfect health, traveled to the UW for an appointment with Brentnall. There she underwent an endoscopic ultrasound, where a tube-like probe is inserted through the patient's mouth and into the stomach. A microchip television camera embedded in the tip of the probe allows the physician to see inside the body without surgery.

"The pancreas is deep in the body and extremely hard to locate," says Brentnall. "It sits behind the stomach, almost against the spine." Larger than the gallbladder and smaller than the liver, it plays a key role in the digestive system, secreting enzymes that join bile from the liver and gallbladder to drain into the small intestine. The pancreas also produces valuable insulin and hormones that control the body's ability to use sugar.

But this vital organ can be a time bomb for some families. Brentnall says pancreatic cancer is clearly hereditary in at least 10 percent of cases, a risk that triples if one first-degree relative is affected and increases to as much as 50 percent if multiple members are affected.

"There are certain risk factors to cancer of the pancreas—chief among them smoking," says Brentnall. "But people with a family history likely have family genes that increase their risk. Losing her mother and brother made Sheri a certain candidate."

Sheri Mayer rests atop her Harley Davidson motorcycle on the day she moved to Montana, where she and her husband are building a log cabin. Photo by Dathan (Dave) Devnich.

Sheri Mayer rests atop her Harley Davidson motorcycle on the day she moved to Montana, where she and her husband are building a log cabin. Photo by Dathan (Dave) Devnich.

Just last year the disease struck three legendary UW leaders. Two former presidents of the Board of Regents, Andrew Smith and Samuel Stroum, died from pancreatic cancer in February and March respectively. Then it hit retired Communications School Director Alex Edelstein, who died that May.

Other well-known victims include comedian Jack Benny; actors Steve McQueen, Rex Harrison, Michael Landon, Donna Reed, Fred Gwynne and Fernando Lamas; musicians Dizzy Gillespie and Henry Mancini; former Dallas Cowboy Harvey Martin; and game show host Art Fleming.

Those with a hereditary risk may be able to hold off the cancer by avoiding tobacco. Smoking increases the risk seven times in men and three times in women with a family history of the disease. It also quickens the onset of the disease by a decade. Exposure to environmental chemicals, such as benzines, hydrocarbons and dry cleaning solutions, can also be harmful.

No one is sure what causes pancreatic cancer, but a team of geneticists that includes Brentnall and scientists at the Fred Hutchinson Cancer Research Center and the University of Pittsburgh have mapped the location of a gene associated with inherited pancreatic cancer (see "Breaking the Genetic Curse"). It is the first genetic defect linked directly to this form of cancer.

While genetic research may benefit Mayer's children and grandchildren, her own fate depended on the UW surveillance program. The first test, in 2000, found no signs of cancer. "Everything came back normal," Mayer remembers, "and they told me to come back in another year."

She went back to her business, her family and Wenatchee, feeling as good as ever. In February 2001 she returned to Seattle for what she thought would be another normal procedure. This time the first tests indicated abnormalities: critical tumor marker chemicals in her blood had risen from 11 (normal) to 53.

These abnormalities meant Mayer would have to undergo more tests—a spiral CT scan and an endoscopic examination of the pancreatic duct. When Mayer awoke from anesthesia, Brentnall was at her side. "She just said, 'I'm sorry to tell you but we found dysplasia (pre-cancer) on your pancreas, and you'll need surgery,' " Mayer says.

The operation didn't necessarily mean Mayer would lose her entire pancreas. Before removing the whole organ, surgeons use a laparascope to confirm that precancerous changes are present. In addition, pathologists look at pancreatic tissue while the patient is still under anesthesia in what is called frozen section analysis. If dysplasia is present, doctors perform a total removal during the same operation.

Mayer scheduled the surgery for March. Byrd, her surgeon, told her he was planning a partial pancreatectomy, removing only a section of the tail of the pancreas. The frozen section analysis on the rest of the pancreas was negative, and Byrd removed six inches of the tail. Seven days later, Mayer returned to Wenatchee to recover.

"I went back to work and I was feeling great. Everything seemed fine," Mayer says. But the final pathology report was still pending. "Near the end of June, I received word that they found dysplasia in the rest of my pancreas," she recalls.

Though the news seemed devastating, Mayer took comfort in the knowledge she had gained from her own medical background, and in the support from her family and doctors. At a conference with Brentnall and Byrd, they told her that she had three options. She could only make one choice—and had less than six months to make it.


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