Experts say cancer likely killed Steve Jobs (AP)

Steve Jobs managed to live more than seven years with a rare form of pancreatic cancer that grows more slowly than the common kind. But his need for a liver transplant two years ago was a bad sign that his troubles with the disease probably were not over.

The Apple founder long kept information on his illness behind a firewall, and no new details emerged immediately after his death.

However, medical experts unconnected with his care say Jobs most likely needed the transplant because his cancer came back or spread. They said his death could have been from cancer, the new liver not working, or complications from immune-suppressing medicines to prevent organ rejection.

A liver transplant can cure Jobs' type of cancer, but "if it were to come back, it's usually in one to two years," said Dr. Michael Pishvaian, a gastrointestinal cancer specialist at Georgetown University's Lombardi Comprehensive Cancer Center.

Jobs declared he was cured after surgery in 2004 for an islet cell neuroendocrine tumor, a much more treatable form of pancreatic cancer than the more common form of the disease that killed actor Patrick Swayze two years ago.

But the Apple chief never revealed whether the cancer had spread to his lymph nodes or liver, or how extensive his surgery was. Many doctors speculated he had a Whipple procedure, in which part of the pancreas, part of the small intestine and in some cases part of the stomach are removed and the digestive system is reconstructed.

"It's a big operation" and patients can have digestive difficulties long afterward, said Dr. Steven Libutti, director of the Montefiore-Einstein Center for Cancer Care in the Bronx.

Several years later, Jobs was dramatically thinner and gaunt. In January 2009, he attributed those problems to a hormone imbalance and said there was a simple treatment for it. A few weeks later, he went on a medical leave and then had a liver transplant that was kept secret for two months.

Even then, Jobs would not say why the transplant was needed, though doctors said spread of his cancer to the liver was the likely explanation.

Usually transplants aren't done for people with cancer, but "there is some support for the idea that a liver transplant can be curative" for a neuroendocrine tumor as long as the cancer has not spread beyond the liver, Pishvaian said.

Average survival for people with neuroendocrine tumors that have spread is seven to eight years, and some patients have survived 20 to 30 years, said Dr. Martin Heslin, cancer surgery chief at Vanderbilt University.

It was not to be for Jobs.

In January, he announced his third and final leave of absence, and resigned in August.

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Marilynn Marchione can be followed at _http://twitter.com/MMarchioneAP

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Doctors say cancer likely killed Steve Jobs (AP)

Apple and the family of Steve Jobs are not saying what caused the death of the company's founder. However, medical experts not involved in his care say that the liver transplant he had two years ago was probably a sign that his cancer had returned.

Jobs declared he was cured in 2004 after surgery for a rare type of pancreatic cancer that grows more slowly and is more treatable than the more common type. Yet this type of cancer often returns or spreads, usually to the liver.

Jobs has been on a medical leave since early this year for medical problems he wouldn't discuss in detail. He resigned as Apple's chief in August.

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Risky pregnancy drug raised daughters' cancer odds (AP)

A drug that millions of pregnant women took decades ago to prevent miscarriage and complications has put their daughters at higher risk for breast cancer and other health problems that are showing up now, a new federal study finds.

Many of these daughters, now over 40, may not even know of their risk if their mothers never realized or told them they had used the drug, a synthetic estrogen called DES.

The new study suggests that infertility is twice as common and that breast cancer risk is nearly doubled in these daughters.

Debbie Wingard is one of them. The 59-year-old San Diego woman adopted two boys after being unable to conceive and has had breast cancer twice � when she was 39 and 49.

"There's no knowing what's going to happen as we age. There's always the fear there's going to be another cancer or another outcome," she said. "I don't think I'll ever get to the point where I feel it's behind me."

The sons of DES users also face health risks � testicular problems and cysts � but these are less well studied and don't seem to be as common. Even less is known about the third generation � "DES grandchildren." Some research suggests these girls start menstruating late and have irregular periods, possible signs of fertility issues down the road.

In the United States alone, more than 2 million women and 2 million men are thought to have been exposed to DES while in the womb and may now want to talk with their doctors about when they should be screened for health problems.

"We don't want to cause a panic of everyone rushing out thinking they're going to get cervical or breast cancer. They just need to have that conversation with their physician," said Dr. Sharmila Makhija, women's health chief at the University of Louisville.

The average woman has about a 1 in 50 chance of developing breast cancer by age 55; for DES daughters it's 1 in 25, the study found. Risks for other health problems vary.

DES, or diethylstilbestrol, was widely used in the United States, Europe and elsewhere from the 1940s through the 1960s to prevent miscarriage, premature birth, bleeding and other problems. Many companies made and sold it as pills, creams and other forms.

Studies later showed it didn't work. The government told doctors to stop using it in pregnancy in 1971, after DES daughters in their late teens and 20s were found to be at higher risk of a rare form of vaginal cancer. Further research has tied DES to infertility and various pregnancy problems.

"They've been identified one at a time. Nobody's been able to get the whole picture," said Dr. Robert Hoover, a researcher at the National Cancer Institute. The new study, which he led, "takes the woman and looks at everything that can happen as a result of this drug," and adds evidence for some previously suspected risks like breast cancer, he said.

Results are in Thursday's New England Journal of Medicine.

The study started in 1992 and involved about 4,600 DES daughters and a comparison group of 1,900 similar women whose mothers had not used DES. Their health was tracked over time through surveys and medical records. Their average age at the last followup was 48.

In the study, researchers found these rates of health problems in DES daughters compared to non-exposed women:

_Breast cancer, 3.9 percent versus 2.2 percent.

_Cervical pre-cancer, 6.9 percent versus 3.4 percent.

_Infertility, 33.3 percent versus 15.5 percent.

_Early menopause, 5.1 percent versus 1.7 percent

These complications were seen among women who were able to become pregnant:

_Preterm delivery, 53.3 percent versus 17.8 percent.

_Miscarriage, 50.3 percent versus 38.6 percent.

_Tubal pregnancy, 14.6 percent versus 2.9 percent.

_Stillbirth, 8.9 percent versus 2.6 percent.

_Preeclampsia (high blood pressure during pregnancy), 26.4 percent versus 13.7 percent.

The claim of added breast cancer risk is being tested by 53 women in a lawsuit against DES makers under way now in Boston. One of them is Jackie White, 48, who lives in Centerburg, Ohio, north of Columbus. She said she had a misshaped uterus and reproductive problems, and found a lump last year that turned out to be breast cancer. Tests showed 20 tumors in one breast, two pre-cancers in the other and spread to her lymph nodes.

"I ate a low-fat diet. I exercise faithfully so I was not overweight. I had none of the normal risk factors," she said.

When and how often to screen women for breast cancer is the subject of much debate. A government task force recommends that women at average risk of breast cancer get mammograms every other year starting at age 50, and talk to their doctors about screening before then. Many medical groups urge starting at age 40.

DES exposure needs to be considered with the whole picture of a woman's risk, said Dr. G. Wright Bates, director of reproductive medicine at the University of Alabama at Birmingham.

"In some cases, frequent Pap smears and early mammography or breast MRI may be warranted for women with DES exposure," he said.

Others are focused on possible risks to the next generation.

Sally Keely, who was part of the federal study, and her husband are both offspring of women who took DES during pregnancy. Keely, 49, of Kalama, Wash., had miscarriages and a tubal pregnancy and required fertility treatments to have a daughter, now 9.

"I would like to push for more funding on the third generation exposed so I would know best how to advise my daughter," she said.

Fran Howell, executive director of DES Action USA, an advocacy group based in Jupiter, Fla., adopted a daughter, now 20, after being unable to conceive.

"So many of the DES daughters worry about problems with their children," she said. "The DES ends with me."

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Online:

Cancer Institute: http://www.cancer.gov/cancertopics/factsheet/Risk/DES.

CDC: http://www.cdc.gov/des/consumers/about/concerns_daughters.html

Advocacy group: http://www.desaction.org

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Marilynn Marchione can be followed at http://twitter.com/MMarchioneAP

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CDC: Self-reported drunk driving is down (AP)

ATLANTA � Health officials say drunken driving has fallen 30 percent in five years, and last year was at its lowest mark in nearly two decades.

The Centers for Disease Control and Prevention study, released Tuesday, is based on a 2010 national telephone survey of U.S. adults. About 1 in 50 said they'd driven drunk at least once in the previous month. Some said they did it daily.

That led to a CDC estimate of more than 112 million episodes of drunk driving in 2010. But that's down from the 161 million incidents in the peak year of 2006.

Other research suggests people drink heavily as much as in years past. CDC officials think more people may now drink at home, perhaps because of the economy.

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Online:

CDC report: http://www.cdc.gov/vitalsigns

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Cervical cancer virus fuels oral cancer type, too (AP)

WASHINGTON � A prolonged sore throat once was considered a cancer worry mainly for smokers and drinkers. Today there's another risk: A sexually transmitted virus is fueling a rise in oral cancer.

The HPV virus is best known for causing cervical cancer. But it can cause cancer in the upper throat, too, and a new study says HPV-positive tumors now account for a majority of these cases of what is called oropharyngeal cancer.

If that trend continues, that type of oral cancer will become the nation's main HPV-related cancer within the decade, surpassing cervical cancer, researchers from Ohio State University and the National Cancer Institute report Monday.

"There is an urgency to try to figure out how to prevent this," says Dr. Amy Chen of the American Cancer Society and Emory University, who wasn't part of the new research.

While women sometimes get oral cancer caused by the HPV, the risk is greatest and rising among men, researchers reported in the Journal of Clinical Oncology. No one knows why, but it begs the question of whether the vaccine given to girls and young women to protect against cervical cancer also might protect against oral HPV.

HPV vaccination is approved for boys to prevent genital warts and anal cancer, additional problems caused by human papillomavirus. But protection against oral HPV hasn't been studied in either gender, says Dr. Maura Gillison, a head-and-neck cancer specialist at Ohio State and senior author of the new research. That's important, because it's possible to have HPV in one part of the body but not the other, she says.

A spokeswoman for Merck & Co., maker of the HPV vaccine Gardasil, said the company has no plans for an oral cancer study.

Monday's research was funded by the NCI and Ohio State. Gillison has been a consultant to Merck.

There are nearly 10,000 new cases of oropharyngeal cancer a year, and overall incidence has risen by 28 percent since 1988 even as other types of head-and-neck cancer have been declining.

Tobacco and alcohol have long been the main causes of these tumors, which occur in the tonsils, base of the tongue and upper throat. But over the past few years, studies have shown HPV is playing a role in that rise, probably due to an increase in oral sex even as tobacco use was dropping.

The new study took a closer look, tracking HPV over time by directly testing tumor tissue from 271 patients that had been stored in cancer registries in Hawaii, Iowa and Los Angeles. The proportion that were HPV-positive rose from just 16 percent in the late 1980s to nearly 73 percent by the early 2000s.

Translate that to the overall population, and the researchers concluded that incidence rates of the HPV-positive tumors more than tripled while HPV-negative tumors dropped by half.

Oral cancer has always been a bigger threat to men than women. Gillison says women account for only about 1 in 4 cases, and their incidence is holding steady while men's is rising. That raises questions about gender differences in sexual behavior or whether oral HPV infection is likely to linger longer in men.

While HPV is the most common sexually transmitted infection, studies show women's bodies usually clear the virus from the cervix quickly; only an infection that persists for years is a cancer risk. It's not known if oral HPV acts similarly or even is as common.

Nor is it clear if oral sex is the only way it's transmitted, cautions Dr. Gregory Masters of the American Society for Clinical Oncology, an oncologist at Delaware's Helen Graham Cancer Center.

Regardless, just over 11,000 cases of cervical cancer will be diagnosed this year, a number that has been dropping steadily thanks to better Pap smears. (It's too soon to know what difference vaccination will make.) Gillison's team calculated that annual cases of cervical cancer will drop to 7,700 by 2020 � compared with about 8,700 cases of HPV-positive oropharyngeal cancer by then, about 7,400 of them in men.

The cancer society's Chen urged caution about those numbers, saying more data is needed. But she says two things are clear: First, patients with HPV-linked oral tumors have better survival odds than those with other types of this cancer, possibly because they tend to be younger. Studies are beginning to test if they can scale back today's treatment and thus suffer fewer long-term side effects such as problems with speech and swallowing.

And "just because you're not a smoker or drinker doesn't mean you can't get throat cancer," Chen says � so get checked for symptoms like a throat that's sore for longer than two weeks.

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EDITOR'S NOTE � Lauran Neergaard covers health and medical issues for The Associated Press.

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Scientist wins Nobel for medicine days after death (AP)

STOCKHOLM � A pioneering cell biologist was awarded the Nobel Prize in medicine Monday for his discoveries about the immune system. Hours later, his university said he had died of pancreatic cancer three days earlier, even as he was using his own research to try to save his life.

The Nobel committee, which is only supposed to consider living scientists, said it was unaware of the death of Ralph Steinman when it awarded the 10 million kronor ($1.5 million) prize.

The Nobel statutes say work "by a person since deceased shall not be considered for an award" but they don't specifically say whether that also applies if the jury mistakenly picks a winner unaware that he or she has died.

"I think you can safely say that this hasn't happened before," Nobel Foundation spokeswoman Annika Pontikis told The Associated Press. The committee was expected to make a statement on the issue later Monday.

The Canadian-born Steinman, 68, who shared the prize with American Bruce Beutler and French scientist Jules Hoffmann, died Sept. 30 of pancreatic cancer, according to Rockefeller University in New York, where he had studied and worked since 1970.

It said Steinman underwent therapy based on his discovery of the immune system's dendritic cells, for which he won the prize.

"He was diagnosed with pancreatic cancer four years ago, and his life was extended using a dendritic-cell based immunotherapy of his own design," the university said.

Beutler and Hoffmann were cited for their discoveries in the 1990s of receptor proteins that can recognize bacteria and other microorganisms as they enter the body, and activate the first line of defense in the immune system, known as innate immunity.

Nobel committee members said the work by the three is being used to develop better vaccines, and in the long run could also help treatment of diseases linked to abnormalities in the immune system, such as rheumatoid arthritis, Type 1 diabetes, multiple sclerosis and chronic inflammatory diseases.

The work could also help efforts to make the immune system fight cancerous tumors, the committee said.

No vaccines are on the market yet, but Nobel committee member Goran Hansson told The Associated Press that vaccines against hepatitis are in the pipeline.

"I am very touched. I'm thinking of all the people who worked with me, who gave everything," Hoffmann said by telephone to a news conference in Paris. "I wasn't sure this domain merited a Nobel."

Beutler said he woke up in the middle of the night, glanced at his cellphone and realized he had a new email message.

"And, I squinted at it and I saw that the title line was 'Nobel Prize,' so I thought I should give close attention to that," Beutler said in an interview posted on the Nobel website. "And, I opened it and it was from Goran Hansson, and it said that I had won the Nobel Prize, and so I was thrilled."

Still, he was a "little disbelieving" until he checked his laptop, "and in a few minutes I saw my name there and so I knew it was real."

Since 1974, the Nobel statutes don't allow posthumous awards unless a laureate dies after the announcement but before the Dec. 10 award ceremony. That happened in 1996 when economics winner William Vickrey died a few days after the announcement.

Before the statutes were changed in 1974 two Nobel Prizes were given posthumously. In 1961, U.N. Secretary-General Dag Hammarskjold was awarded the Nobel Peace Prize less than a month after he died in a plane crash during a peace mission to Congo. Swedish poet Erik Axel Karlfeldt won the Nobel in literature in 1931, although he had died in March of that year.

Hansson said the medicine committee didn't know Steinman was dead when it chose him as a winner and was looking through its regulations.

"It is incredibly sad news," he said. "We can only regret that he didn't have the chance to receive the news he had won the Nobel Prize. Our thoughts are now with his family."

Beutler, 53, holds dual appointments at University of Texas Southwestern Medical Center in Dallas and as professor of genetics and immunology at the Scripps Research Institute in San Diego. He will become a full-time faculty member at UT Southwestern on Dec. 1.

Hoffmann, 70, headed a research laboratory in Strasbourg, France, between 1974 and 2009 and served as president of the French National Academy of Sciences between 2007-08.

Steinman had been head of Rockefeller University's Center for Immunology and Immune Diseases.

"We are all so touched that our father's many years of hard work are being recognized with a Nobel Prize," Steinman's daughter, Alexis Steinman, said in the Rockefeller University statement. "He devoted his life to his work and his family, and he would be truly honored."

Hoffmann's discovery came in 1996 during research on how fruit flies fight infections. Two years later, Beutler's research on mice showed that fruit flies and mammals activate innate immunity in similar ways when attacked by germs.

Steinman's discovery dates back to 1973, when he found a new cell type, the dendritic cell, which has a unique capacity to activate T-cells. Those cells have a key role in adaptive immunity, when antibodies and killer cells fight infections. They also develop a memory that helps the immune system mobilize its defenses next time it comes under a similar attack.

The medicine award kicked off a week of Nobel Prize announcements, and will be followed by the physics prize on Tuesday, chemistry on Wednesday, literature on Thursday and the Nobel Peace Prize on Friday. The winners of the economics award will be announced on Oct. 10.

The coveted prizes were established by wealthy Swedish industrialist Alfred Nobel � the inventor of dynamite � except for the economics award, which was created by Sweden's central bank in 1968 in Nobel's memory. The prizes are always handed out on Dec. 10, on the anniversary of Nobel's death in 1896.

Last year's medicine award went to British professor Robert Edwards for fertility research that led to the first test tube baby.

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Associated Press writer Malin Rising contributed to this report.

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