USPSTF still recommends against pancreatic cancer screening

The U.S. Preventive Services Task Force (USPSTF) recommends against screening for pancreatic cancer in asymptomatic adults. These findings form the basis of a draft recommendation statement published online Feb. 5 by the USPSTF.

07 feb 2019--Nora B. Henrikson, Ph.D., M.P.H., from the Kaiser Permanente Washington Health Research Institute in Seattle, and colleagues conducted a systematic evidence review to support the USPSTF in reaffirming its recommendations on screening for pancreatic cancer. Data were included from 13 unique prospective cohort screening studies reporting results for 1,317 people.

The researchers found no evidence on the accuracy of imaging-based screening tests or endoscopic ultrasonography for pancreatic cancer. No evidence was found for pancreatic cancer screening or treatment of screen-detected cancer improving disease-specific morbidity or mortality or all-cause mortality. Based on the low incidence of pancreatic cancer in the general population, the uncertain accuracy of current screening, and poor prognosis even with early treatment, the potential benefits of screening in asymptomatic adults were considered no more than small. Based on potential harms from false-positive results and the harms of treatment, the harms of screening were considered to be at least moderate. Based on these findings, the USPSTF concludes that there is no evidence to warrant a change in the previous recommendation and consequently reaffirms against screening asymptomatic adults for pancreatic cancer (D recommendation).

The draft recommendation is available for public comment from Feb. 5 to March 4, 2019.

More information: Draft Recommendation Statement 
Draft Evidence Review 
Comment on Recommendation Statement

New center aims for pancreatic cancer prevention

Axial CT image with i.v. contrast. Macrocystic adenocarcinoma of the pancreatic head. Credit: public domain

Pancreatic cancer often causes no symptoms until it has spread to other organs, leading to a very low survival rate after diagnosis.
But a new effort underway at UC San Diego Moores Cancer seeks to increase patients' odds of successful treatment by detecting potential pancreatic problems earlier.

02 dec 2018--Opened this month alongside a recently announced research effort that explores using complementary drugs to treat the disease, the Pancreatic Cancer Prevention and Screening Clinic at Moores is following special risk-based protocols to screen those with known risk factors for early signs of potential malignancy.
Those who carry certain inherited genetic mutations, have a family history of pancreatic cancer, have pancreatic cysts, have chronic pancreatitis or are newly diagnosed with type II diabetes are at increased risk.
By focusing on this subset of patients and potential patients, said Dr. Andrew Lowy, chief of the division of surgical oncology at Moores, the clinic hopes to prevent a cancer with an appallingly-low survival rate—just 9 percent of patients survive five years after diagnosis.
Early risk-factor-based screening, Lowy said, has the potential to spot pancreatic tumors while they still measure in the millimeters. Waiting until they reach centimeter size, he said, significantly increases the chances that they'll spread.
"The bottom line is that nobody is cured unless their tumor is removable with surgery," Lowy said. "The earlier you get that surgery, the better."
Magnetic resonance imaging, often called MRI, is generally used to take a look at a patient's pancreas. If anomalies are spotted, then ultrasound technology inserted in the stomach can be used to determine whether or not a specific spot is likely to become cancerous. Sometimes, the physician noted, it's necessary to wait and watch to see if changes occur. But getting these patients under surveillance early, he said, is the current best solution to save lives with a cancer that is known for its relentless ability to return after treatment.
"Pancreatic cancer is too rare to mass screen the entire population, but this kind of risk-based work we think is valuable," Lowy said.
So far, the clinic has identified about 70 patients who could benefit from screening due to having at least one risk factor.
Family history, loosely defined in this case as someone who has two or more immediate family members who were diagnosed with pancreatic cancer, is the largest risk factor group, with genetics second. Existing cysts and chronic pancreatitis have been less common. Patients often learn they have a cyst or other pancreatic growth when doctors are investigating another suspected medical condition such as gall stones.
MRI and ultrasound imaging studies are expensive, but Lowy said health insurance companies will generally pay for this diagnostic work in cases where there is a significant family history, a cyst or chronic pancreatitis. Having a genetic predisposition alone, however, may need to be accompanied by other evidence.
"We look for new onset of Type 2 diabetes, unexplained weight loss, vague abdominal pain, back pain ... there can be these subtle signs which we often don't recognize but, in a patient with genetic risk factors, those signs can be enough that we would probably get approval," Lowy said.
In the short term, the proactive approach could have Lowy and his colleagues in surgical suite more often as more small but suspicious tumors are spotted. But, in the long run, no one hopes that will be the case.
A team of university researchers just received a $1 million grant from entertainment industry charity Stand Up To Cancer for drug testing that will build on previous work by the recently-launched Pancreatic Cancer Initiative. Working in partnership with the Lustgarten Foundation, a New York nonprofit that funds cutting-edge cancer research, the team used genetic analysis to screen existing drugs and those currently in late-stage clinical trials with the potential to block signals at the cellular level that make pancreatic cancer so resilient.
That work, said lead investigator and UCSD pharmacology professor Tannishtha Reya, hit on several drugs capable of blocking hormone receptors thought to allow cells to enter an immature stem-cell-like state, making them able to survive the onslaught of chemotherapy and resume multiplication.
"Based on the work we've already done, we think that combination of chemotherapy and these sorts of drugs will allow us to eliminate those cells that survive after treatment, and that's exciting," Reya said.
If lab work using human pancreatic cancer tissue cells shows an ability to block growth in the lab, clinical trials could follow within 12 months.

Deadly pancreatic cancer on the rise

Almost always deadly and steadily on the rise, pancreatic cancer is on track to become the second-leading cause of cancer death in the nation within the next two years, according to a recent report.

08 dec 2012--Currently the fourth-leading cancer killer - and the reason behind the death of Apple founder Steve Jobs at age 56 - pancreatic cancer will likely surpass breast, prostate and colorectal cancers to rank behind only lung cancer, the No. 1 cancer killer, said the report from the Pancreatic Cancer Action Network.

The higher ranking is partly because risk factors associated with pancreatic cancer are trending up, while deaths from the other top cancer killers are trending down, said Dr. Bose Debashish, a pancreatic-cancer surgeon at M.D. Anderson Cancer Center in Orlando, Fla.

The incidence of pancreatic cancer has been rising 1.5 percent each year since 2004, according to the American Cancer Society. At the current rate, one in every 71 Americans will develop the disease in his or her lifetime.

One of the risk factors fueling the upward trend is Americans' lengthening lifespans. Nearly 90 percent of pancreatic-cancer patients are older than 55, and more than 70 percent are older than 65, according to the cancer society.

Increasing rates of obesity and diabetes also contribute to the rising trend. So does smoking, which doubles or triples risk, said Debashish.

What also distinguishes this killer is that it's the only top cancer with a survival rate in the single digits: Only 6 percent of those who get it are alive in five years.

"Everyone who gets pancreatic cancer will likely die of it," said Debashish.

A few, like Alicia Decker of Oviedo, Fla., get lucky. Two years ago, the 34-year-old pharmacist and mother of two young children felt a pain in her side. She tried to ignore it but finally went to the emergency room.

A scan turned up something suspicious on her pancreas. That was the bad news.

"My first thought was, 'I'm going to die,' " said Decker, who didn't have any of the risk factors. Though overweight, she was not obese. She did not have diabetes, had never smoked and had no family history of the cancer.

The good news, however, was that the lesion appeared to be "on its way to becoming cancer," meaning it wasn't too late.

Debashish operated and removed part of Decker's pancreas. Today, she is healthy, active and cancer-free.

Debashish wishes he could nip more pancreatic lesions before they become cancer, but this type of cancer usually stays under the radar until it's advanced.

"We used to believe that pancreatic cancer was very aggressive and very fast," he said. "But that's not true. It actually moves slowly, and we're bad at detecting it.

"If you put the disease on a 100-point scale, with zero being when the first cancer cell shows up, we're catching it at 90," Debashish said.

By the time this silent cancer presents with symptoms, he said, 85 percent of patients are not candidates for surgical correction.

Complicating treatment further, tumors in the pancreas - an essential organ responsible for producing insulin and aiding digestion - don't respond well to available chemotherapy agents.

Symptoms of pancreatic cancer include jaundice (which causes the skin to turn yellow), dark urine, a chalky stool, pain in the abdomen above the navel and unexplained weight loss, said Debashish. Some astute physicians spot the disease when a normal-weight patient presents with sudden-onset diabetes, he said.

Currently, the best hope lies in helping the 15 percent of patients who could benefit from a pancreatic resection to get it - and today only about half do.

"We are actually under-treating pancreatic cancer patients who have operable disease," Debashish said. Even patients whose cancers are borderline inoperable can convert to surgical candidates after treating the tumor with radiation and chemo.

"With quick, appropriate intervention," he said, "we can raise the grim 6 percent survival rate."

Metastasis of pancreatic cancer in action

Pancreatic cells spread by blending in. The left panel shows an inflammed pancreatic duct surrounded by what appear to be fibroblasts (blue arrow). Lineage tagging allowed the researchers to see that some of these fibroblast-like cells are actually invading pancreatic epithelial cells in disguise (left panel, white arrow). Such cells have undergone a process of epithelial-to-mesenchymal transition and are able to enter the bloodstream. Credit: Andrew Rhim, PhD, Perelman School of Medicine, University of Pennsylvania; Cell Press

Ben Stanger, MD, PhD, assistant professor of Medicine in the Division of Gastroenterology at the Perelman School of Medicine, University of Pennsylvania, and Andrew Rhim, MD, a Gastroenterology Fellow in the Stanger lab, discovered that pancreatic cancer cells in an animal model begin to spread before clinically obvious tumor tissue is detected. What's more, they showed that inflammation enhances cancer progression in part by facilitating a cellular transformation that leads to entry of cancer cells into the circulation. They report their findings this week in Cell.

19 jan 2012--Metastasis has been difficult to study because it involves a series of unpredictable events. To capture these events, the team developed a sensitive method to tag and track pancreatic epithelial cells in a mouse model of pancreatic cancer. Tagged cells invaded and entered the bloodstream unexpectedly early, before overt malignancy could be detected by rigorous analysis of tissue slides.

Pancreatic cancer is among the most lethal of cancers, with no real treatments, and at the time of diagnosis up to three-quarters of patients have metastatic disease, says Stanger. Little is known about how pancreatic cancer cells spread, "What leads to this are rare events that are hard to catch in tissues. Small numbers of cells break off tumors and move, but how can we find them?"

These wandering cells are associated with a phenomenon called the epithelial-to-mesenchymal transition (EMT). This change in cell motility is an important process during the development of embryos. But when the transition is aberrantly reactivated in adults it can have dire physiological consequences, leading to cancer metastasis as well as other disease processes. Epithelial cells form a covering or lining of a body surface and are the type of cell from which most solid tumors arise. However, when a molecular switch is turned off or absent, epithelial cells acquire characteristics of another cell type, called mesenchymal cells, and gain the ability to migrate and move away from the primary tumor site.

Using a mouse model of pancreatic cancer developed at Penn in 2005, the team delivered mutations in an oncogene and a tumor suppressor protein, K-ras and p53 respectively, in the pancreas. A green marker was also induced in the embryos' still-forming pancreas. At about one to two months, the juvenile mice developed pre-malignant lesions, and at about four to five months full blown pancreatic cancer.

During this time, the mouse pancreatic epithelial cells lost their epithelial characteristics and became more like mesenchymal cells, blending in and making their way to the bloodstream. True epithelial cells are sticky, keeping linings tightly connected, but these imposter epithelial cells changed identity, becoming less sticky.

With the green stain, the researchers were able to detect the transition from epithelial cell to mesenchymal cell in a tissue slide, showing many green cells that had undergone EMT. "We are now able to see what was before before unseeable – the pancreas cells that have taken on a disguise," says Stanger.

What spurs the EMT in first place? The team surmised that it was inflammation, so they blocked inflammation with an immunosuppressant, and at about eight to ten weeks, the green cells undergoing EMT disappeared. Conversely, when they induced pancreatitis- associated inflammation, the EMT green cells increased.

In trying to relate these findings to metastasis, they looked for green EMT cells outside of the pancreas and found them in the blood and distinct tissues such as the liver at eight to ten weeks of age, long before a pathologist would recognize it as cancer.

"These results provide new insight into the earliest events of cellular invasion and suggest that inflammation enhances cancer progression by giving cells increased access to the bloodstream," says Stanger.

The team plans to use the methodology used in this study to enhance the detection of spreading cells in human patients at an early timepoint, when therapy could have a greater impact.

Both the development of the pancreatic cancer mouse model and Dr. Stanger's current work were partially funded by research grants from the Pancreatic Cancer Action Network. "We are highly encouraged by Dr. Stanger's recent results," said Lynn Matrisian, PhD, vice president of Scientific and Medical Affairs at the Pancreatic Cancer Action Network. "A deeper understanding of the disease biology, and in particular metastasis, will move us closer to our goal of doubling the survival rate of pancreatic cancer by the year 2020."

Provided by University of Pennsylvania School of Medicine

Pancreatic cancer declining, but among most deadly

In this Jan. 6, 2004 , Apple CEO Steve Jobs displays the iPod mini at the Macworld Conference and Expo in San Francisco. Jobs, the Apple founder and former CEO who invented and masterfully marketed ever-sleeker gadgets that transformed everyday technology, from the personal computer to the iPod and iPhone, died Wednesday. He was 56.

07 oct 2011-- There are almost as many deaths from it each year as there are new cases. The deaths this week of Apple founder Steve Jobs and Nobelist Ralph Steinman bring unusual attention to this less-well-known type of cancer that has actually been declining despite no big advances in treatment or finding it early.

A decline in smoking, one of the top risk factors for the disease, may be behind the drop in cases.

Jobs lived more than seven years after being diagnosed with a neuroendocrine tumor - a less common, slower-growing and more treatable type of pancreatic cancer than the kind that killed Steinman a week ago and actor Patrick Swayze two years ago.

The Apple chief kept details of his illness behind a firewall and declared he was cured after cancer surgery in 2004. However, five years later, gaunt and having lost a lot of weight, Jobs had a liver transplant. Experts said it was likely because his cancer had returned or spread.

A liver transplant sometimes can cure the type of cancer that Jobs had. But if it comes back, "it's usually in one to two years," said Dr. Michael Pishvaian of Georgetown University's Lombardi Comprehensive Cancer Center.

In January, Jobs announced his third and final leave of absence. He resigned in August and died on Wednesday.

Part of what makes pancreatic cancer so deadly is that the pancreas is as vital as the heart. You can live with just part of a liver or a colon, or only one kidney or lung. But the pancreas is a fish-shaped organ that makes digestive enzymes and insulin and other hormones that enable the body to make energy from food.

In the United States, pancreatic cancer is the fourth leading cause of cancer deaths. About 44,030 people will be diagnosed with it and about 37,660 people will die of it this year in the U.S., the American Cancer Society estimates.

Possible symptoms are fatigue, back pain, abdominal pain, unexplained weight loss, loss of appetite, jaundice and nausea, according to the Lustgarten Foundation, a private group that finances research on the disease.

This cancer often is not found until it is advanced or has spread, and overall survival is dismal: 20 percent after one year and only 4 percent after five years.

However, with a neuroendocrine tumor like the one Jobs had, "people can live a longer time; median survival is five to eight years," said Dr. Alan Venook, a pancreatic cancer specialist at the University of California, San Francisco.

The lifetime risk of developing pancreatic cancer is about 1 in 71, according to the cancer society. Men and blacks account for more cases than women and whites, possibly because of differences in smoking rates. Smokers have two to three times more risk of developing the disease. Use of smokeless tobacco also raises the risk.

Obese people, those who don't exercise much and diabetics also have more risk for pancreatic cancer. Alcohol use might play a role: Most studies haven't tied it to pancreatic cancer, but heavy drinking can lead to diabetes and liver and pancreas problems that pose a cancer risk, the cancer society says.

The best hope for a patient is that the tumor is operable. That was the case in February 2009, when U.S. Supreme Court Justice Ruth Bader Ginsburg had a small, early-stage pancreatic tumor removed at New York's Memorial Sloan-Kettering Cancer Center.

On the horizon are immune system treatments - research that Steinman, the Nobel recipient from Rockefeller University in New York, was studying in the lab and trying on his own pancreatic cancer.

The immune system has a hard time recognizing and fighting cancer because the enemy is not an invading germ but our own cells gone rogue. Treatments called therapeutic cancer vaccines are ways to modify cells to help the immune system recognize the risk.

One such vaccine by NewLink Genetics, a small biotech firm in Ames, Iowa, is in late-stage testing now for pancreatic cancer. The company website says the larger study was initiated after a mid-stage test suggested improvement in survival.

Dr. Roderich Schwarz, chief of surgical oncology at the University of Texas Southwestern Medical Center in Dallas, has enrolled a few patients in some immune therapy studies, which have not paid off in the past.

"Vaccines are coming along," and last year's approval of one for advanced prostate cancer suggests researchers may be learning to overcome some of the drawbacks of the past, he said.

"It's quite possible that vaccines will claim their territory in the treatment of these challenging tumors," Schwarz said. "It's still in the development stage rather than the proven stage."

More information:
Cancer Institute: http://www.cancer.gov/cancertopics/types/pancreatic

Cancer Society: http://www.cancer.org/Cancer/PancreaticCancer/index

Survival rates: http://bit.ly/oAxKl5

Research and support: http://www.curePC.org and http://www.lustgarten.org

Vaccine study: http://www.linkp.com/products/hyperacute-pancreas.html

Researchers uncover novel immune therapy for pancreatic cancer

Researchers at the University of Pennsylvania's Abramson Cancer Center have discovered a novel way of treating pancreatic cancer by activating the immune system to destroy the cancer's scaffolding. The strategy was tested in a small cohort of patients with advanced pancreatic cancer, several of whose tumors shrank substantially. The team believes their findings – and the novel way in which they uncovered them -- could lead to quicker, less expensive cancer drug development.

26 mar 2011--The authors call the results, published in the March 25 issue of Science, a big surprise. "Until this research, we thought the immune system needed to attack the cancer directly in order to be effective," said senior author Robert H. Vonderheide, MD, DPhil, an associate professor of Medicine in the division of Hematology/Oncology and the Abramson Family Cancer Research Institute. "Now we know that isn't necessarily so. Attacking the dense tissues surrounding the cancer is another approach, similar to attacking a brick wall by dissolving the mortar in the wall. Ultimately, the immune system was able to eat away at this tissue surrounding the cancer, and the tumors fell apart as a result of that assault. These results provide fresh insight to build new immune therapies for cancer."

The current study is part of a unique research model designed to move back and forth between the bench and the bedside, with the investigative team consisting of researchers based in both the laboratory and in the clinic. In the clinical trial led at Penn by Peter O'Dwyer, MD, professor of Hematology/Oncology, and Gregory L. Beatty, MD, PhD, instructor of Hematology/Oncology, pancreatic cancer patients received standard gemcitabine chemotherapy with an experimental antibody manufactured by Pfizer Corporation. The antibody binds and stimulates a cell surface receptor called CD40, which is a key regulator of T-cell activation. The team initially hypothesized that the CD40 antibodies would turn on the T cells and allow them to attack the tumor.

The treatment appeared to work, with some patients' tumors shrinking substantially and the vast majority of tumors losing metabolic activity after therapy, although all of the responding patients eventually relapsed. When the researchers looked at post-treatment tumor samples, obtained via biopsy or surgical removal, there were no T cells to be seen. Instead, they saw an abundance of another white blood cell known as macrophages.

To understand what was happening in the tissues of these patients, Vonderheide and Beatty and colleagues turned to a mouse model of pancreatic cancer developed several years ago at Penn. Unlike older mouse models that were simplistic models of human disease, new genetically engineered mice develop spontaneous cancers that are very close reproductions of human tumors. "We can perform preclinical trials in these mice with the same principles we use in our patients," Vonderheide says, noting that the team even used a randomization protocol to assign individual mice to different arms of the study.

When the investigators treated mice that developed pancreatic cancer with gemcitabine in combination with CD40 antibodies, the results looked like those of the human trial. Some mouse tumors shrank and were found to be loaded with macrophages but contained few or no T cells. Closer inspection showed that the macrophages were attacking what is known as the tumor stroma, the supporting tissue around the tumor. Pancreatic tumors secrete chemical signals that draw macrophages to the tumor site, but if left to their own devices, these macrophages would protect the tumor. However, treating the mice (or patients) with CD40 antibodies seemed to flip that system on its head. "It is something of a Trojan horse approach," Vonderheide says. "The tumor is still calling in macrophages, but now we've used the CD40 receptor to re-educate those macrophages to attack – not promote – the tumor."

The researchers believe that the CD40 antibodies also activated T cells in the mice, but the T cells couldn't get into the tumor or its surrounding tissue. "We learned that T cells have a major problem with migration into tumors, and this may be a particular problem for pancreatic cancer," Vonderheide says. "The area surrounding pancreatic cancers is very dense, fibrotic, and hostile. This is one of the main reasons standard therapies for this disease often work so poorly."

The researchers are now working on ways to capitalize on their novel information, testing ways to super-charge the macrophage response and to get the T cells into the tumor microenvironment. Vonderheide thinks his team can speed up clinical research by running pilot trials in the mice to test potential therapeutics. Once they understand responses in the mice, then they can use that information to design better human trials.

"Beyond our specific findings, we think these findings point to a new approach for drug development in cancer -- one where we use state-of-the-art mouse models for preclinical trials to guide which trials we should do next in patients," Vonderheide says. "It should be faster, cheaper and give us a head start in the clinical trials."

Provided by University of Pennsylvania School of Medicine

Stanford study prevents pancreatic tumor growth in mice by inhibiting key protein

STANFORD, Calif., 2 feb 2009— Researchers at Stanford University School of Medicine have identified a protein critical for the growth of pancreatic cancer. Blocking the expression of the protein slowed or prevented tumor growth in mice and made cultured cancer cells vulnerable to the conditions of low oxygen that occur in solid tumors.

"This research clearly shows that inhibiting the protein inhibits the tumor's ability to grow," said cancer biologist Amato Giaccia, PhD. "Ultimately, we'd like to be able to specifically knock out the expression of this protein in pancreatic tumors in humans."

Pancreatic cancer is a highly aggressive and deadly disease that accounts for more than 30,000 deaths in the United States annually, and current therapies are largely ineffective.

"Right now, we have very little to offer these patients," said Giaccia. He is the Jack, Lulu and Sam Willson Professor and professor of radiation oncology and the senior author of the research, which will be published Feb. 1 in the journal Cancer Research. Giaccia is also a member of the Stanford Cancer Center.

The researchers studied a protein called connective tissue growth factor, or CTGF. Also known as CCN2, the protein is involved in the abnormal growth of connective tissue in response to injury or disease. It was also thought to be involved in pancreatic tumor progression, although the exact role it played was unknown.

Giaccia and his collaborators found that human pancreatic cancer cells expressing high levels of CCN2 grew robustly when injected under the skin of mice. In fact, in the developing tumor these cells soon out-competed others that expressed lower levels of the protein. Conversely, pancreatic cancer cells in which CCN2 expression was suppressed were either less likely or unable to form tumors when injected into mice.

The researchers observed similar effects when the cancer cells were injected directly into the animals' pancreases. Cancer cells expressing high levels of CCN2 formed tumors that grew more rapidly and metastasized more aggressively than did those expressing lower levels, and the mice died sooner than others injected with cancer cells expressing less CCN2.

It's difficult for many types of rapidly growing solid tumors to recruit and build enough blood vessels to keep all the cancer cells adequately oxygenated. Normal cells undergo a process of programmed cell death when oxygen levels drop too far. Overcoming this response to low oxygen levels — a condition called hypoxia — is a critical step in tumor progression.

The researchers wondered if CCN2 played a role in keeping tumor cells alive in hypoxic conditions. If so, this might explain why CCN2-expressing cancer cells are favored during tumor growth. They found that blocking CCN2 expression in cultured pancreatic cancer cells made them significantly more sensitive to hypoxia-induced death than their peers. Additionally, CCN2 was more highly expressed in pancreatic tumor samples from human patients than in neighboring tissue and CCN2 expression seemed to correlate with the expression of another protein expressed by hypoxic cells. Finally, hypoxic conditions themselves cause the pancreatic cancer cells to make CCN2.

Many other cellular conditions can also kick-start CCN2 expression, including the presence of CCN2 itself. The activation of other pathways known to be involved in cancer also increases its expression. As a result, many of the events that occur in a developing tumor act as a kind of perfect storm to support the production of ever-larger amounts of CCN2, which then support additional tumor growth and metastasis.

Looking ahead, the researchers would like to know whether people with pancreatic cancer could benefit from therapies targeting CCN2. A phase-1 clinical trial testing the safety of an antibody that binds CCN2 and blocks its activity in a small number of patients began in December at Stanford and Dartmouth-Hitchcock Medical Center. Phase-1 clinical trials are not designed to determine whether a treatment works — only whether it is safe enough for further testing. Albert Koong, MD, PhD, an assistant professor of radiation oncology and a member of the Cancer Center, is the principal investigator for the Stanford arm of the trial.

"We saw a pronounced effect of CCN2 inhibition in these experiments in mice," said Giaccia. "Our hope is that one day a combination of standard therapy and antibody treatment will have an effect on tumor progression in human patients."

###

Giaccia's Stanford collaborators on the research include former post-doctoral scholars Kevin Bennewith, PhD, who is now a research scientist at the British Columbia Cancer Research Centre in Vancouver; Janine Erler, PhD, who is now a group leader at the Institute of Cancer Research at Chester Beatty Laboratories in London; post-doctoral scholars Xin Huang, PhD; and Christine Ham, MD; assistant professor of radiation oncology Edward Graves, PhD; associate professor of pathology Neeraja Kambham, MD; assistant professor of surgery George Yang, MD, PhD ; and Albert Koong.

AMA president speaks of pancreatic cancer struggle

By DON BABWIN
16 june 2008--As a doctor, Ron Davis knew what it meant when he got a diagnosis of advanced pancreatic cancer earlier this year.
So did his audience on Saturday, the American Medical Association. Davis, a doctor of preventive medicine, is the group's president and he got the bad news eight months into his one-year term.
Like most of those diagnosed with the disease, Davis' cancer has spread beyond the pancreas, reducing chances for recovery. Surgery wasn't an option.
"As a physician, I know the survival statistics for someone with stage 4 pancreatic cancer," he said. But if the five-year survival is 5 percent, that's not zero... So, never take away someone's hope."
In an upbeat, sometimes funny and at moments poignant, emotional 45-minute speech, Davis talked about his life and how it has changed, both good and bad since his diagnosis. He spoke of his hopes for the future, his own and that of his fellow doctors and their patients. And he talked about legacy — his and that of everyone listening to him.
"So, whether we are ill or well, we should not waste any of that time before figuring out how to leave our mark on this planet," he said.
Davis urged his fellow doctors, gathered in Chicago for their annual meeting, to help patients live healthier lives. He applauded the AMA for supporting stronger regulation of tobacco and for raising awareness about people who don't have health insurance. And he urged the group to press for even more, raising federal taxes on tobacco and working to avoid Medicare doctor payment cuts.
These are familiar issues for Davis. A native of Chicago who now lives in East Lansing, Mich., he has spent his career working to prevent disease and raise awareness about the risks of tobacco. His agenda as AMA president has included coverage for the uninsured and promoting health quality and safety.
After his diagnosis, he has still managed to keep a dizzying pace of meetings and speeches. During one lecture, he walked on a treadmill to "walk the talk" on prevention of chronic illness through fitness.
He continues on chemotherapy, an aggressive regimen his doctors hope will halt the spread of cancer now in his liver. And though bald, he looks robust. He will turn 52 on Wednesday.
Davis told his listeners of pursuing the "noble cause" of raising awareness about pancreatic cancer, which afflicts 37,000 Americans a year, and kills 34,000. While it is the fourth leading cause of cancer death in the nation, "pancreatic cancer research accounts for less than 2 percent of the National Cancer Institute's research funding," he said.
At times he was funny as he joked about the positives of a terrible diagnosis. People keep giving him hats, he said while slipping a Detroit Red Wings cap on his hairless head. "My son Connor no longer tells me in the morning that I have wacky hair."
It was in speaking of his family that he choked up. The father of three sons said he has spent more time over the last four months with his wife and children.
As he ended his speech, they joined him at the podium for a hug. The standing ovation he got lasted three minutes.

Beer Drinking May Speed Pancreatic Cancer Onset

By Kathleen Doheny
26 may 2008 -- Heavy smoking and drinking, especially beer, may hasten the onset of pancreatic cancer, according to researchers who presented their data Tuesday at the Digestive Disease Week 2008 conference in San Diego.
Beer appears to exert a stronger influence than hard liquor or wine in lowering the age of onset of pancreatic cancer, said researcher Dr. Michelle A. Anderson, assistant professor of medicine at the University of Michigan.
Anderson and her colleagues evaluated patients from The Pancreatic Cancer Collaborative Registry, a multi-center, international patient registry, looking at whether the patients drank or smoked, and if so, how much and what type of liquor.
They evaluated the smoking and drinking (or abstinence) patterns of 453 patients in all, about equal numbers of men and women.
Patients who smoked did tend to develop pancreatic disease at a younger age and there were dose-related effects, Anderson said. Heavy smokers (such as those who have smoked more than a pack a day for 40 years, or more than two packs for 20 years) presented with pancreatic cancer an average of seven years before nonsmokers.
The average age of onset of pancreatic cancer is between 70 to 80, experts noted.
Heavy drinkers, defined as having more than three daily drinks, presented with pancreatic cancer 10 years younger than those who did not drink.
Comparing beer, wine and hard liquor, the team found that beer lowered the age of developing pancreatic cancer most, Anderson said. When she compared beer drinkers to non-beer drinkers, the effect was statistically significant; however, when she considered other variables that may affect cancer onset, the effect disappeared.
Cigarette smoking is already a well-known risk factor for pancreatic cancer. Heavy alcohol intake may induce chronic inflammatory changes that are also linked with cancer, Anderson said.
The combination of chronic smoking plus drinking had no stronger effect on pancreatic risk than either habit alone, the researchers found.
Pancreatic cancer is expected to be diagnosed in nearly 38,000 people in the United States this year, according to the American Cancer Society, and about 34,000 will die of the disease. The lifetime risk is about 1 in 79 but is affected by factors such as advancing age, obesity and family history.
Because it is often emerges without symptoms, pancreatic cancer is often not detected until its later stages, when treatment is less effective. But even if caught at stage one the outlook is bleak, researchers said. At stage one, the 5-year survival from pancreatic malignancy is about 33 percent.
The pancreas, about 6 inches long and less than 2 inches wide, extends across the abdomen. It makes key hormones, including insulin, and helps to balance blood sugar.
Finding pancreatic tumors earlier -- especially important for people with a family history, or other factor indicating high risk -- is the focus of much research. And a new study suggests that combining two methods may provide better screening, according to another researcher, Dr. Richard Zubarik, associate professor of medicine and chief of endoscopy at Fletcher Allen Health Care in Burlington, Vt.
His research team used a blood test called CA19-9 -- a test to detect a tumor marker most often used to monitor disease progress and predict survival rates. They then combined that screen with an endoscopic ultrasound to try to detect the cancer in the earliest stages.
Of the 272 patients enrolled, one patient was diagnosed with pancreatic cancer and one with abnormal pancreatic cell growth.
However, the method is expensive -- it cost $14,000 to detect the cancer and about $11,000 to detect the abnormal cell growth, Zubarik said.
Other strategies are being studied to see if they can increase the bleak survival rates. In another study, researchers compared the records of more than 4,000 patients with pancreatic cancer and divided them into two groups -- those who had the ultrasound (about 12 percent of the sample) and those who did not.
Those who received the ultrasound at diagnosis had a somewhat longer average survival time, said Dr. Ananya Das, associate chair of medicine, Mayo Clinic in Scottsdale, Ariz. Undergoing this screen increased average survival time for patients from 5 months to 9 months.
Going to a center that offers this method may mean that patients receive better overall care, he said. Endoscopic ultrasound is available at leading medical centers, he said.
In patients at very high risk of pancreatic cancer, such as those with a family history, surveillance performed by a team of specialists can also help, said Dr. Teresa A. Brentnall, associate professor of medicine at the University of Washington, Seattle.
"Our goal is to protect them from pancreatic cancer," she said. Her team found that two tests could help. One is the endoscopic ultrasound, the other is called an endoscopic retrograde cholangiopancreatography.
Brentnall's team followed 100 patients using these methods. Of the 100 patients, two developed cancer (one inoperable), and 20 had abnormal cell growths. The combination can help lead to detection of pancreatic pre-cancer, she said.

Allergies may protect against pancreatic cancer

By Michelle Rizzo
Having a history of allergies or hay fever may offer protection from deadly pancreatic cancer, according to a study appearing in the International Journal of Cancer.
Ayelet Eppel, of Mt. Sinai Hospital, Toronto, Ontario, Canada, and colleagues examined the association between a history of allergies or asthma and the risk of pancreas cancer in a population-based, case-control study in Ontario.
They identified cases of pancreatic cancer through the Ontario Cancer Registry and recruited control subjects from the Ontario Familial Colorectal Cancer Registry.
A total of 276 pancreatic cancer cases and 378 controls were included in the study.
The investigators found that a history of allergies or hay fever was associated with a significant 57 percent reduction in the risk of pancreatic cancer.
The reduction in risk was stronger in men than in women. There was no association between history of asthma and the risk of cancer of the pancreas.
"Further research is needed to replicate these findings," Eppel told Reuters Health.
"If replicated, our findings may be of importance to understanding the biological mechanisms involved in pancreas cancer development -- for example, the role of the immune system," the researcher explained, adding: "The association between allergies and certain cancers has been found in other studies."
SOURCE: International Journal of Cancer, December 2007.

Fiber, whole grains may cut pancreatic cancer risk

By Joene Hendry 48 minutes ago
Eating more whole grain and fiber-rich food may lower the risk of pancreatic cancer by about 40 percent, study findings suggest.
Dr. June M. Chan, of the University of California, San Francisco, and colleagues identified this reduced risk among adults who ate two or more servings of whole grains each day compared with those who ate less than one serving a day.
They also noted about a 35 percent reduction in risk among individuals who ate the highest amount of fiber (26.5 grams per day or more) compared with those who ate the least (15.6 grams per day or less).
"There is a possibility that diet can affect one's risk of pancreatic, as well as other cancers," Chan told Reuters Health, "and that eating a diet rich in a wide variety of grains is likely to not only help in the prevention of diabetes and heart disease, but also this very deadly cancer."
The researchers looked at grain intake among 532 people with pancreatic cancer and 1,701 people without pancreatic cancer among the San Francisco Bay area population.
The two groups were similar in age, gender, and body weight, and had a similar history of diabetes, but those with pancreatic cancer were more frequently current smokers, the investigators note in the American Journal of Epidemiology.
Overall, the results of the study suggest that eating more whole grains may protect against pancreatic cancer.
On the other hand, eating two or more servings of doughnuts a week, compared with less than a serving a month, was found to raise the risk of pancreatic cancer. However, so did eating two or more servings a week of cooked breakfast cereals such as oatmeal, which the investigators suspect may be explained by their inability to distinguish between sweetened or 'instant' cereals and less refined cereals.
"The risk reductions associated with some whole grain foods and fiber provide general support for the hypothesis that whole grains are better than more refined and sweetened grains for pancreatic cancer prevention," Chan said. However, "further studies are needed to confirm this," Chan added.
SOURCE: American Journal of Epidemiology, November 15, 2007.

Low Levels of Protein May Predict Risk of Pancreatic Cancer

BOSTON, Aug. 16 -- A previously unsuspected independent risk factor for pancreatic cancer may be a low level of plasma insulin-like growth factor binding protein-1 (IGFBP-1), found researchers here.
IGFBP-1 is a downstream target of insulin and inhibits insulin-like growth factor I (IGF-I) activity. Because IGF-I has growth-promoting effects on pancreatic cancer cells, and elevated fasting serum insulin has been linked to pancreatic cancer risk, the investigators looked to see whether prediagnostic plasma levels of IGFBP-1 are associated with pancreatic cancer risk.
The finding that IGFBP-1 seemed to be a pancreatic cancer risk factor emerged from a prospective, case-control study with 573 participants reported in the Aug. 15 issue of Cancer Research by a team led by Brian Wolpin, M.D., of the Dana-Farber Cancer Institute.
The 144 cases and 429 controls, matched for date of birth, smoking status, and fasting status, came from the Health Professionals Follow-up Study, the Nurses' Health Study, the Physicians' Health Study, and the Women's Health Initiative, said Dr. Wolpin and colleagues.
The investigators collected blood samples from the 573 participants and measured circulating IGFBP-1. The measurements were repeated four or more years later.
Study participants in the lowest quartile of IGFBP-1 were more than twice as likely to develop pancreatic cancer as were those participants with higher levels of plasma IGFBP-1. The influence of IGFBP-1 increased with time since blood collection.
Specifically, participants in the lowest quartile for IGFBP-1 who were diagnosed with pancreatic cancer eight or more years after blood draw had nearly 3.5 times the risk for developing pancreatic cancer as those participants in the upper quartiles.
Participants in the lowest quartile of plasma IGFBP-1 had a relative risk of 2.07 for pancreatic cancer, compared with their counterparts with higher levels of plasma IGFBP-1 (95% CI 1.26-3.39). These findings held even after researchers adjusted for plasma insulin growth factor-1, C-peptide and IGFBP-3; suggesting an independent effect of IGFBP-1 on pancreatic cancer risk.
The adjusted relative risk for participants diagnosed with pancreatic cancer eight or more years after blood collection was 3.47 (95% CI 1.48-8.14). Overall, only patients in the lowest quartile for IGFBP-1 were found to have an increased risk for pancreatic cancer.
Moreover, the study found that the effect of IGFBP-1 was strongest among those participants who never smoked cigarettes (RR 3.30; 95% CI, 1.48-7.48). The influence of low IGFBP-1 also seemed to be greater among participants with higher plasma levels of C-peptide. The study findings also held in participants with diabetes and were not affected by the time between a participant's last meal and the time of the blood draw.
IGFBP-1 is known to decline in response to obesity and a sedentary lifestyle, two suspected risk factors for pancreatic cancer. Although the exact mechanism by which IGFBP-1 may affect pancreatic cancer risk is not known, the researchers speculated that higher amounts of IGFBP-1 are able to absorb more insulin growth factor, leaving less available to encourage pancreatic cancer cell growth.
They also suggested that IGFBP-1 may have some anti-cancer properties of its own. Previous research has linked low levels of plasma IGFBP-1 to a risk of colorectal and endometrial cancer, but not postmenopausal breast cancer or lung cancer.
"Further studies of the interaction of insulin and the IGF axis in pancreatic cancer are needed to better understand the mechanism by which anthropometric factors and plasma levels of insulin and IGFBP-1 alter the risk for this highly lethal malignancy," the study authors concluded.
None of the study authors reported any potential conflicts of interest.Primary source: Cancer ResearchSource reference: Wolpin BM, et al. "Circulating Insulin-Like Growth Factor Binding Protein-1 and the Risk of Pancreatic Cancer." Cancer Res. 2007; 67: 7923-7928.

Study Spots New Pancreatic Cancer Drug Target

MONDAY, July 2 (HealthDay News) -- New research may someday provide another treatment option for patients battling deadly pancreatic cancer.
The University of Cincinnati (UC) team knew that a cellular receptor known as the "RON receptor tyrosine kinase" is active in several cancers, including breast cancer.
In a study appearing in the July 1 issue of Cancer Research, they set out to determine if the receptor was also expressed in pancreatic cancer.
Pancreatic cancer will affect an estimated 37,000 Americans in 2007. It's survival rates are low -- only about 4 percent -- often because the cancer is not detected until it has spread.
In the UC study, the researchers found that the RON receptor was overexpressed in pancreatic cancer cells. In addition, blocking the receptor with targeted antibodies killed more cancer cells than standard drug treatment alone.
"A normal pancreas has very low levels of RON, but our study showed that as tumors progress, so does the level of RON expression in the pancreas cells -- and those overexpressed levels were maintained in metastases, the areas that the tumors spread to," Susan Waltz, an associate professor and director of the oncology research program in UC's surgery department, said in a prepared statement.
The researchers found that the RON receptor was present in 79 percent of primary pancreatic cancers and 83 percent of metastatic cancers -- cancers that have spread to other parts of the body.
"When cells become invasive," Waltz said, "we saw higher levels of RON expression that correlated with the aggressive nature of this disease and cancer metastasis. Clearly, this signaling pathway is associated with pancreatic cancer and merits further investigation."
These findings could be the beginning of the development of a new treatment for pancreatic cancer.
"Our findings suggest that combining antibodies that block the RON receptor and the standard chemotherapy drugs might stop progression of pancreatic cancer more effectively," said Waltz. "RON could be a promising molecular target for future cancer drug development."
More research will be needed before RON receptor blockers become available for human testing, though, Waltz stressed.
More information
The U.S. National Cancer Institute has more about pancreatic cancer.