May 21, 2008 There are new and innovative methods to better understand the risk factors for and improve earlier detection of pancreatic cancer. Specifically, researchers can demonstrate that the development of, new biomarkers, novel treatment targets, innovative approaches to screening and surveillance and improved understanding of risk factors can lead to diagnosis of pancreatic cancer at earlier more treatable stages.
"Pancreatic cancer is the fourth-leading cause of cancer death in the U.S., taking 34,000 lives every year," said Mark P. Callery, MD, MACS, associate professor of surgery, Harvard Medical School, chief, division of general surgery Beth Israel Deaconess Medical Center. "It's vitally important that we make pancreatic cancer a research priority. Signs and symptoms of the disease may not present themselves until advanced stages, when surgical removal of the cancer is no longer possible."
The following research will be presented May 20 at Digestive Disease Week 2008 conference in San Diego, California.
The five-year survival rate for pancreatic cancer is only four percent, but if detected at Stage 1, the survival rate can be as high as 33 percent.
Endosonographic Evaluation Improves Survival in Patients with Pancreatic Cancer
Due to a lack of early detection and treatment options, pancreatic cancer is deadly. In fact, a vast majority of patients with pancreatic cancer die because the disease has spread so far that it can no longer be removed. However, a small percentage of pancreatic cancers are caught early enough for a curative surgery to allow removal of the tumor, which may result in improved survival.
Researchers are fervently searching for new, improved technologies that could either detect pancreatic cancer earlier or treat it once it's detected. Endoscopic ultrasound (EUS) is an expensive treatment, but shows great promise in helping to improve patient outcomes after a diagnosis with pancreatic cancer. Researchers for this study sought to learn about the association between EUS performance and pancreatic cancer survival. To achieve this, investigators reviewed the SEER-Medicare database of patients receiving treatment between January 1994 and December 2002. In all, the records of 4,236 patients with pancreatic cancer were assessed, and broken into two groups -- those who received EUS (only 12 percent of the sample) and those who did not (88 percent).
Researchers found that after they controlled for age, race, gender and comorbidities, those who did receive EUS at the time of diagnosis had a longer average survival time (nine months) than those who did not receive EUS (five months).
"Good initial investigation by EUS makes a significant difference for patients with pancreatic cancer," said Ananya Das, MD, associate chair of medicine, Mayo Clinic, Scottsdale, Arizona. "Though the treatment is expensive and not available everywhere, it has shown to be a marker for better care and treatment planning."
Dose Dependent Effects of Alcohol and Tobacco on Age of Presentation in Pancreatic Cancer (PC): A Multi-Center, International Study
Smoking tobacco and drinking alcohol have an effect on the age at which a patients present with pancreatic cancer. This multi-center, international study shows that among patients with pancreatic cancer, heavy smokers and drinkers show the youngest onset. While the average age for the onset of pancreatic cancer is in the 70 to 80 year age range, smokers and drinkers show onset as early as in their 50s, and the more tobacco and alcohol consumed, the earlier the onset.
A previous study using insurance data showed that tobacco and alcohol use affected the age of onset of pancreatic cancer but the effect of the amount and length of time of its use was unknown.
This study, using The Pancreatic Cancer Collaborative Registry, a multi-center international patient registry, captured data for the first time on the dose amounts of tobacco and alcohol used by pancreatic cancer patients along with data on the type of alcohol consumed. The registry was queried for patient age at diagnosis, gender, race, diabetic status, family history of pancreatic cancer, and tobacco and alcohol use.
"We found that the more smoking and drinking done by the patient, the younger the onset of the cancer, and that of the two, drinking has a worse effect," said Michelle A. Anderson, MD, assistant professor of medicine at the University of Michigan. Heavy drinkers (more than three drinks a day) presented with pancreatic cancer 10 years younger than those who did not drink, while heavy smokers* presented seven years younger than those who did not smoke.
Among the different types of alcohol studied (beer, wine and hard liquor), beer was the strongest in lowering the age of presentation. The median age of onset for those who drank only beer was 62.2 years compared with 68.2 years for those consuming other types of alcohol. "This study strengthens the validity of the data showing that these toxins may be important in the pathogenesis of pancreatic cancer," said Dr. Anderson.
Researchers did not find a synergistic relationship between the use of tobacco and alcohol, meaning that the age of onset was not profoundly worse if the patient used both, although the size of the study may have affected this finding.
Other limitations of the study include the fact that patients were being asked to recall their past use of tobacco and alcohol and a potential for selection bias. Also, because all of the centers using the registry are academic medical centers, the type of patient may be different than the type of patient who would go elsewhere for care.
A heavy smoker is a person with a pack value > 40. Pack values were determined by multiplying the number of years a person has smoked by the pack per day they smoke (e.g. a person who smokes a pack per day for 20 years has a pack value of 20 while a person who smokes half a pack per day for 20 years has a pack value of 10).
Surveillance and Natural History of High Risk Patients who Inherit Pancreatic Cancer
In patients who are at very high risk of inheriting pancreatic cancer, surveillance can be effective if performed by a team of experienced specialists. The findings are important because at least 10 percent of pancreatic cancer is inherited and it is a lethal disease that is often not detected until it is too late, since the pancreas is not easily sampled, looked at or felt.
"For these reasons, detecting abnormalities at the pre-cancerous stage has great potential to save lives," said Teresa A. Brentnall, MD, associate professor of medicine at the division of gastroenterology at the University of Washington, Seattle.
Investigators studied 100 patients for 10 years in a specialized program. The patients were selected from two groups: patients with two or more family members with pancreatic cancer, at least one of whom was a first-degree relative; and patients with a known gene for a lifetime risk of pancreatic cancer of 15 percent or more.
Patients were examined using endoscopic ultrasound (EUS), a combined procedure using endoscopy and ultrasound to obtain information and images about the digestive tract, as well as surrounding organs and tissue. EUS can show whether the pancreas appears to be unhealthy, but it doesn't show exactly what the problem may be or how severe it may be.
Patients whose EUS detected problems were given a choice: either do nothing and let the cancer form -- a risky option, since cells can go from normal to cancerous in one year -- or remove the pancreas, which causes diabetes. "The stakes are very high. The pancreatic cancer survival rate is only about five years. There is also the risk that the patient could suffer complications from diabetes which could be fatal," said Dr. Brentnall.
Of the 100 patients, 52 had an abnormal EUS on initial exam; three of them abstained from alcohol and their status returned to normal. Also, 10 of the 48 who initially had a normal EUS developed new abnormal EUS changes under surveillance. Two patients who went on to have cancer developed new masses at one and four years after surveillance; the masses developed within one year of an abnormal EUS with no masses. Finally, none of the patients with advanced pancreatic pre-cancer who had surgery developed pancreatic cancer during an average follow-up of seven years.
The majority of patients in the study did not opt for surgery and instead were monitored as part of a rigorous surveillance program in which their progress was closely tracked. Physicians worked closely with patients to determine their prognosis and make tailored recommendations. "EUS can assist in the detection of pancreatic neoplasia when performed in a specialized center and can lead to the detection of curable pancreatic pre-cancer," said Dr. Brentnall.
She added that the program can only exist successfully with a staff that is specifically designated as part of a surveillance team, and that the endoscopic training -- and practice -- is rigorous, so many hospitals in different areas of the country would not be likely to have such a program. Another difficulty is that experts tend to disagree on what EUS reveals; images tend to be more suggestive and less definitive, which also complicates detection and therefore treatment.
Pancreatic Cancer Screening in a High-Risk Population
A new screening method using CA19-9, a tumor marker that is most often used to monitor disease progress as well as predict survival rates, with endoscopic ultrasound is more likely to detect pancreatic cancer in its early stages when it is most treatable. The finding is significant because a nationally-accepted screening tool for pancreatic cancer does not exist. Currently, most cases are detected when patients present with symptoms at advanced stages of the disease.
"Pancreatic cancer is more detectable through this process than traditional screening protocols," said Richard Zubarik, MD, associate professor of medicine and chief of endoscopy at Fletcher Allen Health Care, Burlington, Vermont. "Our research finds that the CA 19-9 screening method can detect pancreatic cancer at an earlier stage in high-risk populations." These include people with a first degree relative with pancreatic cancer, people who smoke, people with diabetes, and people aged 50 or older. Dr. Zubarik added that more than 90 percent of the people who develop pancreatic cancer are over the age of 50.
For the study, investigators performed an endoscopic ultrasound if the CA 19-9 level was =37 (reference range 0 -- 37 U/ml). Fine needle aspiration was performed during this process if a lesion was identified. Patients with pancreatic cancer detected through this protocol were compared to patients who were not screened through this method.
Medicare reimbursement rates were used to determine cost data, and investigators concluded that the new screening method is expected to reduce medical costs. The cost to detect pancreatic cancer was just over $14,000, and the cost to detect pancreatic neoplastic tumors (abnormal cell growth) using this method is approximately $11,000.
The new screening method does have limitations. With very small tumors, its sensitivity declines. Still, Stage 1 cancers are significantly more likely to be detected through this protocol than through more traditional methods. "Right now, this appears to be the best test we have. We hope this will help us develop even better screening tools in the future," Dr. Zubarik said.
Development of Monoclonal Antibodies to Aid in the Diagnosis of Pancreatic Cancer
Investigators have developed antibodies that recognize pancreatic cancer. The antibodies were developed through a technique of injecting normal pancreas cells into mice.
Early detection and treatment of pancreatic cancer is critical; the best available treatment for pancreatic cancer is surgery, which is only effective at early stages of the disease. But less than 15 percent of patients are diagnosed with pancreatic cancer at an early stage.
Investigators developed the Oregon Pancreas Tumor Registry, which serves two functions: first, it is intended to keep patients at high risk for pancreatic cancer under surveillance, with the goal of early diagnosis. Also, it acts as a biospecimen repository in which patients and families may provide blood, pancreatic ductal fluid and tissue samples. Doctors may then use the samples for pancreatic cancer research, according to Brett C. Sheppard, MD,Professor and Vice-Chairman of Surgery at the Digestive Health Center at the Oregon Health Sciences University (OHSU).
For this study, OHSU researchers in the Oregon Stem Cell Center and in the Department of General Surgery generated and characterized antibodies. These antibodies were developed following the injection of normal pancreas cells into mice. They next took the spleen cells of the mice and fused them with a myeloma cell line, which yields cells that can be grown for long periods of time in the laboratory. These cells secreted antibodies which researchers were then able to screen for reaction with normal pancreatic and pancreatic cancer tissues.
"The antibodies described in this abstract, recognize normal pancreas cells, specifically a population of ductal cells, but recognize many more cells in pancreatic cancer tissue. In addition to recognizing pancreatic cancer, these antibodies recognize gastrointestinal cancers. The next step is to use these antibodies in a sensitive screening assay to determine their full potential in diagnosis of this devastating disease."
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