October 1, 2007

The Struggle to Fight Pancreatic Cancer
By Kim M. Norton
For The Record
Vol. 19 No. 20 P. 48

The fourth deadliest cancer may also be the least understood and the most difficult to detect.

Often taking a backseat to other more well-known cancers, pancreatic cancer has a mortality rate of 98% with a five-year survival rate of only 5%. It subsequently has become the fourth deadliest cancer, according to the American Cancer Society (ACS).

What makes pancreatic cancer so devastating is the lack of warning signs—in most cases, patients present with vague symptoms. Once a pancreatic cancer diagnosis is determined, the patient is usually too ill to undergo any kind of treatment to maintain a substantive quality of life, according to James L. Abbruzzese, MD, head of the gastrointestinal department at the University of Texas M. D. Anderson Cancer Center in Houston.

Still, hope persists. “With more and more patients receiving high-quality CT scans, there is a greater possibility that tumors in the pancreas can be detected earlier when they are possibly still able to be operated on,” Abbruzzese says. But, even when the tumor is detected before it has spread to other organs, the prognosis is generally lengthened only from weeks to months, he adds.

Despite the poor prognosis, limited lead time in diagnosis, and a general lack of treatment, cancer researchers are hopeful that DNA, microRNAs, and genetic mutations can lead to a better understanding of this lethal cancer. “Unfortunately, we, as a scientific community, are no wiser about pancreatic cancer than we were 100 years ago. The only difference between then and now is that we have perfected the surgery and, even then, with no remarkable success,” says Mark P. Bloomston, MD, a surgical oncologist with the Ohio State University Medical Center Comprehensive Cancer Center in Columbus.

Identifying Pancreatic Cancer
The ACS predicts that in 2007, approximately 37,000 people in the United States will be diagnosed and 33,000 will die from the disease. For most patients, there are few identifying symptoms until the tumor has become large and metastasized into the liver and bile duct.

The major difficulty in early detection lies in the shape and location of the pancreas. The organ, shaped like a thin pear, is approximately 6 inches long by 2 inches wide and is located behind the stomach across the abdomen. Because of its location, tumors can often be overlooked because they cannot be palpitated in a routine exam. Additionally, there are generally no symptoms associated with the cancer until it has restricted the patient’s ability to eat and go to the bathroom, or the patient is experiencing fatigue, explains Abbruzzese.

A CT scan is the most definitive way to detect a pancreatic tumor, but the scan has limitations. “Small tumors and lesions are easily overlooked or are unable to be detected because of their size. This alone is unfortunate because being able to detect the lesion or tumor when it is still small in size and limited to the pancreas is when the patient has the greatest chance of survival from early detection,” says Abbruzzese.

Patients fortunate enough to have their pancreatic cancer detected early generally have an unrelated ailment. Typically, these patients are undergoing an unrelated procedure when the surgeon finds the tumor and is able to operate while it is still small and confined to the pancreas. “Other than in these instances, diagnostic tools have proved primitive in identifying pancreatic tumors, and we must rely on symptoms alone to identify the cancer,” Abbruzzese says.

Symptoms and Presentation
Symptoms of pancreatic cancer are often vague and can be attributed to any number of ailments. The most common symptoms include mild weight loss, loss of appetite, jaundice, abdominal pain, mid-back pain, nausea, general weakness and fatigue, light-colored bowel movements, blood clots, and itchy skin. “We are at the mercy of the disease and how it presents. What is so devastating about the disease is that when these vague symptoms are present, the patient is generally at a very high stage of the cancer and is unable to be helped by surgery and rarely by chemotherapy,” says Abbruzzese.

Roughly 80% of pancreatic cancer occurs in the “head” of the pancreas—the area closest to the common bile duct, according to the Penn State Milton S. Hershey Medical Center College of Medicine. Other less common types of the cancer form in the tail of the pancreas and can block the veins that drain the spleen, which causes it—as well as the varicose veins surrounding the stomach and esophagus—to enlarge. A more rare manifestation occurs when the cancer affects the hormone-secreting portion of the pancreas. In this case, the pancreas will produce too much or too little insulin.

Treatment Options
Surgery
The cancer’s stage and its location will dictate whether the patient is a surgical candidate. In the majority of cases, the tumor is inoperable because it has spread outside the pancreas. However, if the patient is a surgical candidate, the surgical team will go forward, explains Bloomston. “Surgical intervention is really the only shot a patient has at a cure, and the survival rate following surgery coupled with chemotherapy is generally 18 to 24 months,” he says.

If it is determined that the cancerous tumor is confined to the pancreas alone, then the patient is a good candidate for surgery to remove it. The tumor location will determine which type of procedure the patient will undergo.

The Whipple procedure is used when the tumor is limited to the head of the pancreas. In addition to removing the head of the pancreas, part of the small intestine and some tissues around it are removed as well. Enough of the pancreas is left to continue making digestive juices and insulin, according to the ACS. A total pancreatectomy will remove the entire pancreas, part of the small intestine and stomach, the bile duct, gallbladder, spleen, and most of the lymph nodes in the area. Following a total pancreatectomy, the patient will need to take insulin.

The last surgical option is a distal pancreatectomy, which removes only the tail of the pancreas. In addition to surgical removal of the cancerous area, each surgery is traditionally followed by chemotherapy to try to completely destroy any cancerous cells that may not have been removed during the surgery, explains Bloomston.

Pharmacological Therapy
For those patients who are not surgical candidates—prognosis is anywhere from a couple weeks to one year—their only real option is chemotherapy. Gemcitabine is an FDA-approved chemotherapy for pancreatic cancer, but it has not shown any true potential. With gemcitabine, the patient may have an additional 20 days of life as opposed to just a couple days, says Bloomston. It is when surgery and gemcitabine are combined that the patient will see any real improvement in his or her quality of life, he adds.

Researchers are working to find better drugs and chemotherapies to combat pancreatic cancer, but so far, the research has not proven fruitful. “Gemcitabine is truly the foundation in treating pancreatic cancer, and we have found that combining it with other agents does give more of an effect. But, overall, we have found that pancreatic cancer has been resistant to most treatments,” says Abbruzzese.

One agent that has shown success and improved prognosis in patients with advanced pancreatic cancer is Tarceva coupled with gemcitabine. “Tarceva and gemcitabine have shown a slight advantage over other combined agents, but it is considered controversial because of the significant side effects,” Abbruzzese says. Those potential side effects can include a severe rash and interstitial lung disease; however, a recent report in Clinical Cancer Research found that the rash’s presence indicates Tarceva is working.

Risk Factors
Risk factors play a large role in whether a patient will develop pancreatic cancer, with only 10% of cases being genetically linked. Smokers develop the disease more than twice as often as nonsmokers. Other risk factors include chronic pancreatitis (inflammation of the pancreas), alcoholism, gallbladder disease, and a poor diet.

Diet has not been widely studied, but Swedish and German researchers have found a correlation between a diet rich in animal products and dairy foods and low in fruits and vegetables with an increased risk of developing pancreatic cancer. “Although diet is an important component to a person’s overall health, people who generally have some sort of addiction, such as alcoholism, rarely have a balanced diet,” says Bloomston. For now, the most relevant and prevalent risk factor for the cancer is smoking, he says.

Predicting Pancreatic Cancer
With risk factors identified, the medical community is striving to detect DNA mutations that may help predict a patient’s life expectancy once diagnosed with pancreatic cancer. So far, the genetic mutations that have been discovered—P53, Smad4, DPC4, and P16—indicate when pancreatic cancer is present but have not been definitive in differentiating between pancreatitis and pancreatic cancer. These markers have also never been predictive of outcome or survival, explains Bloomston. Currently, the only success that Bloomston and other researchers have had differentiating between a pancreatic tumor and pancreatitis has come through their work with microRNAs.

MicroRNAs are small RNA molecules encoded in genomes, says Bloomston. “MicroRNAs are in every aspect of development, and we focused our attention on them because it does not code for proteins, and when these molecules are modified and go awry, they can cause cancers,” he explains. At first, researchers began looking at microRNAs in lymphomas and leukemias, and then it was discovered that one group of these molecules differentiated between the normal pancreas, chronic pancreatitis, and pancreatic cancer.

Although this data is preliminary, it is giving hope to the cancer community that it could be an area of focus to help predict survival rates and outcomes in patients diagnosed with pancreatic cancer. “We, as a community, are still working to understand how these molecules work. It is a novel idea and one to be pursued but not one that the cancer community should expect to see tangible results from for at least a few decades,” says Abbruzzese.

Preventing pancreatic cancer will likely never happen, but there is hope that medical professionals will be able to more accurately assess a person’s risk and diagnose it earlier. For now, the best measure preventing the disease is to stop smoking. “If you eliminated smoking, you would see a 25% reduction in the number of diagnosed cases each year,” Abbruzzese says.

End-of-Life Comfort
For the majority of patients diagnosed with pancreatic cancer, there is little hope for remission and more of a focus on palliative care. “Every patient that we treat at M. D. Anderson Cancer Center is offered some sort of therapy, be it a combination of chemotherapies or pain medication, to give them some quality of life. We also try to enroll all patients in a clinical trial,” says Bloomston.

How the patient presents will dictate how much can be done to make his or her remaining days more comfortable, Bloomston explains. “Pancreatic cancer patients will find a million ways to die. Some have pain, which we can work to control, while others have uncontrollable pain. Even more so, those patients who are unable to eat any longer, we are truly unable to help,” he says. But for the majority of patients, there is no real moment of death. Rather, there is a gradual cessation of life as their disease slowly leads them through a lack of eating, drinking, and mobility.

Because of the lethality of pancreatic cancer and the limited treatment options, the focus is on learning more about the tumors themselves and better detection and prognosis methods, according to Bloomston. MicroRNAs hold great promise in being able to identify pancreatic cancer, as well as discovering new pharmaceutical agents that can be combined for greater effectiveness in treating tumors in the pancreas.

“As pancreatic cancer moves up the ... ranks in lethality, the medical community is feverishly working to find DNA markers and potential drugs to aid in diagnosing and treating the cancer,” says Abbruzzese. One day, pancreatic cancer may become as well funded and researched as breast cancer to give patients a fighting chance, he adds.

— Kim M. Norton is a New Jersey-based freelance writer specializing in healthcare-related topics for various trade and consumer publications. She can be contacted at kim_norton1@hotmail.com.

Oral health and pancreatic cancer
It is no surprise that with your mouth being a direct connection to the outside world, it could also be a strong indicator of what is going on inside your body. Research has shown that periodontal disease and poor oral hygiene contribute to an increased risk of pancreatic cancer.

According to a prospective study published in the Journal of the National Cancer Institute, men who had a history of periodontal disease were compared with those who had no history of the disease. The study found that those with a history of the disease had a 63% higher risk of developing pancreatic cancer than those with no history of periodontal disease.

“Bacteria and inflammation of the gums have been [linked] to several diseases in the body, including cardiovascular disease, and now with pancreatic cancer, there is a correlation between oral health and the overall health of the body,” says Shepard Goldstein, DMD, president of the American Association of Endodontists and in practice at Endodontic Associates in Framingham, Mass. “The association [between periodontal disease and pancreatic cancer] may be due to systemic inflammation and/or increased levels of carcinogenic compounds generated by bacteria in the oral cavity of individuals with periodontal disease,” the study stated.

With periodontal disease, there are rarely any outward symptoms other than bleeding gums and possible halitosis. To detect it, an x-ray would need to be taken to see the extent of the bone loss, explains Goldstein. “Periodontal disease can be treated, but any bone loss due to the disease is unable to be repaired,” he says.

— KMN