As medical students and residents, we were taught to fear pancreatic cancer. As most people know, the cure rate is dismal and the majority of victims die within the first year of diagnosis. While this has been improving over the past years, the low five year survival rate persists.

According to the American Cancer Society, more than 53,000 people in the US will be diagnosed with pancreatic cancer in 2017. More than 43,000 people will die from this cancer and represents 7% of all cancer deaths. The average lifetime risk of developing pancreatic is 1.5 %.

What are the risk factors for pancreatic cancer?

• Smoking
• Obesity
• Workplace exposure to certain chemicals
• Age
• Male gender
• Race (slightly more common in African Americans)
• Family history
• Inherited Genetic Syndromes
• Diabetes
• Chronic pancreatitis
• Liver cirrhosis
• Certain gastric problems such as infection with pylori

Pancreatic cancer has received more attention in recent years as several well-known figures succumbed to this disease, including Steve Jobs, Nobel Prize winner Ralph Steinman, Patrick Swayze, and Gene Upshaw. It is important to note that there are two different forms of pancreatic cancer: neuroendocrine and exocrine tumors. Compounding the fact of the aggressiveness of this cancer is the fact that it is often diagnosed late because it tends to be asymptomatic in the early stages. (If you have patients with neuroendocrine tumors, you might want to share this patient education on carcinoid syndrome program with them.)

Pancreatic cancer is often called the “silent disease” because it very rarely causes any symptoms early in the disease. Later in the disease, it may only cause non-specific symptoms. Symptoms usually occur when the cancer grows. These may include upper abdominal pain, painless jaundice, anorexia, nausea, vomiting, weight loss, malaise, acholic stool or steatorhhea. Many other diseases may cause the same symptoms making it difficult to diagnose. Trousseau’s sign (or blood clots in portal blood vessels, deep veins of the extremities, or superficial veins) can also be seen in pancreatic cancer. Symptoms from the production of too much hormones can be seen in neuroendocrine tumors. Clinical depression is also sometimes observed.

The five year survival rate depends on the type and stage of the tumor. The overall survival rate for all stages combined remains 20% at one year and 7% by five years. Thus, it is considered largely incurable.

Approximately 95% of pancreatic cancers start in the exocrine cells of the pancreas. These cells form glands or ducts that produce pancreatic enzymes to aid in digestion. The most common exocrine pancreatic cancer is adenocarcinoma. These cancers can block the bile duct while still small and lead to jaundice. This allows diagnosis in this case before other types of pancreatic cancer.

Pancreatic Neuroendocrine tumors can be either benign or malignant and account for less than 5% of pancreatic tumors. They usually grow more slowly than exocrine tumors. They develop from an abnormal growth of islet, or hormone producing cells, in the pancreas. They can be either functional (producing hormones) or nonfunctional. They are classified depending on the hormone they secrete and include: Zollinger-Ellison Syndrome, Glucagonoma, Insulinoma, Somatostatinoma, Verner-Morrison Syndrome, Nonfunctional Islet Cell Tumor, and Multiple Endocrine Neoplasia I (MEN I).

While there is no ready screening test for pancreatic cancer, much research is being conducted. Germline pathogenic mutations are not well-defined for patients with pancreatic adenocarcinoma. BRCA2 was found to be an important predisposing genetic mutation with 6 to 10% of familial pancreatic cancer patients carrying this defect. DNA mismatch genes have also been found to have an increased risk for pancreatic cancer. Several other mutations have been implicated as well. One study suggests that pancreatic cancer is part of a constellation of tumors resulting from these mutations.

Currently, there is much research being conducted to find a “cure” for pancreatic cancer. One study looked at the use of cancer stem cells. A cancer stem cell is a cell inside a tumor that has the ability to self-renew and cause the heterogeneous lineage of cancer cells that produce the tumor. The hypothesis is that cancer stem cells represent the minority of cancer cells and remain behind after conventional therapy. In order for therapy to be effective, these cancer stem cells should be eradicated while not harming normal stem cells. In order to achieve this, physicians will need to be able to determine which cancer stem cells are present in any tumor.

Foxp3 is a transcription factor that is highly expressed in CD4+CD25+ regulatory T cells. Down-regulation of Foxp3 with small interfering RNA in pancreatic carcinoma cells resulted in the up-regulation of IL-6 and IL-8. This shows negative transcriptional activity in these epithelial cells. Pancreatic cancer cells are largely resistant to common chemotherapy and radiation treatments. Based on the above findings, immune based therapies are another focus of research.

Numerous new chemotherapy agents and combinations are additionally being researched. The combination of nab-Paclitaxel plus Gemcitabine was studied. Over 800 patients were included in this study with the primary end point being overall survival. It was a multi-center trial that randomly assigned patients to receive either the stated combination or to receive Gemcitabine alone. The results if this trial showed a statistically significant improvement in survival on patients treated with the combination. Survival at one year increased to 35% vs 22%. Of note, life-threatening side effects were not increased with use of the combination. It has been noted to result in more myelosuppression and neuropathy but these were seen to be reversible.

Since pancreatic cancer can be difficult to diagnose, another area of research being performed is finding a more specific tumor marker to aid in early diagnosis. Currently, tumor markers that are used include CA19-9 and CEA. However, these are non-specific for pancreatic cancer and can be seen in other conditions. In conjunction with other diagnostic tests, these tumor markers can help aid in the diagnosis but more specific tumor markers would be clearly beneficial.

Pancreatic cancer continues to be a deadly cancer. While we have made strides in our fight against this deadly disease it still remains a difficult to diagnose disease where the majority of patients will die in the first year. We need to develop better tools.

About the Author

Linda Girgis MD, FAAFP is a family physician practicing in South River, New Jersey. She was voted one of the top 5 healthcare bloggers in 2016. Follow her on twitter @DrLindaMD.