Pancreatic Cancer

What is Pancreatic Cancer?

Pancreatic cancer is the term used to refer to a malignant tumor that arises in the pancreas. Most of the pancreatic tumors arise from the exocrine glands of the pancreas and 95% of these are adenocarcinomas, meaning that they develop from gland cells. Tumors of the endocrine pancreas are relatively uncommon and receive the collective name of neuroendocrine tumors (NETs) or islet cell tumors. Because pancreatic cancer does not cause obvious symptoms during early stages, it is notoriously difficult to diagnose until it has reached an advanced stage. Most patients present systemic disease and eventually die from it.

Pancreatic cancer is the fourth leading cause of cancer-related deaths in USA. It has been estimated to cause 227,000 deaths per year worldwide. The lifetime risk of developing pancreatic cancer is about 1 in 71, and it is roughly the same for men and women.

What Causes Pancreatic Cancer?

As with other types of cancers, the direct causes for the development of a malignant tumor in the pancreas are not clearly understood, although it is clear that it involves certain changes in normal pancreatic cells that trigger their uncontrolled division. Several risk factors have been determined that significantly increase the chances of suffering from pancreatic cancer. These include smoking, a family history of chronic pancreatitis, advancing age, diabetes mellitus, obesity, non-O blood group, and occupational exposures to certain substances, such as chlorinated hydrocarbon solvents and nickel. Other risk factors that have been associated with pancreatic cancer are African-American ethnic origin, a high-fat diet, a diet high in meat and low in vegetables and folate, Helicobacter pylori infection and periodontal disease.

Of the risk factors for pancreatic cancer that have been defined, the most important ones are family history and smoking. 7–10% of affected individuals have a family history of pancreatic cancer, and first-degree relatives of individuals with familial pancreatic cancer have a ninefold increased risk of this neoplasm over the general population. Patients with familial pancreatic cancer also have more precancerous lesions than those with sporadic pancreatic tumours and increased risk of extra-pancreatic tumor development. Cigarette smoking is considered responsible for 20% of pancreatic tumors, and those tumors present more genetic mutations when compared to those of non-smokers.

Symptoms of Pancreatic Cancer

Pancreatic cancer is clinically silent during the early stages and it only becomes apparent when the tumor invades surrounding tissue or metastasizes to distant organs. At this relatively advanced stage, some of the most common symptoms are:

• Abdominal or mid-back pain
• Obstructive jaundice (yellow pigmentation of the skin)
• Weight loss
• Anorexia
• Pancreatitis
• Venous thrombosis (blood clot within a vein)
• Nausea and vomiting
• Diabetes mellitus

Usually pancreatic cancer is detected after the patient consults the physician regarding some of these symptoms.

Diagnosis of Pancreatic Cancer

CT scans, and tri-phasic pancreatic-protocol CT in particular, is the best initial diagnostic test for pancreatic cancer. As imaging technology continues to improve, the ability of high quality CT scans to detect locally advanced and metastatic diseases has considerably reduced the number of unnecessary laparotomies, as well as the need for staging laparoscopies. Endoscopic ultrasound can also be useful to identify the location and form of the cancer, with the advantage that sampling for diagnostic cytology can be performed at the same time. Magnetic resonance can be used in those patients that do not tolerate the intravenous contrast required for a CT scan.

If a pancreatic mass is observed invading surrounding tissue, the probability of it being a malignant tumor is high, but tissue diagnosis is nevertheless recommended for confirmation and to rule out benign disorders that may cause enlargement of the pancreas, such as autoimmune pancreatitis. Cytological diagnosis is possible using fine-needle aspiration guided by either endoscopic ultrasound or CT.

Clinical staging is an important step that takes place immediately after the initial diagnosis. It classifies the patient into the resectable, borderline resectable, locally advanced, and metastatic disease categories, and therefore it is essential to determine the appropriate initial treatment.

Treatment of Pancreatic Cancer

Since pancreatic cancer is a heterogeneous disease, response to treatment depends on several factors, including the biology of the tumor, the performance status of the patient and the pattern of disease progression. A multidisciplinary team is strongly recommended for the management of patients suffering from pancreatic cancer.

Surgical resection remains the only option as a potential cure of pancreatic cancer, but only 15% to 20% of newly diagnosed patients are considered for this procedure. There are three basic surgical treatments routinely employed in the treatment of pancreatic cancer: Pancreaticoduodenectomy, also known as the Whipple procedure, is the most common, involving the removal of the head and sometimes the body of the pancreas as well. It also involves the removal of surrounding lymph nodes along with the partial removal of the stomach, small intestine and gallbladder. The risk of complications is high, with 5% to 15% of the patients dying in the operation table as a result. Distal pancreatectomy removes the tail of the pancreas and is usually used to treat islet cell tumors, but rarely used for cancers of the exocrine pancreas. Finally, total pancreatectomy (removal of the entire pancreas and spleen) is seldom used these days since it doesn’t have any advantage for the patients.

Pancreatic cancer has a very high rate of post-surgical recurrence, and for this reason chemotherapy is often administered as an adjuvant immediately after surgery or before surgery (neoadjuvant chemotherapy).

In patients with an advanced disease in which curative surgery is no longer an option, chemotherapy is the treatment of choice, provided they have an adequate performance status. Gemcitabine is the most common therapeutic agent used to treat these cases, as it induces a partial response in some patients and can alleviate symptoms. Fractionated radiation therapy can also be used at this stage. When the disease has reached the metastatic stage, gemcitabine in combination with other compounds such as capecitabine or erlotinib is employed to extend survival, although the disease is considered terminal. No standard second-line treatment has been defined at the moment.

Prognosis of Pancreatic Cancer

The prognosis for pancreatic adenocarcinomas is poor, in large part because the absence of symptoms causes the disease to be already advanced at the time of first diagnosis. Although definitive remission is potentially achievable through surgical resection, the median 5-year survival after undergoing the procedure is less than 20% and the disease returns in a majority of patients. The high rates of recurrence suggest that a metastatic spread must have already occurred in the majority of cases at the time of surgery. When all stages are combined together, the median 1-year survival is 20% and the 5-year survival is less than 4%.

Pancreatic endocrine tumors have a much better prognosis, with a 0.28-fold lower risk of mortality.

Preventing Pancreatic Cancer

There are no established guidelines for preventing pancreatic cancer, and therefore the best prevention strategy consists in avoiding the risk factors that have been identified whenever possible. Cigarette smoking is the most important avoidable risk factor, responsible for 20% to 30% of pancreatic cancers. It has also been reported that alcohol intake could increase the risks, with consumption of 10 or more drinks per month having three times the risk of non-drinkers. Meat consumption was also associated with high rates of pancreatic cancer occurrence.

The American Cancer Society recommends eating at least five servings of fruits and vegetables every day, as well as servings of whole grain foods from plant sources such as rice, breads, pasta, and cereals to lower the risk of developing pancreatic cancer, although no consistent association between these kinds of diet and decreased risk has been found.

Living with Pancreatic Cancer

Given the high percentage of recurrence, it is critical for the patient to be closely monitored after surgical resection. Patients suffering pancreatic cancer should therefore adhere to a strict follow-up schedule that is likely to continue until the end of their lives.

Loss of appetite and weight loss are common symptoms in pancreatic cancer, and they can be caused by the treatment or by the cancer itself. Patients are advised to try to eat high-energy foods as well as supplements. Some patients may need to take pancreatic enzymes in pill form in order to be able to digest their food properly, or they may even need a feeding tube placed temporarily into the stomach to improve nutrition and energy levels. Insulin may also need to be administered to regulate sugar levels in the blood depending on the extent of the surgery. The composition of the diet and meal size also needs to be modified in patients with pancreatic cancer. Fatty foods should be avoided, since fat is particularly difficult to digest for these patients.

Pain in the abdomen or back can be a major problem. Opiod agents are often used to relieve pain in pancreatic cancer. Palliative surgery is also an option in some cases.

Finally, as with any disease with a very poor prognosis, being diagnosed with pancreatic cancer implies a heavy emotional burden. Patients should be provided with psychological support and encouraged to discuss their emotional status with professionals.

Current Research of Pancreatic Cancer

The recent advances in molecular biology have allowed the development of molecular targeting agents that are gradually being adopted as part of the standard treatment for pancreatic cancer. An example of this is Erlotinib, an oral inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. Erlotinib is usually administered in combination with more standard therapeutic agents such as gemcitabine or fluorouracil. Monoclonal antibodies are also being tested on clinical trials to target specific molecules that play a role in the development of pancreatic tumors. Examples include Cetuximab (which targets EGFR) and Bevacizumab (which targets the vascular endothelial growth factor).

Improving the chances for early detection is essential for enhancing the chances of survival in patients with pancreatic cancer, and therefore much effort is being invested in developing novel tests to monitor early changes that can cause pancreatic cells to become cancerous. Genes like BRCA2, p16 and HNPCC can exhibit inherited mutations that predispose the carrier to develop a tumor, and they are actively being investigated. New diagnostic tests have also been developed that are capable of detecting acquired changes in the K-ras oncogene from samples of pancreatic juice.