Pancreatic Cancer

What is Pancreatic Cancer? Pancreatic Cancer Symptoms and Causes

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What Is The Pancreas?

The pancreas is a 6-inch long organ located behind the stomach in the back of the abdomen. It is spongy and shaped somewhat like a fish, extended horizontally across the abdomen. The head of the pancreas is on the right side of the abdomen where the stomach is attached to the first part of the small intestine (the duodenum). The tail of the pancreas - its narrowest part - extends to the left side of the abdomen next to the spleen.

The pancreas contains exocrine and endocrine glands that create pancreatic juices, hormones, and insulin. Pancreatic juices, or enzymes, made by the exocrine glands are released into the intestines by way of a series of ducts in order to help digest fat, proteins, and carbohydrates. Over 95% of the pancreas is made up of exocrine glands and ducts. The endocrine cells are arranged in small clusters called islets of Langerhans, which release insulin and glucagon into the bloodstream. These two hormones manage levels of sugar in the blood. When they are not working properly, the result is often diabetes.

More information on the pancreas itself is available in our article What Is The Pancreas? What Does The Pancreas Do?

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What Is Pancreatic Cancer?

Cancer is a class of diseases characterized by out-of-control cell growth, and pancreatic cancer occurs when this uncontrolled cell growth begins in the pancreas. Rather than developing into healthy, normal pancreas tissue, these abnormal cells continue dividing and form lumps or masses of tissue called tumors. Tumors then interfere with the main functions of the pancreas. If a tumor stays in one spot and demonstrates limited growth, it is generally considered to be benign.

More dangerous, or malignant, tumors form when the cancer cells migrate to other parts of the body through the blood or lymph systems. When a tumor successfully spreads to other parts of the body and grows, invading and destroying other healthy tissues, it is said to have metastasized. This process itself is called metastasis, and the result is a more serious condition that is very difficult to treat.

In the United States each year, over 30,000 people are diagnosed with pancreatic cancer. Europe sees more than 60,000 diagnoses each year. Because pancreatic cancer is usually diagnosed late into its development, the five-year survival rate after diagnosis is less than 5%.

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How Is Pancreatic Cancer Classified?

Pancreatic cancer is categorized depending on whether it affects the exocrine or endocrine functions of the pancreas. There is an important distinction between the two broad types of pancreatic cancer because they have different risk factors, causes, symptoms, diagnostic tests, treatments, and prognoses.

Tumors that affect the exocrine functions are the most common type of pancreatic cancer. Sometimes these tumors or cysts are benign, called cystadenomas. However, it is more likely to find malignant tumors called adenocarcinomas, which account for 95% of exocrine pancreatic cancers. Adenocarcinomas typically start in gland cells in the ducts of the pancreas, but they can also arise from pancreatic enzyme cells (acinar cell carcinoma).

Other types of pancreatic cancers that are associated with exocrine functions include adenosquamous carcinomas, squamous cell carcinomas, and giant cell carcinomas, named for their appearances underneath a microscope. There is also a disease called ampullary cancer (carcinoma of the ampulla of Vater) that starts where the bile duct and pancreatic duct meet the duodenum of the small intestine.

Tumors that affect the endocrine functions of the pancreas are called neuroendocrine or islet cell tumors, but these are fairly uncommon. These tumors are named for the type of hormone-producing cell that is initially affected. For example: insulinomas (insulin), glucagonomas (glucagon), gastrinomas (gastrin), somatostatinomas (somatostatin), and VIPomas (vasoactive intestinal peptide or VIP). Functioning islet cell tumors still make hormones, while non-functioning ones do not. Most of these tumors are benign, but non-functioning tumors are more likely to be malignant, islet cell carcinomas.

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What Causes Pancreatic Cancer?

Cancer is ultimately the result of cells that uncontrollably grow and do not die. Normal cells in the body follow an orderly path of growth, division, and death. Programmed cell death is called apoptosis, and when this process breaks down, cancer results. Pancreatic cancer cells do not experience programmatic death, but instead continue to grow and divide. Although scientists do not know exactly what causes these cells to behave this way, they have identified several potential risk factors.

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Genes - The DNA Type

Cells can experience uncontrolled growth if there is damage or mutations in the DNA, and therefore, damage to the genes involved in cell division. Four key types of genes are responsible for the cell division process: oncogenes tell cells when to divide, tumor suppressor genes tell cells when not to divide, suicide genes control apoptosis and tell cells to kill themselves if something goes wrong, and DNA-repair genes instruct cells to repair damaged DNA.

Cancer occurs when a cell's gene mutations make the cell unable to correct DNA damage and unable to commit suicide. Similarly, cancer is a result of mutations that inhibit oncogene and tumor suppressor gene functions, leading to uncontrollable cell growth. If you have DNA mutations of oncogenes or tumor suppressor genes that lead to pancreatic cancer, it is likely that the mutation was a result of factors that affected DNA after you were born rather than a result of inheritance from parents.

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Genes - The Family Type

Cancer can be the result of a genetic predisposition that is inherited from family members. It is possible to be born with certain genetic mutations or a fault in a gene that makes one statistically more likely to develop cancer later in life. About 10% of pancreatic cancers are though to be caused by inherited gene mutations. Genetic syndromes that are associated with pancreatic cancer include hereditary breast and ovarian cancer syndrome, melanoma, pancreatitis, and non-polyposis colorectal cancer (Lynch syndrome).

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Carcinogens

Carcinogens are a class of substances that are directly responsible for damaging DNA, promoting or aiding cancer. Certain pesticides, dyes, and chemicals used in metal refining are thought to be carcinogenic, increasing the risk of developing pancreatic cancer. When our bodies are exposed to carcinogens, free radicals are formed that try to steal electrons from other molecules in the body. Theses free radicals damage cells, affecting their ability to function normally, and the result can be cancerous growths.

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Other Medical Factors

As we age, there is an increase in the number of possible cancer-causing mutations in our DNA. This makes age an important risk factor for pancreatic cancer, especially for those over the age of 60. There are several other diseases that have been associated with an increased risk of cancer of the pancreas. These include cirrhosis or scarring of the liver, helicobacter pylori infection (infection of the stomach with the ulcer-causing bacteria H. pylori), diabetes mellitus, chronic pancreatitis (inflammation of the pancreas), and gingivitis or periodontal disease.

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Traits, Habits, And Diet

Pancreatic cancers are more likely to exist in men than in women, and among African-Americans than among whites. Smoking cigarettes increases one's risk of pancreatic cancer by a factor of 2 or 3. Even smokeless tobacco has been noted as a risk factor.

Diet and obesity have also been linked to cancers of the pancreas. People who do not exercise much and who are obese are more likely to develop pancreatic cancer. In addition, those who eat diets low in vegetables and fruits and high in red meat and fat are more likely to be diagnosed with the disease. Alcohol consumption is also considered a risk factor for pancreatic cancer. Long term, heavy drinking leads to chronic pancreatitis, which is a known risk factor for pancreatic cancer.

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What Are The Symptoms Of Pancreatic Cancer?

Cancer symptoms are quite varied and depend on where the cancer is located, where it has spread, and how big the tumor is. Pancreatic cancer is often called a "silent" disease because it rarely shows early symptoms and presents non-specific later symptoms. Tumors of the pancreas cancers are usually too small to cause symptoms. However, when the cancer grows, symptoms include:

• Pain in the upper abdomen from the tumor pushing against nerves
• A painless yellowing of the skin and eyes and darkening of the urine called jaundice, created when the cancer interferes with the bile duct and the liver.
• Loss of appetite, nausea, and vomiting
• Significant weight loss and weakness
• Acholic stool (pale or grey stool) and steatorrhea (excess fat in stool)

These symptoms of pancreatic cancer have numerous other causes, making it difficult to diagnose the disease before it is in an advanced stage.

Cancers of the pancreas are also associated with Trousseau's sign - spontaneous blood clots formed in the portal blood vessels, deep veins of the arms and legs, or other superficial veins. Clinical depression is another symptom that is sometimes reported before the cancer is diagnosed.

If the cancer spreads, or metastasizes, additional symptoms can present themselves in the newly affected area. Symptoms of metastasis ultimately depend on the location to which the cancer has spread.

Islet cell or neuroendocrine cancers of the pancreas may cause the organ to produce too much insulin or hormones. This may lead to weak or dizzy feelings, chills, muscle spasms, or diarrhea.

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How Is Pancreatic Cancer Diagnosed?

In order to diagnose pancreatic cancer, physicians will request a complete physical exam as well as personal and family medical histories. The way in which the cancer presents itself will differ depending on whether the tumor is in the head or the tail of the pancreas. Tail tumors present with pain and weight loss while head tumors present with steatorrhea, weight loss, and jaundice. Doctors also look for recent onset of atypical diabetes mellitus, Trousseau's sign, and recent pancreatitis.

In general, when making a pancreatic cancer diagnosis, physicians pay special attention to common symptoms such as abdominal or back pain, weight loss, poor appetite, tiredness, irritability, digestive problems, gallbladder enlargement, blood clots (deep venous thrombosis (DVT) or pulmonary embolism), fatty tissue abnormalities, diabetes, swelling of lymph nodes, diarrhea, steatorrhea, and jaundice.

It is also common for doctors to administer blood, urine, and stool tests. Blood tests can detect a chemical called carcinoembryonic antigen (CEA) as well as CA 19-9 - a chemical released into the blood by pancreatic cancer cells. Liver function tests check for bile duct blockage.

Several imaging techniques are employed in order to see if cancer exists and to find out how far it has spread. Common imaging tests include:

• Ultrasound - to visualize tumor
• Endoscopic ultrasound (EUS) - thin tube with a camera and light on one end
• Abdominal computerized tomography (CT) scans - to visualize tumor
• Endoscopic retrograde cholangiopancreatography (ERCP) - to x-ray the common bile duct
• Angiogram - to x-ray blood vessels
• Barium swallows to x-ray the upper gastrointestinal tract
• Magnetic resonance imaging (MRI) - to visualize tumor
• Positron emission tomography (PET) scans - useful to detect if disease has spread

The only absolute way to make a cancer diagnosis is to remove a small sample of the tumor and look at it under the microscope in a procedure called a biopsy. A fine needle aspiration (FNA) biopsy is the most commonly used method. A thin needle is inserted into the pancreas through the skin, and the pathologist uses CT scan or ultrasound images as a guide. Another type is the brush biopsy performed during ERCP to gather cells. A laparotomy is sometimes ordered to determine the stage, or extent, of the disease because it provides access to a large part of the abdominal cavity.

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What Are The Stages Of Pancreatic Cancer?

After a diagnosis is made, doctors find out how far the cancer has spread to determine the stage of the cancer. The stage determines which choices will be available for treatment and informs prognoses. The standard pancreatic cancer staging method is called the TNM (Tumor - Node - Metastasis) system. T indicates the size and direct extent of the primary tumor, N indicates the degree to which the cancer has spread to nearby lymph nodes, and M indicates whether the cancer has metastasized to other organs in the body. A small tumor that has not spread to lymph nodes or distant organs may be staged as (T1, N0, M0), for example.

Group staging, from 0 to IV, for pancreatic cancer follows from TNM categories. Stage 0 is written as (Tis, N0, M0) where Tis stands for carcinoma in situ. This is when the tumor is confined to the top layers of pancreatic duct cells and has not invaded deeper tissues nor spread outside of the pancreas. Stage IV is written as (Any T, Any N, M1) and describes cancer that has spread to distant sites throughout the body.

Physicians also use a simpler staging system that classifies tumors based on the likelihood that they can be surgically removed. Resectable cancers are isolated to the pancreas and can be entirely removed. Locally advanced (unresectable) tumors have not spread to distant organs but cannot be completely removed surgically. Metastatic tumors have spread to distant organs, and surgery would only be used to relieve pain or unblock ducts.

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What Are The Pancreatic Cancer Treatment Options?

Cancer treatment depends on the type of cancer, the stage of the cancer (how much it has spread), age, health status, and additional personal characteristics. There is no single treatment for cancer, and pancreatic cancer is usually only curable when found in its earliest stages. Surgery, radiation, and chemotherapy are the most common treatment types. Treatments seek to remove the cancer and/or relieve painful symptoms that the cancer is causing.

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Surgery

Surgery may be used to remove all or part of the pancreas. If a cancer has not metastasized, it is possible to completely cure a patient by surgically removing the cancer from the body. After the disease has spread, however, it is nearly impossible to remove all of the cancer cells. There are three main surgical procedures that are used when it seems possible to remove all of the cancer:

1. Whipple procedure (most common in cancers of the head of the pancreas): the pancreas head, and sometimes the entire organ, is removed along with a portion of the stomach, duodenum, lymph nodes, and other tissue. The procedure is complex and risky with complications such as leaking, infections, bleeding, and stomach problems.
2. Distal pancreatectomy: the pancreas tail is removed, and sometimes part of the body, along with the spleen. This procedure is usually used to treat islet cell or neuroendocrine tumors.
3. Total pancreatectomy: The entire pancreas and spleen are removed. Although you can live without a pancreas, diabetes often results because your body no longer produces insulin cells.

Palliative surgery is also an option when the cancer in the pancreas cannot be removed. Often, a surgeon will create a bypass around the common bile duct or the duodenum if either is blocked so that bile can still flow from the liver and pain or digestive problems can be kept at a minimum. Bile duct blockage can also be relieved by inserting a small stent in the duct to keep it open, a less invasive procedure using an endoscope.

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Chemotherapy

Chemotherapy utilizes chemicals that interfere with the cell division process - damaging proteins or DNA - so that cancer cells will commit suicide. These treatments target any rapidly dividing cells (not necessarily just cancer cells), but normal cells can usually recover from any chemical-induced damage while cancer cells cannot. Chemotherapy is generally used to treat cancer that has spread or metastasized because the medicines travel throughout the entire body. Treatment occurs in cycles so the body has time to heal between doses. However, there are still common side effects such as hair loss, nausea, fatigue, and vomiting. Combination therapies often include multiple types of chemotherapy or chemotherapy combined with other treatment options.

Gemcitabine (Gemzar) is the chemotherapy drug used most often to treat pancreatic cancer, and it is usually administered intravenously on a weekly basis. Another commonly used drug is 5-fluorouracil (5-FU). Chemotherapy is not always administered with the intent to cure the cancer. Some patients receive treatments after surgery (adjuvant therapy) to kill any cancer cells that were missed, and others receive it as palliative chemotherapy to improve their quality of life if the cancer cannot be cured.

Newer drugs that target specific parts of cancer cells are now being studied. These drugs work differently from standard chemotherapy drugs, and they often have fewer side effects. One such drug, erlotinib (Tarceva), has helped some patients with advanced pancreatic cancer and is taken orally in pill form. This drug has been used in combination with gemcitabine to show modest benefits.

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Radiation

Radiation treatment, also known as radiotherapy, destroys cancer by focusing high-energy rays on the cancer cells. This causes damage to the molecules that make up the cancer cells and leads them to commit suicide. Radiotherapy utilizes high-energy gamma-rays that are emitted from metals such as radium or high-energy x-rays that are created in a special machine. Radiotherapy can be used as a standalone treatment to shrink a tumor or destroy cancer cells, and it is also used in combination with other cancer treatments.

Radiation treatments for pancreatic cancer are usually given 5 days a week for 5 to 6 weeks. Patients may receive radiation treatment in addition to surgery, chemotherapy, or other treatments. In addition, radiation therapy can be palliative, serving to relieve pain or digestive problems when the common bile duct or duodenum is blocked.

Side effects of radiation therapy may include mild skin changes resembling sunburn or suntan, nausea, vomiting, diarrhea, and fatigue. Patients also tend to lose their appetites and have trouble maintaining weight, but most side effects subside a few weeks after completing treatment.

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How Can Pancreatic Cancer Be Prevented?

There are no established guidelines or recommendations for preventing pancreatic cancer, according to the American Cancer Society. However, it is advisable to quit smoking because cigarette use is thought to be a main factor in 20-30% of pancreatic cancers. In general, physicians recommend standard preventive measures such as keeping a healthy weight, exercising, and increasing consumption of fruits, vegetables, and whole grains while decreasing red meat intake. There is no evidence, however, that following these dietary guidelines will prevent or reduce pancreatic cancer.

Some studies suggest that certain vitamins can reduce the risk of pancreatic cancer. Vitamin D has been associated with reducing the risk of several types of cancer, including pancreatic cancer. B vitamins such as B12, B6, and folate that are consumed in food (not in pill or tablet form) have also been suggested to reduce pancreatic cancer risk.