Pancreatic Cancer – Causes, Signs and symptoms

Pancreatic Cancer

Also called: Pancreas Cancer, Exocrine Cancer

Reviewed By:
Martin E. Liebling, M.D., FACP
Mark Oren, M.D., FACP


Pancreatic cancer is one of the most deadly of all cancers. It accounts for only 2 percent of cancer cases but is the fourth leading cause of cancer deaths, according to the American Cancer Society (ACS).

The pancreas is a gland located in the middle of the abdomen behind the stomach. The pancreas has two functions: as an exocrine gland, which produces digestive enzymes, and as an endocrine gland, which produces hormones such as insulin and glucagon, which control blood sugar. Most cases of pancreatic cancers occur in the exocrine cells.

Pancreatic cancer occurs when malignant cells form in the gland. The disease progresses rapidly but usually produces no symptoms in the early stages. Pancreatic cancer usually remains undetected until it has spread locally and invaded surrounding tissues or to other areas of the body. The first signs of the disease are typically weight loss and jaundice, the yellowing of the skin and whites of the eyes.

The causes of pancreatic cancer are not known. However, major risk factors include smoking and hereditary conditions associated with predisposition to cancer. Patients whose immediate family members have had pancreatic cancer have a risk factor up to three times higher than the normal population.

An estimated 37,680 Americans will be diagnosed with pancreatic cancer in 2008, with 34,290 deaths predicted, according to the ACS.  Approximately 5 percent of people diagnosed with cancer of the exocrine pancreas will survive 5 years or more.

About pancreatic cancer

Pancreatic cancer is one of the most deadly of all cancers, but it is rare, accounting for only 2 percent of cancer cases according to the American Cancer Society (ACS). Pancreatic cancer is the fourth leading cause of cancer deaths.

Pancreatic cancer occurs when malignant cells form in the pancreas because of unrepaired damage to the cells’ DNA. The cancer grows rapidly with no symptoms in its early stages. Because of this lengthy silent period, the cancer is usually undetected until it has spread (metastasized) to other areas of the body. Pancreatic cancer can spread to the lymph nodes, intestines, liver, bile duct, bones and lungs.

The pancreas is a gland located in the midsection of the abdomen behind the stomach. It is has a wide end (head), a middle portion (body) and a narrow section (tail). About three-fourths of pancreatic cancers occur in the pancreatic head. The cells of the pancreas actually form two intermingled glands, which produce different chemicals:

  • Exocrine pancreas. Most of the pancreatic cells are exocrine glands and ducts. They produce enzymes and transport them to the digestive tract to help digestion. Cancer can form in the cells, ducts or tissues of the exocrine pancreas. Most pancreatic cancers form in the exocrine cells.

  • Endocrine pancreas. Endocrine cells form clusters called islets throughout the pancreas. These cells produce the hormones insulin and glucagon, which control blood sugar, and somatostatin, which suppresses the release of insulin and glucagon. A small percentage of pancreatic cancers are of this type.

The pancreas is surrounded by other structures and organs, making it difficult to detect abnormalities such as tumors. Pancreatic cancer rarely causes early symptoms. By the time symptoms are apparent, the disease has usually metastasized to neighboring tissues or distant organs. Such late diagnosis contributes to the high mortality rate.

The ACS estimates that 37,680 Americans will be diagnosed with pancreatic cancer in 2008. The risk increases with age. African Americans are 40 to 50 percent more likely than whites to develop pancreatic cancer. The one-year survival rate is 24 percent and the five-year survival rate is about 5 percent for exocrine pancreatic cancer. This rate improves to 20 percent in patients where the cancer is confined to the pancreas, although diagnosis this early is uncommon.

Types and differences of pancreatic cancer

Pancreatic cancer can occur in several types of cells, each of which performs a unique function. Cancers in exocrine and endocrine cells are different from each other in most aspects of the disease, including its symptoms, risk factors, diagnostic methods and treatment processes. It is important for physicians to identify the exact type of cells that are cancerous. The following are pancreatic cancer cell types:

  • Exocrine. Exocrine cells produce enzymes, which are transported through ducts to the digestive system, where they break down food. Most pancreatic cancers are exocrine cancers, and these cancers are further divided by the types of cells in which they occur. About 95 percent of exocrine pancreatic cancers are adenocarcinomas. More uncommon types of exocrine cancer include mucinous cystadenocarcinomas, acinar cell carcinomas, adenosquamous carcinomas, squamous cell carcinomas and large cell carcinomas. The exocrine cells may also develop benign cystoadenomas.

  • Endocrine. Endocrine cells of the pancreas produce hormones, including insulin and glucagon, which control blood sugar. Most of the tumors of these cells are benign, and malignancy is rarer in the endocrine cells of the pancreas than in the exocrine cells. Endocrine pancreatic cancer can cause overproduction of insulin or glucagon, resulting in problems with the body’s production and storage of energy from blood sugar. Cancers of this cell type are called islet cell carcinomas or endocrine tumors. Cancer within insulin-producing cells is called insulinoma. Cancer within glucagon producing cells is called glucagonoma. A small percentage of pancreatic cancers occur in the endocrine cells.

  • Ampulla of Vater. The structure where the bile and pancreatic ducts empty into the upper part of the small intestine, or duodenum. Cancers in this region are called ampullary cancer or carcinoma of the ampulla of Vater. Ampullary cancer may block the bile duct and this is one of the few pancreatic cancers that produces early symptoms. Jaundice is an early sign of this cancer (and a late-stage sign of other pancreatic cancers). Because of this symptom, ampullary cancer it is often detected in the early stages, resulting in a better prognosis than other pancreatic cancers.

Risk factors and causes of pancreatic cancer

Cancer cells develop because of damage to DNA, a substance present in every cell. In most cases, when the DNA becomes damaged, the body is able to repair it. In cancer cells, however, the DNA is not repaired and the abnormal cells can reproduce.  Research has shown that people with pancreatic cancer have mutations or deletions on certain genes, although the relationship between these DNA changes and the development of cancer is not well understood. In other cases, certain factors appear to increase an individual’s risk of developing pancreatic cancer. These risk factors include:

  • Age. Pancreatic cancer almost always occurs in people older than 55. According to the American Cancer Society (ACS), more than 70 percent of pancreatic cancer patients are older than 65.

  • Race and ethnicity. African Americans and Ashkenazi Jews are more likely to develop pancreatic cancer than other populations. African Americans are 40 to 50 percent more likely than white people to develop pancreatic cancer.

  • Tobacco use. This is the greatest controllable risk factor for pancreatic cancer. Heavy cigarette smokers are two to three times more likely than nonsmokers to develop pancreatic cancer, according to the American Cancer Society (ACS). Smoking is linked to 20 to 30 percent of pancreatic cancer cases. Smokers who quit reduce their risk of developing the disease.

  • Heredity. Certain inherited diseases indicate a higher possibility for a patient to develop pancreatic cancer. Studies have shown that people with hereditary predispositions are even more likely to develop pancreatic cancer if they also smoke. Patients with hereditary risk factors also develop pancreatic cancer at younger age. Individuals whose parents or siblings had pancreatic cancer are three times more likely to develop the disease. Several rare inherited conditions may predispose a person to pancreatic cancer. These include familial adenomatous polyposis (FAP) and hereditary nonpolyposis colon cancer (HNPCC). In addition, people with the BRCA2 gene mutation, which increases the risk for breast cancer, may also face an increased risk of pancreatic cancer.

  • Diet. Diets high in animal fat and cholesterol and low in fruits and cruciferous vegetables (those in the cabbage and broccoli family) are associated with increased incidence of cancer. Recent studies show that diets high in red meat may increase the risk of pancreatic cancer.

  • Obesity. Obese people are at greater risk for pancreatic cancer.

  • Diabetes. Patients with diabetes are more likely to develop pancreatic cancer in the first five years after diabetes diagnosis, according to the ACS. When the cancer invades the pancreas, it can affect the production of insulin and glucagon. Imbalances in these hormones can produce diabetes.

  • Chronic pancreatitis. A painful inflammation of the pancreas usually caused by long-term use of alcohol and smoking. This condition is associated with a slightly higher risk of pancreatic cancer.

  • Chemical exposure. People who work with gasoline and other petroleum compounds are at higher risk for developing pancreatic cancer. Also, pesticides and coal products have been associated with this disease.
  • Gastrointestinal conditions. Stomach infections with the bacteria Helicobacter pylori, which causes most peptic ulcers, may increase the risk of pancreatic cancer. There is also an increased risk of pancreatic cancer for patients who have undergone surgery for peptic ulcers. The risk increased depending on the elapsed time since the surgery (i.e., the older the surgery, the greater the risk).

Signs and symptoms of pancreatic cancer

There are usually no symptoms of pancreatic cancer in the early stages of the disease. By the time symptoms appear, the likelihood of metastasis is high. In addition, the location of the pancreas deep inside the body makes it difficult for physicians to detect abnormalities during routine examinations. The most common symptoms are of pancreatic cancer are pain in the abdomen or lower back and jaundice.

Jaundice is a symptom of many conditions. It is caused by a buildup of bilirubin (a substance produced in the liver) that causes a yellowing of the skin and whites of the eyes. Jaundice may also cause darkened urine and light-colored stools. It is important to note that jaundice may be caused by a number of less dangerous conditions, such as anemia.

Other possible symptoms of pancreatic cancer are:

  • Digestive problemswith nausea and vomiting
  • Weight loss
  • Loss of appetite
  • Glucose intolerance
  • Gallbladder enlargement
  • Blood clots or fatty tissue abnormalities

Overproduction of insulin, a possible side effect of endocrine pancreatic cancer, can cause:

  • Dizziness
  • Diarrhea
  • Weakness and fatigue
  • Chills
  • Muscle spasms

Patients exhibiting these symptoms should see a physician. The above symptoms may indicate any number of diseases and diagnostic tests are necessary to determine the cause.

Diagnosis methods for pancreatic cancer

There is no way to screen for pancreatic cancer for early detection. Early detection is difficult because:

  • Symptoms do not appear until the later stages.
  • Symptoms mimic those of other diseases.
  • The pancreas is hidden behind the stomach and intestines, making it difficult to view tumor formations or other abnormalities. It is also difficult to feel (palpate) during a physical examination.

To diagnose pancreatic cancer, the physician will conduct a number of tests, including:

  • Medical history. A personal medical history including family history of disease.

  • Physical examination. An examination of the patient’s body for signs of disease, with particular focus on the abdominal area. The physician will also closely examine the lymph nodes and surrounding organs for signs of swelling. The skin and eyes of the patient will be examined for jaundice, a common symptom of pancreatic cancer.
  • Blood tests. A sample of blood is extracted and tested to determine if levels of certain substances in the body are normal. These may include:

    • Serum bilirubin (orange or yellowish pigment in bile). Abnormal levels of bilirubin in the blood may indicate the liver is diseased or weakened.

    • Liver function test. Abnormal levels of liver enzymes may indicate damage to the liver and may be a sign of metastasis.

    • Tumor marker test. Levels of certain tumor markers (CA 19-9 and CEA) may be higher in individuals with pancreatic cancer. However, the cancer is usually in the advanced stages by the time these markers are elevated.

  • X-rays. The use of radiation to create images of organs in the body. A chest x-ray is taken to show if there are masses in the organs and bones in the chest cavity indicating metastasis to bones and organs.

  • CAT scan (computed axial tomography). Images are taken of the body from different angles to locate tumors in the body using an injected or ingested dye and specialized x-ray equipment. Lumps in the pancreas appear in the images.
  • MRI (magnetic resonance imaging). A test that uses radio waves and magnetic fields analyzed by a computer to create cross sectional images of the body.

  • Ultrasound. A machine that uses sound waves to create images of organs and tissues in the body. This test can help determine the type of tumor present in the pancreas.

  • PET scan  (positron emission tomography). A sugar substance containing a radioactive element is injected into the vein and collects in cancerous tissue. This test is beneficial for detecting cancer that has spread beyond the pancreas and cannot be removed by surgery.  
  • Endoscopic ultrasound (EUS). An endoscope (thin lighted tube) is used with an ultrasound device. This device is passed down the throat into the stomach where sound waves are sent to the pancreas and images of the pancreatic tumors are produced. This ultrasound is effective in imaging small tumors that are difficult to see.

  • Endoscopic retrograde cholangiopancreatography (ERCP).  An endoscope is passed through the esophagus, the stomach and to the small intestine. Air is pumped through to inflate the intestines and make the pancreatic and bile ducts more visible. A dye is passed through the ducts then x-rays are taken to show any obstructions.

  • Percutaneous transhepatic cholangiography (PTC). A dye is injected into the ducts of the liver and an x-ray is taken from several different angles. The x-ray will show any obstructions in the ducts, indicating metastasis. A stent (flexible tube) may be placed in the duct to drain bile. This procedure is performed only in place of ERCP.

  • Laparoscopy. A thin, lighted viewing instrument is inserted through a small incision in the abdomen in a procedure using general anesthesia. Laparoscopy can show the pancreatic tumors and extent of metastasis to the surrounding tissue as well. Tissue sample may be taken.

  • Biopsy. Tissue is removed from the pancreas and examined under a microscope for the presence of cancer cells. Fine needle biopsy is performed with a thin needle inserted through the skin and into the tumor where a sample is taken using local anesthesia. Brush biopsy is performed during an ERCP. A small brush is passed through the endoscope to collect cells from the tumor. This procedure may also be performed during a laparoscopy, endoscopy or through surgery. A biopsy is the definitive way to diagnose cancer.

Treatment options for pancreatic cancer

Early treatment of pancreatic cancer has the best prognosis. However, because pancreatic cancer is difficult to detect, early treatment is rare. Prognosis depends on the following factors:

  • The type and stage (extent of spread) of the cancer
  • If the tumor can be surgically removed
  • Patient’s age and general health
  • Response to treatment
  • Recent diagnosis or recurrence

Treatment options are evaluated by the patient and the cancer care team, healthcare professionals who work together to diagnose and treat cancer. The primary members of the team include a medical oncologist, surgeon and radiation oncologist.

Surgery is the only method that has potential to cure pancreatic cancer and is performed whenever possible. Most physicians who treat patients with pancreatic cancer will perform surgery only if they suspect all of the cancer can be removed during the operation. Only a small percentage of patients have pancreatic cancer that has been contained to the pancreas when it is discovered.

If a patient is a candidate for surgery, the procedures may include:

  • Whipple procedure. The head of the pancreas, duodenum, gallbladder, part of the stomach and the bile duct are removed. The remaining bile duct is attached to the small intestine so that bile can drain into it. Also called pancreatoduodenectomy, this is the most common procedure for resectable (operable) pancreatic cancer. There are several variations of this procedure. Cancer of the ampulla of Vater (area where the bile and pancreatic ducts drain into the small intestine) has a 30 to 50 percent survival rate after five years using this procedure.

  • Total pancreatectomy. The entire pancreas, the common bile duct, gallbladder, spleen, nearby lymph nodes and possibly part of the stomach and part of the small intestine are removed. For both pancreatectomy and the Whipple procedure, the pancreas removal causes diabetes and the patient must then receive insulin daily.

  • Distal pancreatectomy. The tail and sometimes a part of the body of the pancreas are removed. The spleen may also be removed. This form of surgery is used to treat islet cell cancer (endocrine pancreatic cancer).

If the cancer cannot be removed, palliative surgery may be performed to help prevent or reduce the symptoms of cancer that has spread. These procedures include:

  • Surgical biliary bypass. A new pathway to the small intestine is created due to a blocked bile duct. This prevents buildup of bile.

  • Endoscopic stent placement. A stent (flexible tube) is placed in the bile duct to drain the bile into the small intestine or outside the body as needed. This is done when the tumor is blocking the bile duct and there is a buildup of bile.

  • Gastric bypass. A procedure that sews the stomach directly to the small intestine to prevent blockage of food where a tumor has grown. This is done if the tumor is blocking food from the stomach to enable the patient to eat normally.

Almost all patients who have had surgery also undergo other treatments to control the effects of metastasis and the symptoms that accompany the spread of the cancer. These may include:

  • Chemotherapy. Powerful drug therapy used to kill cancer cells. Chemotherapy can be administered before and/or after surgery. It targets all cells in the body regardless of location because it is a chemical method of attacking cells. Chemotherapy is used for all stages of pancreatic cancer, but has limited beneficial results. Gemcitabine is the drug used most often in treating pancreatic cancer that has metastasized to other parts of the body.

  • Radiation therapy. Use of high energy x-rays to destroy or shrink cancer cells. This treatment may be performed before, after or instead of surgery. Studies have shown that radiation therapy is not as effective as chemotherapy in reaching the cancer cells that spread throughout the body through the bloodstream and the lymphatic system. Research has also indicated that radiation therapy can shorten the patient’s life.  Radiation therapy provided directly to the tumor during surgery is also being studied as a possible treatment for pancreatic cancer. 

  • Biological therapy (also called immunotherapy). Use of biological agents to assist the body in its immunity against the diseased cells.

  • Comfort (palliative) care. Patients may receive treatment to reduce the severity of their symptoms when the cancer itself cannot be successfully treated.

Physicians may recommend that some patients participate in clinical trials. These studies  test experimental treatments and medications that are not in widespread use. Generally, patients in the advanced stages of pancreatic cancer seek to participate in such trials because of the limitations of standard treatments. Clinical trials are conducted for all stages of pancreatic cancer. The patient’s physicians can best determine which clinical trial is appropriate for treatment.

Prevention methods for pancreatic cancer

There are no known preventative methods for pancreatic cancer and there any no screening methods for early detection.  Nor are there any screening methods for early detection. However, people with one or more risk factors for pancreatic cancer can decrease the likelihood of their developing the condition by making certain lifestyle changes, including:

  • Quit smoking. Smoking is a major risk factor for pancreatic cancer. Patients should ask their physician about smoking cessation programs.
  • Good nutrition and diet. Patients should consume reduced-fat and low-cholesterol foods and increased amounts of fruits and vegetables. In addition, the ACS recommends reducing the consumption of red meats, especially those that are processed. A healthy diet can help an individual lose weight and reduce the risk of obesity, another factor associated with the disease. Recent studies have also shown reduced risk for pancreatic cancer is associated with consumption of vitamin D supplements and dietary sources of folate.
  • Exercise. Studies have shown that those who exercise regularly are less likely to get pancreatic cancer.
  • Avoid occupational and environmental toxins. Pesticides, coal, gasoline and petroleum products should be avoided because they increase the risk of pancreatic cancer.

Some risk factors cannot be controlled, such as age, gender or heredity. Patients with inherited risk factors should avoid other known risk factors and inform their physician of their  family history. Although there are some tests for detecting pancreatic cancer in individuals with a strong family history, they are complicated and expensive.

Ongoing research regarding pancreatic cancer

Research is being conducted to discover new ways of early detection, prevention, causes and treatments of pancreatic cancer. The objective of this research is to prevent cancer or increase survival rates. Some of the research studies being conducted for pancreatic cancer involve:

  • New hormone therapy methods, used to prevent cancer cells from getting the hormones they need to grow.

  • Numerous studies of different targeted therapies are under way, including farnesyl transferase inhibitors and matrix metalloproteinase inhibitors, that block key enzymes. Biological therapy drugs now approved for other cancers have been tested for pancreatic cancer but thus far are producing disappointing results. Combinations of new therapies like bevacizumab with chemotherapy drugs have shown some improvement in survival times.

  • Other research is concentrating on newer chemotherapy drugs or drug combinations, improved surgical techniques and development of tests for earlier detection of pancreatic cancer.

Staging system for pancreatic cancer

Physicians conduct diagnostic tests to determine the extent of cancer growth. This is a process known as staging. Pancreatic cancer spreads through the bloodstream and the lymph nodes to the other parts of the body. It is therefore considered a systemic disease, because even if the tumors are visible locally, the cancer can be more widespread. The stages are:

  • Stage I. Cancer is located in the pancreas only and has not spread to any other area.

  • Stage II. Cancer is located in the pancreas and outside into the large blood vessels. It may or may not be in nearby lymph nodes. It has not spread to distant organs.

  • Stage III. Cancer is located in the pancreas and has spread locally to the lymph nodes and to major blood vessels near the pancreas but not distant sites.

  • Stage IV. Cancer is located in the pancreas and can be any size, and it has spread to distant sites.

  • Recurrent. Cancer that recurs after treatment and may return to the pancreas or other parts of the body.

The American Joint Committee on Cancer (AJCC) has developed a more detailed “TNM” staging system used by physicians:

  • “T” describes the extent of cancer growth.
  • “N” describes the extent of regional lymph node involvement.
  • “M” describes the extent of distant metastasis.

A simpler staging system is used when the exact extent of cancer growth cannot be precisely determined until surgery is performed. This staging system estimates where the cancer can be removed and to what extent based on physical examination and some imaging tests such as CAT scan. The categories:

  • Resectable. The entire tumor is located in the pancreas and can be removed. Stage I is in this category.

  • Locally advanced. Complete removal is not possible because the cancer has spread locally and blood vessels may be involved. For unresectable cancer, surgery would be performed only to relieve symptoms from obstructions such as in the bile duct or intestinal tract and not for complete removal. Stage II is in this category.

  • Metastatic. For metastatic cancer, the spread is too extensive and distant and surgery is not possible for removing the cancer. Surgery would be performed only to relieve symptoms from obstructions such as in the bile duct or intestinal tract. Stage III and IV are in this category.

About 5 percent of people with pancreatic cancer live for at least five years after diagnosis. This rate improves to 20 percent for the few cases where cancer is confined to the pancreas, according to the American Cancer Society.

Questions for your doctor

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about pancreatic cancer:

  1. How do I know if my symptoms are due to pancreatic cancer?
  2. Which tests will be used to diagnose my cancer?
  3. What type of cancer do I have?
  4. What is the stage of my cancer?
  5. Am I a candidate for surgery and if so, which procedure?
  6. Will my surgery remove all the cancer or is it to help with symptoms?
  7. What other treatments will I need and when will I receive them?
  8. Am I candidate for any clinical trials?
  9. What is the prognosis with my stage and type of cancer?
  10. If surgery removes the cancer, what are the chances of recurrence?
Scroll to Top