Cancer facts
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Prevention and Treatment of Pancreatic Cancer
The pancreas is an organ in the upper abdomen located beneath the stomach and adjacent to the first portion of the small intestine, called the duodenum. The pancreas is composed of glands that are responsible for a wide variety of tasks. The glandular functions of the pancreas can be divided into the following 2 categories:
- * Exocrine: The exocrine glands secrete enzymes into ducts that eventually empty into the duodenum. These enzymes then help in the digestion of food as it moves through the intestines.
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- * Endocrine: The endocrine glands secrete hormones, including insulin, into the bloodstream. Insulin is carried by the blood throughout the rest of the body to assist in the process of using sugar as an energy source. Insulin also controls the levels of sugar in the blood.
The pancreas can be divided into the following 4 anatomical sections:
- Head - The rightmost portion that lies adjacent to the duodenum
- Uncinate process - An extension of the head of the pancreas
- Body - The middle portion of the pancreas
- Tail - The leftmost portion of the pancreas that lies adjacent to the spleen
Intraductal papillary mucinous neoplasia (IPMN) is a type of pancreatic cancer that is beginning to be recognized more frequently. This pancreatic cancer has a better prognosis than other types of pancreatic cancer. Intraductal papillary mucinous neoplasia is usually diagnosed endoscopically (see Exams and Tests).
The most common type of pancreatic cancer arises from the exocrine glands and is called adenocarcinoma of the pancreas. The endocrine glands of the pancreas can give rise to a completely different type of cancer, referred to as pancreatic neuroendocrine carcinoma or islet cell tumor. This article only discusses issues related to the more common type of pancreatic adenocarcinoma.
Pancreatic adenocarcinoma is among the most aggressive of all cancers. By the time that pancreatic cancer is diagnosed, most people already have disease that has spread to distant sites in the body. Pancreatic cancer is also relatively resistant to medical treatment, and the only potentially curative treatment is surgery. In 2004, approximately 31,800 people in the United States were diagnosed with pancreatic cancer, and approximately 31,200 people died of this disease. These numbers reflect the challenge in treating pancreatic cancer and the relative lack of curative options.
PANCREATIC CANCER CAUSES
The main recognized risk factors for pancreatic cancer include the following:
- Smoking
- Advanced age
- Male sex - The male-to-female ratio of pancreatic cancer is 1.3:1.
- Chronic pancreatitis - Inflammation of the pancreas, usually from excessive alcohol intake or gallstones
- Diabetes mellitus
- Family history of pancreatic cancer
PANCREATIC CANCER SYMPTOMS
The main symptoms of pancreatic cancer include the following:
1. Pain in the abdomen, the back, or both
2. Weight loss, often associated with the following:
*Loss of appetite (anorexia)
*Bloating
*Diarrhea or fatty bowel movements that float in water (steatorrhea)
*Rarely may present with new diabetes in a person with weight loss and nausea
3. Jaundice (yellowing of the skin)
The symptoms of pancreatic cancer are generally vague and can easily be attributed to other less serious and more common conditions. This lack of specific symptoms explains the high number of people who have a more advanced stage of disease when pancreatic cancer is discovered.
When to Seek Medical Care
Seeking immediate medical attention is important if any of the symptoms of pancreatic cancer occur. If pain, unexplained weight loss, or jaundice persists despite initial medical treatments, further evaluation should be pursued in a timely fashion.
Exams and Tests
On physical exam, the doctor may feel a mass in the center of the abdomen. However, pancreatic cancer is seldom diagnosed using a physical exam, and the absence of any abnormalities should not dissuade the doctor from obtaining an imaging test if the symptoms of pancreatic cancer are present and persistent. The main imaging tests used to help detect pancreatic cancer are as follows:
- Abdominal ultrasound: This may be the initial test if a person has abdominal pain and jaundice. This test is effective at looking for gallstones, a common condition that presents with similar symptoms as that of pancreatic cancer. If a pancreatic tumor is seen on ultrasound, a CT scan is still necessary to obtain more information.
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- Abdominal computed tomography (CT): This is the test of choice to help diagnose pancreatic cancer. A CT scan can locate small tumors in the pancreas that might be missed by ultrasound. In addition, a CT scan can accurately show whether the mass has extended beyond the pancreas and what the relation is to nearby blood vessels and organs - information vital to a surgeon planning an operation to remove the cancer. If a pancreatic tumor is suspected, then a specialized CT scan, called a pancreatic protocol scan, is preferred prior to surgery.
If a tumor is seen in the pancreas, the doctor may want to perform a biopsy so that a pathologist can confirm that the mass is cancer. A biopsy can be performed in the following ways:
- Percutaneous biopsy: This refers to a biopsy performed by inserting a needle through the skin into the body. A radiologist usually performs this procedure while using an ultrasound or CT scanner to guide the needle into the tumor. The procedure is generally painless.
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- Endoscopic biopsy: A gastroenterologist performs this procedure by inserting a flexible tube with a camera at the tip (called an endoscope) through the mouth, into the stomach, and then into the duodenum. From here, a needle biopsy can be obtained with guidance from an ultrasound at the tip of the endoscope. A person is heavily sedated for this procedure, and it is generally painless.
If a tumor is seen in the pancreas and little doubt exists that the tumor is cancer, a surgeon may choose to remove the cancer completely without first obtaining a biopsy.
Once the diagnosis of pancreatic cancer is confirmed, routine blood studies are also performed to assess overall liver and kidney function.
In addition, a blood test called CA 19-9 is obtained. CA 19-9 is often produced by pancreatic cancers, and its level is elevated in 80% of pancreatic cancer cases. Checking the CA 19-9 levels can be a useful gauge of how the treatment is working. After treatment, the doctor may check the CA 19-9 levels regularly as one indicator of whether the cancer has returned. However, CA 19-9 is not an absolute test for pancreatic cancers, and other conditions may cause a rise in the CA 19-9 levels. Likewise, a normal CA 19-9 level is not a guarantee that the cancer has not returned.
PANCREATIC CANCER TREATMENT
The optimal treatment of pancreatic adenocarcinoma depends on the extent of the disease. The extent of cancer can be divided into the following 3 categories:
- Localized: The cancer is completely confined within the pancreas.
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- Locally advanced: The cancer has extended from the pancreas to involve nearby blood vessels or organs.
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- Metastatic: The cancer has spread outside the pancreas to other parts of the body.
Medical Treatment
Based on the results of the surgery, chemotherapy with or without radiation therapy may be offered to reduce the likelihood that the cancer will return (called adjuvant therapy).
Factors that increase the risk that the cancer may return after surgical removal are as follows:
- Tumor present at the edge of the surgical specimen (referred to as a positive margin)
- Tumor present within blood vessels or lymph channels
- Tumor tracking along nerves
- Surrounding lymph nodes containing cancer
- Options for adjuvant therapy include the following:
- Chemotherapy and radiation therapy given simultaneously
- Chemotherapy alone
No standard recommendation is available for adjuvant therapy, and it remains an area of intense clinical research. Enrolling in a clinical trial should be considered.
For locally advanced pancreatic cancer that cannot be surgically removed safely, a combination of chemotherapy and radiation therapy or chemotherapy alone may be offered. This treatment remains controversial, and various centers have different recommendations based on a number of factors such as size of the disease and symptoms.
Chemotherapy is the cornerstone of treatment of pancreatic cancer that is locally advanced or metastatic. The chemotherapy agent most commonly used in this setting is gemcitabine (see Medications).
At specific intervals while a person is receiving treatment, imaging studies are repeated to help evaluate whether the tumor is getting smaller or bigger. If a time comes when the tumor grows despite chemotherapy, it may indicate that the cancer has become resistant to this particular therapy and an alternative plan needs to be considered.
Medications
The following chemotherapy drugs may be included as part of the treatment regimen depending on the stage of pancreatic cancer:
- Gemcitabine (Gemzar): Gemcitabine is given intravenously once a week for 7 weeks (or until toxicity limits treatment), and then no treatment is given for 1 week. Then, cycles are resumed of gemcitabine once each week for 3 weeks in a row followed by 1 week off. This drug has direct effects on the cancer cells and is usually given alone for the treatment of metastatic pancreatic cancer. Side effects include fatigue, nausea, increased risk of infection because of its effects on the immune system, and anemia.
- Fluorouracil (5-FU): Fluorouracil is usually given intravenously as a continuous infusion using a medication pump. This drug has direct effects on the cancer cells and is usually used in combination with radiation therapy because it makes cancer cells more sensitive to the effects of radiation. The side effects include fatigue, diarrhea, mouth sores, and hand-and-foot syndrome (redness, peeling, and pain on the palms of the hands and the soles of the feet).
- Capecitabine (Xeloda): Capecitabine is given orally and is converted by the body to a compound similar to 5-FU. Capecitabine has similar effects on the cancer cells as 5-FU and is also generally used in combination with radiation therapy. Side effects are similar to intravenous continuous infusion of 5-FU.
Currently, many other drugs are being investigated for the treatment of pancreatic cancer, generally in combination with gemcitabine. These drugs include bevacizumab, vatalanib, cetuximab, and erlotinib. Whether any of these drugs will improve the results obtained with gemcitabine alone is not yet known. Enrollment in clinical trials is encouraged.
Medications are available to alleviate the side effects of the treatments. If side effects occur, an oncologist should be notified so that they can be addressed promptly. An oncologist also monitors blood and urine for signs of toxicity.
Pancrelipase (pancreatic enzyme replacement) may be given if the function of the pancreas is impaired, usually after the surgical removal of a portion of the pancreas. This oral medication is taken with meals to aid in the digestion of food and in the prevention of steatorrhea.
Pain may be associated with pancreatic cancer, and a variety of pain medications exist to help control any discomfort. Good communication with the oncologist and nurses allows for optimal management of pain.
Surgery
The treatment of pancreatic cancer depends on whether complete surgical removal of the cancer is possible. Complete surgical removal of the cancer is the only known cure for pancreatic cancer. Only 15-20% of people with pancreatic cancer have disease that can be surgically removed at the time of diagnosis.
Cancer that is localized may be completely removed and thereby considered resectable. If all the cancer could not be removed with surgery or if a surgery would not be safe to perform, then the cancer is considered unresectable.
The features of unresectable pancreatic cancer include the following:
- The cancer has spread (metastasized) outside of the pancreas to other organs (for example, liver or lungs).
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- The cancer is wrapped around one of the major blood vessels near the pancreas.
If the cancer is resectable and if no other health issues exist that make the surgery unsafe, then a surgeon attempts to remove the cancer.
- Whipple procedure: This is done when the pancreatic cancer is in the head or uncinate process. This procedure removes the head and uncinate process of the pancreas, the duodenum, and the gallbladder. A portion of the stomach is often removed as well.
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- Distal subtotal pancreatectomy: This is performed when the pancreatic cancer is in the body or tail of the pancreas. This procedure removes the body and tail of the pancreas as well as the spleen.
Mortality rates are lower if the surgery is performed in a center where a lot of pancreatic surgeries are performed. Centers that have a low volume of pancreatic surgeries produce a 10%-15% mortality rate. Those centers with a high volume of pancreatic surgeries produce a 2% mortality rate.
Other Therapy
Radiation therapy
Radiation therapy is treatment that uses high-energy x-rays aimed at the cancer to kill cancer cells or to keep them from growing. For pancreatic cancer cases, radiation therapy is usually given in conjunction with chemotherapy.
The goals of radiation therapy are as follows:
- Kill cancer cells that cannot be surgically removed to reduce the risk of the cancer returning or spreading.
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- Treat tumors that cannot be surgically removed and that are causing symptoms, such as pain or jaundice.
Typically, radiation treatments are given 5 days a week, for up to 6 weeks. Each treatment lasts only a few minutes and is completely painless; it is similar to having an x-ray film taken. However, some patients may experience abdominal discomfort during the last few weeks of therapy or for several months following completion of treatment.
The main side effects of radiation therapy include mild skin irritation, loss or appetite, nausea, diarrhea, or fatigue. These side effects usually resolve soon after treatment is complete (within 1-2 months).
Other therapy
Pancreatic cancer may cause symptoms that cannot always be relieved by surgery, chemotherapy, or radiation therapy. These symptoms include the following:
- Pain
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- Jaundice from obstruction of the bile duct
Therapies aimed at relieving the symptoms of pancreatic cancer, but not at treating the cancer itself, include the following:
- Celiac plexus neurolysis (CPN): Sometimes referred to as a celiac block, celiac plexus neurolysis involves an injection of a chemical (usually alcohol) into the collection of nerves called the celiac plexus that receives pain signals from the pancreas. This chemical injection damages or numbs these nerves and reduces the sensation of pain caused by a pancreatic tumor.
- The injection is performed either using an endoscope with ultrasound guidance or through the skin using a CT scanner for guidance.
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- Side effects include temporary diarrhea and lowering of blood pressure; abdominal pain occurs during and immediately after the procedure.
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- Biliary stenting: This involves placing a hollow tube, called a stent, into the bile duct to keep it open despite the external pressure from a growing pancreatic tumor. This prevents jaundice by allowing the bile to flow freely and unimpeded from the liver, past the pancreas, and into the intestine. This procedure is usually performed with an endoscope by a gastroenterologist, but it can also be performed percutaneously (through the skin) under CT guidance by an interventional radiologist.
Follow-up
Because pancreatic cancer has a risk of returning after surgical or medical therapy, continuous vigilant follow-up with the doctor is important. On a routine schedule recommended by the doctor, the following are performed:
- Physical exams
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- Blood studies, including CA 19-9
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- Periodic imaging studies, usually CT scans at 6-month intervals or earlier if needed to assess new symptoms.
- Prevention
- No known preventative measure exists for pancreatic cancer; however, minimizing certain risk factors is important. Risk factors that can be controlled include limiting smoking and excessive alcohol intake.
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- Outlook
- Despite recent advances in the surgical and medical treatment of pancreatic cancer, the prognosis associated with this disease is still relatively poor.
For people who have pancreatic cancers completely removed by surgery, the probability of being alive in 5 years is 20-30%. If lymph nodes were found to contain cancer at the time of surgery, then the probability of being alive in 5 years decreases to 10%.
The addition of chemotherapy after surgical removal of the pancreatic cancer is likely to increase this probability of being alive in 5 years, but only by about 10%.
For people who have unresectable locally advanced pancreatic cancer, surviving beyond 3 years is rare. For those with metastatic pancreatic cancer who have symptoms of weight loss or pain, the chance of surviving 1 year is less than 20% for those undergoing chemotherapy and less than 5% for those who choose not to receive chemotherapy.
These statistics underscore the importance of clinical trials attempting to discover more effective therapies for this disease. People with pancreatic cancers are encouraged to ask their doctor about the possibility of participating in a clinical trial that is well-suited for them.
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