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Pancreatic Cancer

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What is pancreatic cancer?

The normal pancreas

The pancreas is an organ located behind the stomach. It is shaped a little bit like a fish with a wide head, a tapering body, and a narrow, pointed tail. It is about 6 inches long but less than 2 inches wide and extends horizontally across the abdomen. The head of the pancreas is on the right side of the abdomen (belly), behind the place where the stomach meets the duodenum (the first part of the small intestine). The body of the pancreas is located behind the stomach and the tail of the pancreas is on the left side of the abdomen next to the spleen.

The pancreas contains 2 different types of glands: exocrine and endocrine.

The exocrine glands make pancreatic "juice," which is released into the intestines. This juice contains enzymes that help you digest fats, proteins, and carbohydrates in the food you eat. Without these, some of the food you eat would just pass through your intestines without being absorbed. The enzymes are released into tiny tubes called ducts. These tiny ducts merge to form larger ducts that empty into the pancreatic duct. The pancreatic duct merges with the common bile duct (the duct that carries bile from the liver), and empties the pancreatic juice into the duodenum (the first part of the small intestine) at the ampulla of Vater. More than 95% of the cells in the pancreas are exocrine glands and ducts.

A small percentage of the cells in the pancreas are endocrine cells. These cells are arranged in small clusters calledislets (or islets of Langerhans). The islets release important hormones, such as insulin and glucagon, directly into the blood. Insulin reduces the amount of sugar in the blood, while glucagon increases it. Diabetes results from a defect in insulin production.

Types of pancreatic tumors

The exocrine cells and endocrine cells of the pancreas form completely different types of tumors.

Exocrine tumors

Exocrine tumors are by far the most common type of pancreas cancer. When someone says that they have pancreatic cancer, they usually mean an exocrine pancreatic cancer. Benign (non-cancerous) cysts and benign tumors called cystadenomas can occur, but most pancreatic exocrine tumors are malignant (cancerous).

An adenocarcinoma is a cancer that starts in gland cells. About 95% of cancers of the exocrine pancreas are adenocarcinomas. These cancers usually begin in the ducts of the pancreas, but they sometimes develop from the cells that make the pancreatic enzymes (acinar cell carcinomas).

Less common types of cancers of the exocrine pancreas include adenosquamous carcinomas, squamous cell carcinomas, signet ring cell carcinomas, undifferentiated carcinomas, undifferentiated carcinomas with giant cells, and solid pseudopapillary neoplasms of the pancreas. These types are distinguished from one another based on how they look under the microscope.

The treatment of an exocrine pancreatic cancer is mostly based on the stage of the cancer, not its exact type. The stage of the cancer describes how large the tumor is and how far it has spread. Pancreatic cancer staging is described later in this document.

A special type of cancer, called ampullary cancer (or carcinoma of the ampulla of Vater) is a cancer that starts in the place where the bile duct and pancreatic duct come together and empty into the duodenum (the ampulla of Vater). These cancers often block the bile duct while they are still small and have not spread far. This blockage causes bile to build up in the body, which leads to yellowing of the skin and eyes (jaundice) and can turn urine dark. This is an easily recognized sign that something is wrong. This is why ampullary cancers are usually found at an earlier stage than most pancreatic cancers, which means they usually have a better prognosis (outlook) than typical pancreatic cancers.

Ampullary cancers are included with pancreatic cancer in this document because their treatments are very similar.

Endocrine tumors : Tumors of the endocrine pancreas are uncommon. As a group, they are known as pancreatic neuroendocrine tumors (NETs), or sometimes as islet cell tumors. There are several subtypes of islet cell tumors. Each is named according to the type of hormone-making cell it starts in:

Insulinomas come from cells that make insulin.

Glucagonomas come from cells that make glucagon.

Gastrinomas come from cells that make gastrin.

Somatostatinomas come from cells that make somatostatin.

VIPomas come from cells that make vasoactive intestinal peptide (VIP).

PPomas come from cells that make pancreatic polypeptide.

Carcinoid tumors are another type of pancreatic NET. These tumors often make serotonin (also called 5-HT) or its precursor, 5-HTP.

About half of pancreatic NETs make hormones that are released into the blood and so are called functioning tumors. Tumors that do not make hormones are called non-functioning.

Islet cell tumors can be benign or malignant. Benign tumors are called pancreatic neuroendocrine tumors, while malignant tumors are called pancreatic neuroendocrine cancers or carcinomas. Malignant and benign tumors can look very similar under the microscope, so it isn't always clear at the time of diagnosis whether or not a NET is cancer. Sometimes the diagnosis only becomes clear when the tumor has spread outside of the pancreas.

Pancreatic neuroendocrine cancers make up less than 4% of all pancreatic cancers diagnosed. Treatment and prognosis depend on the specific tumor type and the stage (extent) of the tumor but the prognosis is generally better than that of pancreatic exocrine cancers. The most common types of pancreatic endocrine tumors are gastrinomas and insulinomas. The other types occur very rarely.

It is very important to distinguish between exocrine and endocrine cancers of the pancreas. They have distinct risk factors and causes, have different signs and symptoms, are diagnosed using different tests, are treated in different ways, and have different prognoses. In this document, the term pancreatic neuroendocrine tumor is used for both benign and malignant endocrine pancreatic tumors.

What are the risk factors for pancreatic cancer?

A risk factor is anything that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person's age or family history, can't be changed. But risk factors don't tell us everything. Having a risk factor, or even several risk factors, does not mean that you will get the disease. And many people who get the disease may not have had any known risk factors.

Age :  The risk of developing pancreatic cancer increases as people age. Almost all patients are older than 45. Nearly 9 in 10 are at least 55 years old and almost 7 in 10 are at least 65 years old. The average age at the time of diagnosis is 71.

Gender : Men are 30% more likely to develop pancreatic cancer than women. This may be due, at least in part, to increased tobacco use in men. The difference in pancreatic cancer risk was more pronounced in the past (when tobacco use was much more common among men than women), but the gap has closed in recent years.

Race : African Americans are more likely to develop pancreatic cancer than whites. The reasons for this are not clear, but it may be due in part to higher rates of smoking and diabetes in men and being overweight in women.

Cigarette smoking : The risk of getting pancreatic cancer is at least twice as high among smokers compared to those who have never smoked. Scientists think this may be due to cancer-causing chemicals in cigarette smoke that enter the blood and damage the pancreas. About 20% to 30% of exocrine pancreatic cancer cases are thought to be caused by cigarette smoking. Cigar and pipe smoking also increase risk. Quitting smoking helps lower risk – 10 years after quitting, former smokers have the same risk as those who never smoked.

People who use smokeless tobacco are also more likely to get pancreatic cancer.

Obesity and physical activity : Very overweight (obese) people are more likely to develop exocrine pancreatic cancer. Studies looking at the link between physical activity and the risk of pancreatic cancer have had mixed results.

Diabetes : Exocrine pancreatic cancer is more common in people who have diabetes. The reason for this link is not known. Most of the risk is found in people with type 2 diabetes. This type of diabetes most often starts in adulthood. It is often related to being overweight or obese. It is not clear if people with type 1 (juvenile) diabetes have a higher than average risk. In some patients, though, the cancer seems to have caused the diabetes (not the other way around).

Chronic pancreatitis : Chronic pancreatitis is a long-term inflammation of the pancreas. This condition is linked with an increased risk of pancreatic cancer, but most patients with pancreatitis never develop pancreatic cancer. The link between chronic pancreatitis and pancreatic cancer is strongest in smokers.

A small number of cases of chronic pancreatitis appear to be due to an inherited gene mutation (see "Family history"). People with this inherited form of chronic pancreatitis seem to have a high lifetime risk for developing pancreatic cancer (about 40% to 75%).

Cirrhosis of the liver :  Cirrhosis is a scarring of the liver. It develops in people with liver damage from things like hepatitis and alcohol use. People with cirrhosis seem to have an increased risk of pancreatic cancer.

Occupational exposure : Heavy exposure at work to certain pesticides, dyes, and chemicals used in metal refining may increase the risk of developing pancreatic cancer.

Family history :  Pancreatic cancer seems to run in some families. In some of these families, the high risk is due to an inherited syndrome (explained in the next section, "Genetic syndromes"). In other families, the gene causing the increased risk of pancreatic cancer is not known.

Genetic syndromes :  Inherited gene mutations are abnormal copies of certain genes that can be passed from parent to child. These abnormal genes may cause as many as 10% of pancreatic cancers and can cause other problems as well. Examples of the genetic syndromes that can cause exocrine pancreatic cancer include:

Hereditary breast and ovarian cancer syndrome, caused by mutations in the gene BRCA2

Familial melanoma, caused by mutations in the gene p16/CDKN2A

Familial pancreatitis, caused by mutations in the gene PRSS1

Hereditary non-polyposis colorectal cancer (HNPCC), most often caused by a defect in either the gene MLH1 or the gene MSH2. At least 5 other genes can also cause HNPCC: MLH3, MSH6, TGBR2, PMS1, and PMS2. This disorder is also known as Lynch syndrome.

Peutz-Jeghers syndrome (PJS), caused by defects in the gene STK1. This syndrome is also linked with polyps in the digestive tract and several other cancers

Von Hippel-Lindau syndrome, caused by mutations in the gene VHL, can lead to an increased risk of pancreatic cancer and carcinoma of the ampulla of Vater

Pancreatic neuroendocrine tumors and cancers can also be caused by a genetic syndrome, such as:

Neurofibromatosis, type 1, which is caused by mutations in the gene NF1. This syndrome leads to an increased risk of many tumors, including somatostatinomas.

Multiple endocrine neoplasia, type 1, caused by mutations in the gene MEN1, leads to an increased risk of tumors of the parathyroid gland, the pituitary gland, and the islet cells of the pancreas.

Scientists have found the genes that cause the syndromes listed above and they can be recognized by genetic testing. For more information on genetic testing, 

Stomach problems : Infection of the stomach with the ulcer-causing bacteria Helicobacter pylori (H. pylori) may increase the risk of getting pancreatic cancer. Some researchers believe that excess stomach acid might also increase the risk.

Diet : Some studies linked pancreatic cancer and diets high in fat, or those that include a lot of red meat, pork, and processed meat (such as sausage and bacon). Others have found that diets high in fruits and vegetables may help reduce the risk of pancreatic cancer. But not all studies have found such links, and the exact role of diet in relation to pancreatic cancer is still being studied.

Do we know what causes pancreatic cancer?

Scientists still do not know exactly what causes most cases of pancreatic cancer, but they have found several risk factors that can make a person more likely to get this disease. Recent research has shown that some of these risk factors affect the DNA of cells in the pancreas, which can result in abnormal cell growth and may cause tumors to form.

Researchers have made great progress in understanding how certain changes in DNA can cause normal cells to become cancerous. DNA is the chemical in each cell that carries our genes — the instructions for how our cells function. We look like our parents because they are the source of our DNA. But DNA affects more than the way we look. Some genes contain instructions for controlling when our cells grow and divide. Certain genes that promote cell division are called oncogenes. Others that slow down cell division or cause cells to die at the right time are calledtumor suppressor genes. Cancers can be caused by DNA mutations (defects) that turn on oncogenes or turn off tumor suppressor genes.

Several cancer family syndromes have been found in which inherited DNA mutations cause a very high risk of developing certain cancers. In some of these, there is an increased risk of getting pancreatic cancer. Researchers have characterized many of these DNA changes in the past few years.  

Most often, DNA mutations of oncogenes or tumor suppressor genes related to cancers of the pancreas occur after you are born, rather than having been inherited. These acquired mutations may result from cancer-causing chemicals in our environment, diet, or tobacco smoke. Sometimes they occur for no apparent reason.

Often, the DNA changes seen in sporadic (non-inherited) cases of pancreatic cancer are the same as those seen in inherited cases. For example, most sporadic cases of exocrine pancreatic cancer have changes in the p16 gene. This is why scientists are studying inherited cases closely to learn more about what causes pancreatic cancer. Some specific DNA abnormalities recently discovered in pancreatic cancer are discussed in the section “What's new in pancreatic cancer research and treatment?”

Can pancreatic cancer be prevented?

There are no established guidelines for preventing pancreatic cancer. For now, the best approach is to avoid pancreatic cancer risk factors whenever possible.

Cigarette smoking is the most important avoidable risk factor for pancreatic cancer. It is responsible for 20% to 30% of pancreatic cancers. Tobacco use also increases the risk of many other cancers such as cancers of the lung, mouth, larynx (voice box), esophagus, kidney, bladder, and some other organs. 

Maintaining a healthy weight, eating well, and exercising are also important. The American Cancer Society recommends choosing foods and beverages in amounts that help achieve and maintain a healthy weight. Eat a healthy diet, with an emphasis on plant foods. This includes eating at least 2½ cups of vegetables and fruits every day. Choosing whole-grain breads, pastas, and cereals instead of refined grains, and eating fish, poultry, or beans instead of processed meat and red meat may also help lower your risk of cancer, as well as some other diseases. 

Can pancreatic cancer be found early?

One reason for the often poor outlook for people with exocrine pancreatic cancer is that very few of these cancers are found early. The pancreas is located deep inside the body, so early tumors cannot be seen or felt by health care providers during routine physical exams. Patients usually have no symptoms until the cancer has spread to other organs. Right now, there are no blood tests to find early cancers of the pancreas. Doctors are looking to see if something called endoscopic ultrasound can be useful in screening people with a high risk of pancreatic cancer.

Blood tests : A substance called CA 19-9 is released into the blood by exocrine pancreatic cancer cells and can be detected by blood tests. But by the time blood levels are high enough to be consistently detected by available methods, the cancer is no longer in its early stages. This is why the test is not recommended for routine screening of people without symptoms or a known diagnosis of cancer. The CA 19-9 test is sometimes used during treatment to see if the therapy is working or after treatment to see if the cancer has recurred (come back).

Another substance, carcinoembryonic antigen (CEA), can help detect advanced pancreatic cancer in some people. But it isn't sensitive enough to find the cancer early and is not recommended as a screening test.

Genetic testing :  Inherited DNA changes are thought to cause as many as 10% of pancreatic cancers. Because these inherited cases are sometimes linked with other cancers, determining whether a patient's relatives have an increased risk is not simple. Talking to someone with experience in hereditary cancer syndromes such as a genetic counselor, geneticist, or an oncologist (doctor who specializes in caring for people who have cancer) is often helpful.

How is pancreatic cancer diagnosed?

If one or more of the signs and symptoms described here is present, certain exams and tests may be done to find out whether they are caused by pancreatic cancer or by some other disease.

Signs and symptoms of exocrine pancreatic cancer

Jaundice :  Jaundice is yellowing of the eyes and skin caused by the buildup of bilirubin in the body Bilirubin is a dark yellow-brown substance that is made in the liver. Normally, the liver excretes bilirubin into bile. Bile goes through the common bile duct into the intestines, eventually leaving the body in the stool. When the common bile duct becomes blocked, bile can't reach the intestines, and the level of bilirubin builds up. At least half of all people with pancreatic cancer and in all people with ampullary cancer have jaundice.

Cancers that begin in the head of the pancreas are near the common bile duct. These cancers can compress the duct while they are still fairly small. This can lead to jaundice, which may allow these tumors to be found in an early stage. But cancers that begin in the body or tail of the pancreas do not compress the duct until they have spread through the pancreas. By this time, the cancer may have also spread beyond the pancreas.

When pancreatic cancer spreads, it often goes to the liver. This can also lead to jaundice.

Sometimes, the first sign of jaundice is darkening of the urine from bilirubin. As bilirubin levels in the blood increase, the urine becomes brown in color.

If the bile duct is blocked, bile (and bilirubin) can't get through to the bowel. When this happens, a person may notice their stools becoming lighter in color.

When bilirubin builds up in the skin, it turns yellow and starts to itch : Cancer is not the most common cause of jaundice. Other causes, such as gallstones, hepatitis, and other liver diseases, are much more common.

Abdominal or back pain : Pain in the abdomen or back is common in advanced pancreatic cancer. Cancers that start in the body or tail of the pancreas may grow fairly large and start to compress other nearby organs, causing pain. The cancer may also spread to the nerves surrounding the pancreas, which often causes back pain. The pain may be constant or it may come and go. Of course, pancreatic cancer is not a common cause of pain in the abdomen or back. It is more often caused by a non-cancerous disease or even another type of cancer.

Weight loss and poor appetite : Unintended or unexpected weight loss is very common in patients with pancreatic cancer. These people also complain of being very tired and having little or no appetite.

Digestive problems : If cancer blocks the release of the pancreatic juice into the intestine, a person may not be able to digest fatty foods. The undigested fat may cause stools to be unusually pale, bulky, greasy, and to float in the toilet. The cancer may also wrap around the far end of the stomach and partly block it. This can cause nausea, vomiting, and pain that tend to be worse after eating.

Gallbladder enlargement : If the cancer blocks the bile duct, bile can build up in the gallbladder, which then becomes enlarged. This can sometimes be felt by a doctor during a physical exam. It can also be detected by imaging studies.

Blood clots or fatty tissue abnormalities :Sometimes, the first clue that there is a pancreatic cancer is the development of a blood clot in a large vein, often a vein in the leg. This is called a deep venous thrombosis or DVT. Sometimes a clot breaks off and travels to the lungs, making it hard to get enough air. A blood clot in the lungs is called a pulmonary embolism or PE. Still, having a blood clot does not usually mean that you have cancer. Most blood clots are caused by other things.

Another pancreatic cancer clue is the development of uneven texture of the fatty tissue underneath the skin. This is caused by the release of the pancreatic enzymes that digest fat.

Diabetes : Rarely, exocrine cancers of the pancreas cause diabetes (high blood sugar) because they destroy the insulin-making cells. More often, there are slight problems with sugar metabolism that do not cause symptoms of diabetes but can still be recognized by certain blood tests.

Signs and symptoms of pancreatic neuroendocrine tumors

Most of the signs and symptoms of pancreatic neuroendocrine tumors (NETs) are caused by the excess hormones that the tumors release into the bloodstream. Different types of tumors make different hormones.

Gastrinomas : These tumors make gastrin, a hormone that tells the stomach to make more acid. Too much gastrin causes a condition known as Zollinger-Ellison syndrome. The excess gastrin causes the stomach to make too much acid. This leads to stomach ulcers, which can cause pain, nausea, and a decreased appetite. If the ulcer is severe, it may start bleeding. If the bleeding is mild, it can lead to anemia (too few red blood cells). This can cause symptoms like feeling very tired and being short of breath when you exercise. If the bleeding is more severe, it can make stool black and tarry. Severe bleeding can itself be life-threatening. Ulcers in patients with gastrinomas can be hard to treat, requiring high doses of anti-ulcer medication to heal. Patients need to stay on these drugs for a long time, because the ulcers tend to come back if treatment is stopped.

When the stomach makes too much acid it can be released into the small intestine. There it can damage the cells of the intestinal lining and break down digestive enzymes before they have a chance to digest food. This can cause diarrhea and weight loss.

About half of gastrinomas are cancers.

Glucagonomas : These tumors make glucagon, a hormone that increases glucose levels in the blood. Excess glucagon can raise blood sugar, sometimes leading to diabetes. Patients also have problems with diarrhea, weight loss, and malnutrition. The nutrition problems can lead to symptoms like irritation of the tongue (glossitis) and the corners of the mouth (angular cheilosis). Most of the symptoms that can be caused by a glucagonoma are mild and more often are found to be caused by something else.

The symptom that brings most people with glucagonomas to their doctor is a rash called necrolytic migratory erythema. It is a red rash with swelling and blisters and it often travels place to place on the skin. It is the most distinctive feature of a glucagonoma.

Most glucagonomas are cancers.

Insulinomas : These tumors make insulin, which lowers blood glucose levels. Too much insulin leads to low blood sugar (hypoglycemia), with symptoms like weakness, confusion, sweating, and rapid heartbeat. When blood sugar gets very low, it can lead to the patient passing out or even going into a coma and having seizures. These symptoms improve if the patient gets glucose (sugar) — either by mouth (as food) or as an injection into the vein (IV).

Most insulinomas are benign (not cancers).

Somatostatinomas :  These tumors make somatostatin, which helps regulate other hormones. Symptoms of this type of tumor include diarrhea, diabetes, and gallbladder problems. The problems with the gallbladder can lead to abdominal pain, nausea, poor appetite, and jaundice (yellowing of the skin and eyes). Since symptoms of a somatostatinoma tend to be mild and are more often caused by other things, these tumors tend to be diagnosed at an advanced stage.

Most somatostatinomas are cancers. Often, they are not found until they spread to the liver, when they cause problems like jaundice and pain.

VIPomas : These tumors make a substance called vasoactive intestinal peptide (VIP). Too much VIP can lead to problems with diarrhea and low blood levels of potassium. Patients also have low levels of acid in their stomachs, leading to problems digesting food. They may also have high blood glucose levels. The diarrhea may be mild at first, but gets worse over time. By the time they are diagnosed, most patients have severe, watery diarrhea, with as many as 20 bowel movements per day.

Most VIPomas are cancers.

PPomas :  These tumors make pancreatic polypeptide, which helps regulate both the exocrine and endocrine pancreas. They cause problems with abdominal pain and an enlarged liver. Some patients also get watery diarrhea.

Most PPomas are cancers.

Carcinoid tumors : These tumors often make serotonin or its precursor 5-HTP. When a pancreatic tumor makes these substances, they first travel to the liver. The liver breaks down these substances before they can reach the rest of the body and cause problems. This is why carcinoid tumors may not cause symptoms until they spread outside the pancreas. When they do spread, it is most often to the liver. When that happens, the hormones can be released from the cancer cells directly into the blood leaving the liver. This can cause something called the carcinoid syndrome, with symptoms including: flushing (skin turning red with a warm feeling), diarrhea, wheezing, and a rapid heart rate. These symptoms often occur in episodes, and between episodes the patient may feel fine.

Over a long time, these hormone-like substances can damage heart valves, causing shortness of breath, weakness, and a heart murmur (an abnormal heart sound).

Non-functioning tumors : These tumors do not make hormones, so they do not cause symptoms in early stages. Most of these are cancers and start to cause problems as they get larger or spread outside the pancreas.

Symptoms caused by the cancer spreading : When pancreatic NETs spread, they most often spread to the liver. This can enlarge the liver, which can cause pain and a poor appetite. It can also interfere with liver function, sometimes leading to jaundice (yellowing of the skin and eyes) and abnormal lab tests.

Although these cancers often first spread to the liver, they can go on to spread to other organs and tissues. The symptoms depend on where the cancer is growing. For example, cancer spread to the lungs can cause problems breathing and a cough. Spread to bones can cause pain in those bones.

Tests to diagnose pancreatic cancer 

Medical history and physical exam :Your doctor will take a thorough medical history to check for any pancreatic cancer risk factors, and to get information about pain (how long you have had it, its severity, where it is, and what makes it worse or better), appetite, weight loss, tiredness, and other symptoms.

A thorough physical exam will focus mostly on your abdomen to check for any masses or fluid buildup. Your skin and the whites of your eyes will be checked for jaundice (yellowing). Cancers that block the bile duct may also cause the gallbladder to enlarge, which can sometimes be felt on physical exam. Pancreatic cancer may spread to the liver, causing it to enlarge.

The cancer can also spread to lymph nodes above the collarbone and other locations. These areas will be looked at carefully for swelling that might mean cancer spread.

Imaging tests

Computed tomography (CT) scan : The CT scan is an x-ray test that produces detailed cross-sectional images of your body. Instead of taking one picture, like a standard x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into an image of a slice of your body.

A CT scanner has been described as a large donut, with a narrow table in the middle opening. You will need to lie still on the table while the scan is being done. CT scans take longer than regular x-rays, and you might feel a bit confined by the ring while the pictures are being taken.

Before the test, you may be asked to drink 1 to 2 pints of a liquid called oral contrast. This helps outline the intestine so that certain areas are not mistaken for tumors. You may also receive an IV line through which a different kind of contrast dye (IV contrast) is injected. This helps better outline structures such as blood vessels in your body.

The injection can cause some flushing (redness and warm feeling). A few people are allergic to the dye and get hives or, rarely, have more serious reactions like trouble breathing and low blood pressure. Be sure to tell the doctor if you have any allergies or have ever had a reaction to any contrast material used for x-rays.

CT scans are often used to diagnose pancreatic cancer and help stage it (determining the extent of its spread). CT scans show the pancreas fairly clearly and often can confirm the location of the cancer. CT scans can also show the organs near the pancreas, as well as lymph nodes and distant organs where the cancer might have spread. The CT scan can help determine whether surgery will be a good treatment option.

CT-guided needle biopsy: CT scans can also be used to guide a biopsy needle precisely into a suspected tumor. For this procedure, the patient remains on the CT scanning table while the doctor advances a biopsy needle through the skin and toward the tumor. CT scans are repeated until the needle is within the mass. A fine needle biopsy sample or a larger core needle biopsy sample is then removed to be looked at under a microscope.

Magnetic resonance imaging (MRI) : MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed by the body and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into a detailed image of parts of the body. Not only does this produce cross-sectional image slices of the body like a CT scanner, it also produces slices that are parallel with the length of the body. A contrast material might be injected just as with CT scans, this but is used less often.

Most doctors prefer to look at the pancreas with CT scans, but an MRI can sometimes provide more information. MRI scans are also particularly helpful in looking at the brain and spinal cord.

MRI scans take longer than CT scans, often up to an hour. You may have to lie inside a narrow tube, which is confining and can be distressing to some people. Newer, more open MRI machines may be another option. The MRI machine makes loud buzzing and clicking noises that you might find disturbing. Some places give you headphones or earplugs to help block this noise out.

Somatostatin receptor scintigraphy : Somatostatin receptor scintigraphy (SRS), also known as OctreoScan, can be very helpful in diagnosing pancreatic neuroendocrine tumors. It uses a hormone-like substance called octreotide that has been bound to a radioactive substance (indium-111). Octreotide attaches to proteins on the tumor cells of many NETs, but it is less helpful in finding insulinomas.

A small amount of this substance is injected into a vein. It travels through the blood and is attracted to neuroendocrine tumors. About 4 hours after the injection, a special camera can be used to show where the radioactivity has collected in the body. More scans may be done on the following few days as well.

This scan can help diagnose a NET, but it can also help decide on a treatment. If a NET shows up on a SRS scan, it often means that the tumor will stop growing if treated with octreotide.

Positron emission tomography (PET) scan : For a PET scan, a form of radioactive sugar (known as fluorodeoxyglucose or FDG) is injected into the blood. Because cancer cells in the body grow quickly, they absorb large amounts of the radioactive sugar. After about an hour, you will be moved onto a table in the PET scanner. You lie on the table for about 30 minutes while a special camera creates a picture of areas of radioactivity in the body. The picture is not finely detailed like a CT or MRI scan, but it can provide helpful information about your whole body.

This test is useful to look for spread from exocrine pancreatic cancers, but because NETs grow slowly, they do not show up well on PET scans.

PET/CT scans combine a CT scan and a PET scan to even better pinpoint the tumor. This test may be especially useful for spotting exocrine cancer that has spread beyond the pancreas and wouldn't be treatable by surgery. It might be a useful test for staging the cancer. It may even be able to spot early cancers.

Ultrasonography (ultrasound or US) : Ultrasound uses sound waves to produce images of internal organs such as the pancreas. For an abdominal ultrasound, a wand-shaped probe called a transducer is placed on the skin of the abdomen. It emits sound waves and detects the echoes as they bounce off internal organs. The pattern of echoes is processed by a computer to produce an image on a screen.

The echoes made by most pancreatic tumors differ from those of normal pancreas tissue. Different echo patterns can help distinguish some types of pancreatic tumors from one another.

If signs and symptoms indicate that a pancreatic cancer is likely, a CT scan is often more useful than ultrasound for an accurate diagnosis. But if it's not clear whether certain other diseases may account for the patient's signs or symptoms, an ultrasound may be done. Ultrasound is also commonly used to look at the liver, and may be used if someone has symptoms (like jaundice) that point to a liver problem.

Endoscopic ultrasound is more accurate than abdominal ultrasound and is probably the best way to diagnose pancreatic cancer. This test is done with an ultrasound probe that is attached to an endoscope — a thin, lighted, flexible, fiber optic tube — that doctors use to look at the inside of the intestinal tract. Patients are first sedated (given medicine to make them sleepy). The probe is then passed through the mouth or nose, through the esophagus (the tube that connects the mouth to the stomach) and stomach, and into the first part of the small intestine. It can then be pointed toward the pancreas, which sits next to the small intestine. The probe is on the tip of the endoscope, so it can get very close to the tumor to take pictures. This is a very good way to look at the pancreas. It is better than CT scans for spotting small tumors. If a tumor is seen, it can be biopsied during this procedure.

Endoscopic retrograde cholangiopancreatography (ERCP) : For this procedure, an endoscope (a thin, lighted, flexible tube) is passed down the patient's throat, through the esophagus and stomach, and into the first part of the small intestine. The doctor can see through the endoscope to find the ampulla of Vater (where the common bile duct connects to the small intestine). The doctor guides a catheter (a very small tube) from the end of the endoscope into the common bile duct. A small amount of dye (contrast material) is then injected through the tube into the common bile duct and x-rays are taken. This dye outlines the bile duct and pancreatic duct. The x-ray images can show narrowing or blockage in these ducts that might be due to pancreatic cancer. The doctor doing this test can also put a small brush through the tube to remove cells for a biopsy (to view under a microscope to see whether or not they look like cancer). This procedure is usually done while the patient is sedated (given medicine to make them sleepy).

ERCP can also be used to place a stent (small tube) into the bile duct to keep it open if a nearby tumor is pressing on it. This is described in more detail in the section on palliative surgery in the “Surgery for pancreatic cancer” section.

Angiography : This is an x-ray procedure that looks at blood vessels. A small amount of contrast material is injected into an artery to outline the blood vessels, then x-rays are taken.

Angiography can show if blood flow in a particular area is blocked or compressed by a tumor. It can also show any abnormal blood vessels (feeding the cancer) in the area. This test can be useful in finding out if a pancreatic cancer has grown through the walls of certain blood vessels. Mainly, it helps surgeons decide whether the cancer can be completely removed without damaging vital blood vessels and helps them plan the operation.

Angiography can also be used to look for pancreatic neuroendocrine tumors that are too small to be seen on other imaging tests. These tumors cause the body to make more blood vessels to "feed" the tumor. These extra blood vessels can be seen on angiography.

Angiography can be an uncomfortable procedure because the radiologist who performs it has to put a small catheter into the artery leading to the pancreas. Usually the catheter is put into an artery in your inner thigh and threaded up to the pancreas. A local anesthetic is often used to numb the area before inserting the catheter. Then the dye is injected quickly to outline all the vessels while the x-rays are being taken.

Blood tests : Several types of blood tests may be used to help diagnose pancreatic cancer or to help determine treatment options if it is found.

Blood tests that look at levels of different kinds of bilirubin (a chemical made by the liver) are useful in deciding whether a patient's jaundice is caused by liver disease or a blockage (by a gallstone, a tumor, or other disease) of bile flow.

Elevated blood levels of the tumor markers CA 19-9 and carcinoembryonic antigen (CEA) may point to a diagnosis of exocrine pancreatic cancer, but these tests aren't always accurate .

Pancreatic neuroendocrine tumors : Blood tests looking at the levels of certain pancreatic hormones can help diagnose pancreatic neuroendocrine tumors (NETs). For insulinomas, insulin, glucose, and C-peptide levels are measured while the patient is fasting (not eating or drinking). (C peptide is a by-product of insulin production). Blood is drawn every 6 to 8 hours until the patient starts having symptoms of low blood sugar. The diagnosis of an insulinoma is made when there is low blood glucose with high levels of insulin and C-peptide.

Other pancreatic hormones, such as gastrin, glucagon, somatostatin, pancreatic polypeptide, and VIP (vasoactive intestinal peptide) can be measured in blood samples and can be used to diagnose pancreatic NETs. Measuring the level of a substance called chromogranin-A (CgA) can be very helpful. This level goes up in most cases of pancreatic NETs — even the non-functioning tumors.

Gastrin levels go up in patients who are taking a common type of anti-ulcer medicine known as proton pump inhibitors. Examples of these drugs include omeprazole (Prilosec®), esomeprazole (Nexium®), lansoprazole (Prevacid®), and many others. These medicines are commonly used to treat people with stomach pain and heartburn. A patient must be off any proton pump inhibitors for at least a week before measuring a gastrin level, so that the drug doesn't falsely increase the gastrin level. Measurement of gastrin levels is most useful when combined with a test that measures the amount of acid in the stomach. That is because low acid levels can lead to high gastrin levels. When a gastrinoma is present, high gastrin levels are seen along with high acid levels.

Proton pump inhibitors can also raise CgA levels, so patients need to be off these drugs before CgA levels are drawn as well.

For carcinoid tumors, a blood test may be done to look for serotonin, which is made by many of these tumors. The body breaks serotonin down into 5-hydroxyindoleactic acid (5-HIAA), and releases it into the urine. A test commonly used to look for carcinoid syndrome measures the levels of 5-HIAA in a urine sample collected over 24 hours. This test can help diagnose many (but not all) carcinoid tumors.

Sometimes, the tumors do not make much serotonin, but they do make its precursor, 5-HTP, which can be converted to serotonin in the urine. In patients with these tumors, the blood serotonin level may be normal, but the urine levels of serotonin and 5-HTP are high.

Eating foods that contain a lot of serotonin can raise 5-HIAA levels in the urine. Such foods include, bananas, plantains, kiwi, certain nuts, avocado, tomatoes, and eggplant. Medicines, including cough syrup and acetaminophen (Tylenol), can also affect the results. These substances should be avoided before urine and blood testing for carcinoids.

Other commonly used tests to look for carcinoids can include blood tests for chromogranin A (CgA), neuron-specific enolase (NSE), substance P, and gastrin. Depending on where the tumor might be located and the patient's symptoms, doctors might do other blood tests as well.

Biopsy : A patient's medical history, physical exam, and imaging test results may strongly suggest pancreatic cancer, but the only way to be sure is to remove a small sample of tumor and look at it under the microscope. This procedure is called a biopsy.

There are several types of biopsies. The procedure used most often to diagnose pancreatic cancer is called a fine needle aspiration (FNA) biopsy. For this test, a doctor inserts a thin needle through the skin and into the pancreas. The doctor uses CT scan images or endoscopic ultrasonography to look at the position of the needle and make sure that it is in the tumor.

Doctors can also biopsy the tumor using the endoscopic ultrasound to place the needle directly through the wall of the duodenum into the tumor. In either case, small tissue samples can be removed through the needle. The main advantages of the test are that the patient does not need general anesthesia (is not "asleep") during the test, and major side effects are rare.

In the past, surgical biopsies were done more commonly. This type of biopsy requires a laparotomy (a large incision through the skin into the wall of the abdomen to examine internal organs). Areas that look or feel abnormal can be sampled by removing a small portion of tissue with a scalpel or a needle. The surgeon may use a thin needle (as in a fine needle aspiration biopsy). More commonly, surgeons use a wider needle that removes a cylindrical core of tissue about 1/2 inch long and less than 1/8 inch in diameter (called a core needle biopsy). The main drawback of this type of biopsy is that the patient must have general anesthesia and stay in the hospital to recover.

Laparotomy is now rarely recommended. Doctors prefer to use laparoscopy (sometimes called keyhole surgery) as a way of looking at and perhaps taking a piece of the pancreas with a biopsy. Patients are sedated or asleep for this procedure. The surgeon makes several small incisions in the abdomen and inserts small telescope-like instruments into the abdominal cavity. One of these is usually connected to a video monitor. The surgeon can see the abdomen, how big the tumor is, and whether it has spread and they can take tissue samples as well.

The doctor might not do a biopsy on someone who has a tumor in the pancreas that looks like cancer (based on imaging tests) if it looks like surgery can remove all of the cancer. Instead, the doctor will proceed with surgery. If the doctor finds during surgery that the cancer has spread too far to be removed completely, only a sample of the cancer may be removed to confirm the diagnosis, and the rest of the planned operation will be stopped.

If treatment (such as chemotherapy or radiation) is planned before surgery, a biopsy is needed first to be sure of the diagnosis.

How is pancreatic cancer staged?

The stage of a pancreatic cancer (extent of disease at diagnosis) is the most important factor in choosing treatment options and predicting a patient's outlook. The tests described in the section “How is pancreatic cancer diagnosed?” are the ones used to determine the stage of the cancer.

A staging system is a standardized way in which the cancer care team describes the extent that a cancer has spread. The main system used to describe the stages of cancers of the pancreas is the American Joint Committee on Cancer (AJCC) TNM system. The TNM system for staging contains 3 key pieces of information:

T describes the size of the primary tumor(s), measured in centimeters (cm), and whether the cancer has spread within the pancreas or to nearby organs.

N describes the spread to nearby (regional) lymph nodes.

M indicates whether the cancer has metastasized (spread) to other organs of the body. (The most common sites of pancreatic cancer spread are the liver, lungs, and the peritoneum — the space around the digestive organs.)

Numbers or letters appear after T, N, and M to provide more details about each of these factors:

The numbers 0 through 4 indicate increasing severity.

The letter X means "cannot be assessed" because the information is not available.

The letters "is" mean "carcinoma in situ," which means the tumor is contained within the top layers of pancreatic duct cells and has not yet invaded deeper layers of tissue.

T categories

TX: The main tumor cannot be assessed.

T0: No evidence of a primary tumor.

Tis: Carcinoma in situ (very few pancreatic tumors are found at this stage)

T1: The cancer has not spread beyond the pancreas and is smaller than 2 cm (about ¾ inch) across.

T2: The cancer has not spread beyond the pancreas but is larger than 2 cm across.

T3: The cancer has spread from the pancreas to surrounding tissues near the pancreas but not to major blood vessels or nerves.

T4: The cancer has extended further beyond the pancreas into nearby large blood vessels or nerves.

N categories

NX: Regional lymph nodes cannot be assessed.

N0: Regional lymph nodes (lymph nodes near the pancreas) are not involved.

N1: Cancer has spread to regional lymph nodes.

M categories

M0: The cancer has not spread to distant lymph nodes (other than those near the pancreas) or to distant organs such as the liver, lungs, brain, etc.

M1: Distant metastasis is present.

Stage grouping for pancreatic cancer

After the T, N, and M categories of the cancer have been determined, this information is combined to assign a stage, which is expressed in Roman numerals I through IV. The process of assigning a stage number based on TNM stages is called stage grouping.

Stage 0 (Tis, N0, M0): The tumor is confined to the top layers of pancreatic duct cells and has not invaded deeper tissues. It has not spread outside of the pancreas. These tumors are sometimes referred to as pancreatic carcinoma in situ or pancreatic intraepithelial neoplasia III (PanIn III).

Stage IA (T1, N0, M0): The tumor is confined to the pancreas and is less than 2 cm in size. It has not spread to nearby lymph nodes or distant sites.

Stage IB (T2, N0, M0): The tumor is confined to the pancreas and is larger than 2 cm in size. It has not spread to nearby lymph nodes or distant sites.

Stage IIA (T3, N0, M0): The tumor is growing outside the pancreas but not into large blood vessels. It has not spread to nearby lymph nodes or distant sites.

Stage IIB (T1-3, N1, M0): The tumor is either confined to the pancreas or growing outside the pancreas but not into nearby large blood vessels or major nerves. It has spread to nearby lymph nodes but not distant sites.

Stage III (T4, Any N, M0): The tumor is growing outside the pancreas into nearby large blood vessels or major nerves. It may or may not have spread to nearby lymph nodes. It has not spread to distant sites.

Stage IV (Any T, Any N, M1): The cancer has spread to distant sites.

Other factors

Although not formally part of the TNM system, other factors are also important in determining prognosis (outlook). Thegrade of the cancer (how abnormal the cells look under the microscope) is sometimes listed on a scale from G1 to G4, with G1 cancers looking the most like normal cells and having the best outlook.

For patients who have surgery, another important factor is the extent of the resection — whether or not all of the tumor is removed. This is sometimes listed on a scale from R0 (where all visible and microscopic tumor was removed) to R2 (where some visible tumor could not be removed).

Terms commonly used to describe pancreatic cancer : From a practical standpoint, how far the cancer has spread often can't be determined accurately until surgery. That's why doctors use a simpler staging system, which divides cancers into groups based on whether or not it is likely they can be removed surgically. These groups are called resectable, locally advanced (unresectable), and metastatic. These terms are used to describe both exocrine and endocrine pancreatic cancers.

If the cancer is only in the pancreas (or has spread just beyond it) and the surgeon can remove the entire tumor, it is called resectable.
Locally advanced (unresectable)
If the cancer has not yet spread to distant organs but it still can't be completely removed with surgery, it is called locally advanced. Often the reason the cancer can't be removed is because too much of it is present in nearby blood vessels. Since the cancer cannot be removed entirely by surgery, it is also called unresectable. For these tumors, surgery would only be done to relieve symptoms or problems like a blocked bile duct or intestinal tract.
When the cancer has spread to distant organs, it is called metastatic. Surgery may still be done, but the goal would be to relieve symptoms, not to cure the cancer.
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