Any symptoms people do have can be quite vague and may also be a sign of other more common illnesses that affect the gastro-intestinal system (gut) such as heartburn, pancreatitis, gallstones, irritable bowel syndrome or even stress. So it can be particularly difficult for GPs to detect and diagnose pancreatic cancer, especially in its early stages. As there is currently no easy way of detecting pancreatic cancer, diagnosis may sometimes be delayed while GPs or specialists spend time ruling out all the different possible causes for people's symptoms.
If a doctor suspects that a person has pancreatic cancer, he or she will first ask about the person's medical history and examine the person to look for signs of the disease. An appropriate and timely diagnosis is very important, ideally performed at a center that has experience with the disease. The tests listed below may be used to diagnose pancreatic cancer.
Biopsy
A person’s medical history, physical exam, and imaging test results may strongly suggest pancreatic cancer, but usually 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. Biopsies can be done in different ways.
• Endoscopic biopsy
Doctors can also biopsy a tumor during an endoscopy. The doctor passes an endoscope (a thin, flexible, tube with a small video camera on the end) down the throat and into the small intestine near the pancreas. At this point, the doctor can either use endoscopic ultrasound (EUS) to pass a needle into the tumor or endoscopic retrograde cholangiopancreatography (ERCP) to remove cells from the bile or pancreatic ducts. These tests are described in more detail above. You will be sedated (made sleepy) for these tests, but general anesthesia (being put into a deep sleep) is not usually needed. Major side effects from these types of biopsies are rare.
• Percutaneous (through the skin) biopsy
For this test, a doctor inserts a thin, hollow needle through the skin over the abdomen and into the pancreas to remove a small piece of a tumor. This is known as a fine needle aspiration (FNA). The doctor guides the needle into place using images from ultrasound or CT scans.
• Surgical biopsy
Surgical biopsies are now done less often than in the past. They can be useful if the surgeon is concerned the cancer has spread beyond the pancreas and wants to look at (and possibly biopsy) other organs in the abdomen. The most common way to do a surgical biopsy is to use laparoscopy (sometimes called keyhole surgery). You will be sedated or asleep for this procedure. The surgeon makes several small incisions (cuts) in the abdomen and inserts small telescope-like instruments. One of these has a small video camera on the end to let the surgeon see inside the abdomen. The surgeon can look at the pancreas and other organs for tumors and take biopsy samples of abnormal areas. In the past, surgeons often used a laparotomy (a large incision through the skin into the wall of the abdomen) to examine internal organs and take biopsies. But this type of surgery requires a longer recovery and is now rarely used.
Blood Tests
Several types of blood tests can be used to help diagnose pancreatic cancer or to help determine treatment options if it is found.
• Blood tests for pancreatic neuroendocrine tumors
Blood tests looking at the levels of certain pancreatic hormones can often 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 to help 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 tumors that don’t make excess hormones (non-functioning tumors).
People with heartburn or ulcers who are taking medicines known as proton pump inhibitors, such as omeprazole (Prilosec®), esomeprazole (Nexium®), lansoprazole (Prevacid®), often need to stop taking them for a week before having these tests. This is because these medicines can falsely raise gastrin and CgA levels. Measurement of gastrin levels is most useful when combined with a test that measures the amount of acid in the stomach. This 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.
Carcinoid tumors: For carcinoids, 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 common tests to look for carcinoids include blood tests for chromogranin A (CgA), neuron-specific enolase (NSE), substance P, and gastrin. As noted above, medicines called proton-pump inhibitors, which lower stomach acid, can raise CgA and gastrin levels even in people without carcinoid tumors. If you take one of these medicines, talk to your doctor about what you need to avoid before having these blood tests.
• Blood tests for exocrine pancreatic cancers
Liver function tests: Jaundice (yellowing of the skin and eyes) is often one of the first signs of pancreatic cancer, but it can have many causes other than cancer. Doctors often get blood tests to assess liver function in people with jaundice to help determine its cause.
Tumor markers: Tumor markers are substances that can sometimes be found in the blood when cancer is present. Two tumor markers may be helpful in pancreatic cancer:
- CA 19-9 is a substance often released into the blood by exocrine pancreatic cancer cells, although it often can’t be detected until the cancer is already advanced.
- Carcinoembryonic antigen (CEA) is another tumor marker that might help find advanced pancreatic cancer in some people, but it is not used as often as CA 19-9.
In people already known to have pancreatic cancer and who have high CA19-9 or CEA levels, these levels can be followed over time to help tell how well treatment is working. If all of the cancer has been removed, these tests can also be done to look for the cancer coming back.
Imaging Tests
Imaging tests use x-rays, magnetic fields, sound waves, or radioactive substances to create pictures of the inside of your body. Imaging tests might be done for a number of reasons both before and after a diagnosis of pancreatic cancer, including:
- To help determine if treatment is working
- To learn if and how far cancer has spread
- To look for signs of cancer coming back after treatment
- To look for suspicious areas that might be cancer
• Angiography
This is an x-ray test that looks at blood vessels. A small amount of contrast material is injected into an artery to outline the blood vessels, and 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 if the cancer can be removed completely without damaging vital blood vessels and helps them plan the operation.
Angiography can also be used to look for pancreatic NETs 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. Diagnosis of Pancreatic Cancer
X-ray angiography can be an uncomfortable procedure because the doctor 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.
Angiography can also be done with a CT scanner (CT angiography) or an MRI scanner (MR angiography). These techniques are now used more often because they can give information about the blood vessels in or near the pancreas without the need for a catheter in the artery. You might still need an IV line so that a contrast dye can be injected into the bloodstream during the imaging.
• Cholangiopancreatography
A cholangiopancreatogram is an imaging test that looks at the pancreatic and bile ducts to see if they are blocked, narrowed, or dilated. These tests can help show if someone might have a pancreatic tumor that is blocking a duct. They can also be used to help plan surgery. The test can be done in different ways, each of which has pros and cons.
- Endoscopic retrograde cholangiopancreatography (ERCP): In this procedure performed by a gastroenterologist, an endoscope (a thin, lighted tube) is passed into the small intestine through the mouth and stomach. A catheter (smaller tube) is passed through the endoscope and into the bile ducts and pancreatic ducts. Dye is injected into the ducts, and the doctor then takes x-rays that can show whether a duct is compressed or narrowed. Often, a plastic or metal stent can be placed across the obstructed bile duct during ERCP to help relieve any jaundice. Samples of the tissue can be taken during this procedure and can sometimes help confirm the diagnosis of cancer. The patient is lightly sedated during this procedure. ERCP is generally used to place bile duct stents and not as commonly used for diagnosis.
- Magnetic resonance cholangiopancreatography (MRCP): This is a different type of MRI scan that is sometimes used to give clearer pictures of the bile and pancreatic ducts and any blockages in them. The pictures are similar to those from an ERCP but it is less invasive if no other procedures (such as inserting a stent) need to be done. You will usually be asked not to eat or drink anything for two to three hours before the scan. This scan is usually done as an inpatient, though you may still wait up to two weeks for it to be done.
- Percutaneous transhepatic cholangiography (PTC): In this x-ray procedure, a thin needle is inserted through the skin and into the liver. A dye is injected through the needle, so the bile ducts show up on x-rays. By looking at the x-rays, the doctor can tell whether there is a blockage of the bile ducts.
A CT scan uses x-rays to build up a three-dimensional picture of the pancreas and the other organs around it. It is also usual to scan your chest and pelvic area to check for any signs of cancer outside the pancreas. It is more complex than an ultrasound and takes longer. A CT scan can also be used to guide the needle during a biopsy, a procedure where a tissue sample is taken for examination under a microscope.
The CT scan is done in the x-ray department at the hospital. It usually lasts approximately 30 minutes, depending on the exact area to be scanned. The scan is not painful but the couch you lie on is quite hard and can be uncomfortable. You will probably be able to go home straight afterwards.
As with an ultrasound scan you will be asked not to eat anything for six to eight hours beforehand and only drink clear fluids. You will be awake while the scan is done. You will lie on a couch attached to the scanner, which looks like a large ring. A computer moves the couch automatically through the scanner while a series of 360° x-rays are taken to build up a detailed picture. Before the scan you may be asked to swallow a liquid containing a dye, known as a contrast medium. This fills the stomach and intestines and provides a contrast to help identify the different organs. You may also be given an injection of contrast medium (providing you are not allergic to iodine) into a vein to help to show up the blood vessels in the area.
• Magnetic Resonance Imaging (MRI)
MRI scans use magnets and radio frequency waves to build up detailed cross-sectional images of the pancreas and surrounding areas.
There is no special preparation for an MRI, but because it uses powerful magnets you have to fill in a safety questionnaire before your appointment. This asks you whether you have any metal implants in your body (such as pacemaker, eye or ear metallic fragments). You will need to wear loose clothing and make sure you have no metal objects on you, including zips and buttons. The scanner is shaped like a tunnel; you lie on a table that moves into the tunnel for the scan. The magnets make it quite noisy so you may be given earplugs or headphones. You will also be able to hear and talk to the radiographer who operates the scanner from outside the room.
The scan usually takes 20-30 minutes, though it can be shorter or longer, and you will be able to go home straight afterwards. You may have to wait two to three weeks for an appointment.
• Positron Emission Tomography (PET) Scan
A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive sugar substance is injected into the patient’s body. This sugar substance is taken up by cells that use the most energy. Because cancer tends to use energy actively, it absorbs more of the radioactive substance. A scanner then detects this substance to produce images of the inside of the body. A PET scan is often done in combination with a CT scan, with the images placed over each other (called a fusion or integrated CT-PET scan). The combination can provide a more complete picture of the area being evaluated. PET scans are done regularly at some but not all cancer centers for the diagnosis and staging of pancreatic cancer. However, they are not yet considered a standard test to diagnose pancreatic cancer. A PET scan alone should never be used instead of a high-quality CT scan.
• Somatostatin Receptor Scintigraphy (SRS)
This test, also known as OctreoScan, can be very helpful in diagnosing pancreatic neuroendocrine tumors (NETs). It uses a hormone-like substance called octreotide that is 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 attaches to NETs. 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 NETs, but it can also help decide on treatment. NETs that show up on SRS scans will often stop growing if treated with octreotide.
• Ultrasound
An ultrasound uses sound waves to create a picture of the internal organs. There are two types of ultrasound devices: abdominal and endoscopic.
Abdominal ultrasound: For this test, a wand-shaped probe called a transducer is moved over the skin of the abdomen. It gives off sound waves and detects the echoes as they bounce off 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 doctors tell some types of pancreatic tumors from one another.
If it’s not clear what might be causing a person’s abdominal symptoms, an ultrasound might be the first test done because it is easy to do and it doesn’t expose a person to radiation. But if signs and symptoms are more likely to be caused by pancreatic cancer, a CT scan is often more useful for looking at the pancreas than an ultrasound.
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 (EUS): In this test a thin, flexible tube (endoscope) with an ultrasound probe at the end is passed through your mouth into your stomach. The ultrasound creates detailed pictures of the area that help show where the cancer is in the pancreas, how big it is and whether it has spread beyond the pancreas. A needle can also be passed through the tube to take tissue samples; this is a type of biopsy called fine-needle aspiration (FNA).
To prepare for the test you won't be able to eat or drink for six to eight hours beforehand. The test takes between 30-60 minutes. You will be asked to lie down on your left side. You will be given a throat spray of local anaesthetic that helps to stop you coughing during the investigation. Then you will be given a sedative by an injection in your arm or the back of your hand. Although this won't put you to sleep it will make you very drowsy and relaxed; most people don't remember much about the procedure afterwards. It means the doctor can pass the endoscope easily into your stomach. During the procedure the doctor may see areas that need further investigation, in which case they will collect a small number of cells (an EUS FNA).
This test is usually done in specialist centres. You may have to wait two to three weeks for the test to be arranged.
Medical History and Physical Exam
A thorough physical exam will focus mostly on your abdomen (belly) to check for any masses or fluid buildup. Cancers that block the bile duct may cause the gallbladder to enlarge, which can sometimes be felt on physical exam. Pancreatic cancer may spread to the liver, causing it to enlarge. Your skin and the whites of your eyes will be checked for jaundice (yellowing).
Pancreatic cancer can also spread to lymph nodes above the collarbone and other locations. These areas will be looked at carefully for lumps or swelling that might mean cancer spread.
If the results of the exam are abnormal, your doctor will probably order tests to help find the problem. You might also be referred to a gastroenterologist (a doctor who treats digestive system diseases) for further tests and treatment.Diagnosis of Pancreatic Cancer