How are gastrointestinal carcinoid tumors diagnosed?

As mentioned in the last section, gastrointestinal (GI) carcinoids often do not cause any symptoms and may be found when looking for causes of other problems. But some do cause symptoms that may lead to their diagnosis.

Signs and symptoms of gastrointestinal carcinoid tumors

Most GI carcinoids grow slowly and produce vague symptoms that are more often caused by something else. When trying to figure out what's going on, doctors and patients are likely to explore other, more common possible causes first. This can delay a diagnosis, sometimes even for several years.

The symptoms a person develops from a GI carcinoid tumor often depend on where it is located. People with tumors/cancers in their appendix often don’t have symptoms. If it is discovered, it is often when they have their appendix removed during an operation for some other problem. Sometimes, the tumor blocks the opening of the intestine and causes appendicitis. This leads to symptoms like nausea, vomiting, and abdominal (belly) pain.

If the tumor/cancer starts in the small intestine, it can sometimes kink or block the intestines, causing abdominal pain. This pain can be mild and last for a couple of years or more before the carcinoid tumor is found. A tumor usually needs to grow fairly large before it blocks (obstructs) the intestine. When that happens, patients have severe abdominal pain, nausea and vomiting.

Sometimes, a carcinoid can cause intestinal bleeding. This can lead to anemia (too few red blood cells) with fatigue and shortness of breath. These same problems can also occur with carcinoid tumors that start in the colon. Rectal carcinoid tumors are often found during routine exams, even though they can cause pain and bleeding from the rectum.

Carcinoid tumors that develop in the stomach usually grow slowly and often do not cause symptoms. They are sometimes found during an exam of the stomach by an endoscopy looking for other things (endoscopy is described later in this section). Some can cause symptoms such as the carcinoid syndrome.

Carcinoid syndrome

About 1 out of 10 carcinoid tumors release enough hormone-like substances into the bloodstream to cause the symptoms of carcinoid syndrome. These symptoms include:

• Facial flushing (redness and warm feeling)
• Severe diarrhea
• Wheezing
• Fast heartbeat

Many patients find that these symptoms are triggered by factors such as stress, heavy exercise, and drinking alcohol. 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).

Not all GI neuroendocrine tumors/cancers can cause the carcinoid syndrome. For example, rectal carcinoids usually do not make the hormone-like substances that cause these symptoms.

Most cases of carcinoid syndrome occur only after the cancer has already spread to other parts of the body. Normally, blood coming from the GI tract first flows through the liver, where substances made by GI carcinoid tumors are broken down before they can reach the rest of the body. This prevents carcinoid symptoms. But if the neuroendocrine cancer spreads outside the intestine (such as to the liver or lungs), the substances it makes can enter the main bloodstream and reach other parts of the body, where it can cause symptoms.

Cushing's syndrome

Some neuroendocrine tumors/cancers may produce ACTH (adrenocorticotropic hormone), a substance that causes the adrenal glands to make too much cortisol. This can cause Cushing's syndrome, with symptoms of:

• Weight gain
• Muscle weakness
• High blood sugar (even diabetes)
• High blood pressure
• Increased body and facial hair
• Bump of fat on back of neck
• Skin changes like stretch marks (called striae)

Medical history and physical exam

In taking a medical history, the doctor asks questions about the patient's general health, lifestyle habits, symptoms, and risk factors. The doctor also will probably ask about symptoms of the carcinoid syndrome, as well as symptoms that might be caused by a mass (tumor) in the stomach, intestines, or rectum.

Some patients with neuroendocrine tumors/cancers also have cancers or benign tumors of other organs, so doctors may ask about symptoms that might suggest other tumors are present. A thorough physical exam will provide information about signs of neuroendocrine tumors/cancers and other health problems. The doctor may pay special attention to the abdomen, looking for a tumor mass or enlarged liver.

If your medical history and physical exam give the doctor reason to suspect you might have a GI carcinoid, some tests will be ordered to find out if the disease is present.

Imaging tests

Your doctor may order one or more types of imaging tests to help determine the cause of your symptoms.

Barium x-rays

These studies use a barium-containing solution that coats the lining of the esophagus, stomach, and intestines. The coating of barium helps show up abnormalities of the lining of these organs. This type of study is often useful in diagnosing some GI carcinoid tumors. It is least effective in finding small intestine carcinoids. Barium studies can be used to examine the upper or lower parts of the digestive system. You will probably not be able to eat or drink anything (other than water) the night before the test. If the colon is being examined, you may need to take laxatives and/or enemas to cleanse the bowel the night before or the morning of these exams.

Barium swallow: This test (also known as an upper GI series) is used to examine the lining of the esophagus, stomach, and the first part of the small intestine. The patient drinks a barium solution and then x-ray pictures are taken. Sometimes, a test called a small bowel follow-through is used to look for problems in the small intestine. For this procedure, which is a continuation of a barium swallow, x-rays are taken at regular intervals over the course of a few hours as the barium passes through the intestines.

Enteroclysis: This is another way to look at the small intestine. In this test, a thin tube is passed from the mouth or nose down through the stomach to the start of the small intestine. Barium contrast is sent through the tube, along with a substance that creates more air in the intestines, causing them to expand. X-rays of the intestines are then taken. This test may be quicker and give more complete results than a small bowel follow-through, although placement of the tube can be uncomfortable, even when medicine is used to numb the throat.

Barium enema: This test (also known as a lower GI series) is used to look at the inner surface of the large intestine. The barium solution is given as an enema (through the anus) while the patient is lying on the x-ray table. When the colon is about half full of barium, the patient rolls over so the barium spreads throughout the colon. Then x-rays are taken. After the barium is put in the colon, air may be blown in to help spread the barium toward the bowel wall and better coat the inner surface. This is called an air contrast (or double contrast) barium enema. X-rays are then taken.

Barium x-rays are used less these days than in the past. In many cases they are being replaced by endoscopy, where the doctor actually looks into the colon or stomach with a narrow fiber optic scope.

Computed tomography scans

The computed tomography (CT) scan is an x-ray procedure 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 into images that look like slices of the part of your body that is being studied.

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 will take longer than regular x-rays and you might feel a bit confined by the ring while the pictures are being taken.

Before any pictures are taken, you could 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 (intravenous) line through which a different kind of contrast dye (IV contrast) is injected. This helps better outline structures in your body.

The injection can cause some flushing (redness and warm feeling that may last hours to days). A few people are allergic to the dye and get hives. Rarely, more serious reactions like trouble breathing and low blood pressure can occur. Medicine can be given to prevent and treat allergic reactions. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays.

CT scans can help tell if your cancer has spread into lymph nodes or other organs such as your liver. They can also be used to guide a biopsy needle precisely into a suspected area of cancer spread. For a CT-guided needle biopsy, the patient remains on the CT scanning table, while a doctor moves a biopsy needle in the body toward the location of the mass. CT scans are repeated until the doctor is sure that the needle is in the mass. A fine-needle biopsy sample (tiny fragment of tissue) or a core-needle biopsy sample (a thin cylinder of tissue about ½-inch long and less than ¹/₈-inch in diameter) is removed and looked at under a microscope.

Magnetic resonance imaging scans

Magnetic resonance imaging (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 tissue and by certain diseases. A computer translates the pattern into a detailed image of parts of the body. Like a CT scanner, this produces cross-sectional slices of the body. An MRI can produce slices that are parallel with the length of your body. As with a CT scan, a contrast material might be injected into a vein, but it is not needed as often.

MRI scans are a little more uncomfortable than CT scans. They take longer, often up to an hour. You have to be placed inside tube-like equipment, which is confining and can upset people with a fear of enclosed spaces (claustrophobia). If this is a problem for you, let your doctor know before the scan. Sometimes medicine given before the MRI can help. You may also be given the option of having the scan at an "open" MRI machine. Open MRIs are less confining, but the images are not always as clear as with a regular MRI. Also, MRI machines make a buzzing noise that some people might find disturbing. Some places will provide headphones with music to block this sound.

Radionuclide scans

Scans using small amounts of radioactivity and special cameras can be helpful in looking for carcinoid tumors. They can help determine the extent of the tumor, as well as help locate it if doctors aren't sure where it is in the body.

Somatostatin receptor scintigraphy (OctreoScan^®): This is the scan most commonly used to look for carcinoid tumors. It uses a hormone-like substance called octreotide that has been bound to radioactive indium-111. Octreotide attaches to proteins on the carcinoid cells. A small amount of this substance is injected into a vein. It travels through the blood and is attracted to carcinoid 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 over the next few days as well.

I-131 MIBG scan: This is another test that can be used to find carcinoid tumors, but it is used less often than the OctreoScan. This test uses a chemical called MIBG which has radioactive iodine (I-131) attached. This substance is injected into a vein, and the body is scanned several hours or days later with a special camera to look for areas that picked up the radioactivity. These would most likely be carcinoid tumors, although other kinds of neuroendocrine tumors will also pick up this chemical.

Positron emission tomography scans

A positron emission tomography (PET) scan is another imaging test that uses low levels of radioactivity to look for tumors. For most diseases, PET scans use a form of radiolabeled glucose (sugar) to find tumors. But when it is used to look for neuroendocrine tumors/cancers, PET uses a radioactive form of 5-hydroxytryptophan (5-HTP), a chemical that is taken up and used by carcinoid cells. A special camera can detect the radioactivity. Some doctors have found this type of PET scan to be more accurate than CT scans for detecting spread of disease. However, this special type of PET scan is not available in every hospital that has a PET scanner.

Endoscopy

These tests use a flexible lighted tube (endoscope) with a video camera on the end. The camera is connected to a monitor, which lets the doctor see any masses in the lining of the digestive organs clearly. If abnormal areas are found, small pieces of tissue can be removed through the endoscope (biopsy). The tissue can be looked at under the microscope to find out if cancer is present and what kind of cancer it is.

Upper endoscopy

The endoscope is passed down through the mouth to show the esophagus, stomach, and first part of the small bowel. The procedure usually takes 15 to 30 minutes. If you are sedated for the procedure, you will need someone to take you home. This test is also known as esophogogastroduodenoscopy or EGD.

Most patients are given intravenous medicine to make them feel relaxed and sleepy during this procedure. An upper endoscopy may be done in a hospital outpatient department, in a clinic, or in a doctor's office.

Colonoscopy

A special endoscope known as a colonoscope is inserted through the anus up into the colon. Using the colonoscope, the doctor will be able to see the lining of the entire rectum and colon. For a clear view though, the colon must be completely cleaned out before the test. This usually means drinking a large volume of a laxative solution the night before the exam (and then spending much of the night on the toilet). Sometimes an enema is also needed just before the procedure to make sure the bowels are empty.

You will be given intravenous medicine to make you feel relaxed and sleepy during the procedure. A colonoscopy can be done in a hospital outpatient department, in a clinic, or in a doctor's office. It usually takes 15 to 30 minutes, although it may take longer if a tumor is seen and/or a biopsy taken. Because medicine is given to make you sleepy for the procedure, you will need someone with you to take you home (not just a cab). This test is also called lower endoscopy.

Proctoscopy

Proctoscopy may be used to look for a rectal tumor. This involves using a shorter, rigid, hollow tube (a proctoscope), which is about 10 inches long and about 1 inch in diameter and may have a light on the end of it. The doctor coats the proctoscope with a lubricant and then gently pushes it into the anus and rectum. By shining a light into this tube, the doctor has a clear view of the lining of the rectum and anus. This test usually requires that you take laxatives or have an enema beforehand to make sure the bowels are empty.

Capsule endoscopy

Unfortunately, neither upper nor lower endoscopy can reach all areas of the small intestine, where many carcinoid tumors begin. A technique known as capsule endoscopy may help in some cases. This test doesn't really use an endoscope. Instead, the patient swallows a capsule (about the size of a large vitamin pill) that contains a light source and a very small camera. Like any other pill, the capsule goes through the stomach and into the small intestine. As it travels (usually over a period of about 8 hours), it takes thousands of pictures. These images are transmitted electronically to a device worn around the person's waist, while he or she goes on with normal daily activities. The pictures can then be downloaded onto a computer, where the doctor can watch them as a video. The capsule passes out of the body during a normal bowel movement and is discarded.

Double balloon enteroscopy

This is another way to look at the small intestine. The small intestine is too long (20 feet) and has too many curves to be examined well with regular endoscopy. This method gets around these problems by using a special endoscope that is made up of 2 tubes, one inside the other. First the inner tube, which is an endoscope, goes forward about a foot, and then a balloon at its end is inflated to anchor it. Then the outer tube goes forward to near the end of the inner tube and it is then anchored in place with a balloon. This process keeps being repeated over and over, letting the doctor see the intestine a foot at a time. This procedure is done after the patient is given drugs to make him or her sleepy and may be even done under general anesthesia (where the patient is asleep). The main advantage of this test over capsule endoscopy is that the doctor can take a biopsy if something abnormal is seen. As with other tests that are done under sedation, you will need someone to take you home after this procedure (not just a cab).

Endoscopic ultrasound (EUS)

This test uses an endoscope with a small ultrasound probe on the end. This probe releases sound waves and then detects the echoes that bounce off tissues of the digestive tract wall. A computer then translates the pattern of echoes into an image of the wall of the esophagus, stomach, intestine, or rectum. Putting the ultrasound probe on the end of an endoscope lets it get very close to the tumor. Because the probe is close to the area being studied, it can make very detailed pictures. EUS can be used to see how deeply a tumor has grown into the wall of the esophagus, stomach, intestine, or rectum. Endoscopic ultrasound can also help see if certain lymph nodes are enlarged and help a doctor guide a needle into lymph node, tumor, or other suspicious area to do a biopsy. This procedure is done after the patient is given drugs to make him or her sleepy, so you will need someone to take you home after this procedure.

Biopsy

Even if an imaging test finds a mass, it cannot tell if the mass is a carcinoid tumor, some other type of tumor or cancer, or an area of infection. The only way to know for sure is to remove cells from the abnormal area and look at them under a microscope. This procedure is called a biopsy.

There are several ways to take a sample from a gastrointestinal tumor. One way is through the endoscope. When a tumor is found, the doctor can use biopsy forceps (pincers or tongs) through the tube to take a small sample of it. Another way to sample a tumor is with a CT-guided needle biopsy, as was described in the section on CT scans.

Bleeding after a biopsy of a GI carcinoid cancer is a rare but potentially serious problem. If serious bleeding occurs, doctors can sometimes inject drugs into the tumor to constrict blood vessels and slow or stop bleeding.

In rare cases, neither endoscopic biopsy nor a CT-guided needle biopsy will be able to get enough tissue to identify the type of tumor. This is sometimes the case with tumors in the small intestine. In such cases, surgery may be needed to remove a tissue sample.

Blood and urine tests

Blood and urine tests can be very helpful in diagnosing carcinoid syndrome in patients who have symptoms that might be caused by it.

Many carcinoid tumors, especially those in the small intestine, make serotonin (also called 5-HT). It is probably the cause of at least some of the symptoms of carcinoid syndrome. The body breaks it down into 5-hydroxyindoleactic acid (5-HIAA), which is released into the urine. A commonly used test to look for carcinoid syndrome measures the levels of 5-HIAA in a urine sample collected over 24 hours. Measuring the serotonin levels in the blood may also give useful information. These tests can help diagnose many (but not all) carcinoid tumors. Sometimes, the tumors are small and don't release enough serotonin for a positive test result.

In other cases, 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 tests 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. Drugs that lower stomach acid called proton-pump inhibitors (such as omeprazole/Prilosec^®, lansoprazole/Prevacid^®, esomeprazole/Nexium^®, and many others) can make CgA and gastrin levels high even when carcinoid tumors aren’t present, and so patients need to be off these drugs when these levels are drawn. Depending on the tumor’s location and on the patient's symptoms, doctors might do other blood tests as well.

Some of these tests can also be used to show how well treatment is working, since the levels of these substances tend to go down as tumors shrink.