Tests for Gastrointestinal Neuroendocrine Tumors

Medical history and physical exam

You will be asked questions about your general health, lifestyle habits, symptoms, and risk factors. The doctor also will probably ask about symptoms that could be caused by carcinoid syndrome, as well as those that might be caused by a mass (tumor) in the stomach, intestines, or rectum.

Some patients with neuroendocrine tumors 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 and other health problems. The doctor may pay special attention to the abdomen, looking for a tumor mass or an enlarged liver.

If your medical history and physical exam give the doctor reason to suspect you might have a GI neuroendocrine tumor, some tests will be ordered to find out if the disease is present. These might include imaging tests, lab tests, and other procedures.

Imaging tests

Computed tomography (CT) scan

A CT scan uses a special type of x-rays taken from different angles, which are combined by a computer to make detailed pictures of the organs. An iodine-based dye may be injected into your vein before the scan to show details better.  This test is most often used to look at the chest and/or belly (abdomen) to see if GI neuroendocrine tumors have spread to nearby lymph nodes or other organs such as the liver. It can also be used to guide a biopsy needle into an area of concern.

Magnetic resonance imaging (MRI) scan

Like CT scans, MRI scans show detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. A dye (gadolinium) may be injected into a vein before the scan to show details better. An MRI scan sometimes can see cancer that has spread to the liver better than a CT scan.

Radionuclide scans

Scans using small amounts of radioactivity and special cameras can be helpful in looking for GI neuroendocrine tumors. They can help find tumors or look for areas of cancer spread if doctors aren’t sure where it is in the body.

Somatostatin receptor targeted PET-CT (SSTR-PET/CT): This test can be very helpful in finding GI neuroendocrine tumors, except for those that overproduce insulin or are high-grade tumors. The somatostatin receptor (SSTR) is commonly found on neuroendocrine tumors. Somatostatin is a natural hormone in the body that binds to the SSTR. When somatostatin binds to SSTR on the cancer cell, it typically slows its growth and hormone-making abilities.

To identify the presence of GI neuroendocrine tumors, a substance is used that is a combination of an SSTR agonist (a manmade molecule that binds to the SSTR) linked to a radioactive tracer. The SSTR agonist, dotatate, acts like a homing signal by attaching to the SSTR on cancer cells, bringing the radioactive tracer directly to them. The radioactive tracer, gallium-68 or copper-64, can be seen on a PET scan. Combining these two parts (SSTR agonist and radioactive tracer), 68Ga-dotatate, 64Cu-dotatate, and 68Ga-dotatoc are the agents used for somatostatin receptor-based imaging.

This type of imaging scan can be helpful in two ways:

• It can show doctors where the GI neuroendocrine tumor is.
• It can show doctors if treating the neuroendocrine tumor with a somatostatin analog (i.e., octreotide or lanreotide) or Peptide Receptor Radionuclide Therapy (PRRT) would be helpful.

The SSTR-PET scan can be done with a CT scan to give clearer images. A dye may be injected into your vein before the CT scan to show details better.

Somatostatin receptor targeted PET-MRI (SSTR-PET/MRI): The SSTR-PET scan can be done with an MRI scan, as opposed to a CT scan. The decision on which scan to use is based on which organ is of concern. For example, if there is concern that cancer cells have spread to the liver, SSTR-PET/MRI may be a preferred option.

Endoscopy

Endoscopy tests use a flexible lighted tube (endoscope) with a video camera. The camera is connected to a monitor, which lets the doctor see any abnormal areas in the lining of the digestive organs clearly. Small pieces of abnormal areas can be removed (biopsied) through the endoscope. The biopsy samples can be looked at in the lab with a microscope to find out if cancer is present and what kind of cancer it is.

Upper endoscopy

This test is also known as esophagogastroduodenoscopy or EGD. An endoscope is passed through the mouth to look at the esophagus, stomach, and first part of the small bowel (called the duodenum).

An upper endoscopy may be done in a hospital outpatient department, clinic, or doctor’s office. It usually takes 15 to 30 minutes, and most patients are given medicine in a vein to make them feel relaxed and sleepy. If you are sedated for the procedure, you will need someone to take you home.

Colonoscopy

A colonoscopy is also called lower endoscopy. A special endoscope, a colonoscope, is inserted through the anus into the colon. 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. There are different ways to do this, but the most common is drinking a large amount of a laxative solution the night before and the morning of the exam. You will be given directions on which method to use.

You will be given intravenous medicine to make you feel relaxed and sleepy during the procedure. Colonoscopy can be done in a hospital outpatient department, clinic, or doctor's office. It usually takes 15 to 30 minutes, although it may take longer if a tumor is seen and/or a biopsy is taken. Because you will be sedated for the procedure, you will need someone to take you home afterward.

Flexible sigmoidoscopy

Flexible sigmoidoscopy is like a colonoscopy and can be used to look for a rectal tumor and some tumors in the lower part of the colon. This test uses a shorter, flexible, hollow tube with a light on the end that is also inserted through the anus up into the colon.

Capsule endoscopy

Unfortunately, neither an upper nor lower endoscopy can reach all areas of the small intestine, where many NETs begin. A device known as a capsule endoscopy may help in some cases.

This test doesn’t use an endoscope. Instead, the patient swallows a capsule (about the size of a large vitamin pill) that contains a light source and a tiny camera. Like any other pill, the capsule travels through the stomach and into the small intestine. As it travels (usually over about 8 hours), it takes thousands of pictures. These images are transmitted electronically to a device worn around the person’s waist, while they go 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 very long (20 feet [6 meters]) 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 two 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 anchored in place with a balloon. This process is repeated, letting the doctor see the intestine a foot (30 centimeters) at a time.

This procedure is done after the patient is given drugs to make them sleepy and may even be 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.

Endoscopic ultrasound (EUS)

This test uses an endoscope with a small ultrasound probe on the end. This probe releases sound waves and then uses the echoes that bounce back to create images of the digestive tract wall (or nearby lymph nodes). Putting the ultrasound probe on the end of an endoscope lets it get very close to a tumor. Because the probe is close to the area being looked at, 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. It can also help see if certain lymph nodes are enlarged and help the doctor guide a needle into a lymph node, tumor, or other suspicious area to do a biopsy. You will be sedated for this test, so you will need someone to take you home.

Blood tests

Blood tests can help diagnose neuroendocrine tumors (NETS). These include blood tests for chromogranin A (CgA) and gastrin. Medicines that lower stomach acid, called proton-pump inhibitors (such as omeprazole, lansoprazole, esomeprazole, and many others), can make CgA and gastrin levels high even when neuroendocrine tumors aren’t present. If you take any of these medicines, talk to your doctor about what to avoid before having these blood tests. Depending on the tumor’s location and your symptoms, you also might have other blood tests.

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

Urine test

Many GI neuroendocrine tumors, especially those in the small intestine, make serotonin (also called 5-HT).  The body breaks it down into 5-hydroxyindoleactic acid (5-HIAA), releasing it into urine. A common test 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) neuroendocrine tumors. Sometimes, the tumors are small and don’t release enough serotonin for a positive test result.

Foods and drugs to avoid

Some foods, including bananas, plantains, kiwi fruit, certain nuts, avocado, tomatoes, and eggplant, contain a lot of serotonin and can raise 5-HIAA levels in urine. Medicines, including cough syrup and acetaminophen (Tylenol), can also affect the results.

Biopsy

In many cases, the only way to know for sure if a person has a GI neuroendocrine tumor is to remove cells from the tumor and look at them in the lab. This procedure is called a biopsy and can be done in different ways.

Percutaneous (through the skin) biopsy: For this type of biopsy, a doctor inserts a thin, hollow needle through the skin over the abdomen and into the tumor to remove a small piece. This is known as a fine needle aspiration (FNA). The doctor guides the needle into place using images from ultrasound or CT scans.

Endoscopic biopsy: Doctors can also biopsy a tumor during an endoscopy. The doctor passes an endoscope into the throat, down the esophagus, and into the small intestine. At this point, the doctor can pass a needle into the tumor to remove a small piece.

Surgical biopsy: Rarely, an endoscopic biopsy or a CT-guided needle biopsy will not be able to get enough tissue to identify the type of tumor. In such cases, surgery may be needed to remove a tissue sample. Surgical biopsies are done much less often now than in the past since neuroendocrine tumors are mostly diagnosed using: 

• Imaging (CT or MRI scans)
• Somatostatin receptor-based imaging
• EUS biopsy
• Checking for excessive levels of hormones

You can read more about biopsies and how they are tested in Biopsy and Cytology Tests .