Gastrointestinal Stromal Tumors (GISTs)

What is GIST?

Gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal (GI) tract. They start in special cells called the interstitial cells of Cajal (ICCs). ICCs are part of the autonomic nervous system and coordinate the automatic movements of the GI tract. ICCs are sometimes called the "pacemakers" of the GI tract because they send signals to the muscles of the digestive system, telling them to move food and liquid through the GI tract.

GISTs may occur anywhere along the length of the digestive tract from the esophagus to the anus. 

What are the statistics for GIST? 

GISTs are slightly more common in men. Although GISTs are most often diagnosed in people ages 50 or older, they can occur in any age group. GIST appears to occur with increased frequency in people with a history of neurofibromatosis type 1 (NF1 disease, also known as von Recklinghausen disease).

About 60% of all GISTs develop in the stomach, while around 30% will arise in the small intestine, the ACS says. The rest arise mostly in the esophagus, colon, and rectum. 

What are the risk factors for GIST?

The greatest risk factor for GIST is having neurofibromatosis. There are rare instances of familial GIST where several family members have the condition.

Is there screening for GIST?

Unfortunately there is no general screening test to check for GISTs. However, the earlier any tumor is discovered and treated, the better the chance of survival. For this reason, people who notice possible signs or symptoms of GIST should discuss this with their doctor right away.

What are the symptoms of GIST?

People with early stage GIST often don't have any symptoms of the disease. Most GISTs are diagnosed after a person develops symptoms. These may include:

• Abdominal discomfort or pain

• Vomiting

• Blood in stools or vomit

• Fatigue due to anemia (low blood counts)

• Feeling full after eating only a small amount (early satiety)

• Loss of appetite or weight loss

These symptoms may be the result of GIST or of other less serious causes. If you have any of these symptoms, discuss them with your doctor.

Why does GIST develop?

Scientists are beginning to unravel some of the processes that go on inside cells that cause them to develop into GISTs. Normally these cells, like other cells in the body, grow and divide in a controlled fashion. But sometimes things can go wrong, allowing these cells to grow out of control and ultimately become cancerous.

Scientists have discovered that cells may grow in an uncontrolled manner as the result of a defect in their DNA. In most GISTs, a specific gene defect causes the cells to make too much of an enzyme known as KIT. KIT is an enzyme (called a "tyrosine kinase") responsible for sending growth and survival signals inside the cell. If the gene to make KIT is ON, the cell stays alive and grows or proliferates. The overactive, uncontrolled mutant KIT gene triggers the runaway growth of GIST cells. Much less often, GIST cells make too much of a different protein, called PDGFRA, which can also cause the cells to grow. This insight into the way GISTs develop has already helped to identify new treatments.

How is GIST diagnosed?

If you feel a lump or have symptoms that may suggest GIST, discuss them with a doctor. The doctor will take a detailed history and ask questions about your symptoms.

After a careful physical exam, the doctor may do an endoscopy. This test uses a thin, lighted tube with a tiny video camera on the end that is passed down the throat. Other tests may include X-ray tests, CT scan, or MRI. These may be done  to gain more information about whether there is an abnormal growth, where the growth is located, and whether it has spread.

In most cases, a tissue sample, called a biopsy, may be needed. A doctor might get biopsy samples during the endoscopy. In other cases, he or she may take a sample using a thin, hollow needle inserted into the tumor, or take a sample during surgery.

After the biopsy is taken, the sample is examined under a microscope by a doctor called a pathologist. One of the things the pathologist will test for is whether there are detectable amounts of the KIT enzyme. Most GISTs produce KIT, and detection of CD117 (called "expression of CD117" or "CD117 positivity") helps prove that the growth is a GIST. If CD117 is not detected, the sample may be tested for the PDGFRA protein. 

Once a GIST has been identified, it is important to determine the best way to treat it. Ideally, surgery should be considered, to be done by an expert surgeon who has experience in GIST management. GISTs grow differently in each person. The size and location of the tumor and the rate at which they grow are important in determining the risk the tumor presents. The risk of spread to other parts of the body (a process called metastasis) can vary greatly.

Distinguishing non-cancerous (benign) from cancerous (malignant) tumors can be difficult. It is important to recognize that current consensus notes all GISTs as being at some risk of malignant behavior. In some cases even small tumors that are not growing rapidly may spread or metastasize. The location of the tumor seems to affect the tumor's behavior. When a GIST metastasizes it usually spreads to the liver or the lining of the abdominal wall.

How is GIST is treated?

Surgery

Until recently, the only treatment for GIST was surgery. The goal of surgery is to remove the tumor completely. However, surgery alone for larger GISTs, or for GISTs that have spread, has yielded disappointing results.

Targeted therapy drugs

Targeted therapy is the use of medicines that target parts of cancer cells that make them different from normal cells. The targeted therapy medicines used to treat GIST include:

• Imatinib (Gleevec). This drug may be used to treat either early- or advanced-stage GIST. It can be given before surgery to try to shrink the tumor, or after surgery to help lower the risk of the cancer coming back. It may not cure advanced GIST, but it can often help people live longer and feel better. The medicine is taken by mouth as a pill. Side effects are mostly mild to moderate. The most common side effect is mild nausea. Other side effects, usually mild as well, include diarrhea, fluid retention and swelling (often around the eyes), indigestion, muscle cramps, bleeding from the GIST tumor, fatigue, and a skin rash.

• Sunitinib (Sutent). This medicine is often used when imatinib doesn't work or if the side effects of imatinib are a problem. Sunitinib can often shrink tumors or stop them from growing for a time. It may help people with GIST live longer. It is taken by mouth as a pill. The most common side effects are diarrhea, mouth irritation, and changes in skin and hair color. More serious side effects can include high blood pressure, increased risk of bleeding, and swelling.

• Regorafenib (Stivarga). This drug is often used if other medicines are no longer working. It can often shrink tumors or slow their growth for a time. It is taken by mouth as a pill. Side effects can include diarrhea, feeling tired, high blood pressure, mouth sores, hair loss, loss of appetite, and problems with redness and pain in the palms of the hands and soles of the feet.