Gastrointestinal stromal tumors (GISTs) are soft tissue sarcomas that can be located in any part of the digestive system. Their most common sites are the stomach and small intestine.

GISTs start in specialized nerve cells located in the walls of your digestive system. These cells are part of the autonomic nervous system. A specific change in the DNA of one of these cells, which control such digestive processes as movement of food through the intestines, gives rise to a GIST.

Small GISTs may cause no symptoms, and they may grow so slowly that they have no serious effects. People with larger GISTs usually seek medical attention when they vomit blood or pass blood in their stool due to rapid bleeding from the tumor.

Other possible GIST symptoms include:

• Anemia, caused by a slow-bleeding tumor
• Abdominal pain
• A growth you can feel in your abdomen
• Nausea
• Vomiting
• Loss of appetite
• Weight loss
• Difficulty swallowing

GISTs can develop in people of all ages, but they are most common between age 50 and 70, and they almost never occur before age 40. In rare cases, an inherited genetic change (mutation) causes GISTs.

After asking questions about your symptoms and medical history, your doctor will examine you carefully, checking for a growth in your abdomen. If signs and symptoms suggest that you may have a GIST, tests to locate it and then determine its likelihood of spreading (metastasizing) to other organs will follow. These tests may include:

• Contrast-enhanced computerized tomography (CT) scan. For this test, you swallow a liquid that makes your stomach and small intestine more visible on X-rays. You may also receive an injection of a similar substance. Then the scanner takes numerous X-rays as it moves over your abdomen. A computer combines the X-rays into detailed, cross-sectional images of your abdominal organs, showing the size and position of the tumor.
• Upper endoscopy. The doctor examines the inner lining of the esophagus, stomach and the first part of the small intestine with a flexible, lighted tube (endoscope) passed down through your mouth. It may be possible to take small samples of abnormal tissue during an upper endoscopy. During this test, you'll receive a mild relaxing medication (sedative) through an intravenous line.
• Endoscopic ultrasound (EUS). This test also uses an endoscope, but with an ultrasound probe on the tip of the scope. As sound waves from the probe create echoes that bounce back to the probe, a computer translates the echoes into an image of the structures in the abdomen, showing the precise location of the tumor. If the tumor has metastasized to your liver or the lining of your abdomen, these areas may also be visible. An EUS also helps determine the depth of the tumor within the wall of the stomach or other locations in the gastrointestinal tract.

• Fine-needle aspiration biopsy. A small sample of tissue from the tumor is necessary for a definite GIST diagnosis. The preferred method for taking a biopsy sample is endoscopic ultrasound with fine-needle aspiration. This procedure is the same as an EUS, but with a thin, hollow needle on the tip of the endoscope. The needle is used to remove small amounts of tissue for laboratory analysis.

  Sometimes these tests aren't possible, or their results are inconclusive, so a suspected GIST can't be located without surgery. Tissue analysis then takes place after the tumor is removed.

• Laboratory tests on biopsies. These tests provide information on the proteins tumor cells make. One of these tests, immunohistochemistry, detects specific proteins controlled by genes in GIST cells. Identification of these proteins helps guide treatment decisions. Sometimes, actual genetic testing of biopsy samples is necessary to locate GIST genes in tumor DNA. GIST cells are also examined under a microscope to see how many cells out of 50 different microscopic fields are actively dividing. This number is known as the mitotic rate. The higher the mitotic rate in a tumor, the more aggressive it is, and the greater is its likelihood of spreading to other organs.

Small, asymptomatic GISTs found in the course of tests for another condition may be approached with watchful waiting in carefully selected cases.

Surgery

Usually, large or symptomatic GISTs are surgically removed unless they are too large or they involve too many organs and tissues for surgery. Resection is also delayed or avoided in people whose general health makes any surgery too risky to undertake, as well as in those likely to have metastatic GISTs.

It's often possible to resect GISTs using minimally invasive surgery, which involves inserting a viewing tube (laparoscope) and surgical instruments through small incisions in the abdomen.

Targeted drug therapy

Targeted drug treatments focus on specific abnormalities present within cancer cells. By blocking these abnormalities, targeted drug treatments can cause cancer cells to die. For GISTs, the target of these drugs is an enzyme called tyrosine kinase that helps cancer cells grow.

Imatinib (Gleevec) is the first line targeted therapy used to prevent GIST recurrence after surgery. The drug is also used to shrink the tumor before surgery, in situations where surgery isn't possible, as well as for controlling recurrent GIST. Treatment generally continues as long as the drug is effective.

Other drugs that target tyrosine kinase might be recommended if your GIST doesn't respond to or becomes resistant to imatinib over time. Targeted drug therapy is an active area of cancer research and new medications are likely to be available in the future.