A gastrointestinal neuroendocrine tumor forms in neuroendocrine cells in the lining of the digestive tract, appendix, and other organs in the abdomen.

Gastrointestinal neuroendocrine tumors (also called gastrointestinal carcinoid tumors) form from a certain type of neuroendocrine cell (a type of cell that is like a nerve cell and a hormone-making cell). These cells are scattered throughout the chest and abdomen, but most are found in certain organs in the abdomen. Neuroendocrine cells in the digestive tract make hormones that help control digestive juices and the muscles used in moving food through the stomach and intestines.

Most gastrointestinal neuroendocrine tumors in children form in the appendix (a pouch that sticks out from the first part of the large intestine near the end of the small intestine). The tumor is often found during surgery to remove the appendix. They also form in the digestive tract (lining of the stomach or intestines), pancreas, and liver.

These tumors are usually small, slow-growing, and benign (not cancer). Some tumors may be malignant (cancer) and spread to other places in the body.

Certain factors affect prognosis (chance of recovery).

Prognosis depends on the following:

• Where the tumor first formed in the body.
• The size of the tumor.
• Whether the tumor has spread to other parts of the body.
• Whether the tumor is newly diagnosed or has recurred (come back).

The prognosis for neuroendocrine tumors in the appendix in children is usually excellent after surgery to remove the tumor. Gastrointestinal neuroendocrine tumors that are not in the appendix are usually larger or have spread to other parts of the body at the time of diagnosis and do not respond well to chemotherapy. Larger tumors are more likely to recur (come back).

Signs and symptoms of gastrointestinal neuroendocrine tumors depend on where the tumor forms.

Check with your child's doctor if you are concerned about signs and symptoms that may be caused by gastrointestinal neuroendocrine tumors or by other conditions.

Neuroendocrine tumors in the appendix may cause the following signs and symptoms:

• Abdominal pain, especially on the lower right side of the abdomen.
• Fever.
• Nausea and vomiting.
• Diarrhea.

Gastrointestinal neuroendocrine tumors that are not in the appendix may release hormones and other substances. Carcinoid syndrome occurs when a neuroendocrine tumor in the digestive tract releases the hormone serotonin and other substances. It may cause any of the following signs and symptoms. Check with your child’s doctor if your child has any of the following:

• Redness and a warm feeling in the face, neck, and upper chest.
• A fast heartbeat.
• Trouble breathing.
• Sudden drop in blood pressure (restlessness, confusion, weakness, dizziness, and pale, cool, and clammy skin).
• Diarrhea.

Tests that examine the digestive tract, liver, and pancreas are used to diagnose gastrointestinal neuroendocrine tumors.

The following tests and procedures may be used:

• Physical exam and health history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
• Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease.
• MRI (magnetic resonance imaging): A procedure that uses a magnet and radio waves to make a series of detailed pictures of areas inside the body. The pictures are made by a computer. This procedure is also called nuclear magnetic resonance imaging (NMRI).

• PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

• CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

• Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. The picture can be printed to be looked at later.

• Twenty-four-hour urine test: A test in which urine is collected for 24 hours to measure the amounts of certain substances, such as hormones. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. The urine sample is checked to see if it contains 5-HIAA (a breakdown product of the hormone serotonin which may be made by neuroendocrine tumors). This test is used to help diagnose carcinoid syndrome.
• Somatostatin receptor scintigraphy: A type of radionuclide scan that may be used to find tumors. A very small amount of radioactive octreotide (a hormone that attaches to tumors) is injected into a vein and travels through the blood. The radioactive octreotide attaches to the tumor and a special camera that detects radioactivity is used to show where the tumors are in the body. This procedure is also called octreotide scan and SRS.

After a gastrointestinal neuroendocrine tumor has been diagnosed, tests are done to find out if cancer cells have spread to nearby areas or to other parts of the body.

The process used to find out if cancer has spread to nearby areas or other parts of the body is called staging. There is no standard staging system for childhood gastrointestinal neuroendocrine tumors.

Neuroendocrine tumors of the appendix are not known to spread, but other gastrointestinal neuroendocrine tumors may spread. The results of tests and procedures done to diagnose gastrointestinal neuroendocrine tumors are used to help make decisions about treatment.

Sometimes childhood gastrointestinal neuroendocrine tumors recur (come back) after treatment.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

• Tissue. The cancer spreads from where it began by growing into nearby areas.
• Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
• Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

• Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
• Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if neuroendocrine tumor cells in the small intestine spread to the liver, the cancer cells in the liver are actually neuroendocrine tumor cells. The cells in the liver are metastatic neuroendocrine tumor cells, not liver cancer.

Treatment Option Overview

There are different types of treatment for children with gastrointestinal neuroendocrine tumors.

Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

Because cancer in children is rare, taking part in a clinical trial should be considered. Some clinical trials are open only to patients who have not started treatment.

Children with gastrointestinal neuroendocrine tumors not in the appendix should have their treatment planned by a team of doctors who are experts in treating childhood cancer.

Treatment will be overseen by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other pediatric health professionals who are experts in treating children with cancer and who specialize in certain areas of medicine. This may include the following specialists and others:

• Pediatrician.
• Pediatric surgeon.
• Pathologist.
• Pediatric endocrinologist.
• Pediatric nurse specialist.
• Social worker.
• Rehabilitation specialist.
• Psychologist.
• Child-life specialist.

Five types of standard treatment are used:

Surgery

Surgery to remove the tumor is the only treatment needed for neuroendocrine tumors in the appendix.

Embolization

Embolization is a treatment in which contrast dye and particles are injected into the hepatic artery through a catheter (thin tube). The particles block the artery, cutting off blood flow to the tumor. Sometimes a small amount of a radioactive substance is attached to the particles. Most of the radiation is trapped near the tumor to kill the cancer cells. This is called radioembolization.

Hormone therapy

Hormone therapy with a somatostatin analogue (octreotide or lanreotide) may be used to treat gastrointestinal neuroendocrine tumors that have spread or cannot be removed by surgery. This treatment stops extra hormones from being made by the neuroendocrine tumor. Octreotide or lanreotide are somatostatin analogues which are injected under the skin or into the muscle.

Peptide receptor radionuclide therapy

Sometimes a small amount of a radioactive substance is attached to the somatostatin analogue drugs octreotide or lanreotide to kill the cancer cells.

Targeted therapy

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. Targeted therapies usually cause less harm to normal cells than chemotherapy or radiation therapy do.

• Tyrosine kinase inhibitors: These targeted therapy drugs block signals needed for tumors to grow. Sunitinib is used to treat gastrointestinal neuroendocrine tumors that are not in the appendix.
• mTOR inhibitors: A type of targeted therapy that stops the protein that helps cells divide and survive. Everolimus is used to treat gastrointestinal neuroendocrine tumors that are not in the appendix.

New types of treatment are being tested in clinical trials.

Information about clinical trials is available from the NCI website.

Treatment of gastrointestinal neuroendocrine tumors may cause side effects.

Side effects from cancer treatment that begin after treatment and continue for months or years are called late effects. Late effects of cancer treatment may include:

• Physical problems.
• Changes in mood, feelings, thinking, learning, or memory.
• Second cancers (new types of cancer) or other conditions.

Some late effects may be treated or controlled. It is important to talk with your child's doctors about the possible late effects caused by some treatments.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. Information about clinical trials supported by NCI can be found on NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your child's condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment of Gastrointestinal Neuroendocrine Tumors

Treatment of newly diagnosed neuroendocrine tumors in the appendix in children may include the following:

• Surgery to remove the appendix.

Treatment of newly diagnosed neuroendocrine tumors in the large intestine, pancreas, or stomach is usually surgery.

Treatment of newly diagnosed tumors that cannot be removed by surgery, multiple tumors, or tumors that have spread may include the following:

• Embolization.
• Hormone therapy with a somatostatin analogue (octreotide or lanreotide).
• Peptide receptor radionuclide therapy.
• Targeted therapy with a tyrosine kinase inhibitor (sunitinib) or an mTOR inhibitor (everolimus).

Treatment of Recurrent Gastrointestinal Neuroendocrine Tumors

Treatment of recurrent gastrointestinal neuroendocrine tumors in children may include the following:

• A clinical trial that checks a sample of the patient's tumor for certain gene changes. The type of targeted therapy that will be given to the patient depends on the type of gene change.