General Information About Gastrointestinal Carcinoid Tumors
A gastrointestinal carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract.
The gastrointestinal tract includes the stomach, small intestine, and large intestine. These organs are part of the digestive system, which processes nutrients (vitamins, minerals, carbohydrates, fats, proteins, and water) in foods that are eaten and helps pass waste material out of the body. Gastrointestinal carcinoidtumors develop from a certain type of hormone-making cell in the lining of the gastrointestinal tract. These cells produce hormones that help regulate digestive juices and the muscles used in moving food through the stomach and intestines. A gastrointestinal carcinoid tumor may also produce hormones. Carcinoid tumors that start in the rectum (the last several inches of the large intestine) usually do not produce hormones.
Gastrointestinal carcinoid tumors grow slowly. Most of them occur in the appendix (an organ attached to the large intestine), small intestine, and rectum. It is common for more than one tumor to develop in the small intestine. Having a carcinoid tumor increases a person's chance of getting other cancers in the digestive system, either at the same time or later.
Health history can affect the risk of developing gastrointestinal carcinoid tumors.
Risk factors include the following:
- Having a family history of multiple endocrine neoplasia type 1 (MEN1) syndrome.
- Having certain conditions that affect the stomach's ability to produce stomach acid, such as atrophic gastritis, pernicious anemia, or Zollinger-Ellison syndrome.
- Smoking tobacco.
A gastrointestinal carcinoid tumor often has no signs in its early stages. Carcinoid syndrome may occur if the tumor spreads to the liver or other parts of the body.
The hormones produced by gastrointestinal carcinoid tumors are usually destroyed by blood and liverenzymes. If the tumor has spread to the liver, however, high amounts of these hormones may remain in the body and cause the following group of symptoms, called carcinoid syndrome:
- Redness or a feeling of warmth in the face and neck.
- Diarrhea.
- Shortness of breath, fast heartbeat, tiredness, or swelling of the feet and ankles.
- Wheezing.
- Pain or a feeling of fullness in the abdomen.
These symptoms and others may be caused by gastrointestinal carcinoid tumors or by other conditions. A doctor should be consulted if any of these symptoms occur.
Tests that examine the blood and urine are used to detect (find) and diagnose gastrointestinal carcinoid tumors.
The following tests and procedures may be used:
- Complete blood count: A procedure in which a sample of blood is drawn and checked for the following:
- The number of red blood cells, white blood cells, and platelets.
- The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
- The portion of the sample made up of red blood cells.
- Physical exam and 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, such as hormones, 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 in the organ or tissue that produces it. The blood sample is checked to see if it contains a hormone produced by carcinoid tumors. This test is used to help diagnose carcinoid syndrome.
- Twenty-four-hour urine test: A test in which a urine sample is checked 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 produces it. The urine sample is checked to see if it contains a hormone produced by carcinoid tumors. This test is used to help diagnose carcinoid syndrome.
Certain factors affect prognosis (chance of recovery) and treatment options.
The prognosis (chance of recovery) and treatment options depend on the following:
- Whether the cancer can be completely removed by surgery.
- Whether the cancer has spread from the stomach and intestines to other parts of the body, such as the liver or lymph nodes.
- The size of the tumor.
- Where the tumor is in the gastrointestinal tract.
- Whether the cancer is newly diagnosed or has recurred.
Treatment options also depend on whether the cancer is causing symptoms. Most gastrointestinal carcinoid tumors are slow-growing and can be treated and often cured. Even when not cured, many patients may live for a long time.
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Stages of Gastrointestinal Carcinoid Tumors
After a gastrointestinal carcinoid tumor has been diagnosed, tests are done to find out if cancer cells have spread within the stomach and intestines or to other parts of the body.
Staging is the process used to find out how far the cancer has spread. The information gathered from the staging process determines the stage of the disease. There are no standard stages for gastrointestinalcarcinoidtumors. In order to plan treatment, it is important to know the extent of the disease and whether the tumor can be removed by surgery. The following tests and procedures may be used:
- Gastrointestinal endoscopy: A procedure to look inside the gastrointestinal tract for abnormal areas or cancer. An endoscope (a thin, lighted tube) is inserted through the mouth and esophagus into the stomach and first part of the small intestine. Also, a colonoscope (a thin, lighted tube) is inserted through the rectum into the colon (large intestine); this is called a colonoscopy.
- 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. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
- Somatostatin receptor scintigraphy (SRS): A type of radionuclide scan used to find carcinoid tumors. In SRS, radioactiveoctreotide, a drug similar to somatostatin, is injected into a vein and travels through the bloodstream. The radioactive octreotide attaches to carcinoid tumor cells that have somatostatin receptors. A radiation-measuring device detects the radioactive material, showing where the carcinoid tumor cells are in the body. This procedure is also called an octreotide scan.
- Biopsy: The removal of cells or tissues so they can be viewed under a microscope to check for signs of cancer. Tissue samples may be taken during endoscopy and colonoscopy.
- Angiogram: A procedure to look at blood vessels and the flow of blood. A contrast dye is injected into the blood vessel. As the contrast dye moves through the blood vessel, x-rays are taken to see if there are any blockages.
- PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radionuclide 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.
- X-ray of the abdomen: An x-ray of the organs and tissues inside the abdomen. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
There are three ways that cancer spreads in the body.
The three ways that cancer spreads in the body are:
- Through tissue. Cancer invades the surrounding normal tissue.
- Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
- Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.
When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.
Gastrointestinal carcinoid tumors are grouped for treatment based on where they are in the body.
Localized
Cancer is found in the appendix, colon, rectum, small intestine, and/or stomach only.
Regional
Cancer has spread from the appendix, colon, rectum, stomach, and/or small intestine to nearby tissues or lymph nodes.
Metastatic
Cancer has spread to other parts of the body.
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Recurrent Gastrointestinal Carcinoid Tumors
A recurrentgastrointestinalcarcinoidtumor is a tumor
that has recurred (come back) after it has been treated. The tumor may come
back in the stomach or intestines or in other parts of the body.
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Treatment Option Overview
There are different types of treatment for patients with
gastrointestinal carcinoid tumors.
Different types of treatment are available for patients with
gastrointestinalcarcinoidtumors. 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. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
Seven types of standard treatment are used:
Surgery
Treatment of gastrointestinal carcinoid tumors usually includes surgery. One of the following surgical procedures may be used:
- Appendectomy: Removal of the appendix.
- Fulguration: Use of an electric current to burn away the tumor using a special tool.
- Cryosurgery: A treatment that uses an instrument to freeze and destroy abnormaltissue, such as carcinoma in situ. This type of treatment is also called cryotherapy. The doctor may use ultrasound to guide the instrument.
- Resection: Surgery to remove part or all of the organ that contains cancer. Resection of the tumor and a small amount of normal tissue around it is called a localexcision.
- Bowel resection and anastomosis: Removal of the bowel tumor and a small section of healthy bowel on each side. The healthy parts of the bowel are then sewn together (anastomosis). Lymph nodes are removed and checked by a pathologist to see if they contain cancer.
- Radiofrequency ablation: The use of a special probe with tiny electrodes that release high-energy radio waves (similar to microwaves) that kill cancer cells. The probe may be inserted through the skin or through an incision (cut) in the abdomen.
- Hepatic resection: Surgery to remove part or all of the liver.
- Hepatic arteryligation or embolization: A procedure to ligate (tie off) or embolize (block) the hepatic artery, the main blood vessel that brings blood into the liver. Blocking the flow of blood to the liver helps kill cancer cells growing there.
Radiation therapy
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.
Chemotherapy
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy).
Chemoembolization of the hepatic artery is a type of regional chemotherapy that may be used to treat a gastrointestinal carcinoid tumor that has spread to the liver. The anticancer drug is injected into the hepatic artery through a catheter (thin tube). The drug is mixed with a substance that embolizes (blocks) the artery, cutting off blood flow to the tumor. Most of the anticancer drug is trapped near the tumor and only a small amount of the drug reaches other parts of the body. The blockage may be temporary or permanent, depending on the substance used to block the artery. The tumor is prevented from getting the oxygen and nutrients it needs to grow. The liver continues to receive blood from the hepatic portal vein, which carries blood from the stomach and intestine.
The way the chemotherapy is given depends on the type and stage of the cancer being treated.
Percutaneous ethanol injection
Percutaneous ethanol injection is a cancer treatment in which a small needle is used to inject ethanol (alcohol) directly into a tumor to kill cancer cells. This procedure is also called intratumoral ethanol injection.
Biologic therapy
Biologic
therapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.
Hormone therapy
Hormone therapy is a cancer treatment that removes hormones or blocks their action and stops cancer cells from growing. Hormones are substances produced by glands in the body and circulated in the bloodstream. The presence of some hormones can cause certain cancers to grow. If tests show that the cancer cells have places where hormones can attach (receptors), drugs, surgery, or radiation therapy are used to reduce the production of hormones or block them from working.
Other drug therapy
MIBG (metaiodobenzylguanidine) is sometimes used, with or without radioactive iodine (I131), to lessen the symptoms of gastrointestinal carcinoid tumors.
New types of treatment are being tested in clinical trials.
Treatments being studied in clinical trials for gastrointestinal carcinoid tumors include new combinations of chemotherapy.
Information about clinical trials is available from the
NCI Web
site.
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. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's clinical trials database.
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. This is sometimes called re-staging.
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 condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
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Treatment Options for Gastrointestinal Carcinoid Tumors
A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.
Localized Gastrointestinal Carcinoid Tumors
Carcinoid tumors in the appendix
Treatment of localizedgastrointestinalcarcinoidtumors in the appendix may include the following:
- Appendectomy.
- Appendectomy and localexcision.
- Appendectomy, bowelresection with anastomosis, and removal of lymph nodes.
Rectal carcinoid tumors
Treatment of localized gastrointestinal carcinoid tumors in the rectum may include the following:
- Fulguration.
- Local excision.
- Resection.
Surgery that saves the sphincter muscles (the muscles that open and close the anus) may be possible.
Small bowel carcinoid tumors
Treatment of localized gastrointestinal carcinoid tumors in the small intestine may include the following:
- Local excision.
- Resection with removal of nearby lymph nodes.
Gastric, colon, and pancreatic carcinoid tumors
Treatment of localized gastrointestinal carcinoid tumors in the stomach, colon, or pancreas is usually resection.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with localized gastrointestinal carcinoid tumor. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
Regional Gastrointestinal Carcinoid Tumors
Treatment is usually surgery to remove all the cancer that can be seen at the site of the original tumor, as well as nearby tissues and lymph nodes.
If the tumor cannot be completely removed by surgery, treatment is usually palliative therapy to relieve symptoms and improve the patient's quality of life. This may include the following:
- Resection, cryosurgery, or radiofrequency ablation to remove as much of the tumor as possible.
- Chemoembolization to shrink tumors in the liver.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with regional gastrointestinal carcinoid tumor. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
Metastatic Gastrointestinal Carcinoid Tumors
Distant metastases
If the metastatic gastrointestinal carcinoid tumor is not causing symptoms, there may be a period of watchful waiting before treatment is given. Treatment of distant metastases of gastrointestinal carcinoid tumors is usually palliative therapy that may include the following:
- Surgery to bypass or remove part of a tumor blocking the small intestine.
- Chemotherapy, which may include chemoembolization.
- Radiation therapy, sometimes with radioisotopes such as radioactive iodine (I131).
- MIBG (metaiodobenzylguanidine) therapy.
- Biologic therapy and/or hormone therapy.
- Clinical trials of new treatments.
Carcinoid syndrome
Treatment of metastatic gastrointestinal carcinoid tumors that are causing carcinoid syndrome may include the following:
- Resection, cryosurgery, radiofrequency ablation, or percutaneous ethanol injection for tumors in the liver.
- Hepatic arteryligation or embolization, with or without regional or systemic chemotherapy.
- Hormone therapy.
- Biologic therapy with or without chemotherapy.
- Clinical trials of new combinations of chemotherapy.
A heart valve replacement may be done for some patients with carcinoid syndrome.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with metastatic gastrointestinal carcinoid tumor. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
Recurrent Gastrointestinal Carcinoid Tumors
Treatment of recurrent gastrointestinal carcinoid tumors may include the following:
- Surgery to remove part or all of the tumor.
- A clinical trial.
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent gastrointestinal carcinoid tumor. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
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To Learn More About Gastrointestinal Carcinoid Tumors
For more information from the National Cancer Institute about gastrointestinal carcinoid tumors, see the following:
For general cancer information and other resources from the National Cancer Institute, see the following:
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This information is provided by the National Cancer Institute.
This information was last updated on June 13, 2008.
Purpose of This PDQ Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of gastrointestinal carcinoid tumors. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.
Information about the following is included in this summary:
- Cellular classification.
- Staging.
- Treatment options by cancer stage.
This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.
This summary is available in a patient version, written in less technical language, and in Spanish.
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General Information
The majority of carcinoid tumors are slow-growing tumors that can be treated and often
cured, especially in early stages.[1] The occurrence of metastasis from
carcinoid tumors relates directly to the size of the primary tumor (lesions 1
cm or less rarely metastasize; lesions greater than 2 cm
frequently metastasize). They are classified as neuroendocrine or amine
precursor uptake and decarboxylation tumors. Rarely, they may be a part of the
multiple endocrine neoplasia syndrome type 1. Carcinoid
tumors may arise from various sites, most commonly the gastrointestinal tract and the lung. The appendix, small bowel, and
rectum account for over 90% of surgical cases occurring in the gastrointestinal
tract. Small bowel carcinoids may occur in multiple sites in the same patient.
Symptoms may be chronic, suggesting partial obstruction or intussusception.
Carcinoid tumors, except those originating in the rectum, produce a variety of
endocrine substances, the most frequent of which are serotonin
(5-hydroxytryptamine) and kallikrein (an activator of bradykinin release). The
diagnosis of carcinoid syndrome (a syndrome associated with flushing, diarrhea, bronchoconstriction, cardiac valvular lesions, and telangiectasia) is
aided by demonstrating elevated 24-hour urinary 5-hydroxyindoleacetic acid
levels. This test is not useful in the diagnosis of carcinoids at a curable stage,
except in some rare cases in which the tumor arises from a site outside of the
gastrointestinal tract, such as the lung.[2][3][4][5][6][7] Blood chromogranin A assay may
also be a useful, though nonspecific, confirmatory test for carcinoid or
neuroendocrine tumors.[8] Primary carcinoids of the extrapelvic colon are
uncommon, typically present with metastatic disease, and have a poor
prognosis.[9][10] Patients with carcinoid tumor are at increased risk for
synchronous or metachronous second malignancies. The most common site for a
second primary malignancy is the gastrointestinal tract.[11]
The relatively rare carcinoid syndrome relates to the release of bioactive substances, but precise pharmacologic
mechanisms are still unclear. Because of efficient hepatic metabolism of
vasoactive amines, the carcinoid syndrome rarely occurs in the absence of liver
metastases. Exceptions are circumstances where venous blood draining from tumors
enters directly into the systemic circulation (for example, pulmonary
and ovarian primaries, and pelvic or retroperitoneal involvement by metastatic
or locally invasive small bowel carcinoids or extensive bone metastases).
Surgical resection is the standard curative modality. If the primary tumor is
localized and resectable, 5-year survival rates are excellent (70%-90%). Even
in patients with distant metastasis, the disease is usually very indolent, with
median survivals of 2 years or more. When necessary, excellent palliation
may be achieved by bypass surgery or resection of large hepatic metastases
that may produce the carcinoid syndrome. Radiation therapy has a minor role in
patients with regionally unresectable disease and may palliate the pain of bone
metastasis. Patients with carcinoid syndrome can usually be effectively
palliated by injections of somatostatin analogue two to three times a day. A long-acting somatostatin analogue that can be given as an injection once a month,
with equivalent efficacy, is now available.[12]
Patients with symptomatic metastatic carcinoid disease are appropriate
candidates for clinical trials examining combination chemotherapy, since
single-agent standard chemotherapy provides minimal palliation. However,
chemotherapeutic drug combinations occasionally do offer long-lasting (in
excess of 1 year) palliation. In patients with the carcinoid syndrome,
palliation is sometimes obtained with pharmacologic agents that suppress
production or block the action of vasoactive amines; of particular interest is
a somatostatin analogue.[13] Some patients benefit from the use of interferon
alpha. Toxic effects associated with interferon treatment that frequently
outweigh therapeutic gains can occur in some patients, but these effects are
reversible once treatment has been discontinued and usually do not occur with
smaller doses. Anecdotal reports of biologic activity indicate that some
patients may respond to combined octreotide and interferon alpha treatment.[14]
Patients with asymptomatic metastases that cannot be resected for cure will
often remain symptom-free for long periods of time.
References:
Moertel CG: Karnofsky memorial lecture. An odyssey in the land of small tumors. J Clin Oncol 5 (10): 1502-22, 1987.
Kulke MH, Mayer RJ: Carcinoid tumors. N Engl J Med 340 (11): 858-68, 1999.
Mani S, Modlin IM, Ballantyne G, et al.: Carcinoids of the rectum. J Am Coll Surg 179 (2): 231-48, 1994.
Moertel CG, Weiland LH, Nagorney DM, et al.: Carcinoid tumor of the appendix: treatment and prognosis. N Engl J Med 317 (27): 1699-701, 1987.
Martin JK Jr, Moertel CG, Adson MA, et al.: Surgical treatment of functioning metastatic carcinoid tumors. Arch Surg 118 (5): 537-42, 1983.
Moertel CG: Treatment of the carcinoid tumor and the malignant carcinoid syndrome. J Clin Oncol 1 (11): 727-40, 1983.
Delcore R, Friesen SR: Gastrointestinal neuroendocrine tumors. J Am Coll Surg 178 (2): 187-211, 1994.
Roberts LJ, Anthony LB, Oates JA: Disorders of vasodilator hormones: carcinoid syndrome and mastocytosis. In: Wilson JD, Foster DW, Kronenberg HM, et al., eds.: Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa: W.B. Saunders Company, 1998, 1711-1731.
Spread C, Berkel H, Jewell L, et al.: Colon carcinoid tumors. A population-based study. Dis Colon Rectum 37 (5): 482-91, 1994.
Modlin IM, Sandor A: An analysis of 8305 cases of carcinoid tumors. Cancer 79 (4): 813-29, 1997.
Gerstle JT, Kauffman GL Jr, Koltun WA: The incidence, management, and outcome of patients with gastrointestinal carcinoids and second primary malignancies. J Am Coll Surg 180 (4): 427-32, 1995.
Rubin J, Ajani J, Schirmer W, et al.: Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome. J Clin Oncol 17 (2): 600-6, 1999.
Gorden P, Comi RJ, Maton PN, et al.: NIH conference. Somatostatin and somatostatin analogue (SMS 201-995) in treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut. Ann Intern Med 110 (1): 35-50, 1989.
Frank M, Klose KJ, Wied M, et al.: Combination therapy with octreotide and alpha-interferon: effect on tumor growth in metastatic endocrine gastroenteropancreatic tumors. Am J Gastroenterol 94 (5): 1381-7, 1999.
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Cellular Classification
There is no histologic difference between carcinoids arising in various sites
or between metastasizing and nonmetastasizing lesions. Carcinoid tumors are neuroendocrine tumors composed of uniform, round, or polygonal cells. Immunohistochemistry reveals the presence of neuron-specific enolase (NSE) and chromogranin. Electron microscopy shows neurosecretory granules. Morphologic features suggesting malignancy (cellular pleomorphism, hyperchromatic nuclei, necrosis, high mitotic activity) can occasionally be seen. Such cases are designated as atypical carcinoids and usually have an aggressive clinical course. Carcinoids are
classified by their embryologic relationship to the foregut (the anterior part
of the alimentary canal, from the mouth to the intestine or to the entrance of
the bile duct), midgut (the middle part of the alimentary canal, from the
stomach or entrance of the bile duct to or including the large intestine), or
hindgut (the posterior part of the alimentary canal, including the rectum and
sometimes the large intestine), which is correlated with clinical behavior and
the secretion or nonsecretion of various neuroendocrine peptides. Proximal
carcinoids may secrete histamine-like peptides causing a pink flush and
bronchoconstriction. Peptide secretions of midgut carcinoids cause a cyanotic
(purplish) flush, diarrhea, and hypotension. Hindgut carcinoids usually do not
secrete syndrome-producing peptides.
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Stage Information
There is no accepted staging system for carcinoid tumors.
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Localized Gastrointestinal Carcinoid Tumors
Appendiceal Carcinoids
For patients with appendiceal carcinoid tumors less than 1.5 cm in greatest
diameter, appendectomy is adequate treatment with cure rates of essentially
100%.[1] No follow-up management is required if the tumor is confined within
the wall of the appendix. Tumors 1.5 to 2 cm in diameter can be
treated by simple appendectomy or more aggressive surgical treatment. Tumors 2
cm or greater in diameter are less common, but must be considered
malignant. Invasion of the mesoappendix does not alter prognosis, but invasion
of the cecum mandates more extensive resection. When right hemicolectomy is
performed, a lymphadenectomy, as performed for colon cancer, is appropriate.
Rectal Carcinoids
For patients with rectal carcinoid tumors 1 cm or less in diameter, simple
fulguration or local excision is adequate treatment. Cure rates of essentially
100% may be anticipated, and no follow-up management is required.[2]
Tumors 2 cm or larger should be considered malignant and should be
treated by an appropriate cancer operation, but sphincter-preserving procedures
are preferred when possible. Otherwise, standard therapy includes
abdominoperineal resection.
Tumors 1 to 2 cm in diameter can be treated either by local excision
or by more radical resection. The decision should be based on actual size of
the tumor, extent of invasion, and necessity for abdominal perineal resection
versus a sphincter-preserving resection, and estimated operative risk. If
local excision is elected, the patient should be carefully followed.
Small Bowel Carcinoids
For patients with small bowel carcinoid tumors less than 1 cm in diameter,
conservative local resection is sufficient. For tumors greater than 1
cm in diameter, excision of a wedge of mesentery containing regional
nodes is indicated.[3] Patients with tumors 1.5 to 2 cm or larger are
at risk for recurrence; however, a standard surveillance program has not been
established. A search for multiple primary lesions should be made in all
patients with small bowel carcinoids.
Gastric, Pancreatic, and Colon Carcinoids
Carcinoids of other sites in the gastrointestinal tract are rare. Optimal
management of localized disease is aggressive surgical resection, although
carcinoid tumors of the stomach and colon are typically less often localized
than those in other gastrointestinal sites.[4][5]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
localized gastrointestinal carcinoid tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References:
Roggo A, Wood WC, Ottinger LW: Carcinoid tumors of the appendix. Ann Surg 217 (4): 385-90, 1993.
Mani S, Modlin IM, Ballantyne G, et al.: Carcinoids of the rectum. J Am Coll Surg 179 (2): 231-48, 1994.
Moertel CG: Karnofsky memorial lecture. An odyssey in the land of small tumors. J Clin Oncol 5 (10): 1502-22, 1987.
Spread C, Berkel H, Jewell L, et al.: Colon carcinoid tumors. A population-based study. Dis Colon Rectum 37 (5): 482-91, 1994.
Maurer CA, Baer HU, Dyong TH, et al.: Carcinoid of the pancreas: clinical characteristics and morphological features. Eur J Cancer 32A (7): 1109-16, 1996.
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Regional Gastrointestinal Carcinoid Tumors
Patients with carcinoid tumors with gross regional lymphatic metastasis or local extension
should be treated by aggressive surgical resection. If all visible malignant
disease can be removed, long-term survival rates will be excellent.[1]
However, late recurrences (after 5 or 10 years) do occur, implying the need for
prolonged follow-up.
There is no known effective surgical adjuvant treatment and none should be
attempted except as part of a clinical trial.
If the regional disease is found to be unresectable, palliative surgery, such
as partial resection, cryoablation, radiofrequency ablation, or hepatic artery
chemoembolization should be considered. Treatment should be customized for
each patient depending on the growth of the tumor and/or development of
symptoms since some patients with asymptomatic, unresectable disease will
frequently have many months or even years of comfortable life with no further
treatment.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
regional gastrointestinal carcinoid tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References:
Moertel CG: Karnofsky memorial lecture. An odyssey in the land of small tumors. J Clin Oncol 5 (10): 1502-22, 1987.
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Metastatic Gastrointestinal Carcinoid Tumors
Since carcinoid tumors are frequently indolent in growth, and asymptomatic, not
all patients require treatment of metastatic disease at diagnosis. A period of
observation may allow for a decision to be made concerning optimal supportive
care or antitumor treatments.
Treatment options for distant metastasis:
- Surgical treatment: Surgical treatment may frequently provide effective
palliation (even in the presence of known distant metastasis with or without
malignant carcinoid syndrome), particularly through bypass or palliative
resection of obstructing small bowel tumors. Heroic attempts at surgical
debulking, however, are not indicated except for hepatic resection in patients
with the carcinoid syndrome (see section on Carcinoid Syndrome). Although
liver metastases are usually multiple and neither bulky nor clustered, multiple
wedge resections, cryosurgery, or radiofrequency ablation of the lesions can be
considered in patients with carcinoid syndrome.
- Chemotherapy: Although activity with a variety of single agents and drug
combinations has been reported (fluorouracil, doxorubicin, dacarbazine,
cyclophosphamide, fluorouracil + streptozocin, and etoposide + cisplatin [1]),
response rates seldom exceed 30%. Complete responses are uncommon. Duration
of response is usually short, although occasional remissions lasting a year or
more have been noted. Otherwise, there is little evidence that chemotherapy
contributes to patient survival. Chemotherapy should be used only for
palliation in symptomatic patients who should be included in clinical trials
aimed at developing new, more effective treatment. Continuous infusion of
agents such as floxuridine into the hepatic artery has not been prospectively
tested in large series of patients.
- Chemoembolization: Hepatic artery infusion with fluorouracil, doxorubicin,
mitomycin, or cisplatin, combined with embolization of the hepatic artery with
collagen fibers or other material (i.e., gelfoam, lipiodol, or poly vinyl
alcohol) has been reported to decrease tumor bulk of liver metastases from
carcinoid tumors by 50% or more in as many as 60% of patients.[2] Palliative
embolizations that prove effective may be repeated if symptoms return.
- Radiation therapy: The role of radiation therapy in the management of
patients with carcinoid tumors with distant metastasis is restricted to symptomatic
palliation.[3] Although the tumor persists, painful bone metastases can be
palliated.
- I131-MIBG: Therapeutic doses of iodine131-labeled metaiodobenzylguanidine
(MIBG) and unlabeled MIBG have been evaluated, with reduction of symptoms found
in preliminary studies.[4]
- Biological modification (immunotherapy): Low-dose interferon alpha and
octreotide, alone and in combination, have been reported to have activity.[5][6]
Carcinoid Syndrome
Treatment options associated with metastatic carcinoid tumor:
- Surgical treatment: Surgery may sometimes be of considerable value in the
patient who has large or extensive hepatic metastases involving surgically
accessible areas of the liver (single or multiple). Recurrent hepatic
metastases (after previous resection) should be considered for resection if the
lesions are placed in an area where resection can be done with minimal
morbidity. Alternate nonresective surgical ablative techniques include
cryosurgery, radiofrequency ablation, and percutaneous alcohol injections. For
very carefully selected patients with indolent disease and symptomatic
carcinoid heart disease, valve replacement may be indicated.
- Hepatic artery ligation or embolization: For patients with bulky or
symptomatic hepatic metastases, hepatic artery ligation or embolization can
cause substantial tumor necrosis. Toxic effects of embolization are frequent
and can be severe, especially if the entire liver is treated at one time.
Reactions may be attenuated if multiple treatment sessions are possible at
intervals of several weeks or months. These include abdominal pain, fever,
nausea and transient worsening of the syndrome. However, many patients have
subsequent symptomatic relief.[7][8] Such treatment may also be given in
conjunction with systemic chemotherapy in selected patients.[9] Intra-arterial
chemotherapy via the hepatic artery can cause regression of lesions in selected
patients. These regressions tend to be durable as long as treatment is
continued.
- Pharmacologic management: Somatostatin analogue (octreotide) has been
demonstrated to relieve symptoms of malignant carcinoid syndrome in the great
majority of patients, with significant reduction of 5-hydroxyindoleacetic acid
(5-HIAA) levels. Tumor reduction is rarely seen.[10][11][12][13]
Patients benefit from specific pharmacologic interventions that either suppress
production of vasoactive amines or block their peripheral effects. These
agents include cyproheptadine and H2-receptor blockers.
Monoamine oxidase inhibitors and adrenergic agonists are drugs to be
specifically avoided in these patients since they will exacerbate the syndrome
by inhibiting serotonin degradation or producing carcinoid syndrome crisis.
- Interferon alpha preparations may have a role in controlling symptoms of the
carcinoid syndrome or in arresting tumor growth.[14] These benefits have
generally been transient and accompanied by toxic effects that frequently
outweigh therapeutic gains,[15] although interferon alpha has been reported to
reinduce symptom control in patients who did not respond to octreotide.[16] The
combination of interferon alpha and continuous-infusion fluorouracil has
demonstrated antitumor and/or antihormonal activity and, similar to other drug
regimens, can provide useful palliation.[17] Combination of interferon alpha
and octreotide has also been reported to have activity.[5]
- Clinical trials using chemotherapy combinations should be considered for
symptomatic patients.[18]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
metastatic gastrointestinal carcinoid tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References:
Moertel CG, Kvols LK, O'Connell MJ, et al.: Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms. Cancer 68 (2): 227-32, 1991.
Diaco DS, Hajarizadeh H, Mueller CR, et al.: Treatment of metastatic carcinoid tumors using multimodality therapy of octreotide acetate, intra-arterial chemotherapy, and hepatic arterial chemoembolization. Am J Surg 169 (5): 523-8, 1995.
Schupak KD, Wallner KE: The role of radiation therapy in the treatment of locally unresectable or metastatic carcinoid tumors. Int J Radiat Oncol Biol Phys 20 (3): 489-95, 1991.
Taal BG, Hoefnagel CA, Valdes Olmos RA, et al.: Palliative effect of metaiodobenzylguanidine in metastatic carcinoid tumors. J Clin Oncol 14 (6): 1829-38, 1996.
Oberg K: Advances in chemotherapy and biotherapy of endocrine tumors. Curr Opin Oncol 10 (1): 58-65, 1998.
Öberg K: Carcinoid Tumors: Current Concepts in Diagnosis and Treatment. Oncologist 3 (5): 339-345, 1998.
Carrasco CH, Charnsangavej C, Ajani J, et al.: The carcinoid syndrome: palliation by hepatic artery embolization. AJR Am J Roentgenol 147 (1): 149-54, 1986.
Moertel CG, May GR, Martin JK, et al.: Sequential hepatic artery occlusion (HAO) and chemotherapy for metastatic carcinoid tumor and islet cell carcinoma (ICC). [Abstract] Proceedings of the American Society of Clinical Oncology 4: 80, 1985.
Moertel CG, Johnson CM, McKusick MA, et al.: The management of patients with advanced carcinoid tumors and islet cell carcinomas. Ann Intern Med 120 (4): 302-9, 1994.
Kvols LK, Moertel CG, O'Connell MJ, et al.: Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue. N Engl J Med 315 (11): 663-6, 1986.
Kvols LK, Martin JK, Marsh HM, et al.: Rapid reversal of carcinoid crisis with a somatostatin analogue. N Engl J Med 313 (19): 1229-30, 1985.
Gorden P, Comi RJ, Maton PN, et al.: NIH conference. Somatostatin and somatostatin analogue (SMS 201-995) in treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut. Ann Intern Med 110 (1): 35-50, 1989.
Kvols LK: The carcinoid syndrome: a treatable malignant disease. Oncology (Huntingt) 2 (2): 33-41, 1988.
Oberg K, Norheim I, Lind E, et al.: Treatment of malignant carcinoid tumors with human leukocyte interferon: long-term results. Cancer Treat Rep 70 (11): 1297-304, 1986.
Moertel CG, Rubin J, Kvols LK: Therapy of metastatic carcinoid tumor and the malignant carcinoid syndrome with recombinant leukocyte A interferon. J Clin Oncol 7 (7): 865-8, 1989.
Tiensuu Janson EM, Ahlström H, Andersson T, et al.: Octreotide and interferon alfa: a new combination for the treatment of malignant carcinoid tumours. Eur J Cancer 28A (10): 1647-50, 1992.
Andreyev HJ, Scott-Mackie P, Cunningham D, et al.: Phase II study of continuous infusion fluorouracil and interferon alfa-2b in the palliation of malignant neuroendocrine tumors. J Clin Oncol 13 (6): 1486-92, 1995.
Moertel CG: Karnofsky memorial lecture. An odyssey in the land of small tumors. J Clin Oncol 5 (10): 1502-22, 1987.
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Recurrent Gastrointestinal Carcinoid Tumors
The prognosis for any treated carcinoid patient with progressive or recurrent disease is poor. Deciding on further treatment depends on many
factors, including prior treatment, site of recurrence, and
individual patient considerations. Attempts at reresecting slow growing
tumors (e.g., repeat or multiple liver resections) are worthy of consideration
after extensive evaluation, since successful further reduction of tumor volume
may provide long-term palliation. Recurrence in any single site may also be
potentially resectable. Clinical trials are appropriate and should be
considered when possible.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with
recurrent gastrointestinal carcinoid tumor. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
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More Information
About PDQ
Additional PDQ Summaries
Important:
This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
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This information is provided by the National Cancer Institute.
This information was last updated on May 16, 2008.