Carcinoid Tumors

WHAT IS CARCINOID TUMORS?
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.

Serotonin metabolism in carcinoid disease. Primary carcinoid tumors of gastrointestinal tract, ovary, bronchus, and hepatic metastases. TRY=Tryptophan; MAO=monoamine oxidase
Progression of carcinoid disease

WHAT CAN PROMOTE DEVELOPMENT OF CARCINOID TUMOR?
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.

HOW TO FIND CARCINOID TUMOR?
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.
Blood chemistry studies: 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: 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.
Localized Gastrointestinal Carcinoid Tumors
Appendiceal carcinoids
Rectal carcinoids
Small bowel carcinoids
Gastric, pancreatic, and colon carcinoids
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%.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.
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. 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.
Metastatic Gastrointestinal Carcinoid Tumors
Carcinoid syndrome
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.



Carcinoid tumor
Ribbon or sheet architecture
Polygonal cells
Moderate cytoplasm
Regular nuclei
Finely stippled chromatin
Small nucleoli
Delicate capillary stroma
<2 name="4">HOW TO TREAT CARCINOID TUMOR?
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).
Chemotherapy: Although activity with a variety of single agents and drug combinations has been reported (fluorouracil, doxorubicin, dacarbazine, cyclophosphamide, fluorouracil + streptozocin, and etoposide + cisplatin, 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. Palliative embolizations that prove effective may be repeated if symptoms return.
Cryoablation or radiofrequency ablation may be used to ablate tumor in liver. The procedure is often performed under CT or ultrasound guidance percutaneously.
A carcinoid tumor near dome of liver. CT scans following RFA at 3 months and 6 months showing only hypodense scar.
Radiation therapy: The role of radiation therapy in the management of patients with carcinoid tumors with distant metastasis is restricted to symptomatic palliation. 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.
Biological modification (immunotherapy): Low-dose interferon alfa and octreotide, alone and in combination, have been reported to have activity.
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. 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. Such treatment may also be given in conjunction with systemic chemotherapy in selected patients. 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.
Alternate nonresective surgical ablative techniques include cryosurgery, radiofrequency ablation, and percutaneous alcohol injections.
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.
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 alfa preparations may have a role in controlling symptoms of the carcinoid syndrome or in arresting tumor growth. These benefits have generally been transient and accompanied by toxic effects that frequently outweigh therapeutic gains,although interferon alfa has been reported to reinduce symptom control in patients who did not respond to octreotide. The combination of interferon alfa and continuous-infusion fluorouracil has demonstrated antitumor and/or antihormonal activity and, similar to other drug regimens, can provide useful palliation. Combination of interferon alfa and octreotide has also been reported to have activity.
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.

HOW TO ESTIMATE PROGNOSIS OF CARCINOID TUMOR?
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.
Whether the cancer is eliminated
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.