Patho physiology: Carcinoid tumors are a type of neuroendocrine tumor, which means they come from cells of the nervous and endocrine system, and can produce hormones. When they secrete excess hormones such as histamine and serotonin, they can cause symptoms such as flushing, stomach cramps, and diarrhea. This is called carcinoid syndrome. When these tumors spread to the liver, patients usually begin to develop malignant carcinoid syndrome. In fact, this syndrome develops when vasoactive substances produced by a carcinoid tumor escape hepatic degradation and gain access to the systemic circulation.Carcinoids arising in the stomach are usually associated with low gastric acid production, a condition termed hypochlorhydria or achlorhydria. These tumors rarely become malignant and never metastasize, but they sometimes produce histamine.Carcinoid tumors arising in the lung generally produce serotonin, gastrin, adrenocorticotropic hormone (ACTH), and histamine. Carcinoids that develop outside the appendix are often malignant, while tumors developing in the appendix are usually benign if smaller than 2 cm in diameter. Rectal carcinoid tumors often produce polypeptides (PPs), polypeptide Y, neuropeptide Y, and other peptides, but none of the patients with this disease location have symptoms related to the production of such molecules. Few patients have liver metastases, but if they do have liver metastases, they do not have hormone-related symptoms.
Treatment: Somatostatin analogues have been the treatment of choice in symptomatic patients with carcinoid tumors, but more recent studies have indicated a cytostatic effect of somatostatin analogues. Tumor-targeted radioactive treatment based on somatostatin analogues is now under clinical evaluation. Preliminary data indicate interesting clinical potentials. If metastasis of carcinoid tumor has occurred and in cases where surgical excision is not suitable, consider treatment with currently recommended chemotherapy. Chemotherapeutic agents currently used in clinical trials to palliate metastatic carcinoid disease include the following: Alkylating agents, Doxorubicin, 5-Fluorouracil, Dacarbazine, Actinomycin D, Cisplatin, Etoposide, Streptozotocin, Interferon alfa, Somatostatin analogs with a radioactive load. A combination of the agents listed above is typically used.
Research: Cells of the human bronchial carcinoid cell line NCI-H727 and the human pancreatic carcinoid cell line BON-1 were treated with increasing concentrations of imatinib using standard procedures to assess in vitro growth-inhibitory activity. A clinical trial using a two-stage phase II design to assess the response rate and safety profile of imatinib at a dose of 400 mg given twice daily in patients with advanced carcinoid tumors was completed. In both cell lines, there was a dose- and time-dependent cytotoxic effect. The clinical trial enrolled 27 evaluable patients. Median duration on trial was 16 weeks. One patient had a partial response, 17 had stable disease, and 9 had progressive disease by the Response Evaluation Criteria in Solid Tumors criteria. Median progression-free survival time was 24 weeks. Median overall survival is 36 months. Seven patients who achieved a biochemical response had a superior progression-free survival time compared with patients without biochemical response (115 weeks compared with 24 weeks; P = 0.003). An increase in plasma basic fibroblast growth factor was associated with a shorter progression-free survival duration (P = 0.02) Our data suggest that imatinib is active in vitro and has a modest clinical activity in carcinoid patients. Changes in tumor markers may help select patients who are likely to benefit from therapy.
Statistics: Large studies of many individuals indicate that the occurrence of insignificant small carcinoids that seem to last a lifetime and cause no problems and do not spread is fairly common, occurring in approximately 1 out of every 100 individuals. The most common location in which carcinoids form is in the small intestine. Tumors of any kind in the small intestine are rare and comprise only 1% of all the cancers of the gastrointestinal tract. However, carcinoids of clinical importance (not the tiny coincidental tumors mentioned above) comprise about 50% of all small intestinal malignancies. Their size when first diagnosed is very important since the likelihood of having already spread is in direct proportion to their size. If the tumor is greater than 2 cm in diameter (almost 1 inch) chances of spread are greater than 50%. Initially the carcinoid tumor just grows into the wall of the intestine from the lining where it starts. However, eventually it may go through the wall and then extend into nearby lymph nodes, lymph channels, and blood vessels and can later spread to more distant locations such as the liver, lungs, bone, skin, brain and even the heart. Approximately 20% (1/5) of the small intestine carcinoids will develop distant spread (metastases) and roughly 1/3 of those that have spread will develop symptoms of the Carcinoid Syndrome. From these numbers it is apparent that the Carcinoid Syndrome is very rare.