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: Nine patients (mean age 12.2 years) were included: six girls and three boys (2:1), all of them Caucasian. In eight cases (89%), the primary tumor site was the appendix and in one (11%) it was the left bronchus. For those with primary tumor in the appendix, the main complaint was abdominal pain, which led to appendectomy. Only one patient underwent right hemicolectomy due to tumor extension into the serosa. The patient with bronchial tumor underwent left pneumonectomy. All patients had localized disease and are alive and free of disease. They have had follow-ups lasting from 1 to 11 years (mean of 3.5 years).