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.
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: The present series comprises 218 first malignant (i.e., locally infiltrating/metastastising; Levi et al, 1991, 1993) (118 males, 100 females), and 215 benign (77 males, 138 females) carcinoids registered from 1974 to 1997 in the resident population of the Canton. Only first occurrences were considered. In accord with the ICD-O classification (World Health Organization, 1976), the great majority of carcinoids diagnosed in the lung (ICD-O-M morphology code: 8240) were considered as malignant (fifth digit of ICD-O-M code: ≥3). Histological confirmation was 100%. The vital status of each case considered for the present analysis was verified up to December 31, 1999. Twenty malignant cases (9%) and 22 benign cases (10%), discovered at autopsy, were not considered for survival analysis. Losses to follow-up were about 7%. Complete information on five-year survival was available for 343 (79%) uncensored cases and was computed starting from the date of histological confirmation. Relative survival rates (Ederer et al, 1961) were computed after allowance for the general lifetables of the canton (Levi et al, 1992).