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Carcinoid Tumors and Fibrosis: An Association with No Explanation

Carcinoid tumors are slow-growing neuroendocrine neoplasms most commonly associated with the gut and broncho-pulmonary system. In many instances, they are identified at surgery for unexplained bowel obstruction or during exploration of the small bowel in search of a primary tumor once distant metastases have been detected. Carcinoid tumors of the small bowel often present with pronounced fibrosis in the peri-tumoral tissues, distant in the heart or lungs, and locally in the peritoneal cavity. Despite medical and therapeutic advances that have alleviated symptoms and prolonged life, a substantial subset of patients develops mesenteric and small bowel carcinoid fibrosis and/or carcinoid heart disease. Fibrosis, and increasingly cardiac heart disease, are important components of intestinal carcinoid disease and are of considerable clinical concern, as both of these conditions reflect a connective tissue disorder whose etiology, biology, and therapy are unknown. In the past, individuals with carcinoid disease died of metastasis and uncontrollable symptomatology. Currently, there exists no clinical method to determine the development of fibrosis and little is understood about the biological basis of fibrosis. The elucidation of the biology and management of fibrosis is thus an issue of paramount clinical and scientific importance in determining appropriate diagnostic and therapeutic strategy. Therefore, the unraveling of the molecular events indicative of fibrosis in these cells and the identification of appropriate therapeutic targets is of considerable patient-care relevance. We have surveyed the world literature over the past 40 yr to evaluate both the incidence of carcinoid processes and track the evolving understanding of this process. In addition, we have provided more current mechanistic information in regard to the biological basis of fibrosis associated with small bowel carcinoid tumors.