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German pathologist Siegfried Oberndorfer recognized carcinoid tumors as a unique entity in 1907. Prior to his published case reports, these tumors were thought to be benign carcinomas, but Oberndorfer presented six patients with multifocal, pea-sized tumors of the ileum that appeared malignant on histologic examination.1 He named the disease “karzinoide” (carcinoma-like) to more accurately classify their clinical behavior. Today, the term “carcinoid tumor” provokes controversy among those who prefer more specific oncologic terminology for the disease, but it persists as an etymologic honorarium to the man who pioneered the field.2
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The epidemiology of gastrointestinal neuroendocrine tumors (GI NETs) has evolved since data was first catalogued in the Surveillance Epidemiology End Results (SEER) database in 1973. At that time, the prevalence of GI NETs was 1.09 per 100,000 people per year. Forty years later, the prevalence is estimated at 3 per 100,000 people per year and GI NETs represent 0.5% of all newly diagnosed cancers. The cause of this increase is unknown. Common behavioral risk factors such as smoking and excessive alcohol use do not appear to play a role.3 The increased prevalence is therefore attributed to improved diagnostic capabilities and increased awareness of the disease.4
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The term “GI NET” refers to a neuroendocrine tumor originating anywhere in the digestive tract from the stomach to the rectum (excluding the pancreas). Foregut tumors are those that develop between the mouth and the second portion of the duodenum, midgut from D3 to approximately the last third of the transverse colon, and hindgut from this part of the colon to the anus. In the United States, GI NETs are most commonly found in the small bowel (36%), followed by the rectum (34%), colon (15%), stomach (10%), and appendix (5%). These tumors are more common in whites (72.6%), followed by blacks (17.2%), and Asians (7.8%). The median age of onset is 60 and men and women are affected at near-equal rates.4,5 These trends hold true in Europe,6 but in Asia, rectal carcinoids are far more common (88.1% of GI NETs, 61.8% of all NETs).7 In general, gastric, rectal, and appendiceal tumors tend to be diagnosed while still localized. Small bowel and colonic NETs are less predictable, as approximately 30% have distant metastases at diagnosis, 30% have locoregional spread, and 30% have localized disease.5
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Gastrointestinal neuroendocrine tumors arise from endocrine cells that derive from endoderm. These cells comprise only 1% of cells in the intestinal lumen, but are in aggregate the largest group of hormone-producing cells in the body.8-10 There are 17 known neuroendocrine cell types.9 The secretory function of these cells is mediated by G-protein-coupled receptors, ion-gated receptors, and receptors with tyrosine kinase activity. The bioactive peptides and hormones produced by these cells are the cause of the ...