BACKGROUND. The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program has proven to be a significant resource in US neuroendocrine tumor (NET) epidemiology. Norway also holds a robust and detailed cancer registry: the Norwegian Registry of Cancer (NRC). METHODS. SEER NET data were compared with corresponding NRC data in the time period 1993 to 2004 to determine whether there are differences in NET epidemiology between Norway and the United States. RESULTS. The SEER and NRC reported 17,312 and 2030 NETs, respectively. The overall Caucasian SEER NET incidence was 4.44, compared with 3.24 in the NRC. In the SEER white subset, bronchopulmonary NETs were the most common (incidence = 1.42; 32% of all NETs), compared with small intestinal NETs in the NRC (0.81; 26%). A marked increase in SEER NET incidence (37%‐40%) was observed in the period 2000 to 2004, compared with 1993 to 1997; an even more pronounced increase (72%) was seen in the NRC. African Americans exhibited a remarkably high overall NET incidence of 6.50; furthermore, among African Americans, rectal NETs were most common (1.65; 27%). Small intestinal NET incidence was ∼30% higher in men compared with women in all populations. The highest 5‐year survival rates were for rectal NETs (74%‐88%) in both databases, whereas prostatic NETs had the worst outcome (0%‐23%). At diagnosis, NETs were localized in 27% to 46% of patients. CONCLUSIONS. NET incidence in the US Caucasian population and in Norway is similar, but considerably higher (∼50%) among African Americans. NETs have been regarded as indolent tumors; however, the 5‐year survival is only ∼55%. Cancer 2008. © 2008 American Cancer Society.

Mechanisms by which gut luminal content regulates secretion and motility are ill understood. We evaluated whether neuroendocrine enterochromaffin (EC) cells act as luminal sensors for a wide variety of nutrients and defined the secretory mechanisms of this process. Pure (98-99%) FACS-sorted human EC cells and neoplastic EC cells (KRJ-I) were studied. RT-PCR identified transcripts for T2R1 (bitter), OR1G1 (class II olfactory) and trace amine (TAR1) G protein-coupled receptors (GPCRs) and transporters for glutamine (SNAT1/2), glucose (GLUT1/3/SGLT1), and bile salts (ABST). Glutamine and sodium deoxycholate stimulated 5-HT release (EC(50) = 0.002-0.2 microM; 2-fold release) but were 10-100 times more potent in neoplastic EC cells, which also secreted 6-13 times more 5-HT. Tastants (caffeine, tyramine, octopamine) and olfactants (thymol and eugenol) also stimulated normal and neoplastic EC cell 5-HT secretion (EC(50) = 1.2 nM to 2.1 microM and 0.05 nM to 0.1 microM release, respectively); 2-deoxyglucose and the artificial sweetener sucralose also stimulated (EC(50) = 9.2 and 0.38 nM). 5-HT release was associated with ERK phosphorylation (1.5-fold, P < 0.02) and could be inhibited by a somatostatin analog (IC(50) = 1 pM). Eleven secretory associated genes including the vesicle docking inhibitor STXBP3 were upregulated in response to glutamine and bile salt stimulation in neoplastic EC cells. Targeting STXBP3 expression by use of antisense knockdown significantly (P < 0.05) reduced 5-HT secretion. In conclusion, EC cells express GPCRs and transporters for luminal tastants, olfactants, glutamine, glucose, and bile salts. Activation includes a panel of secretory genes, ERK phosphorylation, and 5-HT secretion. Luminal EC cell regulation is likely to be as important as G cell regulation in gastric acid secretion; development of agents to target EC cell function is therefore a critical therapeutic goal.

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These findings show that serotonin may regulate adipocyte function in a direct manner via the blood circulation and/or paracrine and autocrine mechanisms, and not only indirectly via the CNS as previously assumed.