Somatostatin-receptor mediated diagnosis and treatment in gastrointestinal neuroendocrine tumours (GEP-NET's).

Neuroendocrine tumours constitute a group of tumours that originate from neuroendocrine cells throughout the body. That includes endocrine tumours of the thymus, lung, pancreas and gastrointestinal tract. Neuroendocrine gastrointestinal tumours have classically been divided into carcinoid tumours and endocrine pancreatic tumours. Many of these tumours produce hormones that can induce clinical symptoms in the patient [1]. Since these hormones are stored in secretory granules containing chromogranin A, a common feature for patients with neuroendocrine tumours is elevated levels of chromogranin A in plasma. Measurement of this hormone is a very sensitive marker for neuroendocrine tumours [2]. Patients with endocrine pancreatic tumours (EPT) can develop different syndromes according to the hormone produced. These syndromes include the Zollinger-Ellison syndrome for patients producing gastrin, the Verner-Morrison syndrome for patients with vasoactive intestinal peptide (VIP) production, the insulinoma syndrome due to excess of insulin/ /proinsulin and the glucagonoma syndrome for patients with high glucagon production respectively. A subgroup of endocrine pancreatic tumours (30-40%) does not produce any hormone that give rise to clinical symptoms and these tumours are called non-functioning endocrine pancreatic tumours. Patients with gastrointestinal endocrine tumours have traditionally been divided into foregut (gastric, duodenal), midgut (ileal, jejunal, appendicial) and hindgut carcinoids (colonic and rectal). For patients with midgut carcinoid tumours the carcinoid syndrome becomes overt when the patient develops liver metastases. The carcinoid syndrome consists of flushes, diarrhea, the carcinoid heart disease and sometimes bronchial constriction. These tumours produce serotonin and tachykinins and the most frequently measured tumour marker is the urinary 5-HIAA (5-hydroxyindoleacetic acid) which is a degradation product of serotonin. Patients with foregut carcinoid tumours may produce several different hormones including gastrin, ACTH (adrenocorticotropin releasing hormone), ghrelin and somatostatin, and therefore the symptoms may vary considerably in these patients. Recently a new classification has been proposed by WHO. The tumours are divided into well differentiated neuroendocrine tumours, well differentiated neuroendocrine carcinoma, tumours with uncertain behavior and low differentiated carcinoma. Proliferation index (Ki-67, MIB-1), angioinvasion and mitoses are important factors in the classification [3]. This classification is now being introduced into the clinic.