Neuroendocrine Tumors (net) of the Gastrointestinal System: Diagnosis and Therapy

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a rare and heterogeneous group of tumors arising from the cells of diffuse endocrine system (DES) scattered through the mucosa of the gastrointestinal tract and pancreas. Tumors were historically termed carcinoid-«cancer-like» due to better prognosis than adenocarcinoma. Yearly incidence of GEP-NETs is estimated to be 1-2 of 100.000 population , but according to newer population registries data and autopsy reports it has increased by 5-folds, much more than incidence of other gastrointestinal malig-nancies. A special feature of these neoplasms is amine precursor uptake and decarboxylation, leading to production of hormones and bioactive amines (tachyki-nines, bradykinines, etc.), and therefore a potential for causing specifi c hypersecretory syndromes (such as WDHA, Zollinger-Ellison, carcinoid, hypoglycemic, glucagonoma, somatostatinoma etc.). Another characteristic is a potential to arise accompanied by other endocrine gland tumors, associated into syndromes of multiple endocrine neoplasia type I (MEN I), neu-rofi bromatosis type I (NF I), and von Hippel Lindau disease. According to World Health Organization (WHO), GEP-NETs are categorized into well-defi ned tumors (benign or low grade malignant), well-defi ned neuroendocrine carcinoma and poorly differentiated neuroendocrine carcinoma. The classifi cation is based on proliferative activity measured by Ki67 index, number of mitoses, local invasiveness or metastatic potential and according to the secretory status of tumors. Newer classifi cation combines WHO and TNM classifi cation, and categorizes GEP-NETs into G1 and G2-well-differentiated; or G3-low differentiated tumors where T3 and T4 (>4cm and local invasions) defi nes local and N1 (lymphonodes) and M1 (liver) metastases. Due to nonspecifi c symptoms mimicking many different diseases, GEP-NETs are unfortunately often diagnosed late in the course of disease (with on average 5-7 years delay). Most GEP-NETs are actually nonfunctional, i.e. not associated with recognizable clinical syndromes. Prominent symptoms rising suspicion of GEP-NETs are diarrhea and fl ushing, but they are most common when tumors metastasize. Diagnosis of GEP-NETs is based on clinical syndromes, specifi c tumor markers measured in serum or urine of patients, and confi rmed by histopathology reports and imaging techniques. Chromogranin A (CgA) represents a general neuroendocrine marker, important in not only diagnostic procedures but also in follow-up of patients. In patients with carcinoid (serotonin-producing GEP-NETs), important marker is serum serotonin level, or more often measured serotonin metabolite 5-hydroxyindolacetic acid, measured in 24-hour urine output. For the histopathological con-fi rmation of GEP-NETs positive immunohistochemi-cal staining for CgA, synaptophisin, neuron-specifi c enolase (NSE) are needed. Informative histopatholog-ical report …