Neuroendocrine Gastroenteropancreatic Tumors Recent Update on Diagnosis and Treatment

Neuroendocrine Gastroenteropancreatic Tumors Recent Update on Diagnosis and Treatment

Kjell Öberg
US Oncology Review 2006 - December 2005
Published: October 2008
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Neuroendocrine gastroenteropancreatic (GEP) tumors constitute less than 2% of all gastrointestinal (GI) malignancies. The incidence of the largest group of patients, those with small intestinal carcinoid tumors, is two to 2.4 per 100,000 inhabitants.The true incidence is probably underestimated due to sometimes vague clinical presentation and low awareness among physicians. The incidence in autopsy series is significantly higher at 8.4/100,000 inhabitants.1,2
Although neuroendocrine tumors can appear at all ages, those of the lung, mediastinum, and the GI tract are, in general, age-related with the highest incidence from the fifth decade upwards. Exceptions to this are the carcinoids of the appendix, which occur with the highest incidence below 30 years of age. Some of the neuroendocrine tumors of the GI tract are part of inherited diseases such as multiple endocrine neoplasia type 1 (MEN-1) and neurofibromatosis (NF) type 1, and von Hippel-Lindau’s disease. MEN-1 is associated with parathyroid hyperplasia/hyperparathyroidism (90%), pancreatic endocrine tumours (50–80%), pituitary adenomas (30–40%), and adrenal cortical adenomas (10–15%). A specific deletion on chromosome 11q13, harboring the MEN-1 gene, is the genetic background of the disease.This gene encodes a protein called menin, which acts as a tumour suppressor. 3,4

The von Hippel Lindau’s (VHL) syndrome is an autosomal-dominant neoplastic syndrome characterized by hemangio-ablastomas of the central nervous system (CNS), retinal angiomas, renal cell carcinomas, pheochromocytomas, and neuroendocrine pancreatic tumours. The VHL gene has been mapped to chromosome 3p25.3 and the gene is a tumor suppressor gene, implying that loss of function or inactivating mutations of this gene are associated with tumor formation.5,6

The main two groups of neuroendocrine GEP tumors are the so-called carcinoid tumors and endocrine pancreatic tumors.The carcinoid tumors are divided into fore-gut, which are mainly located in the lung, thymus and gastric mucosa, and duodenum, whereas mid-gut carcinoids, the second group, are located in the distal ilium and jejunum. Finally, hind-gut tumors are located in the colon and rectum. Approximately 40–60% of carcinoids are located in the mid-gut area, 25% in the fore-gut area, and the rest in the hind-gut. A specific clinical syndrome related to mid-gut carcinoid tumors is carcinoid syndrome, including flushing, diarrhoea, carcinoid heart disease, bronchial constriction, and high levels of urinary 5-hydroxyindoleacetic acid (5-HIAA). This syndrome is mainly seen in mid-gut carcinoids, but an atypical syndrome can be seen in patients with lung carcinoids, due to histamine production.7,8

Endocrine pancreatic tumors develop within the pancreas and might be divided into functioning and non-functioning tumors. Functioning tumors constitute approximately 60% and include well-known clinical syndromes such as the Zollinger-Ellison (due to secretion of gastrin), hypoglycemic syndrome (related to insulin/pro-insulin over-production), the Verner– Morrison syndrome (related to high circulating levels of vasoactive intestinal polypeptide), and glucagonomas syndrome (due to secretion of high concentrations of glucagon). The non-functioning tumors are secreting agents, which usually do not cause any distinct clinical syndrome, but merely present as ordinary GI cancers. These tumors are usually large and metastatic at diagnosis. They may secret chromogranin A, pancreatic polypeptide, peripheral hormone peptide YY (PYY) and other hormones, which do not cause any hormonerelated clinical symptoms.9–11

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