Treatment of neuroendocrine tumors

Abstract

Neuroendocrine gut and pancreatic tumors constitute about 2% of all malignant neoplasms. The incidence of patients with malignant tumors and the carcinoid syndrome is around 0.5/100 000 and with pancreatic endo crine tumors 0.4/100 000 (1, 2). Many patients with malignant metastasizing tumors demonstrate clinical symptoms related to hormone overproduction. These include the carcinoid syndrome with flushing, diarrhoea, bronchial constriction and right heart failure from midgut carcinoids producing serotonin and tachykinins (I). Syndromes related to pancreatic endocrine tumors are the Zollinger-Ellison syndrome from overproduction of gastrin, and insulinoma causing hypoglycemia because of excessive insulin/proinsulin production. Other distinct clinical entities are the glucagonoma with typical necrolytic migratory erythema, the Verner-Morrison syndrome from high circulating levels of VIP producing severe secretory diarrhoea with various degrees of electrolyte disturbances, and somatostatinoma leading to a syndrome of gall bladder dysfunction, gall stones, steatorrhea and impaired glucose tolerance (2). Carcinoid tumors are divided into three main groups; foregut, midgut and hindgut tumors. Primary foregut tumors are confined to the thymus, lung, gastric mucosa or duodenum (IO-15%), whereas midgut carcinoids are located predominantly in the distal part of ileum, caecum and proximal colon (50-70%). Appendix carcinoids are predominantly benign and rarely give rise to metastatic disease. The hindgut tumors are primarily located in distal colon and rectum and they constitute the second most common type (15-20%) of all carcinoids. The midgut carcinoids dominate the malignant carcinoid tumors, particularly when the carcinoid syndrome, (flushing, diarrhea, bronchial constriction and right heart failure) is present (1,3,4). About one-third of patients with pancreatic endocrine tumors present without any hormone-related syndromes and neuroendocrine tumors of the hindgut (colorectal carcinoids) are not usually associated with peptide hormone-related syndromes (3). Even in advanced stages, tumors with metastases retain well-differentiated diploid features (3). The hormone production and release with related metabolic consequences may sometimes be life threatening even in patients with small tumors and limited metastatic spread. About one-third of the patients with the