Clinical Syndromes Related to Gastrointestinal Neuroendocrine Neoplasms

Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of tumors derived from multipotent neuroendocrine cells that have the inherent ability to synthesize and secrete a variety of substances (peptides and amines). When these substances are bioactive, NENs can present with a related clinical syndrome (functioning NENs) and/or symptoms of mass effects (functioning and nonfunctioning NENs). NENs differ in their pathogenesis, clinical syndromes produced, aspects of biological behavior and response to certain antitumor treatment. The carcinoid syndrome (CS) is the clinical constellation of secretory diarrhea, flushing, wheezing and dyspnea as a result of serotonin production mainly from small intestinal NENs. Complications of CS are frequent and include extensive mesenteric fibrosis, carcinoid heart disease and the life-threatening carcinoid crisis. A variety of substances (mainly hormones) are produced from NENs originating from the pancreas associated with specific symptoms that can lead to their precise diagnosis. NENs may also secrete substances characteristic of other sites of origin and produce a variety of paraneoplastic syndromes and/or change their secretory status with time. Surgery remains the best option for complete tumor resection and symptom relief. Surgery may also be used when medical treatment fails to obtain control of the symptoms along with cytoreductive techniques. Somatostatin analogs (octreotide and lanreotide) constitute the backbone of medical treatment for the majority of functioning NENs as they can alleviate symptoms, stabilize tumor growth and improve the quality of life. Telotristat etiprate is a novel oral agent that inhibits tryptophan hydroxylase, the key enzyme responsible for serotonin production, and can improve the symptoms of CS. Nonspecific and supportive therapies are also used for refractory cases. In this chapter the clinical features of functioning NENs will be analyzed as well as aspects of their diagnosis based on secretory substances and treatment of the hormonal excess.