19th July 2023

Neuroendocrine Neoplasms (NENs) of the GI Tract

GI NENS, previously called neuroendocrine tumours (NETs), are rare slow growing tumours of enterochromaffin cells. Most occur sporadically, however, some occur as part of a genetic syndrome, including MEN1 (10% of all GI NENs), Von Hippel Lindau, Neurofibromatosis-1 and Tuberous Sclerosis. GI NENs are most commonly found in the small bowel, rectum, pancreas, stomach and appendix. Most are non-functional and asymptomatic, leading to delays in diagnosis. Functional NENs (approximately 40%) release large amounts of vasopressor peptides into the circulation causing symptoms. Carcinoid syndrome, affecting <10% of NEN patients, predominantly occurs when the tumour metastasises to the liver and releases hormones including serotonin. This leads to the classic symptoms of Carcinoid syndrome – diarrhoea, flushing, wheeze and abdominal pain. Fibrosis of the right-sided heart valves and right-sided heart failure (carcinoid heart syndrome) can also occur. Other functional NENs that secrete specific hormones are shown in table 1.

Table 1: Functional Neuroendocrine Neoplasms of the GI Tract

Functional NENs can be investigated using a 24-hour urine 5-HIAA test, where levels will be raised. The validity of this test can be affected by foods and drugs that contain or trigger the release of serotonin, causing false positives. Diagnosis is made by CT/MRI abdominal imaging or on histology from biopsies taken during endoscopy. Management is complex and requires regional MDT discussion but typically:

• Localised and resectable tumours – endoscopic or surgical resection
• Functional tumours –monthly somatostatin analogue subcutaneous injections (usually octreotide or lanreotide)
• Metastatic tumours – somatostatin analogues, radionuclide therapy (MIBG), chemotherapy, and embolisation of hepatic metastases