Neuroendocrine tumours arise from cells that secrete peptides that control the functions of other cells in the body. In the pancreas these peptides are secreted directly into the blood, so they are known as hormones, but they also function in neurons (nerve cells) as neurotransmitters, transmitting electrical activity from nerve to nerve.
Some neuroendocrine tumours are classified as "functioning" tumours because they secrete excessive amounts of these hormones, which cause serious physiological effects. Tumours that secrete excessive insulin, for instance, are called insulinomas, which are associated with the results of dangerously low blood glucose levels.
Other "functioning" tumours include:
Most neuroendocrine or non-functioning tumours are not associated with excessive hormone secretion.
Most neuroendocrine tumours behave in a much less aggressive manner than tumours of the exocrine pancreas. Although they are all inherently malignant, in that they can and often do metastasise. These low-grade neuroendocrine tumours usually have receptors for somatostatin on the cell membranes of the tumour cell. Somatostatin, a 14-amino acid peptide, is one of the hormones produced by neuroendocrine cells, and it inhibits other endocrine cells secreting their hormones. Two synthetic eight amino acid analogues of somatostatin (octreotide and lanreotide) are available commercially in South Africa. It has been proven in two major clinical trials (PROMID & CLARINET) that administration of these analogues not only inhibits the secretion of hormones by functioning neuroendocrine tumours but also inhibits proliferation of neuroendocrine tumour cells and significantly prolongs survival of patients with these tumours. These somatostatin analogues can be chemically modified (to DOTANOC, DOTATOC or DOTATATE) to allow attachment of radioactive isotopes, which can then be used for diagnostic and therapeutic applications. Attachment of the isotope 68Ga is used for diagnostic purposes with PET scans, while the isotopes 177Lu or 90Yt attached to DOTATATE are used for treatment, known as peptide receptor radiation therapy (PRRT). Grade 1 and 2 neuroendocrine tumours usually have abundant somatostatin receptors and are amenable to being controlled and treated with somatostatin analogues themselves and PRRT. Grade 1 and 2 neuroendocrine tumours are, conversely, very unlikely to respond to chemotherapy, but the more aggressive grade 3 tumours might respond to combinations of chemotherapy drugs, with the most common being capecitabine and temozolomide in South Africa. A very much more aggressive variant, known as neuroendocrine carcinoma, is very unlikely to react to somatostatin analogue-based therapy but these often do respond to a different combination of chemotherapy drugs, cisplatin and etoposide.
Surgical resection should always be considered for grades 1-3 neuroendocrine tumours, even if metastatic, even if not all of the tumour can be removed entirely because if the overall bulk of the tumour can be significantly reduced, somatostatin analogues and PRRT will likely have a more significant impact on the remaining disease.