Gastrointestinal neuroendocrine tumours
Gastrointestinal neuroendocrine tumours (GI NETS) can be functional or non-functional:
- functional NETS can be challenging to localise as:
- they are often small in size at the time of diagnosis
- arise in many sites throughout the body
- non-functioning and/or malignant NETs often are larger at presentation and therefore easier to locate
Types of gastrointestinal - pancreatic neuroendocrine tumours
- account for 50% of pancreatic NETS
- usually <2cm diameter
- 99% of insulinomas found in pancreas
- 10-15% are malignant
- account for 20-30% of pancreatic NETS
- found in pancreas, lymph nodes and duodenum
- vary in size
- 60-75% are malignant
- non functioning tumours and pancreatic polypeptide secreting tumours
- account for 15-20%
- almost exclusively found in pancreas
- usually malignant
- often large at presentation
vasoactive polypeptide secreting tumour (VIPoma)
- account for 3%
- 90% found in the pancreas
- 10% found in adrenal gland
- 50-60% are malignant
glucagonomas and somatostatinomas
- most commonly located in pancreas
- often malignant
There is no consensus on the best single imaging modality for NETS and depends on the suspected location and local expertise. Combined modalities and techniques are often used 1-3.
- used for suspected gastric, enteric and pancreatic NETS pre and post IV iodinated contrast
- bowel distension with fluid, either by oral intake (CT enterography) or via a nasojejunal tube (CT enteroclysis) improves detection of primary GI NETS
Used for suspected hepatic, pancreatic or retroperitoneal NETS, often with gadolinium contrast. MRI enterography also possible.
- used for monitoring slow growing tumours and/or follow up of metastases.
- ultrasound can also be used to guide biopsies.
- endoscopic/endoluminal US can be used to identify and characterised GI NETS as well as obtaining samples for cytology or histology
- common radiopharmaceutical is 111-indium-pentetreotide, which is a ligand for somatostatin receptor on the cell membrane of many NETS 4,5
- multiple tumour sites and/or metastasis can be identified using a gamma-camera to detect the emitted radiation
- can be used in combination with cross-sectional imaging modalities to aid staging e.g. SPECT or PET-CT or PET-MRI 6
- can be used to predict response to nuclear medicine based therapies, and, in some cases, to assess response to treatment.
- care should be taken with interpretation of images as drugs can interfere with somatostain receptor expression, e.g. interferon.
- NETS can differentiate into tumours that do not express somatostatin receptors can become ‘image negative’ making reoccurrence or metastases more challenging to detect
- other radiopharmaceuticals are also used, based on certain physiological characteristics e.g. cell surface receptors or uptake of molecules.
- gallium-68 labelled somatostatin analogues (PET/CT) – thought to be more sensitive in detecting NETS expect pulmonary and hepatic metastases
- for aggressive, rapidly growing tumours (i.e. high metabolism) Fluoro-di-glucose-PET/CT can be used (FDG-PET)
- F18 DOPA and C11 Hydroxytryptophan may be used in future but are not routinely available
- venous sampling can be used in small functional NETS where cross sec-tional imaging is equivocal.
- multiple endocrine neoplasia type 1 can present with multiple lesions; functional NETS can be identified from these, using calcium stimulation with venous sampling.
- angiography and endovascular procedures, such as trans-arterial chemo-embolization (TACE), can be used to treat hepatic metastases.
Assessing specific gastrointetsinal NET imaging based on location
- gastric or colonic - endoscopy
- small bowel
- c-enhanced CT/MR enterography, +/- radiopharmaceuticals or gallium PET/CT to localize NETS as classically high concentration of Somatostatin receptors and are very vascular
- capsule endoscopy may be helpful to detect small bowel NETs not identified by CT or MRI but precise location difficult
- pancreatic NETs
- non - functioning NETS present late and tend to be larger and have mass effect or non-specific symptoms or signs; these can be identified using CT.
- functioning NETs present early with signs and symptoms, leading to clinical suspicion of tumour which is often smaller and more challenging to locate
- triple Phase thin multi-slice CT (pre-contrast/arterial/portal-venous)
- high resolution MRI with T2, T1, fat saturated and dynamic contrast administration
Assessing malignancy and staging
Signs on CT of malignant NETs include 7
- larger size
- invasion of the surrounding structures
- commonly metastases to lymph nodes and the liver, as well as bone, lung and mesentery
- 40-80% of midgut NETs present with metastases at presentation.
- union for International Cancer Control (UICC) TNM (tumour, node, metastasis) systems or the European Neuroendocrine Tumour Society (ENETS) have TNM staging systems which differ slightly from each other
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- 2. Sahani DV, Bonaffini PA, Fernández-Del Castillo C et-al. Gastroenteropancreatic neuroendocrine tumors: role of imaging in diagnosis and management. Radiology. 2013;266 (1): 38-61. doi:10.1148/radiol.12112512 - Pubmed citation
- 3. Ramage JK, Ahmed A, Ardill J et-al. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs). Gut. 2011;61 (1): 6-32. doi:10.1136/gutjnl-2011-300831 - Free text at pubmed - Pubmed citation
- 4. Teunissen JJ, Kwekkeboom DJ, Valkema R et-al. Nuclear medicine techniques for the imaging and treatment of neuroendocrine tumours. Endocr. Relat. Cancer. 2011;18 Suppl 1 (S1): S27-51. doi:10.1530/ERC-10-0282 - Pubmed citation
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- 6. Beiderwellen KJ, Poeppel TD, Hartung-Knemeyer V et-al. Simultaneous 68Ga-DOTATOC PET/MRI in patients with gastroenteropancreatic neuroendocrine tumors: initial results. Invest Radiol. 2013;48 (5): 273-9. doi:10.1097/RLI.0b013e3182871a7f - Pubmed citation
- 7. Sundin A, Vullierme MP, Kaltsas G et-al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: radiological examinations. Neuroendocrinology. 2009;90 (2): 167-83. doi:10.1159/000184855 - Pubmed citation