8Radiological and nuclear medicine imaging of gastroenteropancreatic neuroendocrine tumours
Introduction
Neuroendocrine tumours (NETs) have unique properties that are important to consider for radiological and nuclear medicine imaging. NETs arise from the cells of the diffuse endocrine system of specialised cells with different function and hormonal production which give rise to a heterogeneous group of tumours with very variable clinical expression [1], ∗[2]. NETs are most frequent in the gastro-intestinal and broncho-pulmonary system. The NET incidence is approximately 5/100 000 per year but the prevalence is much higher, 35/100 000 per year [3].
A NET may be functioning and give rise to hormonal symptoms or it can be non-functioning, although hormonal production from non-functioning NETs may sometimes be shown biochemically. Small bowel NETs generally produce serotonin and functioning pancreatic NETs (pNETs), arising from the islets of Langerhan, produce hormones according to its cell of origin (insulin, glucagon, gastrin, vasointestinal peptide etc.). The vast majority of NETs are slow growing with low proliferation (ki-67 index ≤2%, G1 tumours) and express somatostatin receptors, which forms the basis for somatostatin receptor imaging (SRI) and for therapy. A minor part of NETs have higher proliferation and a clinically more aggressive behaviour (ki-67 index 3–20%, G2) and rarely poorly differentiated neuroendocrine carcinoma (ki-67 index >20%, G3).
Many patients, typically those with small bowel NETs, present with vague diffuse unspecific symptoms. There are therefore often years of both patient's and doctor's delay and approximately half of the patients have disseminated disease at the time of diagnosis. The functioning pNETs can, by contrast, give rise to pronounced hormonal symptoms although the tumour is very small. The non-functioning pNETs usually give rise to abdominal discomfort and pain and often are fairly large at diagnosis.
Because of these very varying tumour properties and clinical behaviour, the presentation of the disease in the individual patients is very diverse. Consequently, the need for imaging varies considerably between patients [4], ∗[5].
The only curative treatment of NET is surgical resection. Surgery is also a means for tumour debulking to decrease hormonal symptoms and for management of locoregional symptoms. For example, patients with small bowel NETs, even in disseminated disease, generally undergo resection of the primary tumour (or tumours because the may be multiple) and of mesenteric metastases to prevent future bowel obstruction and ischaemia. Patients with somatostatin receptor positive NETs generally receive monthly injection therapy with long acting somatostatin analogues to relieve hormonal symptoms but the treatment has also shown an antiproliferative effect [6]. Locoregional therapies include intra- or transarterial (chemo)embolisation of liver metastases (TACE) with gelfoam or 90Y-labelled microspheres.
Local ablative procedures comprise for example radiofrequency ablation (RFA) of liver metastases. Chemotherapy has no role in NET therapy except in highly proliferative pNETs and G3 tumours (poorly differentiated neuroendocrine carcinoma). New targeted therapies such as thyrosine kinase inhibitors, antiangiogenetic agents and mTOR inhibitors are currently evaluated in clinical trials. Somatostatin analogues may be labelled with beta-emitting radionuclides, for internal radiation of the tumours. Most commonly 177Lu labelled octreotate (177Lu-DOTATATE) and 90Y-labelled octreotide (90Y-DOTATOC) are infused intravenously for peptide receptor radiotherapy (PRRT) [7].
Section snippets
Computed tomography (CT)
Computed tomography (CT) is the basic imaging modality for the initial radiological work-up at presentation of the disease [8]. Similarly, CT is used for monitoring of NET therapy and in patients having undergone surgical resection, to detect recurrent disease. In modern CT scanners, a large number of detectors are arranged in parallel rows (multidetector CT, MDCT) and by use of a rapidly rotating X-ray tube, typically more than a hundred 1 mm sections are produced per second. Because the
Gastro-duodenal NETs
Endoscopy is usually sufficient in small Type I and II gastric tumours. In larger >1 cm gastric tumours and duodenal NETs, EUS is used to detect invasion and regional lymph node metastases. For invasive gastric NETs, all Type III tumours and duodenal NETs, staging is performed by CT/MRI and SRI. These NETs typically metastasise to regional lymph nodes and liver. In advanced disease also bone metastases can appear.
Small bowel NETs
The primary tumour, or tumours for they can be multiple, is usually small and
Image monitoring of NET therapy
After surgical resection of a NET with curative intent, surveillance of the patient is generally life-long because recurrences may be seen after many years. For monitoring NET therapy, CT or MRI every 3–6 months is generally appropriate in low-grade tumours and after the first year every six months. In patients with stable disease, examination can be performed yearly. SRI is recommended after one or two years and when results of radiology, biochemistry and the patient's clinical status are
Summary
The diverse features of NETs makes imaging of these tumours a challenge. At the same time, their cellular and molecular characteristics have allowed for development of specialised functional imaging by scintigraphy and PET that utilise their somatostatin receptor expression and uptake and decarboxylation of amine precursors. The recent development of the general morphologic methods, CT and MRI, makes examination faster with better use of intravenous contrast media for imaging in various
Conflict of interest
None.
References (73)
- et al.
Current status of gastrointestinal carcinoids
Gastroenterology
(2005) - et al.
Nuclear imaging of neuroendocrine tumours
Best Pract Res Clin Endocrinol Metab
(2007) - et al.
Somatostatin receptor-targeted radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumors
Endocrinol Metab Clin North Am
(2011) - et al.
Comparison of neuroendocrine tumor detection and characterization using DOTATOC-PET in correlation with contrast enhanced CT and delayed contrast enhanced MRI
Eur J Radiol
(2012) - et al.
Contrast-enhanced ultrasonography in evaluating hepatic metastases from neuroendocrine tumours
Dig Liver Dis
(2010) - et al.
Endosonography in decision-making and management of gastrointestinal endocrine tumors
Eur J Ultrasound
(1999) - et al.
Usefulness of EUS combined with contrast-enhancement in the differential diagnosis of malignant versus benign and preoperative localization of pancreatic endocrine tumors
Gastrointest Endosc
(2010) - et al.
EUS is still superior to multidetector computerized tomography for detection of pancreatic neuroendocrine tumors
Gastrointest Endosc
(2011) - et al.
EUS for pancreatic neuroendocrine tumors: a single-center, 11-year experience
Gastrointest Endosc
(2010) - et al.
PET/CT with 68Gallium-DOTA-peptides in NET: an overview
Eur J Radiol
(2011)
Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas
Am J Gastroenterol
Fluid-fluid level in hepatic metastases: a characteristic sign of metastases of neuroendocrine origin
Eur J Radiol
Pancreatic neuroendocrine tumor: added value of fusion of T2-weighted imaging and high b-value diffusion-weighted imaging for tumor detection
Eur J Radiol
Neuroendocrine tumors of the diffuse neuroendocrine system
Curr Opin Oncol
One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States
J Clin Oncol
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: radiological examinations
Neuroendocrinology
Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group
J Clin Oncol
Imaging of neuroendocrine tumors: accuracy of helical CT versus SRS
Abdom Imaging
Carcinoid metastases to the liver: role of triple-phase helical CT
Radiology
Preoperative detection of pancreatic insulinomas on multiphasic helical CT
AJR Am J Roentgenol
Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging
J Clin Oncol
Assessment of the extent of metastases of gastrointestinal carcinoid tumors using whole-body PET, CT, MRI, PET/CT and PET/MRI
Eur J Med Res
Hepatic metastases from neuroendocrine tumors with a “thin slice” pathological examination: they are many more than you think…
Ann Surg
MRI of carcinoid tumors: spectrum of appearances in the gastrointestinal tract and liver
J Magn Reson Imaging
MR imaging of hepatic metastases caused by neuroendocrine tumors: comparing four techniques
AJR Am J Roentgenol
Endocrine pancreatic tumours: which are the most useful MRI sequences?
Eur Radiol
Prospective evaluation of pancreatic tumors: accuracy of MR imaging with MR cholangiopancreatography and MR angiography
Radiology
Detection of neuroendocrine liver metastases with MnDPDP-enhanced MRI
Neuroendocrinology
Detection of hepatic metastases from carcinoid tumor: prospective evaluation of contrast-enhanced ultrasonography
Dig Dis Sci
Ga-68 DOTATOC PET, endoscopic ultrasonography, and multidetector CT in the diagnosis of duodenopancreatic neuroendocrine tumors: a single-centre retrospective study
Clin Nucl Med
EUS-FNA for pancreatic neuroendocrine tumors: a tertiary cancer center experience
Dig Dis Sci
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: somatostatin receptor imaging with (111)In-pentetreotide
Neuroendocrinology
Neuroendocrine tumors and somatostatin: imaging techniques
J Endocrinol Invest
68Ga-labelled peptides for diagnosis of gastroenteropancreatic NET
Eur J Nucl Med Mol Imaging
68Ga-DOTATOC versus 68Ga-DOTATATE PET/CT in functional imaging of neuroendocrine tumors
J Nucl Med
68Ga-DOTATOC PET/CT and somatostatin receptor (sst1-sst5) expression in normal human tissue: correlation of sst2 mRNA and SUVmax
Eur J Nucl Med Mol Imaging
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