ReviewManagement of neuroendocrine liver metastases
Section snippets
Background
The incidence of neuroendocrine tumors (NET) has been estimated as 1 or 2 cases per 100,000 population per year [7], [8]. The majority arise sporadically, but a small subset forms part of the inherited multiple endocrine neoplasia syndrome type 1 (MEN-1; 29% of patients with MEN-1 develop neuroendocrine malignancies) [9]. The role of menin, the gene product of the MEN-1 gene defect in the pathogenesis of NET has not yet been elucidated [10]. Mutations of tumor suppressor genes retinoblastoma
Diagnosis and clinicopathological classification
Diagnosis of neuroendocrine tumors is commonly made retrospectively, after appendicectomy or after liver biopsy, where the presence of argyrophilic secretory granules within the cytoplasm is characteristic. Tumors may show a variety of architectural patterns such as insular, glandular, trabecular, mixed and undifferentiated, which may occasionally cause difficulty with diagnosis. Preemptive diagnosis is most likely in the case of functional tumors, by evaluation for humoral products either by
Imaging of patients with liver metastases from NET
Liver metastases from NET may be found synchronously with the primary tumor, may occur metachronously at follow-up after resection of a primary tumor, or may occur in the absence of a detectable primary tumor. Several imaging modalities are available for the localization of both primary neuroendocrine tumors and their metastases, including conventional ultrasonography (US), endoscopic ultrasonography (EUS), computed tomography (CT), magnetic resonance imaging (MR), somatostatin receptor
Fine-needle aspiration cytology/core biopsy
Although preoperative diagnosis of suspected neuroendocrine metastases may be attempted by fine-needle aspiration cytology (FNAC), in a recent study the correct diagnosis was obtained in only a third of cases by this method, due to similarities between the cytological features of NET and adenocarcinomas [35]. Since the decision to operate depends on the pattern of disease and its suitability for resection, FNAC or core biopsy is only indicated in patients in whom “curative resection” is not an
Management
For the purpose of management of patients with liver metastases from NET, it is best to consider patients as belonging to one of three groups: those with liver metastases amenable to surgical excision (their primary tumor may or may not be located at the time, but they have no clinically identifiable extrahepatic disease); those with liver metastases that are unresectable in the absence of extrahepatic disease (other than the primary tumor), or recurrent disease after previous liver resection;
Conclusions
Current management strategies for neuroendocrine liver metastases have relied on data from anecdotal evidence and retrospective studies involving small numbers of patients. It is unlikely that this situation will change in the near future, since prospective studies are difficult to perform in such a relatively rare and biologically heterogeneous disease. All patients should be staged at presentation with conventional CT/MRI and somatostatin receptor scintigraphy. Isolated hepatic metastases
References (81)
- et al.
Hepatic neuroendocrine metastasesdoes intervention alter outcomes?
J Am Coll Surg
(2000) - et al.
Malignant endocrine tumors in patients with MEN 1 disease
Surgery
(2001) - et al.
ECL cell tumour and poorly differentiated endocrine carcinoma of the stomachprognostic evaluation and outcome prediction by pathological analysis
Gastroenterology
(1999) - et al.
Endoscopic ultrasound is highly accurate and directs management in patients with neuroendocrine tumors of the pancreas
Am J Gastroenterol
(2000) - et al.
Resection versus transplantation for liver metastases from neuroendocrine tumors
Transplant Proc
(2001) - et al.
Hepatic resection of noncolorectal nonneuroendocrine metastases
Liver Transpl
(2000) - et al.
Particle embolization of hepatic metastases for control of pain and hormonal symptoms
J Vasc Interv Radiol
(1999) - et al.
Octreotide acetate long-acting release in patients with metastatic neuroendocrine tumors pretreated with lanreotide
Ann Oncol
(2000) - et al.
High-dose treatment with lanreotide of patients with advanced neuroendocrine gastrointestinal tumorsclinical and biological effects
Ann Oncol
(1997) - et al.
Bone marrow micrometastases and gastrointestinal cancer detection and significance
Am J Gastroenterol
(2000)
Result of liver resection as treatment for metastases from noncolorectal cancer
J Surg Oncol
Neuroendocrine metastases of the liver
World J Surg
An odyssee in the land of small tumours
J Clin Oncol
Surgical treatment as a principle in patients with advanced abdominal carcinoid tumours
Surgery
Liver transplantation for metastatic neuroendocrine carcinoma
Transplantation
An analysis of 8,305 cases of carcinoid tumours
Cancer
The epidemiology of carcinoid tumours in England and Scotland
Br J Cancer
Positional cloning of the gene of multiple endocrine neoplasia-type 1
Science
Mice deficient in both p53 and Rb develop tumours primarily of endocrine origin
Cancer Res
Oncogene expression in endocrine pancreatic tumours
Virchows Arch B Cell Path
Carcinoid tumours. Frequency in a defined population during a 12-year period
Acta Pathol Microbiol Scand
Gastrointestinal carcinoid tumours. A population-based study
Ital J Gastroenterol Hepatol
Surgical experience with pancreatic and peripancreatic neuroendocrine tumorsreview of 125 patients
J Gastrointest Surg
Tumor markers in neuroendocrine tumors
Digestion
New molecular aspects in the diagnosis and therapy of neuroendocrine tumors of the gastroenteropancreatic system
Recent Res Cancer Res
Neuroendocrine neoplasia. Current concepts
Am J Clin Pathol
Introduction to a revised clinicopathological classification of neuroendocrine tumors of the gastroenteropancreatic tract
Q J Nucl Med
Gastrinomas in the duodenums of patients with multiple endocrine neoplasia type 1 and the Zollinger-Ellison syndrome
N Engl J Med
Prognostic and immunohistochemical validation of the Capella classification of pancreatic neuroendocrine tumoursan analysis of 82 sporadic cases
Histopathology
Neuroendocrine tumors of the lung
Minerva Chir
Comparison of somatostatin receptor imaging, computed tomography and ultrasound in the clinical management of neuroendocrine gastro-entero-pancreatic tumours
Eur J Nucl Med
Receptor scintigraphy with 111In-pentetreotide for endocrine gastroenteropancreatic tumors
Horm Metab Res
Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]- octreotidethe Rotterdam experience with more than 1000 patients
Eur J Nucl Med
Localization of neuroendocrine tumours of the upper gastrointestinal tract
Gut
Endoscopic ultrasonography and somatostatin receptor scintigraphy in the preoperative localization of insulinomas and gastrinomas
Gut
Somatostatin receptor scintigraphyits sensitivity compared with that of other imaging methods in detecting primary and metastatic gastrinomas. A prospective study
Ann Intern Med
Gastrinomascomparison of MR imaging with CT, angiography, and US
Radiology
Localization of gastroenteropancreatic tumours by angiography
Ital J Gastroenterol Hepatol
Results of liver transplantation for gastroentreopancreatic tumor metastases
World J Surg
Gastroenteropancreatic tumor imaging with somatostatin receptor scintigraphy
Semin Oncol
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2014, International Journal of SurgeryCitation Excerpt :Whereas the prognosis of untreated liver metastases from colorectal cancer is very poor with a median survival of less than 12 months,5 resection of colorectal liver metastases representing the only curative treatment option improves the prognosis to a 5-year survival rate of ∼40%6 and 10-year survival rates of up to 25%.7,8 Furthermore, aggressive surgical therapy of neuroendocrine liver metastases has recently been demonstrated to improve clinical symptoms and increase survival rates up to 83% after 3–5 years.9–12 In contrast, there is an ongoing debate on the indication for resection of hepatic metastases from non-colorectal (NCRC) and non-neuroendocrine (NNEC) primary tumours.
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