Review
Management of neuroendocrine liver metastases

https://doi.org/10.1016/j.amjsurg.2003.04.007Get rights and content

Abstract

Background

The optimum management of neuroendocrine liver metastases, particularly the role of liver transplantation is ill-defined. Current strategies are based on anecdotal reports and small retrospective studies, rather than prospective data. This, as well as the failure to standardize treatment, has probably contributed to the reported variations in outcome.

Data sources

To formulate a putative management protocol and to reevaluate the role of liver transplantation in patients with neuroendocrine liver metastases, a review of the published literature (Medline search) was conducted.

Conclusions

Isolated hepatic metastases should be resected when suitable. Chemoembolization of liver metastases should precede resection of bulky disease and be used to palliate those with unresectable disease. Radiofrequency ablation is suitable for smaller metastatic lesions (<3 cm diameter) in the liver. Systemic treatment with somatostatin analogues or radioactive metaiodobenzylguanidine (MIBG) is appropriate to reduce symptoms and slow disease progression, but prospective data is required to define their exact roles as adjuvant and therapeutic agents. Although current systemic chemotherapy, applied in isolation, may have a role in patients in whom other therapies have failed, its efficacy remains unproven. Restriction of liver transplantation to the treatment of patients with carcinoid metastases with biologically favorable features, limited tumor bulk and without systemic disease may make transplantation a curative rather than a palliative treatment option in selected patients.

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

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