Elsevier

Journal of Hepatology

Volume 47, Issue 4, October 2007, Pages 460-466
Journal of Hepatology

Forum on Liver Transplantation
Neuroendocrine tumors metastatic to the liver: How to select patients for liver transplantation?

https://doi.org/10.1016/j.jhep.2007.07.004Get rights and content

Introduction

Neuroendocrine tumors (NET), which originate from different parts of the widespread neuroendocrine system [1], are very rare and originate in about 85% of cases in the gastrointestinal tract (2 cases per 100.000 inhabitants/year with a slight female predominance) and in the pancreas (1–1.5 cases per 100.000 inhabitants/year) [1], [2], [3]. Although the large majority of NET arise sporadically, a small group of patients are affected by inherited multiple endocrine neoplasia type 1 (MEN-1) which are at risk of developing neuroendocrine malignancies in 30% of the cases.

In general, NET which originate in the gastrointestinal tract are slow-growing tumors often discovered in the metastatic phase (40–80% of patients present at diagnosis with metastases), being the liver the most involved organ (40–93%) followed by bone (12–20%) and lung (8–10%). The clinical deterioration of patients affected by NET in advanced stages is almost invariably related to massive liver involvement with hepatomegaly, discomfort and poor quality of life. However, metastases of NET remain usually confined to the liver for a long time, leading to a 5-year survival of 30%, even in untreated patients [4].

Many therapeutic strategies have been attempted over the years for patients with NET. Loco-regional therapies such as hepatic artery embolization and trans-arterial chemo-embolization (TACE), radiofrequency thermal ablation (RFA) and cryoablation are the most commonly used, together with somatostatin analogues and chemotherapy in the effort to reduce the tumor bulk or the metabolic activity in unresectable cases. Surgery is considered as a bare palliation in patients with large tumor bulk and severe symptoms. However, recent progressive adjustments in patient selection and clinical-pathological definition of stages contributed to a re-definition of the role of surgical therapies for metastatic NET. In particular, orthotopic liver transplantation (OLT) is increasingly proposed as an alternative for cure in patients with limited tumor bulk and long expected survival, either because of young age or because of favorable biological behaviour of the tumor itself. Indeed, the current reappraisal of OLT for NET metastatic to the liver also takes into account the many lessons learnt from patients affected by the same disease treated in the last three decades with liver resection.

Nowadays, more precise prognostic information, based on tumor characteristics and clinical features, are favoring OLT as a potentially curative strategy for selected cases; as a consequence of this, hepatic metastases from NET are the only accepted indication to liver replacement in case of a metastatic cancer.

Section snippets

Surgical rationale for treating liver metastases from NET: from resection to transplantation

Recent adjustments of the histological classification reported in Table 1[1] and new markers such as chromogranin A (CgA) can better predict different pattern of disease growth and dissemination. One characteristic of NET’s malignancy is that often the primary tumor site cannot be detected for years, and during this period further spreading to distant organs [1], [2], [3], [4] is likely to occur.

In case of metastatic NET limited to the liver, surgery is thought to be the most rationale

Liver transplantation for metastatic NET: cure rather than palliation

Over the last two decades, the established strategy for the management of patients with metastatic NET takes into account the option of OLT as a salvage therapy, with unfortunately disappointing results as a consequence of suboptimal patient selection (Table 3) [19], [22], [23], [24], [25], [26], [27], [28]. As for other tumors amenable to surgical management, a modern approach to the treatment of NET has to consider multimodal approach carried out by a multidisciplinary team, including

Acknowledgements

This work has been supported by AIRC (Italian Association for Cancer Research). The authors thank Paola Collini MD, Salvatore Andreola MD and Sherrie Bhoori MD for advice and revision. The editorial assistance of Daniela Guarneri is also acknowledged.

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    The authors declare that they do not have anything to disclose regarding conflict of interest with respect to this manuscript.

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