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  • Review Article
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Neuroendocrine neoplasms of the gut and pancreas: new insights

A Correction to this article was published on 13 December 2011

This article has been updated

Abstract

Neuroendocrine neoplasms arise in almost every organ of the body and are variably defined according to the site of origin. This Review focuses on neuroendocrine neoplasms of the digestive tract and pancreas. The 2010 WHO classification of tumors of the digestive system introduces grading and staging tools for neuroendocrine neoplasms. A carcinoid is now defined as a grade 1 or 2 neuroendocrine tumor and grade 3, small-cell or large-cell carcinomas are defined as neuroendocrine carcinoma. Epidemiological data show a worldwide increase in the prevalence and incidence of gastroentero-pancreatic neuroendocrine tumors in the past few decades, which is probably due to improved methods of detection of these tumors. The current diagnostic procedures and treatment options for neuroendocrine neoplasms are defined and summarized in the Review, although evidence-based data are lacking. Surgery remains the treatment mainstay and somatostatin analogues the basis for both diagnosis and therapy as the only 'theranostic' tool. Emerging compounds including chemotherapeutic agents, small molecules and biological therapies may provide new hope for patients.

Key Points

  • Two regulated pathways of secretion are found in neuroendocrine cells that share features of secretory pathways found in endocrine cells and nerve cells

  • The WHO 2010 neuroendocrine neoplasm classification has introduced grading and staging; low to intermediate grade tumors are defined as neuroendocrine tumors (previously carcinoids) whereas high-grade carcinomas are termed neuroendocrine carcinomas

  • Gut and pancreas stem cells are fairly well defined, but data are lacking to support the cancer stem cell theory in neuroendocrine neoplasms

  • Therapy mainstays for gut and pancreas neuroendocrine neoplasms include surgery and the use of somatostatin analogues

  • Questions remain concerning both diagnosis and treatment of these neoplasms in current clinical practice because of a lack of evidence-based studies

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Figure 1: Functional characteristics of neuroendocrine cells with relevant antigens.
Figure 2: Histology of digestive neuroendocrine neoplasms according to tumor grade.
Figure 3: Current therapeutic targets in the neuroendocrine tumor cell.
Figure 4: High-resolution CT scans showing the two distinct metastatic types of ileal neuroendocrine tumors.

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Change history

  • 13 December 2011

    In the version of this article initially published online, in Table 2, the value for the Ki-67 index (%) for NET Grade 1 should have read ≤2 instead of <2. The error has been corrected for the HTML and PDF versions of the article.

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G. Rindi declares associations with the following companies: Ipsen (consultant), Novartis (speakers bureau), Pfizer (speakers bureau). B. Wiedenmann declares associations with the following companies: Ipsen (consultant, speakers bureau), Lexicon (consultant), Novartis (consultant, speakers bureau), Pfizer (consultant, speakers bureau).

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Rindi, G., Wiedenmann, B. Neuroendocrine neoplasms of the gut and pancreas: new insights. Nat Rev Endocrinol 8, 54–64 (2012). https://doi.org/10.1038/nrendo.2011.120

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