Neuroendocrine Tumors of the Pancreas

Ehehalt, Florian; Saeger, H. D.; Schmidt, C. Max; Grützmann, Robert

doi:10.1634/theoncologist.2008-0259

Cited by 221 publications

(179 citation statements)

References 119 publications

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“…Gastrin-producing G cells are present in fetal but not normal adult pancreatic islets [94,95]. The quotient of all pancreatic endocrine cells is 1-2% of the entire pancreatic cell mass [96].…”

Section: Pancreatic Endocrine Tumorsmentioning

confidence: 99%

The diversity and commonalities of gastroenteropancreatic neuroendocrine tumors

Schimmack

Svejda

Lawrence

et al. 2011

Langenbecks Arch Surg

143

130

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The gastrointestinal tract and pancreas exhibit ~17 different neuroendocrine cell types, but neither the cell of origin nor the biological basis of GEP-NETs is understood. This review examines GEP-NETs from the cellular and molecular perspective and addresses the distinct patterns of functional tumor biology pertinent to clinicians. Although grouped as a neoplastic entity (NETs), each lesion is derived from distinct cell precursors, produces specific bioactive products, exhibits distinct chromosomal abnormalities and somatic mutation events and has uniquely dissimilar clinical presentations. GEP-NETs demonstrate very different survival rates reflecting the intrinsic differences in malignant potential and variations in proliferative regulation. Apart from the identification of the inhibitory role of the somatostatin receptors, there is limited biological knowledge of the key regulators of proliferation and hence a paucity of successful targeted therapeutic agents. IGF-I, TGFβ and a variety of tyrosine kinases have been postulated as key regulatory elements; rigorous data is still required to define predictably effective and rational therapeutic strategy in an individual tumor. A critical issue in the clinical management of GEP-NETs is the need to appreciate both the neuroendocrine commonalities of the disease as well as the unique characteristics of each tumor. The further acquisition of a detailed biological and molecular appreciation of GEP-NETs is vital to the development of effective management strategy.

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Section: Pancreatic Endocrine Tumorsmentioning

confidence: 99%

The diversity and commonalities of gastroenteropancreatic neuroendocrine tumors

Schimmack

Svejda

Lawrence

et al. 2011

Langenbecks Arch Surg

143

130

View full text Add to dashboard Cite

show abstract

“…According to the WHO (Solcia et al 2000), these tumors are classified into well-differentiated NETs and carcinomas (wdNET and wdNEC respectively), and poorly differentiated neuroendocrine carcinomas (pdNEC). Moreover, pancreatic endocrine tumors (PETs) are classified into functioning (insulinoma, gastrinoma, glucagonoma, somatostatinoma, and VIPoma) or nonfunctioning neoplasias (Ehehalt et al 2009). Carcinoid tumors are the most frequent gastrointestinal NETs and are able to secrete different molecules, including CgA and 5-hydroxy-indole acetic acid (5-HIAA) that are used as markers for the diagnosis and follow-up of these patients (Haverback et al 1956, Rindi et al 1996, von Wichert et al 2008.…”

Section: Introductionmentioning

confidence: 99%

The association of the angiopoietin/Tie-2 system with the development of metastasis and leukocyte migration in neuroendocrine tumors

Figueroa-Vega

Díaz²,

Adrados³

et al. 2010

Endocrine-Related Cancer

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The aim of this study was to explore the possible involvement of the angiopoietin (Ang)-1, -2/Tie-2 system in the development, growth, and metastases evolution of gastroenteropancreaticneuroendocrine tumors (GEP-NETs). We prospectively examined the serum levels of Tie-2, Ang-1, and Ang-2 by ELISA in 42 patients with proven GEP-NETs and 27 controls. We also determined the expression of the Ang/Tie-2 system in freshly isolated peripheral blood monocytes and in tumor cells from malignant primary tumors and/or liver metastases samples from GEP-NET patients by flow cytometry and/or RT-PCR. Furthermore, the function of the Ang/Tie-2 system in monocytes from controls and patients was assessed by a chemotaxis assay. GEP-NET patients showed enhanced serum levels of soluble form of Tie-2 (sTie-2), Ang-1, and Ang-2 (P!0.05 in all cases), compared to controls. sTie-2 and Ang-2 levels were significantly higher in GEP-NETs with metastases compared to those with no metastases. In addition, a significant correlation was detected between Ang-2 levels and chromogranin A or sTie-2 concentrations or 5-hydroxy-indole acetic acid excretion (rZ0.71, rZ0.60, and rZ0.81 respectively, P!0.01 in all cases). Furthermore, we observed an enhanced expression of Ang-1, Ang-2, and Tie-2 in freshly isolated tumor cells from GEP-NET both by immunohistochemistry and by RT-PCR. Interestingly, an enhanced expression and function of Tie-2 was detected in monocytes from GEP-NET patients. Our data suggest that the Ang/Tie-2 system is involved in the growth and development of metastases of GEP-NETs, and that favors the recruitment of Tie-2 C monocytes to the tumor site, where they can promote inflammation and angiogenesis.

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“…1,2 The combination of low incidence and sporadically uncharacteristic clinical behavior has precluded the controlled evaluation and development of multimodal treatment regimens. [3][4][5] However, the optimal management of gastrointestinal malignancies has increasingly necessitated multidisciplinary approaches with input from both medical and surgical specialties. Our objective was to examine the multidisciplinary management of patients with ICC within a large population-based cancer registry to determine the role of surgical and medical therapies in the management of ICC.…”

Section: Introductionmentioning

confidence: 99%