Endocrine tumors of the pancreas (EPTs) in multiple endocrine neoplasia (MEN1):: up-date on prognostic factors, diagnostic procedures and treatment

Endocrine pancreatic tumors (EPTs) are uncommon tumors, representing 1-2% of all pancreatic neoplasms. They are categorized on the basis of their clinical features into functioning and non-functioning tumors. EPTs may be part of the multiple endocrine neoplasia type I (MEN 1), an autosomal dominant syndrome due to inactivating germline mutation of the menin gene. Somatic mutations of menin are present in about 20% of sporadic neoplasms, particularly gastrinomas and insulinomas. 30-75% of patients with MEN 1 have EPTs. The most prevalent are the gastrinomas (20-60%), then the insulinomas (5-10%), the glucagonamas and VIPomas (6-10%), whereas the nonfunctioning EPTs are present in 20-40% of patients. The most important biochemical screening marker for EPTs is chromogranin A, as it increases in 50-80% of patients. The most important negative prognostic factors are the presence of metastases, the gross invasion of adjacent organs, the angioinvasion, the perineural invasion and an immunopositivity for Ki-67 > 2%. Among the different imaging techniques, echoendoscopy, computed tomography (CT) and magnetic resonance imaging (MRI) are indicated for the detection of the primary tumor, but In-111-octreotide scintigraphy has the highest sensitivity for detecting metastases. The choice of treatment is still debated and is different when the tumor occurs as a part of the MEN syndrome. The surgical treatment is the first choice for insulinomas and is more controversial for gastrinomas. The medical treatment includes somatostatin analogues (SA), chemotherapy and interferon-alpha (IFN-alpha). SA seem to improve the symptoms and have an antiproliferative effect, the most striking effect being seen in patients with VIPomas. Chemotherapy, which is generally proposed as a combination of streptozotocin (STZ) and 5-fluorouracil (5-FU) or doxorubicin, is indicated when the tumors tend to grow. Interferon-alpha (IFN-alpha) stimulates the immune system, blocks the tumor cells in the G1/S-phase of the cell cycle, inhibits protein and hormone synthesis and inhibits angionenesis. Treatment with IFN has been shown to produce symptomatic response in 40-60% of patients, a biochemical response in 30-60% and tumor shrinkage in 10- 15%. (C) 2007 Elsevier Masson SAS. All rights reserved.