Les tumeurs endocrines du pancréas lors de la néoplasie endocrinienne multiple type 1 (NEM1): actualités sur les facteurs pronostiques, l'imagerie et le traitement

Abstract

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 1 (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 MEN1 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 IIIIn-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-α (IFN-α). 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-α (IFN-α) 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%.