Management of Pancreatic Endocrine Tumors in Multiple Endocrine Neoplasia Type 1

Abstract

Introduction: Pancreatic endocrine tumors (PETs) occur in at least 50% of patients with multiple endocrine neoplasia type 1 (MEN1) and are the leading cause of disease-specific mortality. However, the timing and extent of surgery for MEN1-related PETs is controversial owing to the indolent tumor growth seen in most patients and the desire to avoid complications associated with insulin dependence. To help resolve this controversy, we retrospectively analyzed the clinical characteristics, surgical treatment, and clinical outcome of patients with MEN1-related PETs. Methods: All patients had histologic or radiographic confirmation of a PET in the setting of MEN1. Disease progression was defined radiographically as the development of new pancreatic tumors or distant metastases. Progression-free survival (PFS) and overall survival (OS) were used as the endpoints of this analysis. Results: We identified 98 patients with MEN1, 55 (56%) of whom had PETs, including 27 women and 28 men with a median age of 37 years (range 8-69 years) at the time of diagnosis. Functioning PETs were present in 35 (64%) of 55 patients, and nonfunctioning tumors were present in 20 (36%). Pancreatic surgery was performed in 38 (69%) of the 55 patients; and the first operation included enucleation (n = 4), total pancreatectomy (n = 3), Whipple procedure (n = 4), and distal pancreatectomy (n = 27). The median size of the resected tumors was 2.8 cm (range 0.6-11.0 cm). Recurrent disease developed in the residual pancreas in 7 (20%) of 35 at-risk patients a median of 7.8 years after the first operation, and distant metastases occurred in 5 (14 %) of 36 surgically treated patients without distant metastasis (2 patients had distant metastases when surgery on the primary tumor was performed) at a median of 2.7 years following surgery. At last follow-up, 16 (29%) of 55 patients with PETs had died, 12 (22%) were alive with disease, 26 (47%) were alive without evidence of disease, and 1 (2%) was lost to follow-up. The median OS was 19.5 years (range 13-26 years) and was significantly longer for patients who had functioning PETs versus those with nonfunctioning tumors (P = 0.0007), for patients who underwent surgical resection of their PETs versus those who did not (P = 0.0043), and for patients with localized versus metastatic PETs at the time of diagnosis (P < 0.0001). Multivariate analysis revealed that

The Impact of Clinical and Genetic Screenings on the Management of the Multiple Endocrine Neoplasia Type 1

“…25,26 More than 90% of MEN1-associated thymic carcinoids are malignant; [25][26][27] however, these tumors are relatively rare. On the other hand, although gastrinomas are usually less malignant (60%) than thymic carcinoids, 28 they can be detected in up to 75% of MEN1 cases depending on the series (Table 1). Malignancies are responsible for significant lowering ages of death verified for MEN1 (55.4 years for men and 46.8 years for women), as compared to life expectation in the general population (> 70 years).…”

Neuroendocrine tumor disease: an evolving landscape

“…Up to 80% of patients affected by MEN1 develop synchronous or metachronous pancreatic islet cell or duodenal tumors, of them gastrinomas in 54%, insulinomas in 18%, and nonfunctional tumors in 80-100% (Triponez & Cadiot 2007). As occurrence of metastases in nonfunctioning PNENs rises markedly with tumor size (O10 mm), several groups consequently recommend surgical removal of lesions exceeding this size (Bartsch et al 2005, Kouvaraki et al 2006, Triponez et al 2006, You et al 2007, Ekeblad et al 2008, Akerstrom & Hellman 2009). Others claim a tumor size O2 cm as indication for surgery, but it is clear that a large proportion of these patients already have metastases (Bartsch et al 2005, Kouvaraki et al 2006, Triponez et al 2006, Triponez & Cadiot 2007, You et al 2007, Ekeblad et al 2008, Akerstrom & Hellman 2009.…”

“…Elevated serum hormone biomarkers indicate development of functioning lesions even before a clinical hormonal syndrome has occurred (Bartsch et al 2005, Kouvaraki et al 2006, You et al 2007, Ekeblad et al 2008, Akerstrom & Hellman 2009). When such a syndrome has developed, 30-50% of patients already have metastases.…”

Feasibility of Mesenteric Vein Reconstruction with PTFE Prosthesis for Non Functioning Endocrine Pancreatic Tumor Surgery

“…The revision of the NFPETs in MEN1 has clearly shown an association between large primary tumor size, the presence of distant metastases and the mortality due to tumoral progression [7][8][9]. EPTs have been recently stratified, on the basis of the WHO classification, in 3 categories: benign tumors, well-differentiated carcinomas with low-grade malignant behaviour and poorly-differentiated carcinomas with high grade malignant behaviour [10].…”