Epidemiology Data on 108 MEN 1 Patients From the GTE With Isolated Nonfunctioning Tumors of the Pancreas

Abstract

Objective: To analyze the penetrance and clinical course of isolated nonfunctioning tumors of the pancreas (NFTP) in MEN 1 patients, and to propose a strategy for managing them. Summary Background Data: Pancreaticoduodenal tumors develop in a majority of MEN 1 patients and are a major cause of death. The natural history of NFTP is poorly defined, and no clear-cut guidelines have been widely accepted regarding treatment. Methods: Data on 108 patients with isolated NFTP among 579 MEN 1 patients from the French Endocrine Tumor Study Group (GTE) were analyzed. Survival rates were calculated using the Kaplan-Meier method. Results: The penetrance of NFTP was 34% at age 50, making it the most frequent pancreaticoduodenal tumor in MEN 1 patients. Fortythree patients (40%) underwent surgery, 32 of them curatively. No patient died because of surgery. Average life expectancy for patients with NFTP was shorter than that for MEN 1 patients who did not have pancreaticoduodenal tumors. Thirteen patients died during follow-up, 10 due to NFTP. Tumor size was correlated with the risks of metastasis and death. These risks were low for patients with tumors Յ20 mm. Conclusions: NFTP are currently the most common tumors of the pancreaticoduodenal region in patients with MEN 1. Prevention of tumor spread by surgery should be balanced with potential operative mortality and morbidity. We do not recommend routine surgery for NFTP Յ20 mm. (Ann Surg 2006;243: 265-272) M ultiple endocrine neoplasia type 1 (MEN 1) is a rare autosomal dominant condition characterized by the development of endocrine parathyroid, pancreaticoduodenal, and pituitary tumors. In addition, MEN 1 patients are also prone to developing adrenal tumors, neuroendocrine tumors (in particular of the thymus or bronchus), dermal lesions, thyroid disease, and meningeal tumors. 1-7Pancreaticoduodenal tumors are often multiple, have been shown at autopsy to have developed in up to 80% of patients with MEN 1, and are a major cause of premature death in these patients. 8 -12 Most pancreaticoduodenal tumors are functioning tumors, the most frequent of which are gastrinomas and insulinomas, followed by the rare glucagonomas, VIPomas, GRFomas, and somatostatinomas. Surgical resection is the treatment of choice for functioning tumors of the pancreas, although controversy exists regarding the timing of surgery for gastrinomas. [13][14][15][16][17][18] In the absence of hormonal symptoms, nonfunctioning tumors of the pancreas (NFTP) have been recognized as a separate entity whose penetrance in the MEN 1 population is not well known. 19,20 In addition, because large surgical series of patients presenting with isolated NFTP are lacking and few clinical series have followed patients with NFTP, no clear-cut treatment guidelines have been widely accepted. Some authors have recommended a conservative approach for asymptomatic NFTP less than 1, 2, or 3 cm. [21][22][23][24] Others have recommended early surgical excision of all tumors as soon as they are found on imaging studies, or even ea...

GEP–NETS UPDATE: A review on surgery of gastro-entero-pancreatic neuroendocrine tumors

“…On the contrary, total pancreatectomy is highly recommended in the presence of a familial history of disease-related mortality (85). Pancreatic NETs !2 cm are associated with a very low risk of metastases and mortality (88). For this reason, for patients with MEN1 affected by pancreatic NETs !2 cm, a careful watching policy is recommended.…”

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.…”

Ventricular fibrillation resulting from electrolyte imbalance reveals vipoma in MEN1 syndrome

“…The relevant MEN1 case series published in the literature report a 1 % incidence of VIPomas [13,14]. The age at diagnosis is usually younger than in sporadic VIPomas.…”