The Current Strategy for Managing Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is an inherited autosomal dominant disease presenting with pancreatic neuroendocrine tumors (pNETs), parathyroid tumors, or pituitary tumors. Using the PubMed database, we reviewed the literature on information regarding the proper diagnosis and treatment of MEN1-associated pNET. Many cases of MEN1-associated pNET are functioning pNETs. Gastrinomas and insulinomas tend to occur frequently in the duodenum and pancreas, respectively. In addition to diagnostic imaging, the selective arterial secretagogue injection test (SASI test) is useful for localizing functioning pNET. The standard treatment is surgical resection. However, in the case of a functioning pNET, the tumor should first be accurately located using the SASI test before an appropriate surgical method is selected. In cases of a MEN1-associated non-functioning pNET that exceeds 2 cm in diameter, the incidence of distant metastasis is significantly increased, and surgery is recommended. In cases of unresectable pNET, a somatostatin analog has been shown to demonstrate antitumor effects and is considered to be a promising treatment. In addition, molecular-targeted drugs have recently been found to be effective in phase III clinical trials.

Epidemiological trends of pancreatic and gastrointestinal neuroendocrine tumors in Japan: a nationwide survey analysis

“…At present, 4 genetic diseases-MEN-1, von HippelLindau (VHL) disease, von Recklinghausen disease, and tuberous sclerosis-are thought to be associated with NETs [23]. As for PNETs complicated with MEN-1 [24,25] or VHL, [26], screening must be performed at the initial diagnosis of PNETs because of different surveillance methods and treatment guidelines. MEN-1 is reported to be complicated with NF-PNETs, gastrinoma, and insulinoma at frequencies of about 80 %, 50 %, and 20 %, respectively [23].…”

MANAGEMENT OF ENDOCRINE DISEASE: A clinical update on tumor-induced hypoglycemia

“…Surgery is usually performed in MEN1-associated insulinoma even if the tumor cannot be identified by imaging due to the intense symptoms caused by hyperinsulinemia. Lastly, because insulinomas in these patients are usually multicentric, complete surgical resection is more difficult and local tumor resection often results in disease recurrence (52,53).…”

Pancreatic Neuroendocrine Tumors in the 21<sup>st</sup> Century—An Update

“…It is additionally hypothesized that additional oncogenes and tumour suppressor genes may be at 11q, downstream from MEN-1, that play a role in PNET development [29]. [40], though 54% -93% of MEN-1 patients are asymptomatic [41]. Patients more often present with hyperparathyroidism or hyperpituitarism, with the PNET being diagnosed incidentally after confirmatory diagnosis of MEN-1.…”

“…PNETs are often multiple with tiny lesions that may only be detected with EUS/intraductal ultrasonography. Unresectable advanced PNET burden are controlled through hormone regulation, hepatic metastases management, and systemic chemotherapy [40]. There remains no consensus on the best treatment guidelines for non-functional PNETs associated with MEN-1.…”

“…In contrast, insulinomas in patients with MEN-1 should undergo surgical resection including subtotal pancreatic resection with splenic preservation combined with enucleation providing there are no metastases, as cure rates of 83% -100% can be achieved [42] [44]. A distal pancreatectomy is often required to decrease recurrence risk [40]. In these patients, enucleation alone is less effective as tumours are often small and multifocal.…”