The future: surgical advances in MEN1 therapeutic approaches and management strategies

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary autosomal dominant disorder associated with numerous neuroendocrine tumors (NETs). Recent advances in the management of MEN1 have led to a decrease in mortality due to excess hormones; however, they have also led to an increase in mortality from malignancy, particularly NETs. The main challenges are to localize these tumors, to select those that need therapy because of the risk of aggressive behavior and to select the appropriate therapy associated with minimal morbidity. This must be applied to a hereditary disease with a high risk of recurrence. The overall aim of management in MEN1 is to ensure that the patient remains disease-and symptom-free for as long as possible and maintains a good quality of life. Herein, we review the changes that occurred in the last 20 years in the surgical management of MEN1-associated functional and non-functional pancreaticoduodenal NETs and thymic and bronchial NETs.

Multiple Endocrine Neoplasia Type 1 (MEN1): An Update and the Significance of Early Genetic and Clinical Diagnosis

“…In the aforementioned cohort of 160 patients with MEN1 below the age of 21, insulinoma occurred in 10% of patients and as early as 5 years of age (18). These tumors are solitary in 85% and multiple in 6–13% of cases, and are associated with other pNETs at the time of diagnosis in 10% of patients (112). They are scattered across the pancreas and tend to be small, with 82% of these neoplasms measuring less than 2 centimeters and 47% measuring less than 1 centimeter, which may make them difficult to localize (113).…”

“…Metastatic insulinoma is rare, occurring in 4–14% of cases, with the goal of treatment, as in other malignant functioning pNETs, being symptom control and tumor volume reduction with possible resection of lesions that are amenable to surgery (124, 125). In cases with unresectable disease or in patients that need further symptom control, adjuvant therapy may vary from diazoxide and SSAs to everolimus and chemotherapy, as well as local therapies (radiofrequency ablation [RFA], chemoembolization, or radiotherapy) or peptide receptor radionuclide therapy (PRRT) (112).…”

“…The diagnosis of a VIPoma is made through evidence of a fasting stool volume >1–2 liters per day and a significantly increased plasma VIP concentration, in the absence of laxative or diuretic use (8). The treatment approach for both glucagonomas and VIPomas is similar to that for insulinomas as described above (112).…”

“…Previous studies have shown an increased rate of metastases in patients with larger tumors (6, 7, 87, 136). However, there is controversy among experts regarding the tumor size cutoff for offering surgery, with the suggested cutoff ranging between 1 and 3 centimeters (8, 112, 137). There is a consensus that withholding surgery for tumors that reach or exceed 3 centimeters in size leads to a negative prognosis, however the indication for surgical intervention in smaller-sized tumors is unclear (138).…”

“…Most individuals may be asymptomatic at diagnosis, however liver, bone, and lung metastases may be identified. Biochemical evaluation is not useful diagnostically in these patients with the diagnostic studies of choice being CT or MRI of the chest (112, 162). MEN1-associated th-NETs comprise the second most common MEN1-related cause of death and have a high mortality rate, with the 10-year survival rate in several larger studies ranging between 25 and 45% (153, 157, 163).…”