Biochemically curative surgery for gastrinoma in multiple endocrine neoplasia type 1 patients

Mutations of the multiple endocrine neoplasia type 1 (MEN1) gene lead to loss of function of its protein product menin. In keeping with its tumor suppressor function in endocrine tissues, the majority of the MEN1-related neuroendocrine tumors (NETs) show loss of heterozygosity (LOH) on chromosome 11q13. In sporadic NETs, MEN1 mutations and LOH are also reported, indicating common pathways in tumor development. Prevalence of thymic NETs (thNETs) and pulmonary carcinoids in MEN1 patients is 2-8%. Pulmonary carcinoids may be underreported and research on natural history is limited, but disease-related mortality is low. thNETs have a high mortality rate. Duodenopancreatic NETs (dpNETs) are multiple, almost universally found at pathology, and associated with precursor lesions. Gastrinomas are usually located in the duodenal submucosa while other dpNETs are predominantly pancreatic. dpNETs are an important determinant of MEN1-related survival, with an estimated 10-year survival of 75%. Survival differs between subtypes and apart from tumor size there are no known prognostic factors. Natural history of nonfunctioning pancreatic NETs needs to be redefined because of increased detection of small tumors. MEN1-related gastrinomas seem to behave similar to their sporadic counterparts, while insulinomas seem to be more aggressive. Investigations into the molecular functions of menin have led to new insights into MEN1-related tumorigenesis. Menin is involved in gene transcription, both as an activator and repressor. It is part of chromatin-modifying protein complexes, indicating involvement of epigenetic pathways in MEN1-related NET development. Future basic and translational research aimed at NETs in large unbiased cohorts will clarify the role of menin in NET tumorigenesis and might lead to new therapeutic options.

Section: Epidemiologymentioning

confidence: 99%

Section: Epidemiologymentioning

confidence: 99%

Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis

Pieterman¹,

Conemans²,

Dreijerink³

et al. 2014

“…However, this can only be achieved if all gastrinomas are resected, which necessitates aggressive resection (Whipple procedure or partial pancreaticoduodenectomy) (Mignon & Cadiot 1998, Norton et al 2001, Jensen et al 2008, Imamura et al 2011, Lopez et al 2013. Some groups perform duodenectomy without pancreatectomy, associated with lymph node resection (Imamura et al 2011).…”

Section: Peculiarities Of Zes Treatment In Patients With Men1mentioning

confidence: 99%

“…is performed when it is localized to the duodenum/ pancreatic head (Imamura et al 2011, Lopez et al 2013. The endpoint used to compare both types of management (i.e.…”

Section: :10mentioning

confidence: 99%

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

Sadowski¹,

Cadiot²,

Dansin³

et al. 2017

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.

“…Gastrin secreting NETs are mostly located submucosally in the duodenum and then often occur as multiple tumors , Norton et al 2001, Pieterman et al 2014. Rates of pancreatic gastrinomas are only 0-18% in series that include immunohistochemistry in the classification of pNETs (Tonelli et al 2006, Dickson et al 2011, Imamura et al 2011, Lopez et al 2013. Insulinomas occur in about 2-24% of patients , Waldmann et al 2009, Goudet et al 2011.…”

Section: Duodenopancreatic Neuroendocrine Tumorsmentioning

confidence: 99%

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

Leeuwaarde

Laat

Pieterman

et al. 2017

Multiple endocrine neoplasia type 1 is a rare autosomal inherited disorder associated with a high risk for patients to simultaneously develop tumors of the parathyroid glands, duodenopancreatic neuroendocrine tumors and tumors of the anterior pituitary gland. Early identification of MEN1 in patients enables presymptomatic screening of manifestations, which makes timely interventions possible with the intention to prevent morbidity and mortality. Causes of death nowadays have shifted toward local or metastatic progression of malignant neuroendocrine tumors. In early cohorts, complications like peptic ulcers in gastrinoma, renal failure in hyperparathyroidism, hypoglycemia and acute hypercalcemia were the primary causes of early mortality. Improved medical treatments of these complications led to a significantly improved life expectancy. The MEN1 landscape is still evolving, considering the finding of breast cancer as a new MEN1-related manifestation and ongoing publications on follow-up and medical care for patients with MEN1. This review aims at summarizing the most recent insights into the follow-up and medical care for patients with MEN1 and identifying the gaps for future research.