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Seminars in Cancer Biology Feb 2022Neuroendocrine neoplasms (NENs) are relatively rare neoplasms with 6.4-times increasing age-adjusted annual incidence during the last four decades. NENs arise from... (Review)
Review
Neuroendocrine neoplasms (NENs) are relatively rare neoplasms with 6.4-times increasing age-adjusted annual incidence during the last four decades. NENs arise from neuroendocrine cells, which release hormones in response to neuronal stimuli and they are distributed into organs and tissues. The presentation and biological behaviour of the NENs are highly heterogeneous, depending on the organ. The increased incidence is mainly due to increased awareness and improved detection methods both in the majority of sporadic NENs (non-inherited), but also the inherited groups of neoplasms appearing in at least ten genetic syndromes. The most important one is multiple endocrine neoplasia type 1 (MEN-1), caused by mutations in the tumour suppressor gene MEN1. MEN-1 has been associated with different tumour manifestations of NENs e.g. pancreas, gastrointestinal tract, lungs, thymus and pituitary. Pancreatic NENs tend to be less aggressive when arising in the setting of MEN-1 compared to sporadic pancreatic NENs. There have been very important improvements over the past years in both genotyping, genetic counselling and family screening, introduction and validation of various relevant biomarkers, as well as newer imaging modalities. Alongside this development, both medical, surgical and radionuclide treatments have also advanced and improved morbidity, quality of life and mortality in many of these patients. Despite this progress, there is still space for improving insight into the genetic and epigenetic factors in relation to the biological mechanisms determining NENs as part of MEN-1. This review gives a comprehensive update of current evidence for co-occurrence, diagnosis and treatment of MEN-1 and neuroendocrine neoplasms and highlight the important progress now finding its way to international guidelines in order to improve the global management of these patients.
Topics: Biomarkers, Tumor; Diagnostic Techniques, Radioisotope; Gastrinoma; Gastrointestinal Neoplasms; Genetic Predisposition to Disease; Humans; Lung Neoplasms; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pancreatic Neoplasms; Proto-Oncogene Proteins
PubMed: 33905872
DOI: 10.1016/j.semcancer.2021.04.011 -
Seminars in Pediatric Surgery Jun 2020The vast majority of medullary thyroid carcinomas (MTC) in children are inherited as part of the multiple endocrine neoplasia (MEN) syndromes MEN2A and MEN2B, and the... (Review)
Review
The vast majority of medullary thyroid carcinomas (MTC) in children are inherited as part of the multiple endocrine neoplasia (MEN) syndromes MEN2A and MEN2B, and the related variant, familial MTC. Prophylactic surgery in infants and children identified through genetic screening leads to the highest survival in these patients. This article summarizes the current recommendations for screening, treatment, and surveillance of children with MTC to provide a concise clinically relevant review for pediatric practitioners.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Neuroendocrine; Chemotherapy, Adjuvant; Child; Early Detection of Cancer; Genetic Testing; Humans; Multiple Endocrine Neoplasia; Neck Dissection; Neoplasm Metastasis; Postoperative Care; Prophylactic Surgical Procedures; Thyroid Neoplasms; Thyroidectomy; Treatment Outcome
PubMed: 32571506
DOI: 10.1016/j.sempedsurg.2020.150921 -
Presse Medicale (Paris, France : 1983) Sep 2018Multiple endocrine neoplasia type 1 is a rare genetic syndrome, characterized by the co-occurrence, in the same individual or in related individuals of the same family,... (Review)
Review
Multiple endocrine neoplasia type 1 is a rare genetic syndrome, characterized by the co-occurrence, in the same individual or in related individuals of the same family, of hyperparathyroidism, duodenopancraetic neuroendocrine tumors, pituitary adenomas, adrenocortical tumors, and neuroendocrine tumors (carcinoids) in the thymus, the bronchi, or the stomach. Multiple endocrine neoplastic type 2 is a rare genetic syndrome, characterized by the familial occurrence of medullary thyroid carcinoma either isolated or associated with pheochromocytoma, primary hyperparathyroidism, or typical features (Marfanoid habitus, mucosal neuromas). Subjects with clinical MEN1 and those who carry a mutation in the MEN1 gene should be offered biochemical and imaging screening in order to detect tumors and evaluate their progression over time. Children with mutation in the RET gene should have prophylactic total thyroidectomy according to the category of aggressiveness of the detected mutation whereas those with clinical MEN2 should be operated on upon diagnosis. In MEN1 patients, special attention should be paid to evaluate the progression duodenopancraetic neuroendocrine tumors because of their malignant potential. Also, thymic neuroendocrine tumors should be detected as soon as possible because they represent the most lethal tumor. In MEN2, calcitonin and carcinoembryonic antigen (CEA) serve as excellent tumor markers for medullary thyroid carcinoma. Their preoperative levels are correlated with tumor size and predict postoperative cure. Moreover, calcitonin or CEA doubling time has important prognostic value. In both MEN syndromes, multidisciplinary approaches are very important in the care of affected patients. Moreover, those patients should be comprehensively informed and enabled to participate in the decision-making procedure. In addition to multidisciplinary approaches, every effort should be made to follow the recommendations and guidelines issued by national (the French Group of Endocrine Tumors) and international groups.
Topics: Humans; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2a; Mutation; Prognosis
PubMed: 29909163
DOI: 10.1016/j.lpm.2018.03.005 -
AJR. American Journal of Roentgenology Oct 2020Multiple endocrine neoplasia (MEN) syndromes are autosomal-dominant genetic disorders that predispose two or more organs of the endocrine system to tumor development.... (Review)
Review
Multiple endocrine neoplasia (MEN) syndromes are autosomal-dominant genetic disorders that predispose two or more organs of the endocrine system to tumor development. Although the diagnosis relies on clinical and serologic findings, imaging provides critical information for surgical management with the ultimate goal of complete tumor resection. This article reviews abdominal neoplasms associated with the various subtypes of MEN syndromes, with a focus on clinical presentation and characteristic imaging features.
Topics: Abdominal Neoplasms; Humans; Multiple Endocrine Neoplasia; Radiography, Abdominal
PubMed: 32755185
DOI: 10.2214/AJR.19.22542 -
AJR. American Journal of Roentgenology Jul 2021The purpose of this article is to review the clinical manifestations, endocrine tumors types, and multimodality diagnostic tools available to physicians involved in the... (Review)
Review
The purpose of this article is to review the clinical manifestations, endocrine tumors types, and multimodality diagnostic tools available to physicians involved in the management of patients with multiple endocrine neoplasia (MEN) syndrome, in addition to discussing relevant imaging findings and appropriate imaging follow-up. Thorough knowledge of the spectrum of tumors associated with gene mutations aids in the screening, diagnostic workup, and posttreatment monitoring of patients with MEN-related gene mutations.
Topics: Endocrine Glands; Humans; Multimodal Imaging; Multiple Endocrine Neoplasia; Tomography Scanners, X-Ray Computed; Tomography, Emission-Computed, Single-Photon; Ultrasonography
PubMed: 33909463
DOI: 10.2214/AJR.20.22933 -
Gastroenterology Jun 2022
Topics: Deglutition Disorders; Esophageal Stenosis; Esophagoscopy; Humans; Multiple Endocrine Neoplasia
PubMed: 34688705
DOI: 10.1053/j.gastro.2021.10.021 -
Molecular and Cellular Endocrinology Feb 2016Multiple endocrine neoplasia (MEN) syndromes are autosomal dominant diseases with high penetrance characterized by proliferative lesions (usually hyperplasia or adenoma)... (Review)
Review
Multiple endocrine neoplasia (MEN) syndromes are autosomal dominant diseases with high penetrance characterized by proliferative lesions (usually hyperplasia or adenoma) arising in at least two endocrine tissues. Four different MEN syndromes have been so far identified: MEN type 1 (MEN1), MEN2A (also referred to as MEN2), MEN2B (or MEN3) and MEN4, which have slightly varying tumor spectra and are caused by mutations in different genes. MEN1 associates with loss-of-function mutations in the MEN1 gene encoding the tumor suppressor menin. The MEN2A and MEN2B syndromes are due to activating mutations in the proto-oncogene RET (Rearranged in Transfection) and are characterized by different phenotypic features of the affected patients. MEN4 was the most recent addition to the family of the MEN syndromes. It was discovered less than 10 years ago thanks to studies of a rat strain that spontaneously develops multiple endocrine tumors (named MENX). These studies identified an inactivating mutation in the Cdkn1b gene, encoding the putative tumor suppressor p27, as the causative mutation of the rat syndrome. Subsequently, germline mutations in the human ortholog CDKN1B were also found in a subset of patients with a MEN-like phenotype and this led to the identification of MEN4. Small animal models have been instrumental in understanding important biochemical, physiological and pathological processes of cancer onset and spread in intact living organisms. Moreover, they have provided us with insight into gene function(s) and molecular mechanisms of disease progression. We here review the currently available animal models of MEN syndromes and their impact on the elucidation of the pathophysiology of these diseases, with a special focus on the rat MENX syndrome that we have been characterizing.
Topics: Animals; Cyclin-Dependent Kinase Inhibitor p27; Disease Models, Animal; Female; Genetic Predisposition to Disease; Humans; Male; Mice; Multiple Endocrine Neoplasia; Proto-Oncogene Mas; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ret; Rats
PubMed: 26184857
DOI: 10.1016/j.mce.2015.07.004 -
Genes Sep 2023The aim of this study is to evaluate the predictive role of specific clinical factors for the diagnosis of Multiple Endocrine Neoplasia type-1 (MEN1) and type-4 (MEN4)...
UNLABELLED
The aim of this study is to evaluate the predictive role of specific clinical factors for the diagnosis of Multiple Endocrine Neoplasia type-1 (MEN1) and type-4 (MEN4) in patients with an initial diagnosis of gastrointestinal, bronchial, or thymic neuroendocrine tumor (NET).
METHODS
Patients referred to the NET Unit between June 2021 and December 2022 with a diagnosis of NET and at least one clinical criterion of suspicion for MEN1 and MEN4 underwent molecular analysis of the and genes. Phenotypic criteria were: (1) age ≤ 40 years; (2) NET multifocality; (3) MEN1/4-associated manifestations other than NETs; and (4) endocrine syndrome related to NETs or pituitary/adrenal tumors.
RESULTS
A total of 22 patients were studied. In 18 patients (81.8%), the first-level genetic test was negative (Group A), while four patients (25%) were positive for (Group B). No patient was positive for . In Group A, 10 cases had only one clinical criterion, and three patients met three criteria. In Group B, three patients had three criteria, and one met all criteria.
CONCLUSION
These preliminary data show that a diagnosis of NET in patients with a negative family history is suggestive of MEN1 in the presence of ≥three positive phenotypic criteria, including early age, multifocality, multiple MEN-associated manifestations, and endocrine syndromes. This indication may allow optimization of the diagnosis of MEN in patients with NET.
Topics: Humans; Adult; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pituitary Neoplasms; Genetic Testing; Gastrointestinal Tract
PubMed: 37761922
DOI: 10.3390/genes14091782 -
Frontiers in Endocrinology 2023
Topics: Humans; Multiple Endocrine Neoplasia Type 1
PubMed: 37635979
DOI: 10.3389/fendo.2023.1266148 -
Annals of Surgical Oncology Jun 2024Jeffrey A. Norton could have been a professional football player but instead he chose to pursue a career in medicine and in the process became an outstanding academic...
BACKGROUND
Jeffrey A. Norton could have been a professional football player but instead he chose to pursue a career in medicine and in the process became an outstanding academic surgeon. This story recounts his ascent from a small town in Massachusetts to the pinnacle of academic surgery.
METHODS
After graduating from high school in Albany, New York, Jeff continued his education at Dartmouth University, the State University of New York Upstate Medical University at Syracuse (SUNY Upstate Medical University), and the Department of Surgery at the Duke University School of Medicine. When he completed the surgical residency, he spent 10 years at the National Cancer Institute (NCI) where he and his colleagues made significant contributions to the diagnosis and treatment of patients with endocrine tumors. After leaving the NCI, he had highly productive years as a Professor in Departments of Surgery at Washington University, the University of California at San Francisco, and Stanford University. He became a member of every major academic surgical society and won numerous awards for his accomplishments in research. His expertise in educating medical students and surgical residents is legendary.
RESULTS
In addition to his academic accomplishments, Jeff trained legions of young surgeons who subsequently made significant contributions in surgical investigation and clinical surgery.
CONCLUSION
It is most fitting that the Stanford University School of Medicine has assembled a group of Jeffrey Norton's colleagues in academic medicine and surgery to pay tribute to his achievements as a surgical scientist.
Topics: Humans; History, 20th Century; Multiple Endocrine Neoplasia; United States; History, 21st Century
PubMed: 38494562
DOI: 10.1245/s10434-024-15079-1