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Del Rivero J, Gangi A, Annes JP, Jasim S, Keller J, Lundholm MD, Silverstein JM, Vaghaiwalla TM, Wermers RA. American Association of Clinical Endocrinology Consensus Statement on Management of Multiple Endocrine Neoplasia Type 1. Endocr Pract 2025; 31:S1530-891X(25)00038-2. [PMID: 40232217 DOI: 10.1016/j.eprac.2025.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 02/03/2025] [Accepted: 02/03/2025] [Indexed: 04/16/2025]
Abstract
OBJECTIVE This document presents the findings of the American Association of Clinical Endocrinology (AACE) on the diagnosis, management, and surveillance of patients with multiple endocrine neoplasia type 1 (MEN1) and associated tumors. The task force included a diverse group of experts in endocrinology, oncology, genetics, surgery, and patient representation. A comprehensive literature review was conducted to address key issues related to the evaluation, surveillance, and treatment of MEN1-related tumors. METHODS The task force, comprised of 9 members with expertise in endocrinology, surgery, medical oncology, genetics, and patient advocacy, collaborated to develop guidance for the evaluation, surveillance, and management of MEN1-associated tumors. Consensus was defined as ≤1 dissenting vote and significant majority as ≥75%. Relevant studies were identified through a literature review process, and consensus statements were based on the available evidence. RESULTS The task force deliberated on the surveillance, evaluation, and management of MEN1-related tumors including parathyroid, pituitary, and gastroenteropancreatic neuroendocrine tumors and other tumors of relevance. The document also addresses the indications for MEN1 genetic testing. CONCLUSIONS This consensus statement aims to offer evidence-informed guidance for health care providers involved in the care of patients with MEN1 and associated tumors. It provides guidance on diagnostic tools, genetic testing criteria, imaging techniques, surgical interventions, and posttreatment monitoring. The practical, patient-centered approach outlined in this document is intended to improve outcomes for individuals with MEN1 and other high-risk endocrine tumors.
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Affiliation(s)
- Jaydira Del Rivero
- National Institutes of Health, National Cancer Institute Center for Cancer Research, Bethesda, Maryland
| | - Alexandra Gangi
- Department of Surgery, Division of Surgical Oncology, Cedars Sinai, Los Angeles, California
| | - Justin P Annes
- Division of Endocrinology, Department of Medicine, Stanford University, Stanford, California
| | - Sina Jasim
- Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri
| | | | - Michelle D Lundholm
- Department of Endocrinology, Diabetes & Metabolism, Cleveland Clinic, Cleveland, Ohio
| | - Julie M Silverstein
- Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri
| | - Tanaz M Vaghaiwalla
- Division of Endocrine Surgery, DeWitt Daughtry Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
| | - Robert A Wermers
- Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, Mayo Clinic, Rochester, Minnesota
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Schubert L, Gaillard M, Melot C, Delbot T, Cottereau AS, Koumakis E, Bonnet-Serrano F, Groussin L. Management of primary hyperparathyroidism in MEN1: From initial subtotal surgery to complex treatment of the remaining gland. ANNALES D'ENDOCRINOLOGIE 2025; 86:101721. [PMID: 40057116 DOI: 10.1016/j.ando.2025.101721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Accepted: 02/11/2025] [Indexed: 04/18/2025]
Abstract
Multiple endocrine neoplasia type 1 (MEN1) is a rare genetic disease with autosomal dominant transmission, which can cause various tumors, particularly endocrine, in a given patient. Primary hyperparathyroidism (PHPT) is the most common and earliest manifestation, leading to surgery before the age of 50 in most patients. Biological severity and renal and/or bone complications dictate the timing of parathyroid surgery. The objective is to correct hypercalcemia to prevent impact, while minimizing the risk of hypoparathyroidism. The most widely recommended procedure is subtotal parathyroidectomy (3 or 3.5 glands removed), with thymic horn resection via a cervical route. The development of imaging techniques, however, makes it possible to discuss partial surgery (resection of 1 or 2 glands) on a case-by-case basis depending on preoperative imaging and other elements such as patient age. Finally, hypercalcemia recurrence after initial surgery is a common feature of MEN1, and management of the remaining gland is challenging with various options: reoperation, calcimimetics and US-guided ablation or therapeutic abstention.
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Affiliation(s)
- Louis Schubert
- Service d'endocrinologie, hôpital Cochin, université Paris-Cité, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France; Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris-Cité, 75014 Paris, France.
| | - Martin Gaillard
- Service de chirurgie viscérale et endocrinienne, hôpital Cochin, université Paris-Cité, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France; Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris-Cité, 75014 Paris, France
| | - Charlotte Melot
- Service de chirurgie viscérale et endocrinienne, hôpital Cochin, université Paris-Cité, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Thierry Delbot
- Service de médecine nucléaire, hôpital Cochin, université Paris-Cité, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Anne Ségolène Cottereau
- Service de médecine nucléaire, hôpital Cochin, université Paris-Cité, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France; Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris-Cité, 75014 Paris, France
| | - Eugénie Koumakis
- Service de rhumatologie, hôpital Cochin, université Paris-Cité, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France
| | - Fidéline Bonnet-Serrano
- Service d'hormonologie, hôpital Cochin, université Paris-Cité, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France; Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris-Cité, 75014 Paris, France
| | - Lionel Groussin
- Service d'endocrinologie, hôpital Cochin, université Paris-Cité, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France; Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris-Cité, 75014 Paris, France
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Frye CC, Brown TC, Olson JA. Evaluation and Surgical Management of Multiple Endocrine Neoplasias. Surg Clin North Am 2024; 104:909-928. [PMID: 38944508 DOI: 10.1016/j.suc.2024.02.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/01/2024]
Abstract
Multiple endocrine neoplasia (MEN) syndromes are rare autosomal dominant diseases that are associated with a mixture of both endocrine and non-endocrine tumors. Traditionally, there are 2 types of MEN that have unique clinical associations: MEN 1 (parathyroid hyperplasia, pancreatic neuroendocrine tumors, and pituitary tumors) and MEN 2 (medullary thyroid carcinoma and pheochromocytoma), which is further classified into MEN 2A (adds parathyroid adenomas) and 2B (adds ganglioneuromas and marfanoid habitus). Many of the endocrine tumors are resected surgically, and the pre, intra, and postoperative management strategies used must take into account the high recurrence rates asscioated with MEN tumors.
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Affiliation(s)
- C Corbin Frye
- Department of Surgery, General Surgery Resident, Washington University School of Medicine, St. Louis, MO, USA.
| | - Taylor C Brown
- Department of Surgery, Section of Surgical Oncology, Assistant Professor, Washington University School of Medicine, St. Louis, MO, USA
| | - John A Olson
- Department of Surgery, Section of Surgical Oncology, Chair and Professor, Washington University School of Medicine, St. Louis, MO, USA
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Ito T, Ramos-Alvarez I, Jensen RT. Long-Term Proton Pump Inhibitor-Acid Suppressive Treatment Can Cause Vitamin B 12 Deficiency in Zollinger-Ellison Syndrome (ZES) Patients. Int J Mol Sci 2024; 25:7286. [PMID: 39000391 PMCID: PMC11242121 DOI: 10.3390/ijms25137286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/26/2024] [Accepted: 06/28/2024] [Indexed: 07/16/2024] Open
Abstract
Whether the long-term treatment of patients with proton pump inhibitors (PPIs) with different diseases [GERD, Zollinger-Ellison syndrome (ZES), etc.] can result in vitamin B12 (VB12) deficiency is controversial. In this study, in 175 patients undergoing long-term ZES treatment with anti-acid therapies, drug-induced control acid secretory rates were correlated with the presence/absence of VB12 deficiency, determined by assessing serum VB12 levels, measurements of VB12 body stores (blood methylmalonic acid (MMA) and total homocysteine[tHYC]), and other features of ZES. After a mean of 10.2 yrs. of any acid treatment (5.6 yrs. with PPIs), 21% had VB12 deficiency with significantly lower serum and body VB12 levels (p < 0.0001). The presence of VB12 deficiency did not correlate with any feature of ZES but was associated with a 12-fold lower acid control rate, a 2-fold higher acid control pH (6.4 vs. 3.7), and acid control secretory rates below those required for the activation of pepsin (pH > 3.5). Over a 5-yr period, the patients with VB12 deficiency had a higher rate of achlorhydria (73% vs. 24%) and a lower rate of normal acid secretion (0% vs. 49%). In conclusion, in ZES patients, chronic long-term PPI treatment results in marked acid hyposecretion, resulting in decreased serum VB12 levels and decreased VB12-body stores, which can result in VB12 deficiency.
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Affiliation(s)
- Tetsuhide Ito
- Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital, International University of Health and Welfare, 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan
| | | | - Robert T Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA
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Tanaka Y, Niitani T, Matsumoto T, Abe A, Ishida K, Aoki T. Multiple endocrine neoplasia type 1 with MEN1 variant of unknown significance, in a patient after the diagnosed of pancreatic neuroendocrine neoplasia. Int Cancer Conf J 2024; 13:263-267. [PMID: 38962036 PMCID: PMC11217239 DOI: 10.1007/s13691-024-00675-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 03/19/2024] [Indexed: 07/05/2024] Open
Abstract
Duodenopancreatic neuroendocrine neoplasia (DP-NEN) is in approximately 10% of cases of multiple endocrine neoplasia type 1 (MEN1). We encountered a case in which the onset of NEN led to suspicion and diagnosis of MEN1. Although genetic testing showed MEN1 variant of uncertain significance (VUS), we considered it pathological from the clinical course, promoting the provision of genetic counseling and screening for relatives. MEN1 has a variety of clinical manifestations, and DP-NENs are the second-most common manifestation after primary hyperparathyroidism (pHPT). It is important to assume that MEN1 is an underlying cause of NEN.
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Affiliation(s)
- Yuko Tanaka
- Department of Cancer Genome, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsuga District, Tochigi, 321-0293 Japan
| | - Takafumi Niitani
- Department of Endocrinology and Metabolism, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsuga District, Tochigi, 321-0293 Japan
| | - Takatsugu Matsumoto
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsuga District, Tochigi, 321-0293 Japan
| | - Akihito Abe
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsuga District, Tochigi, 321-0293 Japan
| | - Kazuyuki Ishida
- Department of Diagnostic Pathology, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsuga District, Tochigi, 321-0293 Japan
| | - Taku Aoki
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsuga District, Tochigi, 321-0293 Japan
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Papadopoulou-Marketou N, Tsoli M, Chatzellis E, Alexandraki KI, Kaltsas G. Hereditary Syndromes Associated with Pancreatic and Lung Neuroendocrine Tumors. Cancers (Basel) 2024; 16:2075. [PMID: 38893191 PMCID: PMC11171219 DOI: 10.3390/cancers16112075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 05/19/2024] [Accepted: 05/20/2024] [Indexed: 06/21/2024] Open
Abstract
Pancreatic neuroendocrine tumors (PanNETs) and lung NETs (LNETs) represent a rare but clinically significant subgroup of neoplasms. While the majority is sporadic, approximately 17% of PanNETs and a subset of LNETs develop in the context of monogenic familial tumor syndromes, especially multiple endocrine neoplasia type 1 (MEN1) syndrome. Other inherited syndromes associated with PanNETs include MEN4, von Hippel-Lindau (VHL) syndrome, neurofibromatosis type 1 (NF1), and tuberous sclerosis complex (TSC). These syndromes are highly penetrant and their clinical manifestations may vary even among members of the same family. They are attributed to genetic mutations involving key molecular pathways regulating cell growth, differentiation, and angiogenesis. Pancreatic NETs in hereditary syndromes are often multiple, develop at a younger age compared to sporadic tumors, and are associated with endocrine and nonendocrine tumors derived from multiple organs. Lung NETs are not as common as PanNETs and are mostly encountered in MEN1 syndrome and include typical and atypical lung carcinoids. Early detection of PanNETs and LNETs related to inherited syndromes is crucial, and specific follow-up protocols need to be employed to optimize diagnosis and management. Genetic screening is recommended in childhood, and diagnostic screening starts often in adolescence, even in asymptomatic mutation carriers. Optimal management and therapeutic decisions should be made in the context of a multidisciplinary team in specialized centers, whereas specific biomarkers aiming to identify patients denoted to follow a more aggressive course need to be developed.
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Affiliation(s)
- Nektaria Papadopoulou-Marketou
- Neuroendocrine Tumor Unit, EURACAN 4 and ENETS Centre of Excellence, 1st Department of Propaedeutic Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.T.); (G.K.)
| | - Marina Tsoli
- Neuroendocrine Tumor Unit, EURACAN 4 and ENETS Centre of Excellence, 1st Department of Propaedeutic Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.T.); (G.K.)
| | | | | | - Gregory Kaltsas
- Neuroendocrine Tumor Unit, EURACAN 4 and ENETS Centre of Excellence, 1st Department of Propaedeutic Internal Medicine, Laiko General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece; (M.T.); (G.K.)
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Goudet P, Cadiot G, Barlier A, Baudin E, Borson-Chazot F, Brunaud L, Caiazzo R, Cardot-Bauters C, Castinetti F, Chanson P, Cuny T, Dansin E, Gaujoux S, Giraud S, Groussin L, Le Bras M, Lifante JC, Mathonnet M, de Mestier L, Mirallié E, Pattou F, Romanet P, Sebag F, Tresallet C, Vezzosi D, Walter T, Tabarin A. French guidelines from the GTE, AFCE and ENDOCAN-RENATEN (Groupe d'étude des Tumeurs Endocrines/Association Francophone de Chirurgie Endocrinienne/Reseau national de prise en charge des tumeurs endocrines) for the screening, diagnosis and management of Multiple Endocrine Neoplasia Type 1. ANNALES D'ENDOCRINOLOGIE 2024; 85:2-19. [PMID: 37739121 DOI: 10.1016/j.ando.2023.09.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/24/2023]
Affiliation(s)
- Pierre Goudet
- Department of Digestive and Endocrine Surgery, Dijon University Hospital, Dijon, France; INSERM, U1231, EPICAD Team UMR "Lipids, Nutrition, Cancer", Dijon, France; INSERM, CIC1432, Clinical epidemiology Dijon, Dijon, France.
| | - Guillaume Cadiot
- Department of Hepato-Gastro-Enterology and Digestive Oncology, Robert Debré Hospital, Reims, France.
| | - Anne Barlier
- Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology Hospital La Conception, Marseille, France.
| | - Eric Baudin
- Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
| | - Françoise Borson-Chazot
- Federation of Endocrinology, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon1 University and INSERM U1290, Lyon, France.
| | - Laurent Brunaud
- Department of Gastrointestinal, Visceral, Metabolic, and Cancer Surgery (CVMC), University Hospital of Nancy (CHRU Nancy), University of Lorraine, 54511 Vandoeuvre-les-Nancy, France; INSERM U1256 NGERE, Lorraine University, 11, allée du Morvan, 54511 Vandoeuvre-les-Nancy, France.
| | - Robert Caiazzo
- General and Endocrine Surgery Department, University Hospital Center of Lille, Lille, France.
| | | | - Frédéric Castinetti
- Aix Marseille University, Marseille Medical Genetics, INSERM U1251 and Assistance Publique Hopitaux de Marseille, La Conception Hospital, Department of Endocrinology, Marseille, France.
| | - Philippe Chanson
- University Paris-Saclay, INSERM, Endocrine Physiology and Pathophysiology, Assistance Publique-Hôpitaux de Paris, Bicêtre Hospital, Service of Endocrinology and Reproductive Diseases, National Reference Center for Rare Pituitary Diseases, 94275 Le Kremlin-Bicêtre, France.
| | - Thomas Cuny
- APHM, Marseille Medical Genetics, INSERM U1251, Conception Hospital, Endocrinology Department, Aix Marseille University, Marseille, France.
| | - Eric Dansin
- Department of Medical Oncology, Oscar Lambret Center, 59000 Lille, France.
| | - Sébastien Gaujoux
- Department of Endocrine and Pancreatic Surgery, AP-HP, Pitié-Salpêtrière Hospital, Paris, France.
| | - Sophie Giraud
- Cancer Genetics Unit, Institut Bergonié, Bordeaux, France.
| | - Lionel Groussin
- Department of Endocrinology, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Cité, 75014 Paris, France.
| | - Maëlle Le Bras
- Department of Endocrinology, Nantes University Hospital, Nantes, France.
| | - Jean-Christophe Lifante
- Department of Digestive and Endocrine Surgery, University Hospital of Lyon Sud, Lyon, France; EA 7425 HESPER, Health Services and Performance Research, University Claude Bernard Lyon 1, Lyon, France.
| | - Muriel Mathonnet
- Department of Surgery, Dupuytren University Hospital of Limoges, Limoges, France.
| | - Louis de Mestier
- Paris-Cité University, Department of Pancreatology and Digestive Oncology, Beaujon Hospital (AP-HP-Nord), Clichy, France.
| | - Eric Mirallié
- Department of Oncological, Digestive and Endocrine Surgery (CCDE) Hôtel Dieu, CIC-IMAD, Nantes, France.
| | - François Pattou
- Department of General and Endocrine Surgery, University Hospital. Lille, INSERM U1190, Lille, France.
| | - Pauline Romanet
- Aix Marseille University, APHM, INSERM, MMG, Laboratory of Molecular Biology, La Conception Hospital, Marseille, France.
| | - Frédéric Sebag
- Department of General Endocrine and Metabolic Surgery, Conception University Hospital, APHM, Aix Marseille University, Marseille, France.
| | - Christophe Tresallet
- Department of Digestive, Bariatric and Endocrine Surgery, Avicenne University Hospital, Sorbonne Paris Nord Universty, Assistance Pubique des Hôpitaux de Paris (APHP), Paris, France.
| | - Delphine Vezzosi
- Department of Endocrinology and Metabolic Diseases, CHU Larrey, 24 chemin de Pouvourville, TSA 30030, 31059 Toulouse Cedex, France.
| | - Thomas Walter
- Medical Oncology Department, Edouard-Herriot Hospital, Hospices Civils de Lyon, Lyon, France.
| | - Antoine Tabarin
- Endocrinology Department, INSERM Unit 1215, Bordeaux University Hospital, University of Bordeaux, Bordeaux, France.
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Kimura N, Hirata Y, Iwashiro N, Kijima H, Takayasu S, Yamagata S, Sakihara S, Uchino S, Ohara M. Multiple endocrine neoplasia type 1 with Zollinger-Ellison syndrome: clinicopathological analysis of a Japanese family with focus on menin immunohistochemistry. Front Endocrinol (Lausanne) 2023; 14:1221514. [PMID: 37867522 PMCID: PMC10588651 DOI: 10.3389/fendo.2023.1221514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 09/18/2023] [Indexed: 10/24/2023] Open
Abstract
Background Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the occurrence of multiple epithelial neuroendocrine tumors (NETs) and non-NETs in various organs. MEN1 encodes a 610-amino acid-long tumor suppressor protein, menin. The optimal treatment for multiple tumors, identification of the most critical tumors for patient prognosis, and menin immunohistochemistry findings remain controversial. Therefore, we aimed to elucidate these issues through a histological analysis of tumors and tumor-like lesions in a Japanese family, comprising a father and his two sons, who had MEN1 with Zollinger-Ellison syndrome (ZES). Patients and methods All family members had a germline alteration in exon 10, c.1714-1715 del TC of MEN1, and exhibited multiple synchronous and metachronous tumors. The patients had pulmonary NETs, hyperparathyroidism, hypergastrinemia, pituitary adenomas, pancreaticoduodenal NETs, adrenocortical adenoma with myelolipoma, nodular goiter of the thyroid, lipomas, and angiofibroma. Most tumors were resected and histologically examined. We compared their clinical courses and tumor histology, and conducted menin immunohistochemistry (IHC). Results Two patients died of pulmonary NET G2. One patient who underwent pancreaticoduodenectomy was cured of ZES; however, the two other patients who did not undergo pancreaticoduodenectomy suffered persistent ZES despite treatment with octreotide. Menin IHC revealed varying NET intensities, ranging from positive to negative stains. Conclusion Pancreaticoduodenectomy is the most effective treatment for ZES. Long-term follow-up is essential for pulmonary NET G2 owing to the risk of distant metastasis and/or multiplicity. Moreover, the variability of menin IHC in MEN1-related tumors may indicate the pattern of tumor formation rather than the diagnostic utility of menin in MEN1.
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Affiliation(s)
- Noriko Kimura
- Department of Clinical Research, National Hospital Organization Hakodate Hospital, Hakodate, Hokkaido, Japan
- Department of Diagnostic Pathology, National Hospital Organization Hakodate Hospital, Hakodate, Hokkaido, Japan
| | - Yasuji Hirata
- Department of Hematology and Oncology, National Hospital Organization Hakodate Hospital, Hakodate, Hokkaido, Japan
| | - Nozomu Iwashiro
- Department of Surgery, National Hospital Organization Hakodate Hospital, Hakodate, Hokkaido, Japan
| | - Hiroshi Kijima
- Department of Pathology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Shinobu Takayasu
- Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine and Hospital, Hirosaki, Aomori, Japan
| | - Satoshi Yamagata
- Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine and Hospital, Hirosaki, Aomori, Japan
- Institute of Human Nutrition, Columbia University Irving Medical Center, New York, NY, United States
| | - Satoru Sakihara
- Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine and Hospital, Hirosaki, Aomori, Japan
- Division of Diabetes and Endocrinology, Aomori Rosai Hospital, Aomori, Japan
| | - Shinya Uchino
- Department of Endocrine Surgery, Noguchi Thyroid Clinic and Hospital Foundation, Beppu, Oita, Japan
| | - Masanori Ohara
- Department of Surgery, National Hospital Organization Hakodate Hospital, Hakodate, Hokkaido, Japan
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9
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Jha S, Simonds WF. Molecular and Clinical Spectrum of Primary Hyperparathyroidism. Endocr Rev 2023; 44:779-818. [PMID: 36961765 PMCID: PMC10502601 DOI: 10.1210/endrev/bnad009] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 02/09/2023] [Accepted: 03/17/2023] [Indexed: 03/25/2023]
Abstract
Recent data suggest an increase in the overall incidence of parathyroid disorders, with primary hyperparathyroidism (PHPT) being the most prevalent parathyroid disorder. PHPT is associated with morbidities (fractures, kidney stones, chronic kidney disease) and increased risk of death. The symptoms of PHPT can be nonspecific, potentially delaying the diagnosis. Approximately 15% of patients with PHPT have an underlying heritable form of PHPT that may be associated with extraparathyroidal manifestations, requiring active surveillance for these manifestations as seen in multiple endocrine neoplasia type 1 and 2A. Genetic testing for heritable forms should be offered to patients with multiglandular disease, recurrent PHPT, young onset PHPT (age ≤40 years), and those with a family history of parathyroid tumors. However, the underlying genetic cause for the majority of patients with heritable forms of PHPT remains unknown. Distinction between sporadic and heritable forms of PHPT is useful in surgical planning for parathyroidectomy and has implications for the family. The genes currently known to be associated with heritable forms of PHPT account for approximately half of sporadic parathyroid tumors. But the genetic cause in approximately half of the sporadic parathyroid tumors remains unknown. Furthermore, there is no systemic therapy for parathyroid carcinoma, a rare but potentially fatal cause of PHPT. Improved understanding of the molecular characteristics of parathyroid tumors will allow us to identify biomarkers for diagnosis and novel targets for therapy.
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Affiliation(s)
- Smita Jha
- Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1752, USA
| | - William F Simonds
- Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1752, USA
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Malladi UD, Chimata SK, Bhashyakarla RK, Lingampally SR, Venkannagari VR, Mohammed ZA, Vargiya RV. Duodenal neuroendocrine tumor-tertiary care centre experience: A case report. World J Transl Med 2023; 11:1-8. [DOI: 10.5528/wjtm.v11.i1.1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 07/05/2023] [Accepted: 08/17/2023] [Indexed: 08/31/2023] Open
Abstract
BACKGROUND Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms arising from neuroendocrine cells, which contribute a small fraction of gastrointestinal malignancies. Duodenal neuroendocrine tumors (dNETs) represent 2% of all gastroenteropancreatic NENs. NENs are heterogeneous in terms of clinical symptoms, location, and prognosis. Non-functional NETs are mostly asymptomatic and need a high degree of clinical suspicion. Diagnosis of NETs is by endoscopic, endosonographic biopsy, and histopathological examination with immunohistochemistry staining for synaptophysin and chromogranin A.
CASE SUMMARY We present case reports of 5 patients obtained over a period of 10 years in our center with dNETs. One patient had moderately differentiated NET and the remaining four had well-differentiated NET. Surveillance endoscopy was recommended in all the patients and is kept under regular follow-up after performing endoscopic therapy using endoscopic mucosal resection in 4 of them and one patient was advised to undergo a Whipple procedure.
CONCLUSION Recently, the number of reported cases of NETs has increased due to advancements in diagnostic modalities and prevalence because of longer survival duration. The management differs based on the site, size, proliferation grade, and locally invasive pattern. They are slow-growing tumors with a good overall prognosis. The prognosis correlates with local lymph node status and metastasis.
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Affiliation(s)
- Uma Devi Malladi
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Suraj Kumar Chimata
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Ramesh Kumar Bhashyakarla
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Sahitya Reddy Lingampally
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Vikas Reddy Venkannagari
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Zeeshan Ali Mohammed
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
| | - Rahul Vijay Vargiya
- Department of Medical Gastroenterology, Osmania General Hospital, Telangana, Hyderabad 500012, India
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11
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Pierotti L, Pardi E, Dinoi E, Piaggi P, Borsari S, Della Valentina S, Sardella C, Michelucci A, Caligo MA, Bogazzi F, Marcocci C, Cetani F. Cutaneous lesions and other non-endocrine manifestations of Multiple Endocrine Neoplasia type 1 syndrome. Front Endocrinol (Lausanne) 2023; 14:1191040. [PMID: 37484956 PMCID: PMC10360178 DOI: 10.3389/fendo.2023.1191040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 06/13/2023] [Indexed: 07/25/2023] Open
Abstract
Background Multiple Endocrine Neoplasia type 1 is a rare genetic syndrome mainly caused by mutations of MEN1 gene and characterized by a combination of several endocrine and non-endocrine manifestations. The objective of this study was to describe cutaneous lesions and other non-endocrine manifestations of MEN1 in a cohort of patients with familial (F) and sporadic (S) MEN1, compare the prevalence of these manifestations between the two cohorts, and investigate the correlation with MEN1 mutation status. Methods We collected phenotypic and genotypic data of 185 patients with F-MEN1 and S-MEN1 followed from 1997 to 2022. The associations between F-MEN1 and S-MEN1 or MEN1 mutation-positive and mutation-negative patients and non-endocrine manifestations were determined using chi-square or Fisher's exact tests or multivariate exact logistic regression analyses. Results The prevalence of angiofibromas was significantly higher in F-MEN1 than in S-MEN1 in both the whole (p < 0.001) and index case (p = 0.003) cohorts. The prevalence of lipomas was also significantly higher in F-MEN1 than in S-MEN1 (p = 0.009) and in MEN1 mutation-positive than in MEN1 mutation-negative (p = 0.01) index cases. In the whole cohort, the prevalence of lipomas was significantly higher in MEN1 mutation-positive compared to MEN1 mutation-negative patients (OR = 2.7, p = 0.02) and in F-MEN1 than in S-MEN1 (p = 0.03), only after adjustment for age. No significant differences were observed for the other non-endocrine manifestations between the two cohorts. Hibernoma and collagenoma were each present in one patient (0.5%) and meningioma and neuroblastoma in 2.7% and 0.5%, respectively. Gastric leiomyoma was present in 1.1% of the patients and uterine leiomyoma in 14% of women. Thyroid cancer, breast cancer, lung cancer, basal cell carcinoma, melanoma, and colorectal cancer were present in 4.9%, 2.7%, 1.6%, 1.6%, 2.2%, and 0.5% of the whole series, respectively. Conclusions We found a significantly higher prevalence of angiofibromas and lipomas in F-MEN1 compared with S-MEN1 and in MEN1 mutation-positive compared to MEN1 mutation-negative patients. In patients with one major endocrine manifestation of MEN1 , the presence of cutaneous lesions might suggest the diagnosis of MEN1 and a possible indication for genetic screening.
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Affiliation(s)
- Laura Pierotti
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Elena Pardi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Elisa Dinoi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Paolo Piaggi
- Department of Information Engineering, University of Pisa, Pisa, Italy
| | - Simona Borsari
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | | | - Chiara Sardella
- Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy
| | - Angela Michelucci
- Laboratory of Molecular Genetics, University Hospital of Pisa, Pisa, Italy
| | | | - Fausto Bogazzi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Claudio Marcocci
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
- Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy
| | - Filomena Cetani
- Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy
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12
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Dieterle MP, Husari A, Prozmann SN, Wiethoff H, Stenzinger A, Röhrich M, Pfeiffer U, Kießling WR, Engel H, Sourij H, Steinberg T, Tomakidi P, Kopf S, Szendroedi J. Diffuse, Adult-Onset Nesidioblastosis/Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS): Review of the Literature of a Rare Cause of Hyperinsulinemic Hypoglycemia. Biomedicines 2023; 11:1732. [PMID: 37371827 PMCID: PMC10296556 DOI: 10.3390/biomedicines11061732] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 06/13/2023] [Accepted: 06/14/2023] [Indexed: 06/29/2023] Open
Abstract
Differential diagnosis of hypoglycemia in the non-diabetic adult patient is complex and comprises various diseases, including endogenous hyperinsulinism caused by functional β-cell disorders. The latter is also designated as nesidioblastosis or non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). Clinically, this rare disease presents with unspecific adrenergic and neuroglycopenic symptoms and is, therefore, often overlooked. A combination of careful clinical assessment, oral glucose tolerance testing, 72 h fasting, sectional and functional imaging, and invasive insulin measurements can lead to the correct diagnosis. Due to a lack of a pathophysiological understanding of the condition, conservative treatment options are limited and mostly ineffective. Therefore, nearly all patients currently undergo surgical resection of parts or the entire pancreas. Consequently, apart from faster diagnosis, more elaborate and less invasive treatment options are needed to relieve the patients from the dangerous and devastating symptoms. Based on a case of a 23-year-old man presenting with this disease in our department, we performed an extensive review of the medical literature dealing with this condition and herein presented a comprehensive discussion of this interesting disease, including all aspects from epidemiology to therapy.
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Affiliation(s)
- Martin Philipp Dieterle
- Division of Oral Biotechnology, Center for Dental Medicine, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany
| | - Ayman Husari
- Department of Orthodontics, Center for Dental Medicine, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany
| | - Sophie Nicole Prozmann
- Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany
| | - Hendrik Wiethoff
- Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Albrecht Stenzinger
- Institute of Pathology, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Manuel Röhrich
- Department of Nuclear Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Uwe Pfeiffer
- Pfalzklinikum for Psychiatry and Neurology AdÖR, Weinstr. 100, 76889 Klingenmünster, Germany
| | | | - Helena Engel
- Cancer Immune Regulation Group, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
| | - Harald Sourij
- Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, 8010 Graz, Austria
- Interdisciplinary Metabolic Medicine Trials Unit, Medical University of Graz, 8010 Graz, Austria
| | - Thorsten Steinberg
- Division of Oral Biotechnology, Center for Dental Medicine, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany
| | - Pascal Tomakidi
- Division of Oral Biotechnology, Center for Dental Medicine, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany
| | - Stefan Kopf
- Department of Internal Medicine I and Clinical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany
| | - Julia Szendroedi
- Department of Internal Medicine I and Clinical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany
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13
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Massironi S, Rossi RE, Laffusa A, Eller-Vainicher C, Cavalcoli F, Zilli A, Ciafardini C, Sciola V, Invernizzi P, Peracchi M. Sporadic and MEN1-related gastrinoma and Zollinger-Ellison syndrome: differences in clinical characteristics and survival outcomes. J Endocrinol Invest 2023; 46:957-965. [PMID: 36436191 PMCID: PMC10105668 DOI: 10.1007/s40618-022-01961-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 11/04/2022] [Indexed: 11/28/2022]
Abstract
PURPOSE Gastrinoma with Zollinger-Ellison syndrome (ZES) may occur sporadically (Sp) or as part of the inherited syndrome of multiple endocrine neoplasia 1 (MEN-1). Data comparing Sp and MEN-1/ZES are scanty. We aimed to identify and compare their clinical features. METHODS Consecutive patients with ZES were evaluated between 1992 and 2020 among a monocentric Italian patient cohort. RESULTS Of 76 MEN-1 patients, 41 had gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN), 18 of whom had ZES; of 320 Sp-GEP-NEN, 19 had Sp-ZES. MEN-1/ZES patients were younger (p = 0.035) and the primary MEN-1/ZES gastrinoma was smaller than Sp-ZES (p = 0.030). Liver metastases occurred in both groups, but only Sp-ZES developed extrahepatic metastases. 13 Sp-ZES and 8 MEN-1/ZES underwent surgery. 8 Sp-ZES and 7 MEN-1/ZES received somatostatin analogs (SSAs). Median overall survival (OS) was higher in MEN-1/ZES than in Sp-ZES (310 vs 168 months, p = 0.034). At univariate-logistic regression, age at diagnosis (p = 0.01, OR = 1.1), G3 grading (p = 0.003, OR = 21.3), Sp-ZES (p = 0.02, OR = 0.3) and presence of extrahepatic metastases (p = 0.001, OR = 7.2) showed a significant association with OS. At multivariate-COX-analysis, none of the variables resulted significantly related to OS. At univariate-logistic regression, age (p = 0.04, OR = 1.0), size (p = 0.039, OR = 1.0), G3 grade (p = 0.008, OR = 14.6) and extrahepatic metastases (p = 0.005, OR = 4.6) were independently associated with progression-free survival (PFS). In multivariate-COX-analysis, only extrahepatic metastases (p = 0.05, OR = 3.4) showed a significant association with PFS. Among SSAs-treated patients, MEN-1/ZES showed better PFS (p = 0.0227). After surgery, the median PFS was 126 and 96 months in MEN-1 and Sp, respectively. CONCLUSION MEN-1/ZES patients generally show better OS and PFS than Sp-ZES as well as better SSAs response.
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Affiliation(s)
- S Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, San Gerardo Hospital, Via Pergolesi 3, Monza, Italy.
- Department of Medicine and Surgery, European Reference Network on Hepatological Diseases (ERN RARE LIVER), San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
| | - R E Rossi
- Gastroenterology and Endoscopy Unit, IRCCS Humanitas Research Hospital, Via Manzoni 56, Rozzano, 20089, Milan, Italy
| | - A Laffusa
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, San Gerardo Hospital, Via Pergolesi 3, Monza, Italy
- Department of Medicine and Surgery, European Reference Network on Hepatological Diseases (ERN RARE LIVER), San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
| | - C Eller-Vainicher
- Endocrinology, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milan, Italy
| | - F Cavalcoli
- Diagnostic and Therapeutic Endoscopy Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
| | - A Zilli
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy
| | - C Ciafardini
- Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milan, Italy
| | - V Sciola
- Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milan, Italy
| | - P Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, San Gerardo Hospital, Via Pergolesi 3, Monza, Italy
- Department of Medicine and Surgery, European Reference Network on Hepatological Diseases (ERN RARE LIVER), San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy
| | - M Peracchi
- Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milan, Italy
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14
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Wydra A, Cylke-Falkowska K, Czajka-Oraniec I, Kolasińska-Ćwikła A, Ćwikła J, Zgliczyński W, Stelmachowska-Banaś M. Severe ectopic Cushing syndrome in a transgender man with a metastatic gastrinoma and an adrenal tumor-A case report and review of the literature. Front Endocrinol (Lausanne) 2023; 14:1135016. [PMID: 37008936 PMCID: PMC10061007 DOI: 10.3389/fendo.2023.1135016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 02/27/2023] [Indexed: 03/18/2023] Open
Abstract
A 38-year-old transgender man with advanced metastatic functional pancreatic neuroendocrine neoplasm (PanNEN) gastrinoma was admitted to the Department of Endocrinology due to severe ACTH-dependent hypercortisolemia. An ectopic production of ACTH by PanNEN was suspected. The patient qualified for bilateral adrenalectomy after preoperative treatment with metyrapone. Finally, the patient underwent resection of the left adrenal gland with the tumor only, which surprisingly resulted in a significant decrease in ACTH and cortisol levels, leading to clinical improvement. Pathology report revealed an adenoma of the adrenal cortex with positive ACTH staining. The result of the simultaneous liver lesion biopsy confirmed a metastatic NEN G2 with positive ACTH immunostaining as well. We looked for a correlation between gender-affirming hormone treatment and the onset of the disease and its rapid progression. This may be the first case describing the coexistence of gastrinoma and ectopic Cushing disease in a transsexual patient.
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Affiliation(s)
- Arnika Wydra
- Department of Endocrinology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | | | | | - Agnieszka Kolasińska-Ćwikła
- Department of Oncology and Radiotherapy, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw, Poland
- Department of Radiology, Maria Skłodowska-Curie Memorial Cancer Center, Warsaw, Poland
| | - Jarosław Ćwikła
- Department of Cardiology and Internal Medicine, Medical School University of Warmia and Mazury, Olsztyn, Poland
- Diagnostic and Therapy Center – Gammed, Warsaw, Poland
| | - Wojciech Zgliczyński
- Department of Endocrinology, Centre of Postgraduate Medical Education, Warsaw, Poland
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15
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Ito T, Ramos-Alvarez I, Jensen RT. Successful Lifetime/Long-Term Medical Treatment of Acid Hypersecretion in Zollinger-Ellison Syndrome (ZES): Myth or Fact? Insights from an Analysis of Results of NIH Long-Term Prospective Studies of ZES. Cancers (Basel) 2023; 15:1377. [PMID: 36900170 PMCID: PMC10000208 DOI: 10.3390/cancers15051377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/09/2023] [Accepted: 02/15/2023] [Indexed: 02/24/2023] Open
Abstract
Analysis of the efficacy/pharmacology of long-term/lifetime medical treatment of acid hypersecretion in a large cohort of ZES patients in a prospective study. This study includes the results from all 303 patients with established ZES who were prospectively followed and received acid antisecretory treatment with either H2Rs or PPIs, with antisecretory doses individually titrated by the results of regular gastric acid testing. The study includes patients treated for short-term periods (<5 yrs), patients treated long-term (>5 yrs), and patients with lifetime treatment (30%) followed for up to 48 years (mean 14 yrs). Long-term/lifelong acid antisecretory treatment with H2Rs/PPIs can be successfully carried out in all patients with both uncomplicated and complicated ZES (i.e., with MEN1/ZES, previous Billroth 2, severe GERD). This is only possible if drug doses are individually set by assessing acid secretory control to establish proven criteria, with regular reassessments and readjustments. Frequent dose changes both upward and downward are needed, as well as regulation of the dosing frequency, and there is a primary reliance on the use of PPIs. Prognostic factors predicting patients with PPI dose changes are identified, which need to be studied prospectively to develop a useful predictive algorithm that could be clinically useful for tailored long-term/lifetime therapy in these patients.
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Affiliation(s)
- Tetsuhide Ito
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, International University of Health and Welfare, 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan
| | | | - Robert T. Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA
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16
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Robin L, Sauvanet A, Walter T, Najah H, Falconi M, Pattou F, Gaujoux S. Recurrence after surgical resection of nonmetastatic sporadic gastrinoma: Which prognostic factors and surgical procedure? Surgery 2023; 173:1144-1152. [PMID: 36781315 DOI: 10.1016/j.surg.2022.12.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 11/29/2022] [Accepted: 12/30/2022] [Indexed: 02/13/2023]
Abstract
BACKGROUND The only curative treatment of gastrinoma is complete resection, but its surgical management remains controversial and prognostic factors of sporadic nonmetastatic gastrinoma are poorly known. METHODS This was a retrospective study including all patients who underwent elective surgery for nonmetastatic sporadic gastrinoma between 2000 and 2020 in 15 hospitals. The primary and secondary outcomes were overall survival and disease-free survival predictive factors. RESULTS In total, 108 patients were included, of which 68 (63%) were duodenal, 19 (18%) pancreatic, and 21 (19%) primary lymph node gastrinomas, with no major difference in clinical presentation. Among the 68 duodenal gastrinomas, 26% (n = 18) underwent pancreaticoduodenectomy (PD) and 74% (n = 50) underwent duodenotomy with the excision of duodenal wall tumors and lymphadenectomy (DUODX + LN). Overall, the median overall survival was 173 months, and the 5-year overall survival was 94%, with no predictive factors identified. The median disease-free survival was 93 months, and the 5-year disease-free survival was 63%. Tumor size >2 cm (P = .00001), grade (P = .00001), and pancreatic tumor location (P = .0001) were predictive factors of recurrence; however, in multivariate analysis, only tumor size >2 cm (P = .005) and grade (P = .013) were independent predictors of recurrence. Age, sex, preoperative gastrin level, lymphadenectomy <10 resected lymph nodes, and metastatic lymph nodes on surgical specimens were not predictors of recurrence. For duodenal gastrinomas, surgical procedures (PD versus DUODX + LN) did not have a significant effect on overall survival and disease-free survival. CONCLUSION Sporadic nonmetastatic gastrinomas had an excellent overall survival. Recurrence is frequent and influenced by tumor size and grade. Regarding sporadic duodenal gastrinoma, duodenotomy with excision of duodenal wall tumors with lymphadenectomy could be considered a valid surgical option, in the absence of clear oncologic superiority of PD.
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Affiliation(s)
- Léa Robin
- Department of General, Visceral, and Endocrine Surgery, Pitié-Salpêtrière Hospital, AP-HP, Paris, France; Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Paris, France; School of Medicine, Sorbonne University, Paris, France
| | - Alain Sauvanet
- Department of Hepato-Biliary and Pancreatic Surgery, Beaujon Hospital, AP-HP, Clichy, France; School of Medicine, Paris University, Paris, France
| | - Thomas Walter
- Service d'Oncologie Médicale et Hépato-gastro-entérologie, Hospices Civil de Lyon, France; School of Medicine, Lyon University, Lyon, France
| | - Haythem Najah
- Department of Digestive and Endocrine Surgery, CHU de Bordeaux, Groupe Hospitalier Sud, Hôpital Haut-Lévêque, Centre Magellan, Pessac, France
| | - Massimo Falconi
- School of Medicine, Vita Salute San Raffaele University, Milan, Italy; Division of Pancreatic Surgery, IRCCS Ospedale San Raffaele, Università Vita-Salute, Milan, Italy; Department of Surgery, Division of Pancreatic Surgery, San Raffaele Scientific Institute, Milan, Italy
| | - François Pattou
- Univ Lille, Inserm, CHU Lille, Institut Pasteur Lille, U1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, Integrated Center of Obesity, France; Department of General and Endocrine Surgery, Lille University Hospital, France
| | - Sébastien Gaujoux
- Department of General, Visceral, and Endocrine Surgery, Pitié-Salpêtrière Hospital, AP-HP, Paris, France; Department of Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP, Pitié-Salpêtrière Hospital, Paris, France; School of Medicine, Sorbonne University, Paris, France.
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17
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Krolevets TS, Livzan MA, Mozgovoy SI. Hyperplasia of enterochromaffin-like (ECL) cells as a precursor of neuroendocrine gastric tumors in autoimmune gastritis. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2022:147-152. [DOI: 10.31146/1682-8658-ecg-205-9-147-152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Abstract
The purpose of this publication is to update knowledge about chronic autoimmune gastritis and about cases of hyperplasia of enterochromaffin-like (ECL) cells as precursors of the development of neuroendocrine gastric tumor type 1 due to clinical example’s demonstration. Discussion: the types and main characteristics of neuroendocrine tumors of the stomach were discussed, in particular tumors type 1 associated with autoimmune gastritis. The mechanisms of formation of neuroendocrine tumors in the stomach against the background of an autoimmune process were presented, two clinical examples presenting the algorithm of diagnosis of autoimmune gastritis and associated neuroendocrine tumors were presented. Both clinical examples demonstrated the presence of subepithelial formations of the stomach body according to FGDS, which have not been morphologically identified. Timely repeated FGDS with sampling of biopsies according to the OLGA standard made it possible to verify the formations, and the serological markers helped in clarifying the diagnosis and morphological nature of tumors. Conclusion: analysis of clinical data, anamnesis and esophagoduodenoscopy with morphological evaluation of the gastric mucosa biopsy may help to find out the cause and nature of chronic inflammation in the gastric mucosa. Atrophy of the glands in the stomach body, pseudopiloric metaplasia, hyperplasia of enterochromaffin (ECL) cells are sufficient morphological criteria for autoimmune gastritis. The study of the level of chromogranin A in blood serum can be considered as a marker of the development of type 1 neuroendocrine gastric tumor in patients with autoimmune gastritis and the presence of polyps in the stomach body.
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18
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Kusano K, Uno K, Koike T, Miura S, Kume K, Nakahori M, Fujishima F, Ohtsuka H, Unno M, Masamune A. A case of refractory esophageal stricture due to occult gastrinoma of the duodenum. Clin J Gastroenterol 2022; 15:859-863. [DOI: 10.1007/s12328-022-01657-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 06/06/2022] [Indexed: 12/01/2022]
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Pieterman CRC, Valk GD. Update on the clinical management of multiple endocrine neoplasia type 1. Clin Endocrinol (Oxf) 2022; 97:409-423. [PMID: 35319130 PMCID: PMC9540817 DOI: 10.1111/cen.14727] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 02/22/2022] [Accepted: 02/28/2022] [Indexed: 11/30/2022]
Abstract
This review provides an overview of novel insights in the clinical management of patients with Multiple Endocrine Neoplasia Type 1, focusing on the last decade since the last update of the MEN1 guidelines. With regard to Diagnosis: Mutation-negative patients with 2/3 main manifestations have a different clinical course compared to mutation-positive patients. As for primary hyperparathyroidism: subtotal parathyroidectomy is the initial procedure of choice. Current debate centres around the timing of initial parathyroidectomy as well as the controversial topic of unilateral clearance in young patients. For duodenopancreatic neuroendocrine tumours (NETs), the main challenge is accurate and individualized risk stratification to enable personalized surveillance and treatment. Thymus NETs remain one of the most aggressive MEN1-related tumours. Lung NETs are more frequent than previously thought, generally indolent, but rare aggressive cases do occur. Pituitary adenomas are most often prolactinomas and nonfunctioning microadenomas with an excellent prognosis and good response to therapy. Breast cancer is recognized as part of the MEN1 syndrome in women and periodical screening is advised. Clinically relevant manifestations are already seen at the paediatric age and initiating screening in the second decade is advisable. MEN1 has a significant impact on quality of life and US data show a significant financial burden. In conclusion, patient outcomes have improved, but much is still to be achieved. For care tailored to the needs of the individual patient and improving outcomes on an individual basis, studies are now needed to define predictors of tumour behaviour and effects of more individualized interventions.
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Affiliation(s)
| | - Gerlof D. Valk
- Department of Endocrine OncologyUniversity Medical Center UtrechtUtrechtThe Netherlands
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20
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de Jorge Huerta L, Solares Fernández I, Sánchez-Moreno B, Males Maldonado D, de Ibarrola Andrés C, Díaz-Simón R. Sporadic, non-functional, gastrin-producing duodenal neuroendocrine tumors: A retrospective study of an infrequent disease. J Dig Dis 2022; 23:455-461. [PMID: 36168962 PMCID: PMC10099524 DOI: 10.1111/1751-2980.13129] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 07/19/2022] [Accepted: 09/25/2022] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Non-functioning gastrin-producing neuroendocrine neoplasms (NEN) of the duodenum are rare gastrointestinal tumors without a clinical syndrome due to gastrin production. Their incidence has significantly increased as an incidental finding during endoscopic studies. The aim of this study was to describe the characteristics and prognostic factors of this emergent and infrequent neoplasm. METHODS We performed a retrospective observational study based on the duodenal NENs samples with positive staining for gastrin at the Department of Pathology, University Hospital 12-de-Octubre (Madrid, Spain) between 2000 and 2017. Patients with clinically functional tumors ([Zollinger-Ellison syndrome] or gastrin >1000 pg/mL), with previously diagnosed multiple endocrine neoplasia (MEN) syndrome or synchronous neoplasia were excluded. Clinicopathological and therapeutic variables, follow-up, recurrence, and mortality data were collected. RESULTS In all, 21 patients were included. Most of the tumors were diagnosed incidentally as a single small polypoid lesion limited to mucosa/submucosa and with a low histological grade. Four (19.0%) patients presented with metastatic involvement at diagnosis (lymphatic and/or hepatic). These four patients also had a high or intermediate mitotic grade and infiltration further than submucosa. Local resection was applied in most cases as curative treatment. There were two cases of tumor recurrence and two tumor-related deaths with a 5-year disease-free survival of 81.0%. CONCLUSIONS The majority of these tumors were diagnosed at a localized stage and had a good prognosis with treatment. Nevertheless, given the potential metastatic risk, a close follow-up is necessary, especially in those with aggressive pathological factors such as deep infiltration or high histological grade.
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Affiliation(s)
- Lucía de Jorge Huerta
- Department of Internal Medicine, Hospital Universitario 12 de Octubre, Instituto de Investigación i + 12, Madrid, Spain
| | - Isabel Solares Fernández
- Department of Internal Medicine, Hospital Universitario 12 de Octubre, Instituto de Investigación i + 12, Madrid, Spain
| | - Beatriz Sánchez-Moreno
- Department of Internal Medicine, Hospital Universitario 12 de Octubre, Instituto de Investigación i + 12, Madrid, Spain
| | - David Males Maldonado
- Department of Endocrinology and Metabolism, Hospital Universitario 12 de Octubre, Instituto de Investigación i + 12, Madrid, Spain
| | - Carolina de Ibarrola Andrés
- Department of Anatomical Pathology, Hospital Universitario 12 de Octubre, Instituto de Investigación i + 12, Madrid, Spain
| | - Raquel Díaz-Simón
- Department of Internal Medicine, Hospital Universitario 12 de Octubre, Instituto de Investigación i + 12, Madrid, Spain
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Ranaweerage R, Perera S, Sathischandra H. Occult insulinoma with treatment refractory, severe hypoglycaemia in multiple endocrine neoplasia type 1 syndrome; difficulties faced during diagnosis, localization and management; a case report. BMC Endocr Disord 2022; 22:68. [PMID: 35296318 PMCID: PMC8925226 DOI: 10.1186/s12902-022-00985-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 03/09/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Multiple endocrine neoplasia type 1 (MEN 1) syndrome is a rare, complex genetic disorder characterized by increased predisposition to tumorigenesis in multiple endocrine and non-endocrine tissues. Diagnosis and management of MEN 1 syndrome is challenging due to its vast heterogeneity in clinical presentation. CASE PRESENTATION A 23-year-old female, previously diagnosed with Polycystic Ovarian Syndrome (PCOS) and pituitary microprolactinoma presented with drowsiness,confusion and profuse sweating developing over a period of one day. It was preceded by fluctuating, hallucinatory behavior for two weeks duration. There was recent increase in appetite with significant weight gain. There was no fever, seizures or symptoms suggestive of meningism. Her Body mass index(BMI) was 32 kg/m2.She had signs of hyperandrogenism. Multiple cutaneous collagenomas were noted on anterior chest and abdominal wall. Her Glasgow Coma Scale was 9/15. Pupils were sluggishly reactive to light. Tendon reflexes were exaggerated with up going planter reflexes. Moderate hepatomegaly was present. Rest of the clinical examination was normal. Laboratory evaluation confirmed endogenous hyperinsulinaemic hypoglycaemia suggestive of an insulinoma. Hypercalcemia with elevated parathyroid hormone level suggested a parathyroid adenoma. Presence of insulinoma, primary hyperparathyroidism and pituitary microadenoma, in 3rd decade of life with characteristic cutaneous tumours was suggestive of a clinical diagnosis of MEN 1 syndrome. Recurrent, severe hypoglycaemia complicated with hypoglycaemic encephalopathy refractory to continuous, parenteral glucose supplementation and optimal pharmacotherapy complicated the clinical course. Insulinoma was localized with selective arterial calcium stimulation test. Distal pancreatectomy and four gland parathyroidectomy was performed leading to resolution of symptoms. CONCLUSIONS Renal calculi or characteristic cutaneous lesions might be the only forewarning clinical manifestations of an undiagnosed MEN 1 syndrome impending a life-threatening presentation. Comprehensive management of MEN 1 syndrome requires multi-disciplinary approach with advanced imaging modalities, advanced surgical procedures and long-term follow up due to its heterogeneous presentation and the varying severity depending on the disease phenotype.
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Affiliation(s)
- Rasika Ranaweerage
- Registrar in General Medicine, National Hospital of Sri Lanka, Ward 45/46, Colombo, Sri Lanka.
| | - Shehan Perera
- Registrar in General Medicine, National Hospital of Sri Lanka, Ward 45/46, Colombo, Sri Lanka
| | - Harsha Sathischandra
- Registrar in General Medicine, National Hospital of Sri Lanka, Ward 45/46, Colombo, Sri Lanka
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22
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Lee L, Ramos-Alvarez I, Jensen RT. Predictive Factors for Resistant Disease with Medical/Radiologic/Liver-Directed Anti-Tumor Treatments in Patients with Advanced Pancreatic Neuroendocrine Neoplasms: Recent Advances and Controversies. Cancers (Basel) 2022; 14:1250. [PMID: 35267558 PMCID: PMC8909561 DOI: 10.3390/cancers14051250] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/08/2022] [Accepted: 02/23/2022] [Indexed: 12/14/2022] Open
Abstract
Purpose: Recent advances in the diagnosis, management and nonsurgical treatment of patients with advanced pancreatic neuroendocrine neoplasms (panNENs) have led to an emerging need for sensitive and useful prognostic factors for predicting responses/survival. Areas covered: The predictive value of a number of reported prognostic factors including clinically-related factors (clinical/laboratory/imaging/treatment-related factors), pathological factors (histological/classification/grading), and molecular factors, on therapeutic outcomes of anti-tumor medical therapies with molecular targeting agents (everolimus/sunitinib/somatostatin analogues), chemotherapy, radiological therapy with peptide receptor radionuclide therapy, or liver-directed therapies (embolization/chemoembolization/radio-embolization (SIRTs)) are reviewed. Recent findings in each of these areas, as well as remaining controversies and uncertainties, are discussed in detail, particularly from the viewpoint of treatment sequencing. Conclusions: The recent increase in the number of available therapeutic agents for the nonsurgical treatment of patients with advanced panNENs have raised the importance of prognostic factors predictive for therapeutic outcomes of each treatment option. The establishment of sensitive and useful prognostic markers will have a significant impact on optimal treatment selection, as well as in tailoring the therapeutic sequence, and for maximizing the survival benefit of each individual patient. In the paper, the progress in this area, as well as the controversies/uncertainties, are reviewed.
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Affiliation(s)
- Lingaku Lee
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA; (L.L.); (I.R.-A.)
- National Kyushu Cancer Center, Department of Hepato-Biliary-Pancreatology, Fukuoka 811-1395, Japan
| | - Irene Ramos-Alvarez
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA; (L.L.); (I.R.-A.)
| | - Robert T. Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA; (L.L.); (I.R.-A.)
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23
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Multiple Endocrine Neoplasia in Childhood: An Update on Diagnosis, Screening, Management and Treatment. ENDOCRINES 2022. [DOI: 10.3390/endocrines3010007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Multiple endocrine neoplasia (MEN) is a group of heterogenous syndromes characterized by the occurrence of two or more endocrine gland tumors in a patient or related individuals in the same family. They are inherited in an autosomal dominant fashion and are highly penetrant. There are three types of MEN syndromes: MEN type 1 (MEN1), MEN type 2 (MEN2), and MEN type 4 (MEN4). MEN2 is further divided into MEN2A, MEN2B (formerly known MEN3), and familial medullary thyroid carcinoma (FMTC). Although MEN syndromes are rare, it is crucial to identify individuals at risk for potentially life-threatening neoplasias. This review article provides an update on each MEN syndrome, its genetics, diagnosis, and management in children.
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24
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Waguespack SG. Beyond the "3 Ps": A critical appraisal of the non-endocrine manifestations of multiple endocrine neoplasia type 1. Front Endocrinol (Lausanne) 2022; 13:1029041. [PMID: 36325452 PMCID: PMC9618614 DOI: 10.3389/fendo.2022.1029041] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 09/26/2022] [Indexed: 11/13/2022] Open
Abstract
Multiple endocrine neoplasia type 1 (MEN1), an autosomal-dominantly inherited tumor syndrome, is classically defined by tumors arising from the "3 Ps": Parathyroids, Pituitary, and the endocrine Pancreas. From its earliest descriptions, MEN1 has been associated with other endocrine and non-endocrine neoplastic manifestations. High quality evidence supports a direct association between pathogenic MEN1 variants and neoplasms of the skin (angiofibromas and collagenomas), adipose tissue (lipomas and hibernomas), and smooth muscle (leiomyomas). Although CNS tumors, melanoma, and, most recently, breast cancer have been reported as MEN1 clinical manifestations, the published evidence to date is not yet sufficient to establish causality. Well-designed, multicenter prospective studies will help us to understand better the relationship of these tumors to MEN1, in addition to verifying the true prevalence and penetrance of the well-documented neoplastic associations. Nevertheless, patients affected by MEN1 should be aware of these non-endocrine manifestations, and providers should be encouraged always to think beyond the "3 Ps" when treating an MEN1 patient.
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25
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Pitsava G, Maria AG, Faucz FR. Disorders of the adrenal cortex: Genetic and molecular aspects. Front Endocrinol (Lausanne) 2022; 13:931389. [PMID: 36105398 PMCID: PMC9465606 DOI: 10.3389/fendo.2022.931389] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 07/15/2022] [Indexed: 11/13/2022] Open
Abstract
Adrenal cortex produces glucocorticoids, mineralocorticoids and adrenal androgens which are essential for life, supporting balance, immune response and sexual maturation. Adrenocortical tumors and hyperplasias are a heterogenous group of adrenal disorders and they can be either sporadic or familial. Adrenocortical cancer is a rare and aggressive malignancy, and it is associated with poor prognosis. With the advance of next-generation sequencing technologies and improvement of genomic data analysis over the past decade, various genetic defects, either from germline or somatic origin, have been unraveled, improving diagnosis and treatment of numerous genetic disorders, including adrenocortical diseases. This review gives an overview of disorders associated with the adrenal cortex, the genetic factors of these disorders and their molecular implications.
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Affiliation(s)
- Georgia Pitsava
- Division of Intramural Research, Division of Population Health Research, Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
- Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda MD, United States
| | - Andrea G. Maria
- Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda MD, United States
| | - Fabio R. Faucz
- Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda MD, United States
- Molecular Genomics Core (MGC), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda MD, United States
- *Correspondence: Fabio R. Faucz,
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26
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Ito T, Masui T, Komoto I, Doi R, Osamura RY, Sakurai A, Ikeda M, Takano K, Igarashi H, Shimatsu A, Nakamura K, Nakamoto Y, Hijioka S, Morita K, Ishikawa Y, Ohike N, Kasajima A, Kushima R, Kojima M, Sasano H, Hirano S, Mizuno N, Aoki T, Aoki T, Ohtsuka T, Okumura T, Kimura Y, Kudo A, Konishi T, Matsumoto I, Kobayashi N, Fujimori N, Honma Y, Morizane C, Uchino S, Horiuchi K, Yamasaki M, Matsubayashi J, Sato Y, Sekiguchi M, Abe S, Okusaka T, Kida M, Kimura W, Tanaka M, Majima Y, Jensen RT, Hirata K, Imamura M, Uemoto S. JNETS clinical practice guidelines for gastroenteropancreatic neuroendocrine neoplasms: diagnosis, treatment, and follow-up: a synopsis. J Gastroenterol 2021; 56:1033-1044. [PMID: 34586495 PMCID: PMC8531106 DOI: 10.1007/s00535-021-01827-7] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 09/13/2021] [Indexed: 02/04/2023]
Abstract
Neuroendocrine neoplasms (NENs) are rare neoplasms that occur in various organs and present with diverse clinical manifestations. Pathological classification is important in the diagnosis of NENs. Treatment strategies must be selected according to the status of differentiation and malignancy by accurately determining whether the neoplasm is functioning or nonfunctioning, degree of disease progression, and presence of metastasis. The newly revised Clinical Practice Guidelines for Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs) comprises 5 chapters-diagnosis, pathology, surgical treatment, medical and multidisciplinary treatment, and multiple endocrine neoplasia type 1 (MEN1)/von Hippel-Lindau (VHL) disease-and includes 51 clinical questions and 19 columns. These guidelines aim to provide direction and practical clinical content for the management of GEP-NEN preferentially based on clinically useful reports. These revised guidelines also refer to the new concept of "neuroendocrine tumor" (NET) grade 3, which is based on the 2017 and 2019 WHO criteria; this includes health insurance coverage of somatostatin receptor scintigraphy for NEN, everolimus for lung and gastrointestinal NET, and lanreotide for GEP-NET. The guidelines also newly refer to the diagnosis, treatment, and surveillance of NEN associated with VHL disease and MEN1. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the first edition was published.
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Affiliation(s)
- Tetsuhide Ito
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan.
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan.
| | - Toshihiko Masui
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Izumi Komoto
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Ryuichiro Doi
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Robert Y Osamura
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Akihiro Sakurai
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Masafumi Ikeda
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Koji Takano
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Hisato Igarashi
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Akira Shimatsu
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Kazuhiko Nakamura
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Yuji Nakamoto
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Susumu Hijioka
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Koji Morita
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Yuichi Ishikawa
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Nobuyuki Ohike
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Atsuko Kasajima
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Ryoji Kushima
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Motohiro Kojima
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Hironobu Sasano
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Satoshi Hirano
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Nobumasa Mizuno
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Taku Aoki
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Takeshi Aoki
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Takao Ohtsuka
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Tomoyuki Okumura
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Yasutoshi Kimura
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Atsushi Kudo
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Tsuyoshi Konishi
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Ippei Matsumoto
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Noritoshi Kobayashi
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Nao Fujimori
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Yoshitaka Honma
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Chigusa Morizane
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Shinya Uchino
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Kiyomi Horiuchi
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Masanori Yamasaki
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Jun Matsubayashi
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Yuichi Sato
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Masau Sekiguchi
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Shinichi Abe
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Takuji Okusaka
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Mitsuhiro Kida
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Wataru Kimura
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Masao Tanaka
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Yoshiyuki Majima
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Robert T Jensen
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Koichi Hirata
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Masayuki Imamura
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
| | - Shinji Uemoto
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
- Department of Gastroenterology, Graduate School of Medical Sciences, Internal University of Health and Welfare, 3-6-45 Momochihama, Sawara-ku, Fukuoka, 814-0001, Japan
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27
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Yozgat A, Kekilli M, Altay M. Time to give up traditional methods for the management of gastrointestinal neuroendocrine tumours. World J Clin Cases 2021; 9:8627-8646. [PMID: 34734042 PMCID: PMC8546836 DOI: 10.12998/wjcc.v9.i29.8627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 05/19/2021] [Accepted: 08/24/2021] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumors (NETs) are a rare and heterogeneous disease group and constitute 0.5% of all malignancies. The annual incidence of NETs is increasing worldwide. The reason for the increase in the incidence of NETs is the detection of benign lesions, incidental detection due to the highest use of endoscopic and imaging procedures, and higher recognition rates of pathologists. There have been exciting developments regarding NET biology in recent years. Among these, first of all, somatostatin receptors and downstream pathways in neuroendocrine cells have been found to be important regulatory mechanisms for protein synthesis, hormone secretion, and proliferation. Subsequently, activation of the mammalian target of rapamycin pathway was found to be an important mechanism in angiogenesis and tumor survival and cell metabolism. Finally, the importance of proangiogenic factors (platelet-derived growth factor, vascular endothelial growth factor, fibroblastic growth factor, angiopoietin, and semaphorins) in the progression of NET has been determined. Using the combination of biomarkers and imaging methods allows early evaluation of the appropriateness of treatment and response to treatment.
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Affiliation(s)
- Ahmet Yozgat
- Department of Gastroenterology, Ufuk University, Ankara, 06510, Turkey
| | - Murat Kekilli
- Department of Gastroenterology, Gazi University, Ankara 06560, Turkey
| | - Mustafa Altay
- Department of Endocrinology and Metabolism, University of Health Sciences Turkey, Keçiören Health Administration and Research Center, Ankara 06190, Turkey
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28
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Köseoğlu H, Duzenli T, Sezikli M. Gastric neuroendocrine neoplasms: A review. World J Clin Cases 2021; 9:7973-7985. [PMID: 34621854 PMCID: PMC8462212 DOI: 10.12998/wjcc.v9.i27.7973] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 05/19/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric neuroendocrine neoplasms (g-NENs) or neuroendocrine tumors are generally slow-growing tumors with increasing incidence. They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features. Type 1 and 2 are gastrin dependent, whereas type 3 and 4 are sporadic. The reason for hypergastrinemia is atrophic gastritis in type 1, and gastrin releasing tumor (gastrinoma) in type 2 g-NEN. The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy. g-NENs are positively stained with chomogranin A and synaptophysin. Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis. It is crucial to discriminate between types of g-NENs, because the management, treatment and prognosis differ significantly between subtypes. Treatment options for g-NENs include endoscopic resection, surgical resection with or without antrectomy, medical treatment with somatostatin analogues, netazepide or chemotherapy regimens. Follow-up without excision is another option in appropriate cases. The prognosis of type 1 and 2 g-NENs are good, whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.
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Affiliation(s)
- Hüseyin Köseoğlu
- Department of Gastroenterology, Hitit University, Faculty of Medicine, Çorum 19200, Turkey
| | - Tolga Duzenli
- Department of Gastroenterology, Hitit University Erol Olçok Education and Research Hospital, Çorum 19200, Turkey
| | - Mesut Sezikli
- Department of Gastroenterology, Hitit University, Faculty of Medicine, Çorum 19200, Turkey
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29
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Rossi RE, Elvevi A, Citterio D, Coppa J, Invernizzi P, Mazzaferro V, Massironi S. Gastrinoma and Zollinger Ellison syndrome: A roadmap for the management between new and old therapies. World J Gastroenterol 2021; 27:5890-5907. [PMID: 34629807 PMCID: PMC8475006 DOI: 10.3748/wjg.v27.i35.5890] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/29/2021] [Accepted: 08/10/2021] [Indexed: 02/06/2023] Open
Abstract
Zollinger-Ellison syndrome (ZES) associated with pancreatic or duodenal gastrinoma is characterized by gastric acid hypersecretion, which typically leads to gastroesophageal reflux disease, recurrent peptic ulcers, and chronic diarrhea. As symptoms of ZES are nonspecific and overlap with other gastrointestinal disorders, the diagnosis is often delayed with an average time between the onset of symptoms and final diagnosis longer than 5 years. The critical step for the diagnosis of ZES is represented by the initial clinical suspicion. Hypergastrinemia is the hallmark of ZES; however, hypergastrinemia might recognize several causes, which should be ruled out in order to make a final diagnosis. Gastrin levels > 1000 pg/mL and a gastric pH below 2 are considered to be diagnostic for gastrinoma; some specific tests, including esophageal pH-recording and secretin test, might be useful in selected cases, although they are not widely available. Endoscopic ultrasound is very useful for the diagnosis and the local staging of the primary tumor in patients with ZES, particularly in the setting of multiple endocrine neoplasia type 1. Some controversies about the management of these tumors also exist. For the localized stage, the combination of proton pump inhibitory therapy, which usually resolves symptoms, and surgery, whenever feasible, with curative intent represents the hallmark of gastrinoma treatment. The high expression of somatostatin receptors in gastrinomas makes them highly responsive to somatostatin analogs, supporting their use as anti-proliferative agents in patients not amenable to surgical cure. Other medical options for advanced disease are super-imposable to other neuroendocrine neoplasms, and studies specifically focused on gastrinomas only are scant and often limited to case reports or small retrospective series. The multidisciplinary approach remains the cornerstone for the proper management of this composite disease. Herein, we reviewed available literature about gastrinoma-associated ZES with a specific focus on differential diagnosis, providing potential diagnostic and therapeutic algorithms.
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Affiliation(s)
- Roberta Elisa Rossi
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan 20122, Italy
| | - Alessandra Elvevi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza 20033, Italy
| | - Davide Citterio
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
| | - Jorgelina Coppa
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
| | - Pietro Invernizzi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza 20033, Italy
| | - Vincenzo Mazzaferro
- HPB Surgery, Hepatology and Liver Transplantation, ENETS Center of Excellence, Fondazione IRCCS Istituto Nazionale Tumori (INT, National Cancer Institute), Milan 20133, Italy
- Department of Oncology and Hemato-Oncology, University of Milan, Milan 20122, Italy
| | - Sara Massironi
- Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza 20900, Italy
- European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, Monza 20033, Italy
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30
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Manoharan J, Anlauf M, Albers MB, Denzer UW, Mintziras I, Wächter S, Di Fazio P, Bollmann C, Bartsch DK. Gastric enterochromaffin-like cell changes in multiple endocrine neoplasia type 1. Clin Endocrinol (Oxf) 2021; 95:439-446. [PMID: 33506527 DOI: 10.1111/cen.14430] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 12/08/2020] [Accepted: 01/10/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Gastric enterochromaffin-like cell (ECL) tumours can occur in patients with multiple endocrine neoplasia type 1 (MEN1), especially in those affected by Zollinger Ellison syndrome (ZES). Since the prevalence of ECL lesions is not well defined yet, the present study evaluated the presence and extent of ECL lesions in MEN1 patients with and without ZES. METHODS Multiple endocrine neoplasia type 1 patients being part of a regular screening program (2014-2018) underwent gastroduodenoscopies with biopsies of the stomach and determination of serum gastrin and chromogranin A levels. Haematoxylin- and immunostaining with chromogranin A, gastrin and VMAT I and II (vesicular monoamine transporter I and II) of the biopsies were performed. RESULTS Thirty-eight MEN1 patients, of whom 16 (42%) were diagnosed and treated earlier for ZES, were analysed. In ten of 16 (62.5%) ZES patients, a locally scattered, mixed image of diffuse, linear and micronodular mild hyperplasia was present. In addition, two of these patients (13%) showed small (max 1.5 mm in size) intramucosal ECL tumours. Neither ECL changes, nor tumours were found in MEN1 patients without ZES (n = 22). In MEN1/ZES patients, the median serum gastrin level was significantly elevated compared to MEN1 patients without ZES (206 pg/ml vs. 30.5 pg/ml, p < .001). A subgroup analysis of the serum gastrin and chromogranin A levels of MEN1/ZES patients with or without ECL hyperplasia did not show significant differences (gastrin level: p = .302, chromogranin A: p = .464). CONCLUSION Enterochromaffin-like cell hyperplasia and gastric carcinoids occur only in MEN1 patients with ZES, but less frequently than reported.
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Affiliation(s)
- Jerena Manoharan
- Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany
| | - Martin Anlauf
- Institute of Pathology and Cytology, Wetzlar, Germany
| | - Max B Albers
- Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany
| | - Ulrike W Denzer
- Department of Gastroenterology, Philipps University Marburg, Marburg, Germany
| | - Ioannis Mintziras
- Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany
| | - Sabine Wächter
- Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany
| | - Pietro Di Fazio
- Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany
| | - Carmen Bollmann
- Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany
| | - Detlef K Bartsch
- Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany
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31
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Effraimidis G, Knigge U, Rossing M, Oturai P, Rasmussen ÅK, Feldt-Rasmussen U. Multiple endocrine neoplasia type 1 (MEN-1) and neuroendocrine neoplasms (NENs). Semin Cancer Biol 2021; 79:141-162. [PMID: 33905872 DOI: 10.1016/j.semcancer.2021.04.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 01/03/2021] [Accepted: 04/16/2021] [Indexed: 12/14/2022]
Abstract
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.
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Affiliation(s)
- Grigoris Effraimidis
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Ulrich Knigge
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Surgery and Transplantation, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Maria Rossing
- Centre for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Peter Oturai
- Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Åse Krogh Rasmussen
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark
| | - Ulla Feldt-Rasmussen
- ENETS Neuroendocrine Tumor Centre of Excellence, Rigshospitalet, Copenhagen University Hospital, Denmark; Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Denmark; Institute of Clinical Medicine, Faculty of Health Sciences, Copenhagen University, Denmark.
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32
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Geslot A, Vialon M, Caron P, Grunenwald S, Vezzosi D. New therapies for patients with multiple endocrine neoplasia type 1. ANNALES D'ENDOCRINOLOGIE 2021; 82:112-120. [PMID: 33839123 DOI: 10.1016/j.ando.2021.03.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 03/18/2021] [Accepted: 03/26/2021] [Indexed: 02/06/2023]
Abstract
In 1953, for the first time, Paul Wermer described a family presenting endocrine gland neoplasms over several generations. The transmission was autosomal dominant and the penetrance was high. Forty years later in 1997, the multiple endocrine neoplasia type 1 (MEN1) gene was sequenced, thus enabling diagnosis and early optimal treatment. Patients carrying the MEN1 gene present endocrine but also non-endocrine tumors. Parathyroid, pancreatic and pituitary impairment are the three main types of endocrine involvement. The present article details therapeutic management of hyperparathyroidism, neuroendocrine pancreatic tumors and pituitary adenomas in patients carrying the MEN1 gene. Significant therapeutic progress has in fact been made in the last few years. As concerns the parathyroid glands, screening of family members and regular monitoring of affected subjects now raise the question of early management of parathyroid lesions and optimal timing of parathyroid surgery. As concerns the duodenum-pancreas, proton-pump inhibitors are able to control gastrin-secreting syndrome, reducing mortality in MEN1 patients. Mortality in MEN1 patients is no longer mainly secondary to uncontrolled hormonal secretion but to metastatic (mainly pancreatic) disease progression. Tumor risk requires regular monitoring of morphological assessment, leading to iterative pancreatic surgery in a large number of patients. Finally, pituitary adenomas in MEN1 patients are traditionally described as aggressive, invasive and resistant to medical treatment. However, regular pituitary screening showed them to be in fact infra-centimetric and non-secreting in the majority of patients. Consequently, it is necessary to regularly monitor MEN1 patients, with regular clinical, biological and morphological work-up. Several studies showed that this regular monitoring impairs quality of life. Building a relationship of trust between patients and care provider is therefore essential. It enables the patient to be referred for psychological or psychiatric care in difficult times, providing long-term support and preventing any breakdown in continuity of care.
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Affiliation(s)
- Aurore Geslot
- Service d'endocrinologie, hôpital Larrey, 24, chemin de Pouvourville, 31029 Toulouse cedex 9, France
| | - Magaly Vialon
- Service d'endocrinologie, hôpital Larrey, 24, chemin de Pouvourville, 31029 Toulouse cedex 9, France
| | - Philippe Caron
- Service d'endocrinologie, hôpital Larrey, 24, chemin de Pouvourville, 31029 Toulouse cedex 9, France
| | - Solange Grunenwald
- Service d'endocrinologie, hôpital Larrey, 24, chemin de Pouvourville, 31029 Toulouse cedex 9, France
| | - Delphine Vezzosi
- Institut CardioMet, Toulouse, France; Service d'endocrinologie, hôpital Larrey, 24, chemin de Pouvourville, 31029 Toulouse cedex 9, France.
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33
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Al-Salameh A, Cadiot G, Calender A, Goudet P, Chanson P. Clinical aspects of multiple endocrine neoplasia type 1. Nat Rev Endocrinol 2021; 17:207-224. [PMID: 33564173 DOI: 10.1038/s41574-021-00468-3] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/07/2021] [Indexed: 01/31/2023]
Abstract
Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome characterized by the co-occurrence of primary hyperparathyroidism, duodenopancreatic neuroendocrine tumours (NETs) and/or pituitary adenomas. MEN1 can predispose patients to other endocrine and non-endocrine tumours, such as cutaneous tumours, central nervous system tumours and breast cancer. Endocrine tumours in patients with MEN1 differ from sporadic tumours in that they have a younger age at onset, present as multiple tumours in the same organ and have a different clinical course. Therefore, patients with overt MEN1 and those who carry a MEN1 mutation should be offered tailored biochemical and imaging screening to detect tumours and evaluate their progression over time. Fortunately, over the past 10 years, knowledge about the clinical phenotype of these tumours has markedly progressed, thanks to the implementation of national registries, particularly in France and the Netherlands. This Review provides an update on the clinical management of MEN1-related tumours. Epidemiology, the clinical picture, diagnostic work-up and the main lines of treatment for MEN1-related tumours are summarized. Controversial therapeutic aspects and issues that still need to be addressed are also discussed. Moreover, special attention is given to MEN1 manifestations in children and adolescents.
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Affiliation(s)
- Abdallah Al-Salameh
- Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, Le Kremlin-Bicêtre, France
- Service d'Endocrinologie, Maladies Métaboliques et Nutrition, CHU Amiens Picardie, Amiens, France
| | - Guillaume Cadiot
- Service d'Hépato-Gastro-Entérologie et de Cancérologie Digestive, Hôpital Robert Debré, Reims, France
| | - Alain Calender
- Unité Médicale des Cancers et Maladies Multifactorielles, Service de Génétique, Hospices Civils de Lyon, Lyon, France
| | - Pierre Goudet
- Service de Chirurgie Endocrinienne, Hôpital du Bocage, Dijon, France
| | - Philippe Chanson
- Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l'Hypophyse, Le Kremlin-Bicêtre, France.
- Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Le Kremlin-Bicêtre, France.
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34
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Wu W, Chen J, Bai C, Chi Y, Du Y, Feng S, Huo L, Jiang Y, Li J, Lou W, Luo J, Shao C, Shen L, Wang F, Wang L, Wang O, Wang Y, Wu H, Xing X, Xu J, Xue H, Xue L, Yang Y, Yu X, Yuan C, Zhao H, Zhu X, Zhao Y. The Chinese guidelines for the diagnosis and treatment of pancreatic neuroendocrine neoplasms (2020). JOURNAL OF PANCREATOLOGY 2021; 4:1-17. [DOI: 10.1097/jp9.0000000000000064] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Abstract
Pancreatic neuroendocrine neoplasms (pNENs) are highly heterogeneous, and the management of pNENs patients can be intractable. To address this challenge, an expert committee was established on behalf of the Chinese Pancreatic Surgery Association, which consisted of surgical oncologists, gastroenterologists, medical oncologists, endocrinologists, radiologists, pathologists, and nuclear medicine specialists. By reviewing the important issues regarding the diagnosis and treatment of pNENs, the committee concluded evidence-based statements and recommendations in this article, in order to further improve the management of pNENs patients in China.
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Affiliation(s)
- Wenming Wu
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Jie Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
| | - Chunmei Bai
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Yihebali Chi
- Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Yiqi Du
- Department of Gastroenterology, Changhai Hospital Affiliated to Navy Medical University, Shanghai
| | - Shiting Feng
- Department of Radiology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
| | - Li Huo
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Yuxin Jiang
- Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Jingnan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Wenhui Lou
- Department of General Surgery, Zhongshan Hospital of Fudan University
| | - Jie Luo
- Department of Pathology, China-Japan Friendship Hospital, Beijing
| | - Chenghao Shao
- Department of Pancreatic-biliary Surgery, Changzheng Hospital, Navy Medical University, Shanghai
| | - Lin Shen
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing
| | - Feng Wang
- Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province
| | - Liwei Wang
- Department of Oncology, Renji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai
| | - Ou Wang
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Yu Wang
- Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
| | - Huanwen Wu
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Xiaoping Xing
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Jianming Xu
- Department of Gastrointestinal Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing
| | - Huadan Xue
- Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
| | - Ling Xue
- Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai
| | - Chunhui Yuan
- Department of General Surgery, Peking University Third Hospital, Beijing
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing
| | - Xiongzeng Zhu
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Yupei Zhao
- Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing
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Pancreatoduodenectomy for Neuroendocrine Tumors in Patients with Multiple Endocrine Neoplasia Type 1: An AFCE (Association Francophone de Chirurgie Endocrinienne) and GTE (Groupe d'étude des Tumeurs Endocrines) Study. World J Surg 2021; 45:1794-1802. [PMID: 33649917 PMCID: PMC8093175 DOI: 10.1007/s00268-021-06005-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/30/2021] [Indexed: 12/18/2022]
Abstract
Aim To assess postoperative complications and control of hormone secretions following pancreatoduodenectomy (PD) performed on multiple endocrine neoplasia type 1 (MEN1) patients with duodenopancreatic neuroendocrine tumors (DP-NETs). Background The use of PD to treat MEN1 remains controversial, and evaluating the right place of PD in MEN1 disease makes sense. Methods Thirty-one MEN1 patients from the Groupe d’étude des Tumeurs Endocrines MEN1 cohort who underwent PD for DP-NETs between 1971 and 2013 were included. Early and late postoperative complications, secretory control and overall survival were analyzed. Results Indication for surgery was: Zollinger–Ellison syndrome (n = 18; 58%), nonfunctioning tumor (n = 9; 29%), insulinoma (n = 2; 7%), VIPoma (n = 1; 3%) and glucagonoma (n = 1; 3%). Mean follow-up was 141 months (range 0–433). Pancreatic fistulas occurred in 5 patients (16.1%), distant metastases in 6 (mean onset of 43 months; range 13–110 months), postoperative diabetes mellitus in 7 (22%), and pancreatic exocrine insufficiency in 6 (19%). Five-year overall survival was 93.3% [CI 75.8–98.3] and ten-year overall survival was 89.1% [CI 69.6–96.4]. After a mean follow-up of 151 months (range 0–433), the biochemical cure rate for MEN-1 related gastrinomas was 61%. Conclusion In MEN1 patients, pancreatoduodenectomy can be used to control hormone secretions (gastrin, glucagon, VIP) and to remove large NETs. PD was found to control gastrin secretions in about 60% of cases.
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Okamoto T, Yoshimoto T, Ohike N, Fujikawa A, Kanie T, Fukuda K. Spontaneous regression of gastric gastrinoma after resection of metastases to the lesser omentum: A case report and review of literature. World J Gastroenterol 2021; 27:129-142. [PMID: 33505155 PMCID: PMC7789063 DOI: 10.3748/wjg.v27.i1.129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Revised: 11/28/2020] [Accepted: 12/16/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Gastric gastrinoma and spontaneous tumor regression are both very rarely encountered. We report the first case of spontaneous regression of gastric gastrinoma. CASE SUMMARY A 37-year-old man with a 9-year history of chronic abdominal pain was referred for evaluation of an 8 cm mass in the lesser omentum discovered incidentally on abdominal computed tomography. The tumor was diagnosed as grade 2 neuroendocrine neoplasm (NEN) on endoscopic ultrasound-guided fine-needle aspiration. Screening esophagogastroduodenoscopy revealed a 7 mm red polypoid lesion with central depression in the gastric antrum, also confirmed to be a grade 2 NEN. Laparoscopic removal of the abdominal mass confirmed it to be a metastatic gastrinoma lesion. The gastric lesion was subsequently diagnosed as primary gastric gastrinoma. Three months later, the gastric lesion had disappeared without treatment. The patient remains symptom-free with normal fasting serum gastrin and no recurrence of gastrinoma during 36 mo of follow-up. CONCLUSION Gastric gastrinoma may arise as a polypoid lesion in the gastric antrum. Spontaneous regression can rarely occur after biopsy.
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Affiliation(s)
- Takeshi Okamoto
- Department of Gastroenterology, St. Luke's International Hospital, Tokyo 104-8560, Japan
| | - Takaaki Yoshimoto
- Department of Gastroenterology, St. Luke's International Hospital, Tokyo 104-8560, Japan
| | - Nobuyuki Ohike
- Department of Pathology, Shizuoka Cancer Center, Shizuoka 411-8777, Japan
| | - Aoi Fujikawa
- Department of Surgery, St. Luke’s International Hospital, Tokyo 104-8560, Japan
| | - Takayoshi Kanie
- Department of Cardiology, St. Luke’s International Hospital, Tokyo 104-8560, Japan
| | - Katsuyuki Fukuda
- Department of Gastroenterology, St. Luke's International Hospital, Tokyo 104-8560, Japan
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Niederle B, Selberherr A, Bartsch DK, Brandi ML, Doherty GM, Falconi M, Goudet P, Halfdanarson TR, Ito T, Jensen RT, Larghi A, Lee L, Öberg K, Pavel M, Perren A, Sadowski SM, Tonelli F, Triponez F, Valk GD, O'Toole D, Scott-Coombes D, Thakker RV, Thompson GB, Treglia G, Wiedenmann B. Multiple Endocrine Neoplasia Type 1 and the Pancreas: Diagnosis and Treatment of Functioning and Non-Functioning Pancreatic and Duodenal Neuroendocrine Neoplasia within the MEN1 Syndrome - An International Consensus Statement. Neuroendocrinology 2021; 111:609-630. [PMID: 32971521 DOI: 10.1159/000511791] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 09/18/2020] [Indexed: 11/19/2022]
Abstract
The better understanding of the biological behavior of multiple endocrine neoplasia type 1 (MEN1) organ manifestations and the increase in clinical experience warrant a revision of previously published guidelines. Duodenopancreatic neuroendocrine neoplasias (DP-NENs) are still the second most common manifestation in MEN1 and, besides NENs of the thymus, remain a leading cause of death. DP-NENs are thus of main interest in the effort to reevaluate recommendations for their diagnosis and treatment. Especially over the last 2 years, more clinical experience has documented the follow-up of treated and untreated (natural-course) DP-NENs. It was the aim of the international consortium of experts in endocrinology, genetics, radiology, surgery, gastroenterology, and oncology to systematically review the literature and to present a consensus statement based on the highest levels of evidence. Reviewing the literature published over the past decade, the focus was on the diagnosis of F- and NF-DP-NENs within the MEN1 syndrome in an effort to further standardize and improve treatment and follow-up, as well as to establish a "logbook" for the diagnosis and treatment of DP-NENs. This shall help further reduce complications and improve long-term treatment results in these rare tumors. The following international consensus statement builds upon the previously published guidelines of 2001 and 2012 and attempts to supplement the recommendations issued by various national and international societies.
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Affiliation(s)
- Bruno Niederle
- Department of Surgery, Medical University of Vienna, Vienna, Austria,
| | | | - Detlef K Bartsch
- Department of Visceral, Thoracic and Vascular Surgery, Philipps University Marburg, Marburg, Germany
| | - Maria L Brandi
- Firmo Lab, Fondazione F.I.R.M.O. and University Florence, Florence, Italy
| | - Gerard M Doherty
- Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Massimo Falconi
- Pancreatic Surgery, San Raffaele Scientific Institute, "Vita-Salute" University, Milan, Italy
| | - Pierre Goudet
- Service de Chirurgie Viscérale et Endocrinienne, Centre Hospitalier Universitaire François Mitterand, Dijon, France
| | | | - Tetsuhide Ito
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital and Department of Gastroenterology, Graduate School of Medical Sciences, International University of Health and Welfare, Sawara-ku, Fukuoka, Japan
| | - Robert T Jensen
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Alberto Larghi
- Digestive Endoscopy Unit, Fondazione Policlinico A. Gemelli IRCCS and Center for Endoscopic Research, Therapeutics and Training, Catholic University, Rome, Italy
| | - Lingaku Lee
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Kjell Öberg
- Endocrine Oncology, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden
| | - Marianne Pavel
- Endocrinology and Diabetology, Department of Medicine 1, University Clinic of Erlangen, Erlangen, Germany
| | - Aurel Perren
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Samira M Sadowski
- Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Francesco Tonelli
- Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
| | - Frédéric Triponez
- Thoracic and Endocrine Surgery, University Hospital of Geneva, Geneva, Switzerland
| | - Gerlof D Valk
- Department of Endocrine Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Dermot O'Toole
- Department of Clinical Medicine, St. James's Hospital and St Vincent's University Hospital and Trinity College, Dublin, Ireland
| | - David Scott-Coombes
- Department of Endocrine Surgery, University Hospital of Wales, Cardiff, United Kingdom
| | - Rajesh V Thakker
- Academic Endocrine Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, United Kingdom
| | - Geoffrey B Thompson
- Section of Endocrine Surgery, Department of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Giorgio Treglia
- Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Bertram Wiedenmann
- Department of Gastroenterology and Hepatology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Ravizza D, Fiori G. Gastric Neuroendocrine Tumors. NEUROENDOCRINE NEOPLASIA MANAGEMENT 2021:179-190. [DOI: 10.1007/978-3-030-72830-4_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Chagpar R, Naples R, Siperstein AE. Pancreatic Neuroendocrine Tumors. PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2021:938-948.e4. [DOI: 10.1016/b978-0-323-67293-1.00084-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Ito T, Jensen RT. Perspectives on the current pharmacotherapeutic strategies for management of functional neuroendocrine tumor syndromes. Expert Opin Pharmacother 2020; 22:685-693. [PMID: 33131345 DOI: 10.1080/14656566.2020.1845651] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Introduction: In the past, controlling the hormone-excess-state was the main determinant of survival in Functional-Neuroendocrine-Neoplasm-syndromes (F-NENs). This was difficult because the pharmacological-armamentarium available was limited. Recently, new therapeutic strategies have increased but it also generated controversies/uncertainties.Areas covered: The authors briefly review: established/proposed F-NENs; the rationale for treatments; the recommended initial-pharmacotherapeutic-approach to controlling F-NENs hormone-excess-state; the secondary-approaches if the initial approach fails or resistance develops; and the approach to deal with the malignant nature of the NEN. Also discussed are controversies/uncertainties related to new treatments.Expert opinion: Unfortunately, except for patients with insulinomas (>90-95%), gastrinomas (<20-40%), a minority with the other F-panNENs and 0-<1% with Carcinoid-syndrome is curative-surgery possible. Except for insulinomas, gastrinomas, and ACTHomas, long-acting somatostatin-analogs are the initial-pharmacological-treatments for hormone-excess-state. For insulinomas prior to surgery/malignancy, diazoxide is the initial drug-treatment; for gastrinomas, oral PPIs; and for ACTHomas, steroidogenesis inhibitors. There are now several secondary pharmacotherapeutic treatments. Surgery and liver-directed therapies also have a role in selected patients. Particularly promising is the recent results with PRRT for the hormone-excess-state, independent of its anti-growth effect. The sequence to use various agents and the approach to syndrome diagnosis while taking various agents remains unclear/controversial in many cases.
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Affiliation(s)
- Tetsuhide Ito
- Neuroendocrine Tumor Centre, Fukuoka Sanno Hospital, International University of Health and Welfare, Fukuoka, Japan
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41
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Surgical Management of Neuroendocrine Tumours of the Pancreas. J Clin Med 2020; 9:jcm9092993. [PMID: 32947997 PMCID: PMC7565036 DOI: 10.3390/jcm9092993] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 09/07/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumours of the pancreas (pNET) are rare, accounting for 1-2% of all pancreatic neoplasms. They develop from pancreatic islet cells and cover a wide range of heterogeneous neoplasms. While most pNETs are sporadic, some are associated with genetic syndromes. Furthermore, some pNETs are 'functioning' when there is clinical hypersecretion of metabolically active peptides, whereas others are 'non-functioning'. pNET can be diagnosed at a localised stage or a more advanced stage, including regional or distant metastasis (in 50% of cases) mainly located in the liver. While surgical resection is the cornerstone of the curative treatment of those patients, pNET management requires a multidisciplinary discussion between the oncologist, radiologist, pathologist, and surgeon. However, the scarcity of pNET patients constrains centralised management in high-volume centres to provide the best patient-tailored approach. Nonetheless, no treatment should be initiated without precise diagnosis and staging. In this review, the steps from the essential comprehensive preoperative evaluation of the best surgical approach (open versus laparoscopic, standard versus sparing parenchymal pancreatectomy, lymphadenectomy) according to pNET staging are analysed. Strategies to enhance the short- and long-term benefit/risk ratio in these particular patients are discussed.
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42
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Chen Cardenas SM, El-Kaissi S, Jarad O, Liaqat M, Korbonits M, Hamrahian AH. Unusual Combination of MEN-1 and the Contiguous Gene Deletion Syndrome of CAH and Ehlers-Danlos Syndrome (CAH-X). J Endocr Soc 2020; 4:bvaa077. [PMID: 32715272 PMCID: PMC7371387 DOI: 10.1210/jendso/bvaa077] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Indexed: 11/19/2022] Open
Abstract
The contiguous gene deletion syndrome of congenital adrenal hyperplasia and Ehlers-Danlos syndrome, named CAH-X, is a rare entity that occurs because of a deletion of a chromosomal area containing 2 neighboring genes, TNXB and CYP21A. Here, we describe a patient from a consanguineous family in which coincidentally MEN-1 syndrome is associated with CAH-X, causing particular challenges explaining the phenotypic features of the patient. A 33-year-old man with salt-wasting congenital adrenal hyperplasia and classic-like Ehlers-Danlos syndrome presented with an adrenal crisis with a history of recurrent hypoglycemia, abdominal pain, and vomiting. He was found to have primary hyperparathyroidism, hyperprolactinemia, and pancreatic neuroendocrine tumors, as well as primary hypogonadism, large adrenal myelolipomas, and low bone mineral density. A bladder diverticulum was incidentally found. Genetic analysis revealed a heterozygous previously well-described MEN1 mutation (c.784-9G > A), a homozygous complete deletion of CYP21A2 (c.1-?_1488+? del), as well as a large deletion of the neighboring TNXB gene (c.11381-?_11524+?). The deletion includes the complete CYP21A2 gene and exons 35 through 44 of the TNXB gene. CGH array found 12% homozygosity over the whole genome. This rare case illustrates a complex clinical scenario with some initial diagnostic challenges.
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Affiliation(s)
- Stanley M Chen Cardenas
- Division of Endocrinology, Diabetes, and Metabolism. The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Samer El-Kaissi
- Department of Endocrinology, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE
| | - Ola Jarad
- Department of Endocrinology, Cleveland Clinic Abu Dhabi, Abu Dhabi, UAE
| | - Muneezeh Liaqat
- Pathology and Laboratory Medicine Institute, Cleveland Clinic Abu Dhabi and National Reference Laboratory, Abu Dhabi, UAE
| | - Márta Korbonits
- Department of Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Amir H Hamrahian
- Division of Endocrinology, Diabetes, and Metabolism. The Johns Hopkins University School of Medicine, Baltimore, Maryland
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Mozgovoi SI, Livzan MA, Krolevets TS, Shimanskaya AG. Neuroendocrine Tumour as a Diagnostic and Prognostic Criterion for Autoimmune Gastritis. RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2020; 29:49-59. [DOI: 10.22416/1382-4376-2019-29-6-49-59] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
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Chen YJ, Ojeaburu JV, Vortmeyer A, Yu S, Jensen RT. Alterations of chromosome 3p in 24 cases of gastrinomas and their correlations with clinicopathological and prognostic features. JOURNAL OF PANCREATOLOGY 2020; 3:42-49. [DOI: 10.1097/jp9.0000000000000034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Abstract
Purpose:
The pathogenesis of gastrinomas is largely unknown, and there is a lack of reliable genetic determinants that are useful to distinguish malignant and benign forms of this tumor or predict the prognosis of patients with this disease. Loss of heterozygosity (LOH) on chromosome 3p is reported to occur in pancreatic neuroendocrine tumors (PNETs) as well as in non-PNETs and its presence is reported to correlate with tumor prognosis in non-endocrine tumors. However, little data are available from prospective studies on gastrinomas.
Experimental design:
We assessed occurrence of 3p LOH in 24 gastrinomas and correlated its presence with tumor biological behavior and other clinicopathological features of gastrinomas.
Results:
Either 3p LOH or microsatellite instability involving 3p occurred in 11 of 24 tumors (46%). Seven (29%) gastrinomas had 3p LOH. Of the 7 gastrinomas with 3p LOH, 5 (71%) had 3p12 LOH with the marker D3S2406, which was the shortest region of highest overlap (SRO). Chromosome 3p LOH was not associated with aggressive biological behavior of gastrinomas or with poor prognosis of patients with gastrinoma. Similarly, 3p12 LOH (SRO) was not correlated with aggressive growth of tumors and/or liver metastases.
Conclusion:
Gastrinomas have a relative high frequency of 3p12 LOH suggesting this area may harbor putative tumor suppressor gene(s), which may play a role in the tumorigenesis, but not aggressiveness, of a subset of these tumors.
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Affiliation(s)
- Yuan-Jia Chen
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
- Digestive Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases
| | - Jeremiah V. Ojeaburu
- Digestive Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases
| | - Alexander Vortmeyer
- Molecular Pathogenesis Unit, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA
| | - Shuang Yu
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Robert T. Jensen
- Digestive Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases
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45
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Asban A, Patel AJ, Reddy S, Wang T, Balentine CJ, Chen H. Cancer of the Endocrine System. ABELOFF'S CLINICAL ONCOLOGY 2020:1074-1107.e11. [DOI: 10.1016/b978-0-323-47674-4.00068-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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46
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Hain E, Sindayigaya R, Fawaz J, Gharios J, Bouteloup G, Soyer P, Bertherat J, Prat F, Terris B, Coriat R, Gaujoux S. Surgical management of pancreatic neuroendocrine tumors: an introduction. Expert Rev Anticancer Ther 2019; 19:1089-1100. [PMID: 31825691 DOI: 10.1080/14737140.2019.1703677] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Introduction: Neuroendocrine tumors of the pancreas (pNETs) represent only 1% to 2% of all pancreatic neoplasms. These tumors can be classified as functional or nonfunctional tumors; as sporadic or from a genetic origin; as neuroendocrine neoplasms or carcinoma. Over the last decade, diagnosis of pNETs has increased significantly mainly due to the widespread use of cross-sectional imaging. Those tumors are usually associated with a good prognosis. Surgery, the only curative option for those patients, should always be discussed, ideally in a multidisciplinary team setting.Areas covered: We discuss i), the preoperative management of pNETs and the importance of accurate diagnosis, localization, grading and staging with computed tomography, magnetic resonance imaging, endoscopic ultrasound, and nuclear medicine imaging; ii), surgical indications and iii), the surgical approach (standard pancreatectomy vs pancreatic-sparing surgery).Expert opinion: The treatment option of all patients presenting with pNETs should be discussed in a multidisciplinary team setting with surgeon's experienced in both pancreatic surgery and neuroendocrine tumor management. A complete preoperative imaging assessment - morphological and functional - must be performed. Surgery is usually recommended for functional pNETs, nonfunctional pNETs >2 cm (nf-pNETs) or for symptomatic nf-pNETs.
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Affiliation(s)
- Elisabeth Hain
- Department of Digestive, Hepato-biliary and Endocrine Surgery, Cochin Hospital, APHP, Paris, France.,Facultéde Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Rémy Sindayigaya
- Department of Digestive, Hepato-biliary and Endocrine Surgery, Cochin Hospital, APHP, Paris, France
| | - Jade Fawaz
- Department of Digestive, Hepato-biliary and Endocrine Surgery, Cochin Hospital, APHP, Paris, France
| | - Joseph Gharios
- Department of Digestive, Hepato-biliary and Endocrine Surgery, Cochin Hospital, APHP, Paris, France
| | - Gaspard Bouteloup
- Department of Digestive, Hepato-biliary and Endocrine Surgery, Cochin Hospital, APHP, Paris, France
| | - Philippe Soyer
- Department of Radiology, Cochin Hospital, APHP, Paris, France
| | - Jérôme Bertherat
- Department of Endocrinology, Cochin Hospital, APHP, Paris, France
| | - Frédéric Prat
- Facultéde Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.,Department of Gastroenterology, Cochin Hospital, APHP, Paris, France
| | - Benoit Terris
- Facultéde Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.,Department of Pathology, Cochin Hospital, APHP, Paris, France
| | - Romain Coriat
- Facultéde Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.,Department of Gastroenterology, Cochin Hospital, APHP, Paris, France
| | - Sébastien Gaujoux
- Department of Digestive, Hepato-biliary and Endocrine Surgery, Cochin Hospital, APHP, Paris, France.,Facultéde Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France
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Lee L, Ramos-Alvarez I, Ito T, Jensen RT. Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger-Ellison Syndrome. Int J Mol Sci 2019; 20:5128. [PMID: 31623145 PMCID: PMC6829234 DOI: 10.3390/ijms20205128] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 10/08/2019] [Accepted: 10/13/2019] [Indexed: 02/07/2023] Open
Abstract
The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25-70% of total). An increasing number of patients with moderate to advanced gastroesophageal reflux disease are remaining on PPI indefinitely. Whereas numerous studies show PPIs remain effective and safe, most of these studies are <5 years of duration and little data exist for >10 years of treatment. Recently, based primarily on observational/epidemiological studies, there have been an increasing number of reports raising issues about safety and side-effects with very long-term chronic treatment. Some of these safety issues are related to the possible long-term effects of chronic hypergastrinemia, which occurs in all patients taking chronic PPIs, others are related to the hypo-/achlorhydria that frequently occurs with chronic PPI treatment, and in others the mechanisms are unclear. These issues have raised considerable controversy in large part because of lack of long-term PPI treatment data (>10-20 years). Zollinger-Ellison syndrome (ZES) is caused by ectopic secretion of gastrin from a neuroendocrine tumor resulting in severe acid hypersecretion requiring life-long antisecretory treatment with PPIs, which are the drugs of choice. Because in <30% of patients with ZES, a long-term cure is not possible, these patients have life-long hypergastrinemia and require life-long treatment with PPIs. Therefore, ZES patients have been proposed as a good model of the long-term effects of hypergastrinemia in man as well as the effects/side-effects of very long-term PPI treatment. In this article, the insights from studies on ZES into these controversial issues with pertinence to chronic PPI use in non-ZES patients is reviewed, primarily concentrating on data from the prospective long-term studies of ZES patients at NIH.
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Affiliation(s)
- Lingaku Lee
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA.
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
| | | | - Tetsuhide Ito
- Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital, International University of Health and Welfare 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan.
| | - Robert T Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA.
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Norton JA, Foster DS, Blumgart LH, Poultsides GA, Visser BC, Fraker DL, Alexander HR, Jensen RT. Incidence and Prognosis of Primary Gastrinomas in the Hepatobiliary Tract. JAMA Surg 2019; 153:e175083. [PMID: 29365025 DOI: 10.1001/jamasurg.2017.5083] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
| | - Deshka S. Foster
- Department of Surgery, Stanford University, Stanford, California
| | - Leslie H. Blumgart
- Department of Surgery, Memorial Sloan Kettering Cancer Institute, New York, New York
| | | | | | | | | | - Robert T. Jensen
- Digestive Diseases Branch, National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland
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Alekberzade AV, Krylov NN, Garmanova TN, Shahbazov R, Azari F, Zuykova KS, Litovchenko ED. [Duodenal neuroendocrine tumors]. Khirurgiia (Mosk) 2019:87-95. [PMID: 31355821 DOI: 10.17116/hirurgia201907187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Significant augmentation of the incidence of duodenal neuroendocrine tumors duodenum has been observed in recent decades. There are 5 histological types of these tumors: gastrinoma (50-60%), somatostatin-producing tumor (15%), inactive serotonin-containing tumors (20%), poorly differentiated neuroendocrine carcinoma (<3%) and gangliocytic paraganglioma (<2%). The majority of tumors are localized within the bulb and postbulbar part of duodenum, 20% are found in periampular area. Treatment strategy depends on dimensions, localization, histological class, stage and type of tumor. It is believed that endoscopic resection is permissible for small inactive tumors (G1) located above major duodenal papilla. The majority of other neoplasms requires surgical resection. Personal experience of various surgeons is limited by small group of patients. Therefore, it is necessary to summarize results for selection of optimal treatment.
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Affiliation(s)
- A V Alekberzade
- Sechenov First Moscow State Medical University of Ministry of Health of Russia, Moscow, Russia
| | - N N Krylov
- Sechenov First Moscow State Medical University of Ministry of Health of Russia, Moscow, Russia
| | - T N Garmanova
- Sechenov First Moscow State Medical University of Ministry of Health of Russia, Moscow, Russia
| | - R Shahbazov
- Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, USA
| | - F Azari
- Department of Surgery, University of Pennsylvania, Philadelphia PA, USA
| | - K S Zuykova
- Sechenov First Moscow State Medical University of Ministry of Health of Russia, Moscow, Russia
| | - E D Litovchenko
- Sechenov First Moscow State Medical University of Ministry of Health of Russia, Moscow, Russia
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Zhu X, Jing H, Yao T. Clinical characteristics of early neuroendocrine carcinoma in stomach: A case report and review of literature. Medicine (Baltimore) 2019; 98:e16638. [PMID: 31348317 PMCID: PMC6709248 DOI: 10.1097/md.0000000000016638] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
INTRODUCTION Gastric neuroendocrine carcinoma (NEC) is rare. It is considered to be aggressive and has a poor prognosis since the diagnosis is usually made at its advanced stage. However, the survival rate is increased in some early gastric NECs. This study showed a case and reviewed the clinical characteristics of early NECs in stomach. PATIENT CONCERNS A 38-year-old man displayed no symptoms and underwent the gastric endoscopy test for his health examination, which showed a red slightly depressed lesion 1.0 cm in size on the lesser curvature of gastric cardia. Magnifying endoscopy with narrow-band imaging (NBI) revealed a clear demarcation and an irregular mesh in vessels within the depressed area. The background mucosa was negative for atrophic gastritis and Helicobacter Pylori infection. A contrast-enhanced computed tomography (CT) scan disclosed no obvious thickening of stomach and lymphadenopathy. Blood tests and physical examination were unremarkable. He had not received any surgical treatment and denied a family history of cancer and any genetic disorders. The pathologic result of biopsy from the lesion was suspicious of superficial carcinoma. Then endoscopic submucosal dissection (ESD) was performed. DIAGNOSIS Gastric NEC G3 in the early stage (T1aN0M0). INTERVENTIONS Concerning this patient's situation, we considered the ESD as a curable treatment. And no radical surgery or adjuvant chemotherapy was arranged. OUTCOMES The patient is doing well and displays no recurrence for 11 months, who is still in follow-up. LESSONS SUBSECTIONS AS PER STYLE The early diagnosis and effective treatment by endoscopy would contribute to improve the prognosis of gastric NECs.
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Affiliation(s)
| | - Haiyan Jing
- Department of Pathology, Shandong Provincial Hospital affiliated to Shandong University, Jinan 250021, China
| | - Takashi Yao
- Department of Human Pathology, Juntendo University, Tokyo 113-8421, Japan
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