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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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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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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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Marcal LP, Chuang HH, Tran Cao HS, Halperin DM. Pancreatic Neuroendocrine Tumors. ONCOLOGIC IMAGING : A MULTIDISCIPLINARY APPROACH 2023:197-217. [DOI: 10.1016/b978-0-323-69538-1.00014-8] [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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Frey S, Mirallié E, Le Bras M, Regenet N. What Are the Place and Modalities of Surgical Management for Pancreatic Neuroendocrine Neoplasms? A Narrative Review. Cancers (Basel) 2021; 13:5954. [PMID: 34885063 PMCID: PMC8656750 DOI: 10.3390/cancers13235954] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 12/14/2022] Open
Abstract
Pancreatic neuroendocrine neoplasms (panNENs) are a heterogeneous group of tumors derived from cells with neuroendocrine differentiation. They are considered malignant by default. However, their outcomes are variable depending on their presentation in the onset of hereditary syndromes, hormonal secretion, grading, and extension. Therefore, although surgical treatment has long been suggested as the only treatment of pancreatic neuroendocrine neoplasms, its modalities are an evolving landscape. For selected patients (small, localized, non-functional panNENs), a "wait and see" strategy is suggested, as it is in the setting of multiple neuroendocrine neoplasia type 1, but the accurate size cut-off remains to be established. Parenchyma-sparring pancreatectomy, aiming to limit pancreatic insufficiency, are also emerging procedures, which place beyond the treatment of insulinomas and small non-functional panNENs (in association with lymph node picking) remains to be clarified. Furthermore, giving the fact that the liver is generally the only metastatic site, surgery keeps a place of choice alongside medical therapies in the treatment of metastatic disease, but its modalities and extensions are still a matter of debate. This narrative review aims to describe the current recommended surgical management for pancreatic NENs and controversies in light of the actual recommendations and recent literature.
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Affiliation(s)
- Samuel Frey
- Université de Nantes, Quai de Tourville, 44000 Nantes, France; (S.F.); (E.M.)
- L’institut du Thorax, Université de Nantes, CNRS, INSERM, CHU de Nantes, 44000 Nantes, France
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
| | - Eric Mirallié
- Université de Nantes, Quai de Tourville, 44000 Nantes, France; (S.F.); (E.M.)
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
| | - Maëlle Le Bras
- Endocrinologie, Diabétologie et Nutrition, L’institut du Thorax, CHU Nantes, 44000 Nantes, France;
| | - Nicolas Regenet
- Chirurgie Cancérologique, Digestive et Endocrinienne, Institut des Maladies de l’Appareil Digestif, CHU de Nantes, 44000 Nantes, France
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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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Fujii Y, Tzeng CW, Chiang YJ, Halperin DM, Dasari A, Kim MP, Katz MHG, Lee JE, Ikoma N. Incidence of Lymph Node Metastases and Impact of Radical Surgery for Duodenal Neuroendocrine Tumors. J Surg Res 2021; 268:419-431. [PMID: 34416414 DOI: 10.1016/j.jss.2021.06.085] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 05/25/2021] [Accepted: 06/30/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND Despite the high frequency of regional lymph node (LN) metastases associated with duodenal neuroendocrine tumors (D-NETs), the impact of these metastases on survival and the ideal extent of LN dissection are unknown. We used the National Cancer Database (NCDB) to investigate factors associated with survival, including LN metastases and types of surgery, in patients with D-NETs. METHODS All patients with D-NETs recorded in the NCDB between 2004 and 2016 were included in the study. We applied a multivariate Cox regression model to assess the relationship between the clinicopathological characteristics and overall survival (OS). RESULTS We identified 7613 patients, among whom 4886 local excisions and 233 radical surgeries had been performed. Among patients with at least 1 LN pathologically examined, the overall incidence of LN metastasis was 41.2%. For all patients, the median OS was 10.6 years. Univariate analyses showed equivalent OS in N0 and N1 groups (HR,0.83; 95% CI,0.64-1.09) and diminished OS in those who had undergone radical surgery compared with those who had undergone local resection (HR,1.35; 95% CI,1.02-1.8). In multivariable analyses, tumor size >50 mm and having more than 9 positive LNs were associated with diminished OS (HR,1.64 and 5.2; 95% CI,1.25-2.16 and 1.91-14.18), whereas the type of surgery did not remain in the model. CONCLUSION Our study revealed that the presence of regional LN metastases and extent of surgery did not affect OS among patients with D-NETs. Radical resection to clear occult LN metastases for nonfunctioning, sporadic D-NETs was not supported by the current study.
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Affiliation(s)
- Yuki Fujii
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Gastroenterological Surgery 1, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
| | - Ching-Wei Tzeng
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Yi-Ju Chiang
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Daniel M Halperin
- GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Arvind Dasari
- GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Michael P Kim
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Matthew H G Katz
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jeffrey E Lee
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Naruhiko Ikoma
- Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Lorenzo D, Maire F, Hentic O, Prat F, Ruszniewski P, de Mestier L. Endoscopic diagnosis and treatment of neuroendocrine tumors. CURRENT OPINION IN ENDOCRINE AND METABOLIC RESEARCH 2021; 18:201-206. [DOI: 10.1016/j.coemr.2021.03.014] [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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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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Total gastrectomy for severe proton pump inhibitor-induced hypomagnesemia in a MEN1/Zollinger Ellison syndrome patient. Pancreatology 2021; 21:236-239. [PMID: 33309626 DOI: 10.1016/j.pan.2020.12.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 12/01/2020] [Accepted: 12/02/2020] [Indexed: 12/11/2022]
Abstract
We report here the first case of life-threatening hypomagnesemia in a Zollinger-Ellison syndrome patient with multiple endocrine neoplasia type 1 (MEN1) syndrome. The severe symptomatic hypomagnesemia proved to be due to proton pump inhibitors (PPIs), but withdrawal of PPIs led to early severe peptic complications despite a substitution by histamine H2-receptor antagonist therapy. Simultaneous management of life-threatening hypomagnesemia, severe gastric acid hypersecretion and MEN1-associated gastrinomas was complex. A total gastrectomy was performed in order to definitely preclude the use of PPIs in this frail patient who was not eligible for curative pancreatoduodenal resection.
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Cloyd JM, Poultsides GA. The Landmark Series: Pancreatic Neuroendocrine Tumors. Ann Surg Oncol 2020; 28:1039-1049. [PMID: 32948965 DOI: 10.1245/s10434-020-09133-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 08/29/2020] [Indexed: 12/23/2022]
Abstract
Pancreatic neuroendocrine tumors (PNETs) comprise a heterogeneous group of neoplasms arising from pancreatic islet cells that remain relatively rare but are increasing in incidence worldwide. While significant advances have been made in recent years with regard to systemic therapies for patients with advanced disease, surgical resection remains the standard of care for most patients with localized tumors. Although formal pancreatectomy with regional lymphadenectomy is the standard approach for most PNETs, pancreas-preserving approaches without formal lymphadenectomy are acceptable for smaller tumors at low risk for lymph node metastases. Furthermore, observation of small, asymptomatic, low-grade PNETs is a safe, initial strategy and is generally recommended for tumors < 1 cm in size. In this Landmark Series review, we highlight the critical studies that have defined the surgical management of PNETs.
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Affiliation(s)
- Jordan M Cloyd
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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12
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Howe JR, Merchant NB, Conrad C, Keutgen XM, Hallet J, Drebin JA, Minter RM, Lairmore TC, Tseng JF, Zeh HJ, Libutti SK, Singh G, Lee JE, Hope TA, Kim MK, Menda Y, Halfdanarson TR, Chan JA, Pommier RF. The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors. Pancreas 2020; 49:1-33. [PMID: 31856076 PMCID: PMC7029300 DOI: 10.1097/mpa.0000000000001454] [Citation(s) in RCA: 259] [Impact Index Per Article: 51.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the surgical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The group reviewed a series of questions of specific interest to surgeons taking care of patients with pancreatic neuroendocrine tumors, and for each, the available literature was reviewed. What follows are these reviews for each question followed by recommendations of the panel.
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Affiliation(s)
- James R. Howe
- Department of Surgery, University of Iowa Carver College of Medicine, Iowa City, IA
| | | | - Claudius Conrad
- Department of Surgery, St. Elizabeth Medical Center, Tufts University School of Medicine, Boston, MA
| | | | - Julie Hallet
- Department of Surgery, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Canada
| | - Jeffrey A. Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Rebecca M. Minter
- Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI
| | | | | | - Herbert J. Zeh
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX
| | - Steven K. Libutti
- §§ Department of Surgery, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ
| | - Gagandeep Singh
- Department of Surgery, City of Hope Comprehensive Cancer Center, Duarte, CA
| | - Jeffrey E. Lee
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Thomas A. Hope
- Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA
| | - Michelle K. Kim
- Department of Medicine, Mt. Sinai Medical Center, New York, NY
| | - Yusuf Menda
- Department of Radiology, University of Iowa Carver College of Medicine, Iowa City, IA
| | | | - Jennifer A. Chan
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
| | - Rodney F. Pommier
- Department of Surgery, Oregon Health & Sciences University, Portland, OR
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Alekberzade AV, Krylov NN, Lipnitskiy EM, Shakhbazov RO, Azari F. [Gastric neuroendocrine tumors]. Khirurgiia (Mosk) 2019:111-120. [PMID: 31825351 DOI: 10.17116/hirurgia2019121111] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Gastrointestinal neuroendocrine tumors are rare neoplasms. Currently, incidence of gastric neuroendocrine tumors (gNETs) is being significantly increased. There are 3 groups of gNETs: types I, II and III. Each type has important features regarding clinical picture, prognosis and treatment strategy. Type I is the most common (70-80%) and associated with chronic atrophic gastritis including autoimmune gastritis and Helicobacter associated atrophic gastritis. Type II (5-6%) is associated with multiple endocrine neoplasia type I and Zollinger-Ellison syndrome (MEN I - ZES). Both types are characterized by hypergastrinemia and small tumor dimension. These neoplasms are multiple and mostly benign. On the contrary, NETs type III (10-15%) is not associated with hypergastrinemia and represented by single large neoplasms. Tumors are malignant as a rule. Therefore, surgical resection and chemotherapy are preferred for these tumors. Endoscopic surgery followed by observation is acceptable for almost all NETS type I and II. At the same time, this approach is advisable only for small and highly differentiated neoplasms type III.
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Affiliation(s)
- A V Alekberzade
- Sechenov First Moscow State Medical University, Moscow, Russia
| | - N N Krylov
- Sechenov First Moscow State Medical University, Moscow, Russia
| | - E M Lipnitskiy
- Sechenov First Moscow State Medical University, Moscow, Russia
| | - R O Shakhbazov
- Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, USA
| | - F Azari
- Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia PA, USA
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Case report: optimal tumor cytoreduction and octreotide with durable disease control in a patient with MEN-1 and Zollinger-Ellison syndrome-over a decade of follow-up. World J Surg Oncol 2019; 17:213. [PMID: 31818296 PMCID: PMC6902565 DOI: 10.1186/s12957-019-1758-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Accepted: 11/25/2019] [Indexed: 12/24/2022] Open
Abstract
Background Zollinger-Ellison syndrome (ZES) is a rare condition characterized by hypersecretion of gastrin by gastrinoma tumors leading to severe peptic ulcer disease with potential development of gastric carcinoid tumors. Herein, we report the clinical course of a 68-year-old patient with multiple endocrine neoplasia type 1 (MEN-1) who underwent several surgeries to ultimately undergo optimal tumor cytoreduction of locally advanced gastrinomas and symptomatic gastric carcinoids. The patient was subsequently maintained on octreotide long-acting release (LAR). This case report supports consideration for aggressive tumor cytoreduction and octreotide in similar patients with MEN-1-associated ZES for durable disease control and symptom management. Case presentation The patient is a 68-year-old male with multiple endocrine neoplasia type 1 (MEN-1), diagnosed in 1993 after presenting with recurrent renal calculi and hypercalcemia. Soon thereafter, he presented with symptoms and elevated gastrin levels suggestive of ZES prompting abdominal exploration with partial resection of the duodenum to remove gastrinoma tumor nodules. Within 4 years of the operation, he represented with intractable hypergastrinemia despite optimal medical management with peak gastrin levels exceeding 29,000 pg/mL, in 2006. In January 2007, the patient returned to the operating room for resection of regional peripancreatic and perigastric lymph nodes and enucleation of pancreatic body and tail gastrinoma tumors. Although his gastrin level decreased to 5000 pg/mL with resultant improvement of symptoms, in less than 2 years, he developed disease progression with obstructive symptomatology from enlarging gastric carcinoids and rising gastrin levels. In May of 2008, he underwent pancreaticoduodenectomy and near-total gastrectomy. Since June of 2008, the patient shows no demonstrable progression of disease and remains asymptomatic on LAR octreotide (30 mgs). Gastrin levels have been well controlled (range, 100–624 pg/mL; current 114 pg/mL). Conclusion Success of this procedure in our case report highlights the potential role for optimal tumor cytoreduction and LAR octreotide to control disease progression in a patient with MEN-I and Zollinger-Ellison syndrome with locally advanced gastrinoma and secondary large gastric carcinoids.
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Gong S, Li Z, Liu XB, Wang X, Shen WW. Gastrinoma in multiple endocrine neoplasia type 1 after total pancreatectomy: A case report. Medicine (Baltimore) 2019; 98:e18275. [PMID: 31852099 PMCID: PMC6922403 DOI: 10.1097/md.0000000000018275] [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: 02/05/2023] Open
Abstract
RATIONALE Surgery for patients with multiple endocrine neoplasia type 1(MEN-1) related gastrinoma remains controversial and total pancreatectomy (TP) has rarely been performed. We reported a case of patient with MEN-1 related gastrinoma treated by TP. PATIENT CONCERNS A 46-year-old female was admitted to our hospital due to abdominal distension and diarrhea for 2 years. The patient underwent pituitary tumor resection and kidney stone lithotripsy 10 years ago. DIAGNOSES Abdominal computed tomography showed single lesion in the duodenum and multiple lesions throughout the pancreas. The patient's gastrin level was significantly increased (1080 pg/ml). These findings in combination with the pituitary tumor history suggested the presence of gastrinoma associated with MEN-1 syndrome. INTERVENTION An exploratory laparotomy was performed. Intraoperative ultrasound confirmed the numerous tumors diffusely distributed throughout the pancreas and the patient eventually underwent TP. OUTCOMES Twelve months later, the patient was hospitalized again for anastomotic fistula and underwent a partial gastrectomy, small bowel resection and drainage of the abscess. One month later, she received gastrostomy and jejunostomy due to digestive tract fistula, and died a month later (14 months after TP). LESSONS There still might be the possibility of recurrence even after radical surgical resection of gastrinomas, and we suggest the need to measure the basal acid output and maintain regular anti-acid therapy in the long-term follow-up of patients with MEN-1 related gastrinoma.
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Affiliation(s)
- Shu Gong
- Department of Pancreatic Surgery
| | - Zhi Li
- Department of Pancreatic Surgery
| | | | - Xin Wang
- Department of Pancreatic Surgery
| | - Wen-Wu Shen
- Outpatient Department, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
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Albers MB, Manoharan J, Bartsch DK. Contemporary surgical management of the Zollinger-Ellison syndrome in multiple endocrine neoplasia type 1. Best Pract Res Clin Endocrinol Metab 2019; 33:101318. [PMID: 31521501 DOI: 10.1016/j.beem.2019.101318] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
About 30% of patients with MEN1 develop a Zollinger-Ellison syndrome. Meanwhile it is well established that the causative gastrinomas are almost exclusively localized in the duodenum and not in the pancreas, MEN1 gastrinomas occur multicentric and are associated with hyperplastic gastrin cell lesions and tiny gastrin-producing micro tumors in contrast to sporadic duodenal gastrinomas. Regardless of the high prevalence of early lymphatic metastases, the survival is generally good with an aggressive course of disease in only about 20% of patients. Symptoms can be controlled medically. The indication, timing, type, and extent of surgery are highly controversial and are discussed in detail in this article by a thorough and critical review of literature. More radical procedures, like partial pancreaticoduodenectomy, are weighed against less aggressive local excision of gastrinomas and the pros and cons of both approaches are discussed in terms of long-term morbidity, biochemical cure, and survival.
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Affiliation(s)
- Max B Albers
- Department of Visceral, Thoracic, and Vascular Surgery, Philipps University Marburg, Baldingerstr, 35037 Marburg, Germany.
| | - Jerena Manoharan
- Department of Visceral, Thoracic, and Vascular Surgery, Philipps University Marburg, Baldingerstr, 35037 Marburg, Germany
| | - Detlef K Bartsch
- Department of Visceral, Thoracic, and Vascular Surgery, Philipps University Marburg, Baldingerstr, 35037 Marburg, Germany
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Shao QQ, Zhao BB, Dong LB, Cao HT, Wang WB. Surgical management of Zollinger-Ellison syndrome: Classical considerations and current controversies. World J Gastroenterol 2019; 25:4673-4681. [PMID: 31528093 PMCID: PMC6718045 DOI: 10.3748/wjg.v25.i32.4673] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 04/29/2019] [Accepted: 05/03/2019] [Indexed: 02/06/2023] Open
Abstract
Zollinger-Ellison syndrome (ZES) is characterized by gastric acid hypersecretion causing severe recurrent acid-related peptic disease. Excessive secretion of gastrin can now be effectively controlled with powerful proton pump inhibitors, but surgical management to control gastrinoma itself remains controversial. Based on a thorough literature review, we design a surgical algorithm for ZES and list some significant consensus findings and recommendations: (1) For sporadic ZES, surgery should be routinely undertaken as early as possible not only for patients with a precisely localized diagnosis but also for those with negative imaging findings. The surgical approach for sporadic ZES depends on the lesion location (including the duodenum, pancreas, lymph nodes, hepatobiliary tract, stomach, and some extremely rare sites such as the ovaries, heart, omentum, and jejunum). Intraoperative liver exploration and lymphadenectomy should be routinely performed; (2) For multiple endocrine neoplasia type 1-related ZES (MEN1/ZES), surgery should not be performed routinely except for lesions > 2 cm. An attempt to perform radical resection (pancreaticoduodenectomy followed by lymphadenectomy) can be made. The ameliorating effect of parathyroid surgery should be considered, and parathyroidectomy should be performed first before any abdominal surgery for ZES; and (3) For hepatic metastatic disease, hepatic resection should be routinely performed. Currently, liver transplantation is still considered an investigational therapeutic approach for ZES. Well-designed prospective studies are desperately needed to further verify and modify the current considerations.
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Affiliation(s)
- Qian-Qian Shao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China
| | - Bang-Bo Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China
| | - Liang-Bo Dong
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China
| | - Hong-Tao Cao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China
| | - Wei-Bin Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China
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18
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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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Abstract
OBJECTIVE To determine the role of reoperation in patients with persistent or recurrent Zollinger-Ellison Syndrome (ZES). BACKGROUND Approximately, 0% to 60% of ZES patients are disease-free (DF) after an initial operation, but the tumor may recur. METHODS A prospective database was queried. RESULTS A total of 223 patients had an initial operation for possible cure of ZES and then were subsequently evaluated serially with cross sectional imaging-computed tomography, magnetic resonance imaging, ultrasound, more recently octreoscan-and functional studies for ZES activity. The mean age at first surgery was 49 years and with an 11-year mean follow-up 52 patients (23%) underwent reoperation when ZES recurred with imageable disease. Results in this group are analyzed in the current report. Reoperation occurred on a mean of 6 years after the initial surgery with a mean number of reoperations of 1 (range 1-5). After reoperation 18/52 patients were initially DF (35%); and after a mean follow-up of 8 years, 13/52 remained DF (25%). During follow-up, 9/52 reoperated patients (17%) died, of whom 7 patients died a disease-related death (13%). The overall survival from first surgery was 84% at 20 years and 68% at 30 years. Multiple endocrine neoplasia type 1 status did not affect survival, but DF interval and liver metastases did. CONCLUSIONS These results demonstrate that a significant proportion of patients with ZES will develop resectable persistent or recurrent disease after an initial operation. These patients generally have prolonged survival after reoperation and 25% can be cured with repeat surgery, suggesting all ZES patients postresection should have systematic imaging, and if tumor recurs, advise repeat operation.
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Abstract
This article reviews the role of surgical and medical management in patients with Zollinger-Ellison syndrome (ZES) due to a gastrin-secreting neuroendocrine tumor (gastrinoma). It concentrates on the status at present but also briefly reviews the changes over time in treatment approaches. Generally, surgical and medical therapy are complementary today; however, in some cases, such as patients with ZES and multiple endocrine neoplasia type 1, the treatment approach remains controversial.
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Affiliation(s)
- Jeffrey A Norton
- Department of Surgery, Stanford University School of Medicine, 291 campus Drive, Stanford, CA 94305-5101, USA
| | - Deshka S Foster
- Department of Surgery, Stanford University School of Medicine, 291 campus Drive, Stanford, CA 94305-5101, USA
| | - 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, National Institutes of Health, Building 10, Room 9C-103, Bethesda, MD 20892-1804, USA.
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Liu E, Paulson S, Gulati A, Freudman J, Grosh W, Kafer S, Wickremesinghe PC, Salem RR, Bodei L. Assessment of NETest Clinical Utility in a U.S. Registry-Based Study. Oncologist 2018; 24:783-790. [PMID: 30158287 DOI: 10.1634/theoncologist.2017-0623] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Accepted: 04/09/2018] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND The clinical relevance of molecular biomarkers in oncology management has been recognized in breast and lung cancers. We evaluated a blood-based multigene assay for management of neuroendocrine tumors (NETs) in a real-world study (U.S. registry NCT02270567). Diagnostic accuracy and relationship to clinical disease status in two cohorts (treated and watch-and-wait) were evaluated. MATERIALS AND METHODS Patients with NETs (n = 100) were followed for 6-12 months. Patients' primary tumors were gastroenteropancreatic (68%), lung 20%, and of unknown origin (12%). Characteristics included well-differentiated, low-grade tumors (97%), stage IV disease (96%); treatment with surgery (70%); and drug treatment (56%). NETest was measured at each visit and disease status determined by RECIST. Scores categorized as low (NETest 14%-40%) or high (≥80%) defined disease as stable or progressive. Multivariate analyses determined the strength of the association with progression-free survival (PFS). RESULTS NETest diagnostic accuracy was 96% and concordant (95%) with image-demonstrable disease. Scores were reproducible (97%) and concordant with clinical status (98%). The NETest was the only feature linked to PFS (odds ratio, 6.1; p < .0001). High NETest correlated with progressive disease (81%; median PFS, 6 months), and low NETest correlated with stable disease (87%; median PFS, not reached). In the watch-and-wait cohort, low NETest was concordant with stable disease in 100% of patients, and high NETest was associated with management changes in 83% of patients. In the treated cohort, all low NETest patients (100%) remained stable. A high NETest was linked to intervention and treatment stabilization (100%). Use of NETest was associated with reduced imaging (biannual to annual) in 36%-38% of patients. CONCLUSION Blood NETest is an accurate diagnostic and can be of use in monitoring disease status and facilitating management change in both watch-and-wait and treatment cohorts. IMPLICATIONS FOR PRACTICE A circulating multigene molecular biomarker to guide neuroendocrine tumor (NET) management has been developed because current biomarkers have limited clinical utility. NETest is diagnostic (96%) and in real time defines the disease status (>95%) as stable or progressive. It is >90% effective in guiding treatment decisions in conjunction with diagnostic imaging. Monitoring was effective in watch-and-wait or treatment groups. Low levels supported no management change and reduced the need for imaging. High levels indicated the need for management intervention. Real-time liquid biopsy assessment of NETs has clinical utility and can contribute additional value to patient management strategies and outcomes.
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Affiliation(s)
- Eric Liu
- Rocky Mountain Cancer Center, Denver, Colorado, USA
| | - Scott Paulson
- Texas Oncology - Baylor Charles A Sammons Cancer Center, Dallas, Texas, USA
| | | | - Jon Freudman
- Freudman Healthcare Consulting, San Rafael, California, USA
| | - William Grosh
- Emily Couric Cancer Center, University of Virginia, Charlottesville, Virginia, USA
| | | | | | - Ronald R Salem
- Yale University School of Medicine, Department of Surgery, New Haven, Connecticut, USA
| | - Lisa Bodei
- Memorial Sloan Kettering Cancer Center, New York, New York, USA
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Guarnotta V, Martini C, Davì MV, Pizza G, Colao A, Faggiano A. The Zollinger-Ellison syndrome: is there a role for somatostatin analogues in the treatment of the gastrinoma? Endocrine 2018; 60:15-27. [PMID: 29019150 DOI: 10.1007/s12020-017-1420-4] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Accepted: 09/02/2017] [Indexed: 12/17/2022]
Abstract
PURPOSE Analyze the role of somatostatin analogues (SSAs) in the treatment of sporadic and MEN1-related gastrinomas, trying to define whether recent trials have changed the landscape of gastrinoma therapy. METHODS We evaluate the rationale of SSA use in the treatment of gastrinomas, summarize the current literature concerning the effect of SSAs on the control of Zollinger-Ellison syndrome (ZES) and gastrinomas tumor progression and discuss their role in the most recent guidelines. RESULTS The medical treatment of gastrinoma and related ZES is aimed at controlling acid hypersecretion and tumor progression, in inoperable patients. The use of proton pump inhibitors (PPIs) to control the syndrome is a cornerstone in the ZES therapy. SSAs are not usually indicated for antisecretory purpose, because PPIs are considered the treatment of choice, due to their long lasting high efficacy and oral availability. The antiproliferative effect of SSAs has been established by two placebo-controlled trials that have clearly demonstrated a significant increase in progression free survival in patients affected by non-functioning well-differentiated advanced neuroendocrine tumors (NETs). The recent ENETS guidelines recommend the use of SSAs in advanced well differentiated NETs as antiproliferative agents. CONCLUSIONS The high sstr-expression in gastrinomas make them highly responsive to SSAs and support the use of such drugs to counteract the tumour growth in patients not amenable to surgical cure. Unfortunately, limited data, mainly case reports or small series, support the use of SSAs in advanced gastrinomas, therefore, it is difficult to quantify their ability to control tumour growth and disease progression.
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Affiliation(s)
- Valentina Guarnotta
- Biomedical Department of Internal and Specialist Medicine (DIBIMIS), Section of Endocrine-Metabolic Diseases, University of Palermo, Palermo, Italy
| | - Chiara Martini
- Clinica Medica 3^, Department of Medicine, DIMED, University of Padova, Padova, Italy.
| | - Maria Vittoria Davì
- Section of Endocrinology, Medicina Generale e Malattie Aterotrombotiche e Degenerative, Department of Medicine, University of Verona, Verona, Italy
| | - Genoveffa Pizza
- Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Annamaria Colao
- Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Antongiulio Faggiano
- Thyroid and Parathyroid Surgery Unit, Istituto Nazionale per lo studio e la cura dei tumori "Fondazione G. Pascale" - IRCCS, Naples, Italy
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23
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Metz DC, Cadiot G, Poitras P, Ito T, Jensen RT. Diagnosis of Zollinger-Ellison syndrome in the era of PPIs, faulty gastrin assays, sensitive imaging and limited access to acid secretory testing. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2017; 4:167-185. [PMID: 29326808 PMCID: PMC5757869 DOI: 10.2217/ije-2017-0018] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Accepted: 09/14/2017] [Indexed: 12/12/2022] Open
Abstract
In recent years the diagnosis of Zollinger-Ellison syndrome (ZES) has become increasingly controversial with several new approaches and criteria proposed, differing from the classical biochemical criterion of inappropriate hypergastrinemia (i.e., hypergastrinemia in the presence of hyperchlorhydria) (Table 1). These changes have come about because of the difficulty and potential dangers of stopping proton pump inhibitors (PPIs) for gastric acid analysis; the recognition than many of the current assays used to assess gastrin concentrations are unreliable; the development of sensitive imaging modalities that detect neuroendocrine tumors (NETs) including an increasing number of the primary gastrinomas; the increased use of percutaneous or endoscopic ultrasound (EUS)-directed biopsies/cytology and the general lack of availability of acid secretory testing. In this article we will discuss the basis for these controversies, review the proposed changes in diagnostic approaches and make recommendations for supporting the diagnosis of ZES in the modern era.
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Affiliation(s)
- David C Metz
- Division of Gastroenterology, Hospital of the University of Pennsylvania, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, PA, 19104, USA
| | - Guillaume Cadiot
- Service d"Hepato-Gastroenterologie, Centre Hospitalier Universitaire de Reims, Hopital Robert Debre, F-51092, Reims, France
| | - Pierre Poitras
- Department of Gastroenterology, CHUM, Université de Montréal, Montreal, Canada
| | - 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, Maryland, 20817, USA
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Catching the Zebra: Clinical Pearls and Pitfalls for the Successful Diagnosis of Zollinger-Ellison Syndrome. Dig Dis Sci 2017; 62:2258-2265. [PMID: 28776139 DOI: 10.1007/s10620-017-4695-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Accepted: 07/26/2017] [Indexed: 12/11/2022]
Abstract
Zollinger-Ellison syndrome (ZES) results from an ectopic gastrin-secreting tumor leading to peptic ulcer disease, reflux, and chronic diarrhea. While early recognition portends an excellent prognosis with >80% survival at 15 years, symptoms are often nonspecific making the diagnosis difficult to establish. Diagnosis involves a series of tests, including fasting gastrin, gastric pH, chromogranin A, and secretin stimulation. Performing these tests in the correct sequence and at the proper time is essential to avoid inaccurate results. Tumor localization is equally nuanced. Although providers have classically used 111indium-radiolabeled octreotide with somatostatin receptor scintigraphy to evaluate tumor size and metastases, recent studies have shown superior results with newer imaging modalities. In particular, 68gallium (68Ga)-labeled somatostatin radiotracers (i.e., 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE) used with positron emission tomography/computed tomography can provide excellent results. Endoscopic ultrasound is another useful modality, particularly in patients with ZES in the setting of multiple endocrine neoplasia type 1. This review aims to provide clinicians with an overview of ZES with a focus on both clinical presentation and the proper utilization of the various biochemical and imaging tests available.
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Shamimi-Noori S, Gonsalves CF, Shaw CM. Metastatic Liver Disease: Indications for Locoregional Therapy and Supporting Data. Semin Intervent Radiol 2017; 34:145-166. [PMID: 28579683 DOI: 10.1055/s-0037-1602712] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Metastatic liver disease is a major cause of cancer-related morbidity and mortality. Surgical resection is considered the only curative treatment, yet only a minority is eligible. Patients who present with unresectable disease are treated with systemic agents and/or locoregional therapies. The latter include thermal ablation and catheter-based transarterial interventions. Thermal ablation is reserved for those with limited tumor burden. It is used to downstage the disease to enable curative surgical resection, as an adjunct to surgery, or in select patients it is potentially curative. Transarterial therapies are indicated in those with more diffuse disease. The goals of care are to palliate symptoms and prolong survival. The indications and supporting data for thermal ablation and transarterial interventions are reviewed, technical and tumor factors that need to be considered prior to intervention are outlined, and finally several cases are presented.
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Affiliation(s)
- Susan Shamimi-Noori
- Division of Interventional Radiology, Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | - Carin F Gonsalves
- Division of Interventional Radiology, Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
| | - Colette M Shaw
- Division of Interventional Radiology, Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania
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Hatta W, Koike T, Iijima K, Asanuma K, Asano N, Musha H, Inomata Y, Sano T, Endo H, Ikehata A, Horii T, Ohyauchi M, Yokosawa S, Kasajima A, Fujishima F, Sasano H, Nakaya N, Nakamura T, Shimosegawa T. The Risk Factors for Metastasis in Non-Ampullary Duodenal Neuroendocrine Tumors Measuring 20 mm or Less in Diameter. Digestion 2017; 95:201-209. [PMID: 28315861 DOI: 10.1159/000459619] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Accepted: 02/03/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND/AIMS The treatment strategy for non-ampullary duodenal neuroendocrine tumors (NAD-NETs) ≤20 mm in diameter has not been established. In this study, we aimed to evaluate the detailed characteristics of NAD-NETs ≤20 mm in diameter to clarify the risk factors of subsequent metastasis. METHODS The patients with NAD-NETs ≤20 mm in diameter who had been treated at 12 institutions between 1992 and 2013 were enrolled. Clinical records were retrieved, and histopathological findings of all cases were centrally reviewed by 2 pathologists. RESULTS We studied 49 patients with a mean follow-up period of 66.5 months. Thirty-five patients were initially treated with endoscopic resection (ER), and 14 with surgery. A univariate analysis revealed the ORs and 95% CIs of the risk factors for metastasis were lymphovascular invasion (12.5 [2.01-77.9]), multiple tumors (9.75 [1.46-65.4]), a tumor size of 11-20 mm (6.67 [1.21-36.6]), and World Health Organization grade G2 (7.13 [1.16-43.9]). Five-year overall and disease-specific survival rates were 86.1 and 97.2%, respectively. CONCLUSION This is the first study to demonstrate the risk factors of metastasis in NAD-NETs ≤20 mm in diameter. These findings may be helpful for determining the appropriate therapeutic approach and the clinical strategy of treatment following ER.
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Affiliation(s)
- Waku Hatta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
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Jensen RT, Norton JA. Treatment of Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1: Some Clarity But Continued Controversy. Pancreas 2017; 46:589-594. [PMID: 28426491 PMCID: PMC5407310 DOI: 10.1097/mpa.0000000000000825] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Robert T Jensen
- From the *Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; and the †Department of Surgery, Stanford University School of Medicine, Stanford, CA
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Sato Y, Hashimoto S, Mizuno KI, Takeuchi M, Terai S. Management of gastric and duodenal neuroendocrine tumors. World J Gastroenterol 2016; 22:6817-6828. [PMID: 27570419 PMCID: PMC4974581 DOI: 10.3748/wjg.v22.i30.6817] [Citation(s) in RCA: 102] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 06/16/2016] [Accepted: 07/06/2016] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, like all NETs. However, the incidence of GI-NETS has been increasing in recent years. Gastric NETs (G-NETs) and duodenal NETs (D-NETs) are the common types of upper GI-NETs based on tumor location. G-NETs are classified into three distinct subgroups: type I, II, and III. Type I G-NETs, which are the most common subtype (70%-80% of all G-NETs), are associated with chronic atrophic gastritis, including autoimmune gastritis and Helicobacter pylori associated atrophic gastritis. Type II G-NETs (5%-6%) are associated with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome (MEN1-ZES). Both type I and II G-NETs are related to hypergastrinemia, are small in size, occur in multiple numbers, and are generally benign. In contrast, type III G-NETs (10%-15%) are not associated with hypergastrinemia, are large-sized single tumors, and are usually malignant. Therefore, surgical resection and chemotherapy are generally necessary for type III G-NETs, while endoscopic resection and follow-up, which are acceptable for the treatment of most type I and II G-NETs, are only acceptable for small and well differentiated type III G-NETs. D-NETs include gastrinomas (50%-60%), somatostatin-producing tumors (15%), nonfunctional serotonin-containing tumors (20%), poorly differentiated neuroendocrine carcinomas (< 3%), and gangliocytic paragangliomas (< 2%). Most D-NETs are located in the first or second part of the duodenum, with 20% occurring in the periampullary region. Therapy for D-NETs is based on tumor size, location, histological grade, stage, and tumor type. While endoscopic resection may be considered for small nonfunctional D-NETs (G1) located in the higher papilla region, surgical resection is necessary for most other D-NETs. However, there is no consensus regarding the ideal treatment of D-NETs.
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29
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Hain E, Coriat R, Dousset B, Gaujoux S. [Management of gastrinoma]. Presse Med 2016; 45:986-991. [PMID: 27262229 DOI: 10.1016/j.lpm.2016.04.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Accepted: 04/19/2016] [Indexed: 12/12/2022] Open
Abstract
Gastrinoma is a very rare tumor leading to gastrin hypersecretion and characterised by Zollinger-Ellisson syndrome (ZES) i.e. severe gastric and duodenal ulceration and profuse diarrhea. This disease can be sporadic or familial within a multiple endocrine neoplasia type 1 (MEN-1) syndrome. Diagnosis is based on hypergastrinemia/hypercholrhydria. Tumors are usually located in the duodeno-pancreas. Preoperative tumor location by CT, echoendoscopy and fibroscopy is not always possible because of the small size of the lesion that are frequently multiple. The aim of gastrinoma treatment is 1/to control the hormonal hypersecretion 2/to remove the neoplasm when it is possible. Surgery is the only chance to cure. Gastrinoma is a slow-growing tumor, and overall survival is good with a median survival above 10years and a 5-year survival above 80 % in surgically resected patients. Recurrence is frequent, a biochemical recurrence is observed in 65 % of cases and morphological recurrence in 40 % of patients at 2years. Metastases are associated with a dismal prognosis.
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Affiliation(s)
- Elisabeth Hain
- AP-HP, hôpital Cochin, service de chirurgie digestive hépato-biliaire et endocrienne, Paris, France
| | - Romain Coriat
- AP-HP, hôpital Cochin, service de gastroentérologie, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France; Université Paris Descartes, 12, rue de l'École-de-Médecine, 75006 Paris, France
| | - Bertrand Dousset
- AP-HP, hôpital Cochin, service de chirurgie digestive hépato-biliaire et endocrienne, Paris, France; Université Paris Descartes, 12, rue de l'École-de-Médecine, 75006 Paris, France
| | - Sébastien Gaujoux
- AP-HP, hôpital Cochin, service de chirurgie digestive hépato-biliaire et endocrienne, Paris, France; Université Paris Descartes, 12, rue de l'École-de-Médecine, 75006 Paris, France.
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Zhang WD, Liu DAR, Wang P, Zhao JG, Wang ZF, Chen LI. Clinical treatment of gastrinoma: A case report and review of the literature. Oncol Lett 2016; 11:3433-3437. [PMID: 27123130 DOI: 10.3892/ol.2016.4397] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2015] [Accepted: 03/03/2016] [Indexed: 01/03/2023] Open
Abstract
Gastrinoma is a gastrin-secreting tumor that is associated with Zollinger-Ellison syndrome. The majority of cases occur in the pancreas, followed by the duodenum. Early diagnosis is difficult due to the relative rarity of the tumor and the lack of specific symptoms. In the current study, a 68-year-old female patient presented at the Second Affiliated Hospital, Zhejiang University (Hangzhou, China) due to intermittent abdominal pain and watery diarrhea. The patient was treated by surgical resection and was pathologically diagnosed with a well-differentiated pancreatic neuroendocrine tumor (gastrinoma; grade 1). No evidence of recurrence was observed during 1 year of follow-up. Furthermore, a review of the Chinese literature was performed, which analyzed an additional 17 published cases of gastrinoma. The tumor size ranged between 0.5×0.5 cm and 7.5×6.3×5.1 cm. The pancreas was the most common site of occurrence, accounting for 72% (13/18) of cases, followed by the duodenum (28%; 5/18). The most common initial symptom was abdominal pain (89%; 16/18), followed by diarrhea (56%; 10/18). In 18 cases, including the present case and 17 previous cases, the level of gastrin ranged between 137 and 1,550 pg/ml (normal range, 5-100 pg/ml). Of the 17 previous cases, 11 patients underwent surgery and 6 patients received conservative therapy due to metastasis or patient choice. Overall, gastrinoma remains a rare disease. Complete removal of the lesion is the standard curative treatment and conservative treatment is only recommended for patients unsuitable for surgery or for those with widespread metastasis.
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Affiliation(s)
- Wei-Dong Zhang
- Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
| | - DA-Ren Liu
- Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
| | - Pei Wang
- Department of Pathology, Dongyang People's Hospital, Dongyang, Zhejiang 322103, P.R. China
| | - Jian-Gang Zhao
- Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
| | - Zhe-Fang Wang
- Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
| | - L I Chen
- Department of Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
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Ende AR, Sedarat A, Shah P, Jhala N, Fraker DL, Drebin JA, Metz DC, Kochman ML. Risk factors for aggressive nonfunctional pancreatic neuroendocrine tumors and the role of endoscopic ultrasound guided fine-needle aspiration. Endosc Ultrasound 2016; 5:49-54. [PMID: 26879167 PMCID: PMC4770623 DOI: 10.4103/2303-9027.175897] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background: Nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) are increasingly being diagnosed but management, especially of small tumors, remains a clinical dilemma. Endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) is now routinely used for diagnosis of pancreatic neuroendocrine tumors (pNETs) but has not been well studied as a tool for identifying aggressive disease. Materials and Methods: A systematic search of the cytology database identified all patients at our center who underwent EUS-FNA from 1999 through 2011 and were diagnosed with NF-pNET. Results: A total of 50 patients were identified. Though patients with metastatic disease had a mean tumor size of 40 mm compared to 25 mm in patients without metastatic disease (P = 0.04), we also identified several patients with tumors <20 mm who presented with metastatic disease. Furthermore, we found no statistically significant difference in metastatic disease between tumors <20 mm and >20 mm (P = 0.13). Using receiver operating characteristic (ROC) analysis, we found that using a cutoff point of 20 mm only led to a sensitivity of 85% in screening for metastases, while lowering the cutoff point to 18 mm allowed for a sensitivity of 95%. Conclusion: Currently, guidelines suggest that only patients with tumors greater than 20 mm undergo surgical resection, as tumors less than this size are thought to have low risk of metastases. Our analysis suggests that these recommendations could lead to undertreating patients with small tumors. Tumor size alone may be inadequate as a marker for aggressive NF-pNETs. Given this, other risk factors for aggressive pNETs should be studied to help identify the patients most likely to benefit from surgery.
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Affiliation(s)
- Alexander R Ende
- Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA
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Ito T, Jensen RT. Imaging in multiple endocrine neoplasia type 1: recent studies show enhanced sensitivities but increased controversies. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2016; 3:53-66. [PMID: 26834963 PMCID: PMC4728712 DOI: 10.2217/ije.15.29] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Accepted: 10/27/2015] [Indexed: 01/08/2023] Open
Abstract
In multiple endocrine neoplasia type 1 (MEN1) patients, a number of recent studies compare the ability of different, new imaging modalities to existing modalities to localize the important neuroendocrine tumors (NETs) that contribute to their decreased life expectancy (pancreatic NETs [pNETs] and thymic carcinoids). These included the use of 68Ga-DOTATOC-PET/CT, endoscopic ultrasound and MRI. The current paper analyzes these results in light of current guidelines and controversies involved in the treatment/management of MEN1 patients. Particular attention is paid to results in these studies with thymic carcinoids and nonfunctional pNETs/gastrinomas, which recent studies show are particularly important in determining long-term survival. These studies show a number of promising imaging results but also raise a number of controversies, which will need to be addressed both in their use initially and for serial studies in these patients.
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Affiliation(s)
- Tetsuhide Ito
- Department of Medicine & Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
| | - Robert T Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20817, USA
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Henderson-Jackson E, Sheikh U, Muhammad J, Coppola D, Nasir A. Neuroendocrine Neoplasms of the Stomach. NEUROENDOCRINE TUMORS: REVIEW OF PATHOLOGY, MOLECULAR AND THERAPEUTIC ADVANCES 2016:217-244. [DOI: 10.1007/978-1-4939-3426-3_12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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34
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Wang KA, Chou YH, Huang SH, Chen TJ. Primary jejunal gastrinoma: a case report and review of the literature. World J Surg Oncol 2015; 13:313. [PMID: 26546053 PMCID: PMC4636740 DOI: 10.1186/s12957-015-0728-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2015] [Accepted: 11/02/2015] [Indexed: 12/03/2022] Open
Abstract
Background Primary jejunal gastrinomas are exceedingly rare, and data for long-term follow-up is limited. Until now, only six cases of gastrinomas arising from the jejunum have been reported in the English literature. Case Presentation Presented is a case of a primary gastrinoma located in the proximal jejunum. After surgical resection of the tumor, eugastrinemia was quickly achieved and after a 10-year follow-up period, the patient was still disease-free. Conclusions This case report demonstrates that surgical resection of a primary jejunal gastrinoma without evidence of metastasis can be curative, with a good long-term prognosis.
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Affiliation(s)
- Kevin A Wang
- Division of General Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wenchang Rd., Shilin Dist., Taipei, 11101, Taiwan, Republic of China.
| | - Yenn-Hwei Chou
- Division of General Surgery, Department of Surgery, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wenchang Rd., Shilin Dist., Taipei, 11101, Taiwan, Republic of China.
| | - Shu-Han Huang
- Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wenchang Rd., Shilin Dist., Taipei, 11101, Taiwan, Republic of China
| | - Tong-Jong Chen
- Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wenchang Rd., Shilin Dist., Taipei, 11101, Taiwan, Republic of China
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Bartsch DK, Albers MB. Controversies in surgery for multiple endocrine neoplasia type 1-associated Zollinger–Ellison syndrome. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2015. [DOI: 10.2217/ije.15.17] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Zollinger–Ellison syndrome (ZES) is a common manifestation of multiple endocrine neoplasia type 1 (MEN1). At least 90% of MEN1-ZES patients have multiple duodenal gastrinomas, making the duodenum the target organ of ZES. The indication and the timing of surgery in MEN1-ZES is controversial, since there is yet no parameter that indicates an aggressive course of disease and long-term survival is generally good. An imageable, most likely nonfunctioning pancreatic neuroendocrine neoplasm (pNEN) >1–2 cm seems to be a good surrogate parameter to indicate surgery in order to prevent distant metastatic pNEN disease, although some groups indicate surgery at the time of biochemical ZES evidence. The optimal surgical procedure is also controversial. Different strategies encomprise local excision via duodenotomy with or without distal pancreatic resection and regional lymphadenectomy to partial pancreaticoduodenectomy. At present, the timing and type of surgery for MEN1-ZES should be individualized according to patient’s characteristics and preference.
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Affiliation(s)
- Detlef K Bartsch
- Department of Visceral, Thoracic & Vascular Surgery, University Hospital Gießen/Marburg GmbH, Philipps-University Marburg, Baldingerstrasse, 35043 Marburg, Germany
| | - Max B Albers
- Department of Visceral, Thoracic & Vascular Surgery, University Hospital Gießen/Marburg GmbH, Philipps-University Marburg, Baldingerstrasse, 35043 Marburg, Germany
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Yates CJ, Newey PJ, Thakker RV. Challenges and controversies in management of pancreatic neuroendocrine tumours in patients with MEN1. Lancet Diabetes Endocrinol 2015; 3:895-905. [PMID: 26165399 DOI: 10.1016/s2213-8587(15)00043-1] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Accepted: 03/03/2015] [Indexed: 01/05/2023]
Abstract
Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder, is characterised by the occurrence of pancreatic neuroendocrine tumours (P-NETs) in association with parathyroid and pituitary tumours. P-NETs, which include gastrinomas, insulinomas, and non-functioning tumours, occur in more than 80% of MEN1 patients and account for 50% of disease-specific deaths. However, there is no consensus about the optimal methods for detecting and treating P-NETs in MEN1 patients, and extrapolations from approaches used in patients with non-familial (sporadic) P-NETs require caution because of differences, such as the younger age of onset, multi-focality of P-NETs, and concomitant presence of other tumours in MEN1 patients. Thus, the early detection of P-NETs by circulating biomarkers and imaging modalities, and their appropriate treatments by surgical approaches and/or radionuclide therapy, chemotherapy, and biotherapy pose challenges and controversies. These challenges and controversies will be reviewed and possible approaches proposed.
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Affiliation(s)
- Christopher J Yates
- Academic Endocrine Unit, Radcliffe Department of Clinical Medicine, University of Oxford, Oxford, UK; Department of Diabetes and Endocrinology, Melbourne Health, Melbourne, VIC, Australia; Department of Diabetes and Endocrinology, Western Health, Melbourne, VIC, Australia; Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
| | - Paul J Newey
- Academic Endocrine Unit, Radcliffe Department of Clinical Medicine, University of Oxford, Oxford, UK; Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
| | - Rajesh V Thakker
- Academic Endocrine Unit, Radcliffe Department of Clinical Medicine, University of Oxford, Oxford, UK.
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37
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Sowa‐Staszczak A, Stefańska A, Jabrocka‐Hybel A, Hubalewska‐Dydejczyk A. Somatostatin Receptor Scintigraphy in Management of Patients with Neuroendocrine Neoplasms. SOMATOSTATIN ANALOGUES 2015:90-111. [DOI: 10.1002/9781119031659.ch9] [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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Doi R. Determinants of surgical resection for pancreatic neuroendocrine tumors. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2015; 22:610-7. [PMID: 25773163 DOI: 10.1002/jhbp.224] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Accepted: 01/14/2015] [Indexed: 12/14/2022]
Abstract
Pancreatic neuroendocrine tumors (pNETs) include functioning and non-functional tumors. Functioning tumors consist of tumors that produce a variety of hormones and their clinical effects. Therefore, determinants of resection of pNETs should be discussed for each group of tumors. Less than 10% of insulinomas are malignant, therefore more than 90% of the cases can be cured by surgical resection. Lymphadenectomy is generally not necessary in insulinoma operation. If preoperative localization of the insulinoma is completed, enucleation from the pancreatic body or tail, and distal pancreatectomy can be performed safely by laparoscopy. When preoperative localization of a sporadic insulinoma is not confirmed, surgical exploration is needed. Intraoperative localization of a tumor, intraoperative insulin sampling and frozen section are required. The crucial purpose of surgical resection is to control inappropriate insulin secretion by removing all insulinomas. Gastrinomas are usually located in the duodenum or pancreas, which secrete gastrin and cause Zollinger-Ellison syndrome (ZES). Duodenal gastrinomas are usually small, therefore they are not seen on preoperative imaging studies or endoscopic ultrasound, and can be found only at surgery if a duodenotomy is performed. In addition, lymph node metastasis is found in 40-60% of cases. Therefore, the experienced surgeons should direct operation for gastrinomas. Surgical exploration with duodenotomy should be performed at a laparotomy. Other functioning pNETs can occur in the pancreas or in other locations. Curative resection is always recommended whenever possible after optimal symptomatic control of the clinical syndrome by medical treatment. Indications for surgery depend on clinical symptom control, tumor size, location, extent, malignancy and presence of metastasis. A lot of non-functioning pNETs are found incidentally according to the quality improvement of imaging techniques. Localized, small, malignant non-functioning pNETs should be operated on aggressively, while in possibly benign tumors smaller than 2 cm the surgical risk-benefit ratio should be carefully weighted. Surgical liver resection is generally proposed in curative intent to all patients with operable metastases from G1 or G2 pNET. The benefits of surgical resection of liver metastases have been demonstrated in terms of overall survival and quality of life. Complete resection is associated with better long-term survival.
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Affiliation(s)
- Ryuichiro Doi
- Department of Surgery, Otsu Red Cross Hospital, 1-1-35 Nagara, Otsu, Shiga, 520-8511, Japan
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39
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Fernández-Cruz L, Pelegrina A. [Surgery for gastrinoma: Short and long-term results]. Cir Esp 2015; 93:390-5. [PMID: 25748044 DOI: 10.1016/j.ciresp.2014.10.016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2014] [Revised: 10/19/2014] [Accepted: 10/26/2014] [Indexed: 01/25/2023]
Abstract
INTRODUCTION Zollinger-Ellison syndrome (Z-E) is characterized by gastrin-secreting tumors, responsible for causing refractory and recurrent peptic ulcers in the gastrointestinal tract. The optimal approach and the extension of tumor resection remains the subject of debate. METHODS During the period February 2005 and February 2014, 6 patients with Z-E underwent surgery, 4 men and 2 women with a median age 46.8 years (22-61). Two patients were affected with multiple endocrine neoplasia type-1 (MEN-1). Fasting gastrin levels greater than 200pg/ml (NV: <100) was diagnostic. Radiologic imaging to localize the lesion included octreoscan 6/6, computer tomography (CT) 6/6, and endoscopic ultrasonography (EUS) 1/6. RESULTS The octreoscan was positive in 5 patients. The CT localized the tumor in the pancreas in 2 patients, in the duodenum in 3 patients (1 confirmed by EUS) and between the common bile duct and vena cava in one patient. The laparoscopic approach was used in 4 patients, 2 patients converted to open surgery. The following surgical techniques were performed: 2 pylorus-preserving pancreatico-duodenectomy (PPPD), one spleen-preserving distal pancreatectomy, one duodenal nodular resection, 1 segmental duodenectomy and one extrapancreatic nodular resection. Pathological studies showed lymph nodes metástasis in 2 patients with pancreatic gastrinomas, and in one patient with duodenal gastrinoma. The median follow-up was 76,83 months (5-108) and all patients presented normal fasting gastrin levels. CONCLUSIONS Surgery may offer a cure in patients with Z-E. The laparoscopic approach remains limited to selected cases.
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Affiliation(s)
- Laureano Fernández-Cruz
- Departamento de Cirugía, Universidad de Barcelona, Hospital Clínic de Barcelona, Barcelona, España.
| | - Amalia Pelegrina
- Departamento de Cirugía, Universidad de Barcelona, Hospital Clínic de Barcelona, Barcelona, España
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Imamura M, Nakamoto Y, Uose S, Komoto I, Awane M, Taki Y. Diagnosis of functioning pancreaticoduodenal neuroendocrine tumors. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2015; 22:602-9. [PMID: 25624017 DOI: 10.1002/jhbp.209] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2014] [Accepted: 12/11/2014] [Indexed: 12/15/2022]
Abstract
Functioning pancreaticoduodenal neuroendocrine tumors (PD-NETs) are popular in a textbook, but they are still unfamiliar to a general clinician, and delay of diagnosis or misdiagnosis has been reported even today. It is a consensus that sporadic functioning PD-NET is cured only by surgical resection. So, early detection and early resection is the gold standard for the treatment of functioning PD-NET. Functioning PD-NETs in patients with multiple endocrine neoplasia type 1 (MEN 1) are often multiple. You should check about MEN 1 whenever you encountered multiple PD-NET. They are diagnosed in younger age than sporadic cases. In most cases they are accompanied with numerous microscopic or macroscopic nonfunctioning P-NETs, which are potentially metastatic and the most common cause of death in MEN 1 patients.
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Affiliation(s)
- Masayuki Imamura
- Neuroendocrine Tumor Center, Kansai Electric Power Hospital, 2-1-7 Fukushima, Fukushima, Osaka, 553-0003, Japan
| | - Yuji Nakamoto
- Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Suguru Uose
- Department of Gastroenterology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Izumi Komoto
- Neuroendocrine Tumor Center, Kansai Electric Power Hospital, 2-1-7 Fukushima, Fukushima, Osaka, 553-0003, Japan.,Department of Surgery, Kansai Electric Power Hospital, Fukushima, Osaka, Japan
| | - Masaaki Awane
- Department of Surgery, Kansai Electric Power Hospital, Fukushima, Osaka, Japan
| | - Yoshiro Taki
- Department of Surgery, Kansai Electric Power Hospital, Fukushima, Osaka, Japan
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Kondo NI, Ikeda Y. Practical management and treatment of pancreatic neuroendocrine tumors. Gland Surg 2014; 3:276-83. [PMID: 25493259 DOI: 10.3978/j.issn.2227-684x.2013.12.05] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Accepted: 12/26/2013] [Indexed: 12/16/2022]
Abstract
Pancreatic neuroendocrine tumors (NETs) are uncommon disease, about which little is known. Pancreatic NETs are usually slow growing and their malignant potential are often underestimated. The management of this disease poses a challenge because of the heterogeneous clinical presentation and varying degrees of aggressiveness. Recently, several guidelines for the management of pancreatic NETs have been established and help to devise clinical strategy. In the treatment algorithms, however, a lot of uncertain points are included. Practical treatment decisions of pancreatic NETs are still sometimes made in a patient- and/or physicians-oriented manner. The tumor grading system proposed by the European Neuroendocrine Tumor Society (ENETS) gives important prognostic information, however, the implication of grading regarding medical treatment strategies to choose has not yet been clarified. Moreover, the place of surgical treatment is unclear in the overall management course of advanced pancreatic NETs. In some cases, practical management and treatment have to be individualized depending on predominant symptoms, tumor spread, and general health of the patients. Current issues and a few points to make a strategy in the management of pancreatic NETs would be reviewed.
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Affiliation(s)
- Naoko Iwahashi Kondo
- Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka City, Japan
| | - Yasuharu Ikeda
- Department of Gastroenterological Surgery, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka City, Japan
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McKenna LR, Edil BH. Update on pancreatic neuroendocrine tumors. Gland Surg 2014; 3:258-75. [PMID: 25493258 DOI: 10.3978/j.issn.2227-684x.2014.06.03] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2014] [Accepted: 05/27/2014] [Indexed: 12/12/2022]
Abstract
Pancreatic neuroendocrine tumors (pNETs) are relatively rare tumors comprising 1-2% of all pancreas neoplasms. In the last 10 years our understanding of this disease has increased dramatically allowing for advancements in the treatment of pNETs. Surgical excision remains the primary therapy for localized tumors and only potential for cure. New surgical techniques using laparoscopic approaches to complex pancreatic resections are a major advancement in surgical therapy and increasingly possible. With early detection being less common, most patients present with metastatic disease. Management of these patients requires multidisciplinary care combining the best of surgery, chemotherapy and other targeted therapies. In addition to surgical advances, recently, there have been significant advances in systemic therapy and targeted molecular therapy.
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Affiliation(s)
- Logan R McKenna
- Department of Surgery, University of Colorado, Academic Office One, Aurora, CO, USA
| | - Barish H Edil
- Department of Surgery, University of Colorado, Academic Office One, Aurora, CO, USA
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Primary lymph node gastrinoma. A diagnosis of exclusion. A case for duodenotomy in the setting of a negative imaging for primary tumor: A case report and review of the literature. Int J Surg Case Rep 2014; 5:849-52. [PMID: 25462049 PMCID: PMC4245667 DOI: 10.1016/j.ijscr.2014.08.019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2014] [Revised: 08/19/2014] [Accepted: 08/19/2014] [Indexed: 01/20/2023] Open
Abstract
INTRODUCTION Zollinger–Ellison syndrome (ZES) is caused by uninhibited secretion of gastrin from a gastrinoma. Gastrinomas most commonly arise within the wall of the duodenum followed by the pancreas. Primary lymph node gastrinomas have also been reported in the literature. This is a case of ZES where preoperative localization revealed a gastrinoma in a solitary portacaval lymph node, presumed to be a primary lymph node gastrinoma. PRESENTATION OF CASE The patient is a 57 year old female diagnosed with ZES, suspected of having a primary lymph node gastrinoma. The patient underwent an exploratory laparotomy and excision of a portacaval lymph node with a frozen section which was positive for gastrinoma. Intraoperative sonography of the pancreas, upper endoscopy with transillumination of the duodenum, and a duodenotomy with bimanual examination of the duodenal wall were also performed. The patient was found to have a 4 mm duodenal mass near the pylorus, which was excised. DISCUSSION Pathology showed that the duodenal mass was primary gastrinoma. Serum gastrin levels taken four months postoperatively were normal and the repeat octreotide scan did not show any evidence of recurrence. CONCLUSION Primary lymph node gastrinoma is a diagnosis of exclusion. The duodenum and pancreas must be fully explored to rule out a primary gastrinoma that may be occult.
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Frilling A, Clift AK. Therapeutic strategies for neuroendocrine liver metastases. Cancer 2014; 121:1172-86. [PMID: 25274401 DOI: 10.1002/cncr.28760] [Citation(s) in RCA: 124] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Revised: 04/09/2014] [Accepted: 04/10/2014] [Indexed: 12/16/2022]
Abstract
Patients who have neuroendocrine tumors frequently present with liver metastases. A wide panel of treatment options exists for these patients. Liver resection with curative intent achieves the best long-term results. Highly selected patients may be considered for liver transplantation. Substantial recurrence rates reported after surgical approaches call for neoadjuvant and adjuvant concepts. Liver-directed, locally ablative procedures are recommended for patients with limited, nonresectable tumor burden. Angiographic liver-directed techniques, such as transarterial embolization, transarterial chemoembolization, and selective internal radiotherapy, offer excellent palliation for patients with liver-predominant disease. Peptide receptor radionuclide therapy is a promising palliative procedure for patients with hepatic and/or extrahepatic metastases. The efficacy of these treatment options needs to be evaluated in randomized trials. Somatostatin analogues have demonstrated effectiveness not only for symptomatic relief in patients with secreting tumors but also for the control of proliferation in small intestinal neuroendocrine tumors and most recently also in those originating from the pancreas. Chemotherapy is an option mainly for those with pancreatic neuroendocrine tumors and high-grade tumors irrespective of the origin. Novel drugs targeting specific pathways within the tumor cell have produced improved progression-free survival compared with placebo in patients with pancreatic neuroendocrine tumors. Despite such a diverse armamentarium, there is uncertainty with regard to the optimal treatment regimens. Newly introduced molecular-based markers, along with the conduction of clinical trials comparing the efficacy of treatment modalities, offer a chance to move the treatment of neuroendocrine tumor disease toward personalized patient care. In this report, the authors review the approaches for treatment of neuroendocrine liver metastases, identify shortcomings, and anticipate future perspectives. Furthermore, clinical practice recommendations are provided for currently available treatment options. Although multiple modalities are available for the treatment of neuroendocrine liver metastases, optimal management is unclear. The current knowledge pertaining to these treatment options is analyzed.
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Affiliation(s)
- Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
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Abstract
Neuroendocrine tumors have a disposition toward metastasis to the liver. A range of treatment modalities for neuroendocrine liver metastases is available in the clinical arena, the indications for which depend on tumor characteristics such as patterns of metastasis, tumor grade, and anatomical origin. The complete surgical resection of liver deposits represents the only option with the intent to cure and is the gold standard approach, whereas cytoreductive resection (debulking) presents another surgical option aiming to ameliorate the symptoms and prolong survival. Liver transplantation is generally an accepted option for highly selected patients. For patients ineligible for radical surgery, liver-directed therapies-transarterial embolization/chemoembolization, selective internal radiotherapy, and local tumor ablation-present alternative strategies. Systemic therapies include peptide receptor radiotherapy, somatostatin analogues, cytotoxic chemotherapeutics, and novel molecularly targeted drugs. However, despite the variety of treatments available, there exists little evidence to guide optimal clinical practice with currently available data predominantly retrospective in nature. In this review, we discuss the diagnostic procedures that influence the trajectory of treatment of patients with neuroendocrine liver metastases before critically appraising the evidence pertaining to these therapeutic strategies.
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Affiliation(s)
| | - Andrea Frilling
- Prof. Andrea Frilling, Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, DuCane Road, London W12 0NN, United Kingdom, T: 00442083833210, F: 00442083833963,
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Krampitz GW, Norton JA. WITHDRAWN: Current Problems in Surgery: Pancreatic Neuroendocrine Tumors. Curr Probl Surg 2014. [DOI: 10.1067/j.cpsurg.2013.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Abstract
Zollinger-Ellison syndrome (ZES) is an endocrinopathy characterized by gastrin-secreting tumors, responsible for causing the formation of multiple, refractory, and recurrent peptic ulcers in the distal duodenum and proximal jejunum. Two main variants have been described, sporadic and those found in association with parathyroid and pituitary tumors, a genetic disorder known as multiple endocrine neoplasia-1 (MEN-1). Biochemical serum evaluation for elevated gastrin, followed by radiological or nuclear localization of the primary lesion, is mandated for establishing diagnosis. The mainstays of treatment include management of hypersecretory state with medical suppression of gastric acid production and surgical resection of primary tumor for the prevention of malignant transformation and metastatic complications. Medical therapy with proton pump inhibitors has virtually eliminated the need for acid-reducing surgical procedures. Surgical approach to sporadic and MEN-1-associated ZES varies based on our understanding of the natural history of the condition and the probability of cure; however, resection to a negative microscopic margin is indicated in both cases. Postoperative surveillance involves measurement of gastrin level, followed by imaging if elevation is detected. Re-excision of recurrent or resection of metastatic disease is a subject of controversy; however, at the present time aggressive cytoreductive approach is favored.
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Affiliation(s)
- Irene Epelboym
- Department of Surgery, Columbia University Medical Center, New York, New York, USA; Department of Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel
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Abstract
PURPOSE OF REVIEW To review the recent advances and current controversies in patients with Zollinger-Ellison syndrome (ZES). RECENT FINDINGS Recent advances in the management of ZES include: improved understanding of the pathogenesis of gastrinoma and pancreatic neuroendocrine tumors, new prognostic classification systems, new diagnostic algorithms, more sensitive localization studies, new treatment strategies including improved control of gastric acid secretion and role for surgery, and new approaches to patients with advanced disease. Controversies include: the best approach to a patient with hypergastrinemia suspected of possibly having ZES, the appropriate gastrin assay to use, the role of surgery in patients with ZES, especially those with multiple endocrine neoplasia type 1, and the precise order of therapeutic modalities in the treatment of patients with advanced disease. SUMMARY This review updates clinicians regarding important advances and controversies required to optimally diagnose and manage patients with ZES.
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Affiliation(s)
- Tetsuhide Ito
- aDepartment of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan bDigestive Diseases Branch, NIDDK, NIH, Bethesda, Maryland, USA
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