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1
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Akay O, Guler M, Sevik H, Abut YC, Tatar C, Idiz UO. Is Endoscopic Resection Essential for Patients with Type 1 Gastric Neuroendocrine Tumor? J Laparoendosc Adv Surg Tech A 2024; 34:1064-1068. [PMID: 39510824 DOI: 10.1089/lap.2024.0154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024] Open
Abstract
Background: The gastric neuroendocrine tumor (g-NET) is now more frequently diagnosed due to the widespread use and advancement of endoscopy. In our study, we aimed to discuss the superiority, if any, between the watch-and-wait approach and endoscopic treatment methods for the controversial management of type 1 g-NETs, as well as to evaluate their long-term outcomes. Materials and Methods: The data of 81 patients who underwent gastroscopy due to complaints related to the upper gastrointestinal system and were diagnosed with type 1 g-NET as a result of biopsy taken from suspicious stomach lesions were examined. After exclusion criteria, 48 patients were included in the study. Patients were categorized into two groups: the watch-and-wait group, where no invasive procedure was performed, and the group that underwent any form of endoscopic resection. Results: Thirty-seven patients were followed up regularly without any treatment. Eleven patients were followed up after endoscopic resection (endoscopic submucosal dissection-endoscopic mucosal resection). Endoscopic resection was performed in 5 of 37 patients with tumor size <10 mm and in 6 of 11 patients with tumor size between 10 and 20 mm. The median follow-up duration for all patients was 5 years, during which no instances of metastasis, tumor progression, or mortality were observed in any patient, regardless of whether they underwent endoscopic resection or not. Conclusion: This outcome prompts a questioning of the necessity for invasive treatment methods such as endoscopic resection, which comes with a relatively high cost and the potential for complications, in this particular patient group.
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Affiliation(s)
- Omer Akay
- Department of General Surgery, Istanbul Teaching and Research Hospital, Istanbul, Turkey
| | - Mert Guler
- Department of General Surgery, Istanbul Teaching and Research Hospital, Istanbul, Turkey
| | - Husnu Sevik
- Department of General Surgery, Istanbul Teaching and Research Hospital, Istanbul, Turkey
| | - Yesim Cokay Abut
- Department of Anesthesiology and Reanimation, Istanbul Teaching and Research Hospital, Istanbul, Turkey
| | - Cihad Tatar
- Department of General Surgery, Taksim Acibadem Hospital, Istanbul, Turkey
| | - Ufuk Oguz Idiz
- Department of General Surgery, Istanbul Teaching and Research Hospital, Istanbul, Turkey
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2
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Asmundo L, Ambrosini V, Anderson MA, Fanti S, Bradley WR, Campana D, Mojtahed A, Chung R, Mcdermott S, Digumarthy S, Ursprung S, Nikolau K, Fintelmann FJ, Blake M, Fernandez-Del Castillo C, Qadan M, Pandey A, Clark JW, Catalano OA. Clinical Intricacies and Advances in Neuroendocrine Tumors: An Organ-Based Multidisciplinary Approach. J Comput Assist Tomogr 2024; 48:614-627. [PMID: 38626756 DOI: 10.1097/rct.0000000000001596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/18/2024]
Abstract
ABSTRACT Neuroendocrine neoplasms (NENs) are rare neoplasms originating from neuroendocrine cells, with increasing incidence due to enhanced detection methods. These tumors display considerable heterogeneity, necessitating diverse management strategies based on factors like organ of origin and tumor size. This article provides a comprehensive overview of therapeutic approaches for NENs, emphasizing the role of imaging in treatment decisions. It categorizes tumors based on their locations: gastric, duodenal, pancreatic, small bowel, colonic, rectal, appendiceal, gallbladder, prostate, lung, gynecological, and others. The piece also elucidates the challenges in managing metastatic disease and controversies surrounding MEN1-neuroendocrine tumor management. The article underscores the significance of individualized treatment plans, underscoring the need for a multidisciplinary approach to ensure optimal patient outcomes.
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Affiliation(s)
| | | | - Mark A Anderson
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | | | - William R Bradley
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Davide Campana
- Department of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy
| | - Amirkasra Mojtahed
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Ryan Chung
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Shaunagh Mcdermott
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Subba Digumarthy
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Stephan Ursprung
- Department of Radiology, University Hospital Tuebingen, Tuebingen, Germany
| | - Konstantin Nikolau
- Department of Radiology, University Hospital Tuebingen, Tuebingen, Germany
| | - Florian J Fintelmann
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Michael Blake
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | | | - Motaz Qadan
- Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Ankur Pandey
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Jeffrey W Clark
- Department of Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Onofrio A Catalano
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA
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3
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Sok C, Ajay PS, Tsagkalidis V, Kooby DA, Shah MM. Management of Gastric Neuroendocrine Tumors: A Review. Ann Surg Oncol 2024; 31:1509-1518. [PMID: 38062290 PMCID: PMC10922891 DOI: 10.1245/s10434-023-14712-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 11/20/2023] [Indexed: 01/30/2024]
Abstract
Gastric neuroendocrine tumors (G-NET) are rare tumors arising from enterochromaffin-like cells of the gastric mucosa. They belong to a larger group called gastroenteropancreatic neuroendocrine tumors and are classified as low, intermediate, or high-grade tumors based on their proliferative indices. They are further categorized into three subtypes based on their morphologic characteristics, pathogenesis, and behavior. Types 1 and 2 tumors are characterized by elevated serum gastrin and are usually multifocal. They typically occur in the setting of atrophic gastritis or MEN1/Zollinger Ellison syndrome, respectively. Type 2 tumors are associated with the most symptoms, such as abdominal pain and diarrhea. Type 3 tumors are associated with normal serum gastrin, are usually solitary, and occur sporadically. This type has the most aggressive phenotype and metastatic potential. Treatment and prognosis for G-NET is dependent on their type, size, and stage. Type 1 has the best prognosis, and Type 3 has the worst. This review discusses the presentation, workup, and surgical management of these tumors.
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Affiliation(s)
- Caitlin Sok
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Pranay S Ajay
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Vasileios Tsagkalidis
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA
| | - David A Kooby
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA
| | - Mihir M Shah
- Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.
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4
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Chronic Treatment with Somatostatin Analogues in Recurrent Type 1 Gastric Neuroendocrine Tumors. Biomedicines 2023; 11:biomedicines11030872. [PMID: 36979851 PMCID: PMC10045480 DOI: 10.3390/biomedicines11030872] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 03/09/2023] [Accepted: 03/10/2023] [Indexed: 03/14/2023] Open
Abstract
Background: Type 1 gastric neuroendocrine tumors (GC-1) represent an uncommon subtype of neoplasms. Endoscopic resection has been proposed as the treatment of choice; active surveillance may be performed in those smaller than 1 cm, while gastric surgery may be performed for those with frequent recurrences. The antiproliferative effect of somatostatin analogues (SSA) is well known, and their action on GC-1s has been postulated as a chronic treatment to reduce recurrence. Methods: A two-centered, retrospective, observational study that included nine patients (55.6% women) diagnosed with GC-1, receiving long-term treatment with SSA, with a median follow-up from baseline of 22 months, was undertaken. Endoscopic follow-up, extension study, and analytical values of chromogranin A (Cg A) and gastrin were collected. Results: In total, 88.9% of patients presented partial or complete response. Treatment with SSA was the only independent factor with a trend to prevent tumor recurrence (Odds Ratio 0.054; p = 0.005). A nonsignificant tendency toward a decrease in CgA and gastrin was observed; lack of significance was probably related to concomitant treatment with proton pump inhibitors in some patients. Conclusions: Chronic treatment with SSA is a feasible option for recurrent GC-1s that are difficult to manage using endoscopy or gastrectomy. Randomized clinical trials to provide more scientific evidence are still needed.
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Hirai R, Haruma K, Okada H, Itakura J, Mizuno M. A case of enterochromaffin-like cell neuroendocrine tumor associated with parietal cell dysfunction which was successfully treated with somatostatin analogue. Clin J Gastroenterol 2022; 15:363-367. [PMID: 34982362 DOI: 10.1007/s12328-021-01581-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 12/18/2021] [Indexed: 11/29/2022]
Abstract
We report here a case of a 62-year-old woman with multiple gastric enterochromaffin-like cell neuroendocrine tumor caused by hypergastrinemia due to parietal cell dysfunction that was successfully treated with somatostatin analogue. Esophagogastroduodenoscopy revealed several G1 neuroendocrine tumors, 10 mm in diameter, in the body of the stomach. No evidence of autoimmune gastritis, Helicobacter pylori infection, neuroendocrine neoplasia type 1, or Zollinger-Ellison syndrome was identified. The pattern of immunohistochemical staining of the background gastric mucosa was suggestive of parietal cell dysfunction. She was treated with long-acting release octreotide acetate. Complete response was confirmed after 9 months and was maintained for 22 months.
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Affiliation(s)
- Ryosuke Hirai
- Department of Gastroenterology and Hepatology, Okayama University Hospital, 2-5-1, Shikata, Kitaku, Okayama, Okayama, 700-8558, Japan.
| | - Ken Haruma
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, 2-6-1, Nakasange, Kitaku, Okayama, Okayama, 700-8505, Japan
| | - Hiroyuki Okada
- Department of Gastroenterology and Hepatology, Okayama University Hospital, 2-5-1, Shikata, Kitaku, Okayama, Okayama, 700-8558, Japan
| | - Junya Itakura
- Department of Anatomic Pathology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan
| | - Motowo Mizuno
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan
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6
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Odisho T, Shi D, Aburashed A. Successful endoscopic resection of an unusually enlarged and pedunculated type I gastric carcinoid tumour. BMJ Case Rep 2021; 14:e244292. [PMID: 34413045 PMCID: PMC8378368 DOI: 10.1136/bcr-2021-244292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/08/2021] [Indexed: 11/04/2022] Open
Abstract
Three distinct gastric carcinoid (GC) tumour types have been described based on differing biological behaviour and prognoses. Type I GC tumours account for the vast majority (70%-80%), are associated with chronic atrophic gastritis and have a low metastatic potential. Type II carcinoid tumours are the least common (5%-10%), are related to Zollinger-Ellison syndrome and occur in relation to multiple neoplasia type I. Sporadic type III tumours (15%-25%) are the most aggressive type, are unrelated to gastrin over secretion and carry the worst prognosis. In this case report, we present a patient with longstanding gastroesophageal reflux disease (GERD) who presented with epigastric abdominal pain and tarry stools and was found to have a large gastric polyp on endoscopy. Despite current literature recommending surgical resection for larger GC tumours, endoscopic resection was successfully used to excise the tumour with pathology demonstrating complete resection with negative margins.
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Affiliation(s)
- Tanya Odisho
- Department of Surgery, Detroit Medical Center, Detroit, Michigan, USA
| | - Dongping Shi
- Department of Pathology, Detroit Medical Center, Detroit, Michigan, USA
| | - Ahmad Aburashed
- Department of Gastroenterology, Detroit Medical Center, Detroit, Michigan, USA
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7
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Ravizza D, Fiori G. Gastric Neuroendocrine Tumors. NEUROENDOCRINE NEOPLASIA MANAGEMENT 2021:179-190. [DOI: 10.1007/978-3-030-72830-4_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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8
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Roberto GA, Rodrigues CMB, Peixoto RD, Younes RN. Gastric neuroendocrine tumor: A practical literature review. World J Gastrointest Oncol 2020; 12:850-856. [PMID: 32879663 PMCID: PMC7443841 DOI: 10.4251/wjgo.v12.i8.850] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 05/05/2020] [Accepted: 07/19/2020] [Indexed: 02/05/2023] Open
Abstract
Gastric neuroendocrine tumors are gastric neoplasms originating from enterochromaffin type cells and are inserted in a larger group, named gastroenteropancreatic neuroendocrine tumors. They are considered rare and variable in terms of their clinical, morphological and functional characteristics and may be indolent or aggressive. They are classified into types I, II and III, according to their pathophysiology, behavior and treatment. Their diagnosis occurs, in most cases, incidentally during upper digestive endoscopies, presenting as simple gastric polyps. Most cases (type I and type II) are related to hypergastrinemia, can be multiple and are treated by endoscopic resection, whenever possible. The use of somatostatin analogs for tumor control may be one of the options for therapy, in addition to total or subtotal gastrectomy for selected cases. Adjuvant chemotherapy is only reserved for poorly differentiated neuroendocrine carcinomas. Although rare, gastric neuroendocrine tumors have an increasing incidence over the years, therefore deserving more comprehensive studies on its adequate treatment. The present study reviews and updates management recommendations for gastric neuroendocrine tumors.
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Affiliation(s)
- Gabriel Antonio Roberto
- Bachelor Medicine, União das Faculdades dos Grandes Lagos, São José do Rio Preto 15030070, Brazil
| | | | - Renata D’Alpino Peixoto
- Department of Oncology, Hospital Alemão Oswaldo Cruz, São Paulo 01327001, Brazil
- Universidade Nove de Julho, São Paulo 01327001, Brazil
| | - Riad Naim Younes
- Department of Thoracic Surgery, Hospital Alemão Oswaldo Cruz, São Paulo 01327001, Brazil
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9
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Rossi RE, Invernizzi P, Mazzaferro V, Massironi S. Response and relapse rates after treatment with long-acting somatostatin analogs in multifocal or recurrent type-1 gastric carcinoids: A systematic review and meta-analysis. United European Gastroenterol J 2020; 8:140-147. [PMID: 32213066 PMCID: PMC7079271 DOI: 10.1177/2050640619890465] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Accepted: 10/29/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Type-1 gastric neuroendocrine tumors represent a recurring disease and long-acting somatostatin analogs can inhibit both gastrin release and endocrine cell proliferation. The efficacy and timing of this treatment are still unclear. We performed a systematic review of the literature to clarify the role of somatostatin analog treatment in type-1 gastric neuroendocrine tumors. METHODS A computerized literature search was performed using relevant keywords to identify all the pertinent articles published in the last 15 years. RESULTS Eight studies were included in this systematic review on somatostatin analogs in type-1 gastric neuroendocrine tumors. A complete response rate ranged from 25-100%. When only the six prospective studies were considered, no significant heterogeneity was observed, and the pooled cumulative complete response rate was 84.5% (confidence interval 73.8-92.8). Three studies evaluated the type-1 gastric neuroendocrine tumor recurrence, with a cumulative relapse rate of 30.2% (confidence interval 13.1-50.6) after 34 months. CONCLUSION Somatostatin analogs, namely lanreotide and octreotide, have an excellent response rate, with a good safety profile in selected type-1 gastric neuroendocrine tumors, which cannot be safely managed by endoscopic follow-up or resection due to multiple or frequently recurring disease. After therapy discontinuation, the cumulative relapse rate observed after a median 34-month follow-up was relatively high (30.2%).
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Affiliation(s)
- Roberta Elisa Rossi
- Gastrointestinal and Hepato-Pancreatic Surgery and Liver Transplantation Unit, Fondazione, RCCS Istituto Nazionale Tumori (INT, National Cancer Institute) and Università degli Studi di Milano, Milan, Italy
| | - Pietro Invernizzi
- Department of Gastroenterology and Center for Liver Autoimmune Diseases, San Gerardo Hospital, Monza, Italy
| | - Vincenzo Mazzaferro
- Gastrointestinal and Hepato-Pancreatic Surgery and Liver Transplantation Unit, Fondazione, RCCS Istituto Nazionale Tumori (INT, National Cancer Institute) and Università degli Studi di Milano, Milan, Italy
| | - Sara Massironi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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10
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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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11
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Mujica-Mota R, Varley-Campbell J, Tikhonova I, Cooper C, Griffin E, Haasova M, Peters J, Lucherini S, Talens-Bou J, Long L, Sherriff D, Napier M, Ramage J, Hoyle M. Everolimus, lutetium-177 DOTATATE and sunitinib for advanced, unresectable or metastatic neuroendocrine tumours with disease progression: a systematic review and cost-effectiveness analysis. Health Technol Assess 2019; 22:1-326. [PMID: 30209002 DOI: 10.3310/hta22490] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Neuroendocrine tumours (NETs) are a group of heterogeneous cancers that develop in cells in the diffuse neuroendocrine system. OBJECTIVES To estimate the clinical effectiveness of three interventions [everolimus (Afinitor®; Novartis International AG, Basel, Switzerland), lutetium-177 DOTATATE (177Lu-DOTATATE) (Lutathera®; Imaging Equipment Ltd, Radstock, UK) and sunitinib (Sutent®; Pfizer Inc., New York, NY, USA)] for treating unresectable or metastatic NETs with disease progression and establish the cost-effectiveness of these interventions. DATA SOURCES The following databases were searched from inception to May 2016: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Daily, Epub Ahead of Print, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. REVIEW METHODS We systematically reviewed the clinical effectiveness and cost-effectiveness literature on everolimus, 177Lu-DOTATATE and sunitinib for treating advanced, unresectable or metastatic progressive NETs. The following NET locations were considered separately: pancreas, gastrointestinal (GI) tract and lung, and GI tract (midgut only). We wrote a survival partition cohort-based economic evaluation in Microsoft Excel® 2013 (Microsoft Corporation, Redmond, WA, USA) from the UK NHS and Personal Social Services perspective. This comprised three health states: (1) progression-free survival (PFS), (2) progressed disease and (3) death. RESULTS Three randomised controlled trials (RCTs), RADIANT-3 [RAD001 in Advanced Neuroendocrine Tumors, Third Trial; pancreatic NETs (pNETs): everolimus vs. best supportive care (BSC)], A6181111 (pNETs: sunitinib vs. BSC) and RADIANT-4 (RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial; GI and lung NETs: everolimus vs. BSC), met the inclusion criteria for the clinical effectiveness systematic review. The risk of bias was low. Although the NETTER-1 (Neuroendocrine Tumors Therapy) RCT, of 177Lu-DOTATATE plus 30 mg of octreotide (Sandostatin®, Novartis) compared with 60 mg of octreotide, was excluded from the review, we nonetheless present the results of this trial, as it informs our estimate of the cost-effectiveness of 177Lu-DOTATATE. The pNETs trials consistently found that the interventions improved PFS and overall survival (OS) compared with BSC. Our indirect comparison found no significant difference in PFS between everolimus and sunitinib. Estimates of OS gain were confounded because of high rates of treatment switching. After adjustment, our indirect comparison suggested a lower, but non-significant, hazard of death for sunitinib compared with everolimus. In GI and lung NETs, everolimus significantly improved PFS compared with BSC and showed a non-significant trend towards improved OS compared with BSC. Adverse events were more commonly reported following treatment with targeted interventions than after treatment with BSC. In the base case for pNETs, assuming list prices, we estimated incremental cost-effectiveness ratios (ICERs) for everolimus compared with BSC of £45,493 per quality-adjusted life-year (QALY) and for sunitinib compared with BSC of £20,717 per QALY. These ICERs increased substantially without the adjustment for treatment switching. For GI and lung NETs, we estimated an ICER for everolimus compared with BSC of £44,557 per QALY. For GI (midgut) NETs, the ICERs were £199,233 per QALY for everolimus compared with BSC and £62,158 per QALY for a scenario analysis comparing 177Lu-DOTATATE with BSC. We judge that no treatment meets the National Institute for Health and Care Excellence's (NICE) end-of-life criteria, although we cannot rule out that sunitinib in the A6181111 trial does. LIMITATIONS A RCT with included comparators was not identified for 177Lu-DOTATATE. The indirect treatment comparison that our economic analysis was based on was of a simple Bucher type, unadjusted for any differences in the baseline characteristics across the two trials. CONCLUSIONS Given NICE's current stated range of £20,000-30,000 per QALY for the cost-effectiveness threshold, based on list prices, only sunitinib might be considered good value for money in England and Wales. FUTURE WORK Further analysis of individual patient data from RADIANT-3 would allow assessment of the robustness of our findings. The data were not made available to us by the company sponsoring the trial. STUDY REGISTRATION This study is registered as PROSPERO CRD42016041303. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Ruben Mujica-Mota
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Jo Varley-Campbell
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Irina Tikhonova
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Chris Cooper
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Ed Griffin
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Marcela Haasova
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Jaime Peters
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Stefano Lucherini
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Juan Talens-Bou
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - Linda Long
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
| | - David Sherriff
- Plymouth Oncology Centre, Plymouth Hospitals NHS Trust, Plymouth, UK
| | - Mark Napier
- Exeter Oncology Centre, Royal Devon & Exeter NHS Foundation Trust, Exeter, UK
| | - John Ramage
- Neuroendocrine Tumour Service, King's College Hospital NHS Foundation Trust, London, UK
| | - Martin Hoyle
- Peninsula Technology Assessment Group (PenTAG), University of Exeter, Exeter, UK
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12
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Carlini M, Apa D, Spoletini D, Grieco M, Appetecchia M, Rota F, Palazzo S, Turano S. Management of Gastric Neuroendocrine Tumors. Updates Surg 2018. [DOI: 10.1007/978-88-470-3955-1_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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13
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Chin JL, O'Toole D. Diagnosis and Management of Upper Gastrointestinal Neuroendocrine Tumors. Clin Endosc 2017; 50:520-529. [PMID: 29207862 PMCID: PMC5719910 DOI: 10.5946/ce.2017.181] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Accepted: 11/19/2017] [Indexed: 12/14/2022] Open
Abstract
Upper gastrointestinal neuroendocrine tumors (NETs) are rare tumors which are increasingly recognised by practising endoscopists. After confirmation by endoscopic biopsies of these focal lesions, many questions may arise. As NETs are less frequently encountered compared to other malignancies or gastrointestinal pathology, many endoscopists may not fully understand the natural history, diagnosis and management of these tumors. In this review, we aim to update the practising endoscopist on the key clinical features and management of patients with upper gastrointestinal NET.
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Affiliation(s)
- Jun Liong Chin
- Department of Gastroenterology, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland
| | - Dermot O'Toole
- Department of Gastroenterology, St. Vincent's University Hospital, University College Dublin, Dublin, Ireland.,Department of Clinical Medicine, Trinity College Dublin, The University of Dublin, Dublin, Ireland
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14
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Manfredi S, Walter T, Baudin E, Coriat R, Ruszniewski P, Lecomte T, Laurenty AP, Goichot B, Rohmer V, Roquin G, Cojocarasu OZ, Lombard-Bohas C, Lepage C, Morcet J, Cadiot G. Management of gastric neuro-endocrine tumours in a large French national cohort (GTE). Endocrine 2017; 57:504-511. [PMID: 28664309 DOI: 10.1007/s12020-017-1355-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2017] [Accepted: 06/13/2017] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Gastric neuro-endocrine tumours are rare. European guidelines for the management of neuro-endocrine tumours have been published in 2012. The aim of our survey was to study the management of gastric neuro-endocrine tumours registered in the national cohort. A prospective national cohort registers the Neuro-endocrine tumours in France since January 2003 (GTE network). We reviewed all the individual medical reports of gastric neuro-endocrine tumours in order to collect data on treatment. RESULTS One hundred and ninety seven gastric neuro-endocrine tumours diagnosed between 1964 and 2013 in 20 centres were registered. For 181 cases data were considered complete for our survey. Eighty four tumours were type 1 (46.4%); five types 2 (2.8%); 52 types 3 (28.7%) and 40 types 4 (22.1%). Types 1 and 2 were first endoscopically managed in 93 and 60% of cases, respectively, whereas surgery was first done in 45 and 42%, respectively, of types 3 and 4. Systemic treatment, chemotherapy and/or somatostatin analogue, was first administered exclusively for types 3 and 4. Near 3% of types 1 and 40% of types 2 received at a time somatostatin analogue treatment. Five-year survival rates were 98.3, 100, 63.2 and 31.8% for types 1, 2, 3 and 4, respectively. CONCLUSION The great majority of gastric neuro-endocrine tumours registered in this national cohort are treated in accordance with the current guidelines. The survival rates we reported must be interpreted with caution, because this cohort registered preferentially selected patients eligible for treatment. The registration of all the gastric neuro-endocrine tumours, in particular type 1 considered as benign and type 4 not eligible for specific anti-cancer treatment must be encouraged.
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Affiliation(s)
- Sylvain Manfredi
- CHU Dijon, hepato-gastroenterology unit, University of Bourgogne Franche-Comté, INSERM, LNC UMR1231, F-21000, Dijon, France.
| | - Thomas Walter
- Département d'Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, 69437, Lyon, cedex 03, France
| | - Eric Baudin
- Gustave Roussy, Département d'Oncologie Endocrinienne, 94805, Villejuif cedex, France
| | - Romain Coriat
- Department of Gastroenterology and Digestive Oncology, Cochin Teaching Hospital, Paris Descartes University, Paris, France
| | | | - Thierry Lecomte
- CHRU de Tours, service d'Hépato-Gastroenterologie, CNRS, UMR 7292, GICC & Université Francois-Rabelais, Tours, France
| | | | - Bernard Goichot
- Department of Internal Medicine, Endocrinology and Nutrition, Hôpitaux Universitaires de Strasbourg, Faculté de Médecine, Université de Strasbourg, Strasbourg, France
| | - Vincent Rohmer
- Service d'endocrinologie et maladies métaboliques, CHU d'Angers, 4 rue Larrey, 49100, Angers, France
| | | | | | - Catherine Lombard-Bohas
- Département d'Oncologie Médicale, Hospices Civils de Lyon, Hôpital Edouard Herriot, 69437, Lyon, cedex 03, France
| | - Côme Lepage
- CHU Dijon, hepato-gastroenterology unit, University of Bourgogne Franche-Comté, INSERM, LNC UMR1231, F-21000, Dijon, France
| | | | - Guillaume Cadiot
- Department of Hepato-Gastroenterology and Digestive Oncology, Robert-Debré University Hospital, Reims, France
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15
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Tan H. Advances in the diagnosis and treatment of gastric neuroendocrine neoplasms. Transl Gastroenterol Hepatol 2016; 1:87. [PMID: 28138652 PMCID: PMC5244774 DOI: 10.21037/tgh.2016.11.03] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Accepted: 10/31/2016] [Indexed: 12/14/2022] Open
Abstract
Gastric neuroendocrine neoplasms (g-NENs) are a group of heterogeneous tumors arising from the endocrine cells of stomach. Most g-NENs progresses slowly and have a long disease course; however, some other g-NENs grow rapidly, similar to the progression of gastric adenocarcinoma. g-NENs have complex and diverse clinical manifestations and their prognosis and treatment strategies depend highly on clinical subtype, pathological grade, tumour stage, and other factors. Due to their low prevalence, most clinicians have limited knowledge about g-NENs. Missed diagnosis and excessive/inadequate treatment is common in clinical settings. Thus, the diagnosis and treatment of g-NENs needs to be further standardized.
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Affiliation(s)
- Huangying Tan
- Department of Integrative Oncology, China-Japan Friendship Hospital, Beijing 100029, China
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16
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Boyce M, Moore AR, Sagatun L, Parsons BN, Varro A, Campbell F, Fossmark R, Waldum HL, Pritchard DM. Netazepide, a gastrin/cholecystokinin-2 receptor antagonist, can eradicate gastric neuroendocrine tumours in patients with autoimmune chronic atrophic gastritis. Br J Clin Pharmacol 2016; 83:466-475. [PMID: 27704617 DOI: 10.1111/bcp.13146] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Revised: 09/29/2016] [Accepted: 10/02/2016] [Indexed: 12/11/2022] Open
Abstract
AIMS Netazepide, a gastrin/cholecystokinin 2 receptor antagonist, once daily for 12 weeks reduced the number of tumours and size of the largest one in 16 patients with autoimmune chronic atrophic gastritis (CAG), achlorhydria, hypergastrinaemia and multiple gastric neuroendocrine tumours (type 1 gastric NETs), and normalized circulating chromogranin A (CgA) produced by enterochromaffin-like cells, the source of the tumours. The aim was to assess whether longer-term netazepide treatment can eradicate type 1 gastric NETs. METHODS After a mean 14 months off netazepide, 13 of the 16 patients took it for another 52 weeks. Assessments were: gastroscopy; gene-transcript expression in corpus biopsies using quantitative polymerase chain reaction; blood CgA and gastrin concentrations; and safety assessments. RESULTS While off-treatment, the number of tumours, the size of the largest one, and CgA all increased again. Netazepide for 52 weeks: cleared all tumours in 5 patients; cleared all but one tumour in one patient; reduced the number of tumours and size of the largest one in the other patients; normalized CgA in all patients; and reduced mRNA abundances of CgA and histidine decarboxylase in biopsies. Gastrin did not increase further, confirming that the patients had achlorhydria. Netazepide was safe and well tolerated. CONCLUSIONS A gastrin/cholecystokinin 2 receptor antagonist is a potential medical and targeted treatment for type 1 gastric NETs, and an alternative to regular gastroscopy or surgery. Treatment should be continuous because the tumours will regrow if it is stopped. Progress can be monitored by CgA in blood or biomarkers in mucosal biopsies.
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Affiliation(s)
- Malcolm Boyce
- Hammersmith Medicines Research, Cumberland Avenue, London, NW10 7EW, UK
| | - Andrew R Moore
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool, L69 3GE, UK
| | - Liv Sagatun
- Department of Gastroenterology and Hepatology, St. Olav's Hospital, and the Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Bryony N Parsons
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool, L69 3GE, UK
| | - Andrea Varro
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool, L69 3GE, UK
| | - Fiona Campbell
- Department of Pathology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, L7 8XP, UK
| | - Reidar Fossmark
- Department of Gastroenterology and Hepatology, St. Olav's Hospital, and the Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Helge L Waldum
- Department of Gastroenterology and Hepatology, St. Olav's Hospital, and the Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - D Mark Pritchard
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool, L69 3GE, UK
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17
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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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18
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Tan HY. Subtype classification and management of gastric neuroendocrine neoplasms. Shijie Huaren Xiaohua Zazhi 2016; 24:3329-3336. [DOI: 10.11569/wcjd.v24.i22.3329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Gastric neuroendocrine neoplasms (g-NENs) are a group of heterogeneous tumors arising from endocrine cells in the stomach. Because of the low incidence, clinical misdiagnosis and mismanagement of g-NENs may occasionally occur. In this review, I summarize the epidemiology, pathology, tumor staging, clinical classification, diagnostic algorithm, treatment and prognosis of g-NENs, to explain the standard diagnosis and management, as well as the latest advances in g-NEN research. The author advocates the four-type classification of g-NENs, and emphasizes that type 1 g-NENs are a recurrent disease which needs long-term follow-up. Molecular mechanism of recurrence of and medical therapy for type 1 g-NENs are the future research direction for neuroendocrine neoplasms.
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19
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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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20
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Campana D, Ravizza D, Ferolla P, Faggiano A, Grimaldi F, Albertelli M, Berretti D, Castellani D, Cacciari G, Fazio N, Colao A, Ferone D, Tomassetti P. Clinical management of patients with gastric neuroendocrine neoplasms associated with chronic atrophic gastritis: a retrospective, multicentre study. Endocrine 2016; 51:131-9. [PMID: 25814125 DOI: 10.1007/s12020-015-0584-z] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2015] [Accepted: 03/19/2015] [Indexed: 12/19/2022]
Abstract
To provide data regarding clinical presentation, pathological features, management, and response to different treatments of patients with type I gastric neuroendocrine tumors in stages 0-2A. The study design consist of an Italian multicentre, retrospective analysis of patients with type I gastric neuroendocrine tumors managed with different therapeutic approaches: surgery, endoscopic surveillance, endoscopic resection, or somatostatin analog therapy. Among the 97 patients included, 3 underwent surgery, 45 (46.4%) radical endoscopic resection of the neoplastic lesions, 13 (13.4%) follow-up with upper endoscopy, and 36 (37.1%) somatostatin analog therapy. At the end of the follow-up, all patients were alive and there was no evidence of metastatic disease. Somatostatin analog therapy resulted in a complete response in 76.0% of the patients and stable disease in 24.0%. A prolonged period of therapy, the use of a full dose of somatostatin analogs and higher gastrin levels at diagnosis were related to a complete response to the therapy. The recurrence rate was 26.3% in patients treated with somatostatin analog therapy and 26.2% in patients treated with endoscopic resection, without a statistically significant difference in terms of disease-free survival. Regarding recurrence of the disease, no statistical difference was found according to type of therapy, number of neoplastic lesions, and 2010 WHO classification. The only risk factor for tumor recurrence was a short period of medical treatment. In conclusion, our study suggested that endoscopic surveillance, endoscopic resection and somatostatin analog therapy represent valid options in the management of patients with type I gastric neuroendocrine tumors in stages 0-2A.
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Affiliation(s)
- Davide Campana
- Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, University of Bologna, Via Massarenti, 9, 40138, Bologna, Italy.
| | - Davide Ravizza
- Division of Endoscopy and Unit of Gastrointestinal and Neuroendocrine Tumours, European Institute of Oncology, Milan, Italy
| | - Piero Ferolla
- Department of Medical Oncology, Multidisciplinary NET Center, Umbria Regional Cancer Network, Umbria, Italy
| | - Antongiulio Faggiano
- Division of Endocrinology, Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Franco Grimaldi
- Endocrinology and Metabolism Unit, University Hospital S. Maria della Misericordia, Udine, Italy
| | - Manuela Albertelli
- Endocrinology, Department of Internal Medicine and Medical Specialties (DiMI) and Center of Excellence for Biomedical Research (CEBR), University of Genova, Genoa, Italy
- IRCCS-AOU San Martino-IST, Genoa, Italy
| | - Debora Berretti
- Endocrinology and Metabolism Unit, University Hospital S. Maria della Misericordia, Udine, Italy
| | - Danilo Castellani
- Department of Gastroenterology, Multidisciplinary NET Center, Umbria Regional Cancer Network, Umbria, Italy
| | - Giulia Cacciari
- Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, University of Bologna, Via Massarenti, 9, 40138, Bologna, Italy
| | - Nicola Fazio
- Division of Endoscopy and Unit of Gastrointestinal and Neuroendocrine Tumours, European Institute of Oncology, Milan, Italy
| | - Annamaria Colao
- Division of Endocrinology, Department of Clinical Medicine and Surgery, "Federico II" University of Naples, Naples, Italy
| | - Diego Ferone
- Endocrinology, Department of Internal Medicine and Medical Specialties (DiMI) and Center of Excellence for Biomedical Research (CEBR), University of Genova, Genoa, Italy
- IRCCS-AOU San Martino-IST, Genoa, Italy
| | - Paola Tomassetti
- Department of Medical and Surgical Sciences, S.Orsola-Malpighi University Hospital, University of Bologna, Via Massarenti, 9, 40138, Bologna, Italy
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21
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Massironi S, Zilli A, Fanetti I, Ciafardini C, Conte D, Peracchi M. Intermittent treatment of recurrent type-1 gastric carcinoids with somatostatin analogues in patients with chronic autoimmune atrophic gastritis. Dig Liver Dis 2015; 47:978-983. [PMID: 26321479 DOI: 10.1016/j.dld.2015.07.155] [Citation(s) in RCA: 31] [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: 06/07/2015] [Revised: 07/27/2015] [Accepted: 07/30/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND Optimal management and treatment of type-1 gastric carcinoids is under debate. AIMS This prospective study evaluates the outcome of patients with recurrent type-1 gastric carcinoids treated with somatostatin analogues. METHODS From 2000 to 2013, among a population of 107 chronic atrophic gastritis patients, 25 (20% males, median age 62 years) developed type-1 gastric carcinoids and underwent regular clinical and endoscopic follow-up (median 77 months, range 6-165) after the initial treatment. Those patients showing recurrent disease were treated with somatostatin analogues until carcinoid disappearance. RESULTS 12/25 patients (33% males, median age 65 years) showed recurrent gastric carcinoids and were treated with somatostatin analogues for a median duration of 12 months. Median gastrin and chromogranin A levels, which were 802 pg/mL and 33 U/L, respectively, decreased to 299 pg/mL (p=0.002) and 15.6 U/L (p=0.001) at the end of the treatment. Gastric carcinoids disappeared after a median length of treatment of 12 months. After a median time of 19.5 months from somatostatin analogues discontinuation, 4/12 patients (25% males, median age 56 years) showed a further recurrence. A new cycle of treatment was performed successfully. CONCLUSIONS This study confirms that type-1 gastric carcinoids are a recurring disease and somatostatin analogues, administered on 12-month cycles, represent an effective treatment.
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Affiliation(s)
- Sara Massironi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
| | - Alessandra Zilli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Postgraduate School of Gastroenterology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Ilaria Fanetti
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Postgraduate School of Gastroenterology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Clorinda Ciafardini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Postgraduate School of Gastroenterology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Dario Conte
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Postgraduate School of Gastroenterology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - Maddalena Peracchi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Postgraduate School of Gastroenterology, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
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22
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Massironi S, Zilli A, Conte D. Somatostatin analogs for gastric carcinoids: For many, but not all. World J Gastroenterol 2015; 21:6785-6793. [PMID: 26078554 PMCID: PMC4462718 DOI: 10.3748/wjg.v21.i22.6785] [Citation(s) in RCA: 8] [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: 01/20/2015] [Revised: 02/22/2015] [Accepted: 04/16/2015] [Indexed: 02/06/2023] Open
Abstract
Gastric carcinoids (GCs) are classified as: type I, related to hypergastrinemia due to chronic atrophic gastritis (CAG), type II, associated with Zollinger-Ellison syndrome in multiple endocrine neoplasia type 1, and type III, which is normogastrinemic. The management of type-I gastric carcinoids (GC1s) is still debated, because of their relatively benign course. According to the European Neuroendocrine Tumor Society guidelines endoscopic resection is indicated whenever possible; however, it is not often feasible because of the presence of a multifocal disease, large lesions, submucosal invasion or, rarely, lymph node involvement. Therefore, somatostatin analogs (SSAs) have been proposed as treatment for GC1s in view of their antisecretive, antiproliferative and antiangiogenic effects. However, in view of the high cost of this therapy, its possible side effects and the relatively benign course of the disease, SSAs should be reserved to specific subsets of "high risk patients", i.e., those patients with multifocal or recurrent GCs. Indeed, it is reasonable that, after the development of a gastric neuroendocrine neoplasm in patients with a chronic predisposing condition (such as CAG), other enterochromaffin-like cells can undergo neoplastic proliferation, being chronically stimulated by hypergastrinemia. Therefore, definite indications to SSAs treatment should be established in order to avoid the undertreatment or overtreatment of GCs.
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23
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Sato Y. Endoscopic diagnosis and management of type I neuroendocrine tumors. World J Gastrointest Endosc 2015; 7:346-353. [PMID: 25901213 PMCID: PMC4400623 DOI: 10.4253/wjge.v7.i4.346] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Revised: 12/09/2014] [Accepted: 01/12/2015] [Indexed: 02/05/2023] Open
Abstract
Type I gastric neuroendocrine tumors (TI-GNETs) are related to chronic atrophic gastritis with hypergastrinemia and enterochromaffin-like cell hyperplasia. The incidence of TI-GNETs has significantly increased, with the great majority being TI-GNETs. TI-GNETs present as small (< 10 mm) and multiple lesions endoscopically and are generally limited to the mucosa or submucosa. Narrow band imaging and high resolution magnification endoscopy may be helpful for the endoscopic diagnosis of TI-GNETs. TI-GNETs are usually histologically classified by World Health Organization criteria as G1 tumors. Therefore, TI-GNETs tend to display nearly benign behavior with a low risk of progression or metastasis. Several treatment options are currently available for these tumors, including surgical resection, endoscopic resection, and endoscopic surveillance. However, debate persists about the best management technique for TI-GNETs.
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24
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Carcinoid Tumors. Surg Oncol 2015. [DOI: 10.1007/978-1-4939-1423-4_26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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25
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Sato Y. Clinical features and management of type I gastric carcinoids. Clin J Gastroenterol 2014; 7:381-6. [PMID: 26184015 DOI: 10.1007/s12328-014-0528-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Accepted: 09/02/2014] [Indexed: 12/14/2022]
Abstract
Type I gastric carcinoids (TIGCs) are related to chronic atrophic gastritis and are characterized by hypergastrinemia and hyperplasia of enterochromaffin-like cells. TIGCs are the most frequently diagnosed of all gastric carcinoids, accounting for about 70-80 %. Endoscopically, TIGCs are present as small (<10 mm), polypoid lesions or, more frequently, as smooth, rounded submucosal lesions. Histologically, TIGCs arise in the deep mucosa, with some invading the submucosa. Most TIGCs are well-differentiated tumors, with metastasis being rare. Therefore, patients with TIGCs generally have an excellent prognosis. Among the currently available treatment options are total gastrectomy, partial resection, antrectomy, endoscopic resection, and endoscopic surveillance, although no consensus has been reached on their optimal management. Further studies are needed to develop better management options for patients with TIGC.
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Affiliation(s)
- Yuichi Sato
- Department of Gastroenterology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata, 951-8121, Japan,
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26
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Basuroy R, Srirajaskanthan R, Prachalias A, Quaglia A, Ramage JK. Review article: the investigation and management of gastric neuroendocrine tumours. Aliment Pharmacol Ther 2014; 39:1071-84. [PMID: 24628514 DOI: 10.1111/apt.12698] [Citation(s) in RCA: 69] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2013] [Revised: 12/04/2013] [Accepted: 02/20/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND Gastric carcinoids (GCs) or neuroendocrine tumours (NETs) are increasingly identified at endoscopy, and account for 0.6-2% of all gastric polyps identified. The SEER database in the US has demonstrated a rising incidence of gastric NETs amongst all NETs; from 2.2% between 1950 and 1969 to 6.0% between 2000 and 2007. AIM To review the literature and assist clinicians in managing patients with GCs. METHODS A literature search was conducted through MEDLINE using search terms: gastric, carcinoid, neuroendocrine tumour, therapy, endoscopy, mucosal resection, submucosal dissection. Relevant articles were identified through manual review. The reference lists of these articles were reviewed to include further appropriate articles. RESULTS There are three types of GCs with important epidemiological, pathophysiological, histological and endoscopic differences that affect prognosis and management. Type 1 and 2 GCs develop in the context of hypergastrinaemia that originates from achlorhydria in atrophic gastritis and a gastrinoma, respectively. Type 3 GCs occur sporadically and independent of gastrin. The histological type, grade and Ki67 index are used to determine prognosis and direct clinical management. Type 1 GCs >1 cm in size and type 2 GCs should be assessed for invasion beyond the submucosa with EUS prior to endoscopic resection with EMR or ESD. Type 3 GCs should be managed as per recommendations for gastric adenocarcinoma. The treatment of advanced disease is multimodal. CONCLUSIONS Patients with gastric carcinoids should be discussed in a specialist neuroendocrine tumour multidisciplinary meeting to ensure all treatment options are explored in localised and advanced disease. Areas of controversy exist that need further research.
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Affiliation(s)
- R Basuroy
- ENETS Neuroendocrine Centre of Excellence, Institute of Liver studies, Kings College Hospital, London, UK
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Grozinsky-Glasberg S, Thomas D, Strosberg JR, Pape UF, Felder S, Tsolakis AV, Alexandraki KI, Fraenkel M, Saiegh L, Reissman P, Kaltsas G, Gross DJ. Metastatic type 1 gastric carcinoid: a real threat or just a myth? World J Gastroenterol 2013; 19:8687-8695. [PMID: 24379587 PMCID: PMC3870515 DOI: 10.3748/wjg.v19.i46.8687] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Revised: 08/25/2013] [Accepted: 09/03/2013] [Indexed: 02/06/2023] Open
Abstract
AIM To describe disease characteristics and treatment modalities in a group of rare patients with metastatic gastric carcinoid type 1 (GCA1). METHODS Information on clinical, biochemical, radiological, histopathological findings, the extent of the disease, as well as the use of different therapeutic modalities and the long-term outcome were recorded. Patients' data were assessed at presentation, and thereafter at 6 to 12 monthly intervals both clinically and biochemically, but also endoscopically and histopathologically. Patients were evaluated for the presence of specific symptoms; the presence of autoimmune disorders and the presence of other gastrointestinal malignancies in other family members were also recorded. The evaluation of response to treatment was defined using established WHO criteria. RESULTS We studied twenty consecutive patients with a mean age of 55.1 years. The mean follow-up period was 83 mo. Twelve patients had regional lymph node metastases and 8 patients had liver metastases. The primary tumor mean diameter was 20.13 ± 10.83 mm (mean ± SD). The mean Ki-67 index was 6.8% ± 11.2%. All but one patient underwent endoscopic or surgical excision of the tumor. The disease was stable in all but 3 patients who had progressive liver disease. All patients remained alive during the follow-up period. CONCLUSION Metastatic GCA1 carries a good overall prognosis, being related to a tumor size of ≥ 1 cm, an elevated Ki-67 index and high serum gastrin levels.
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Moore AR, Boyce M, Steele IA, Campbell F, Varro A, Pritchard DM. Netazepide, a gastrin receptor antagonist, normalises tumour biomarkers and causes regression of type 1 gastric neuroendocrine tumours in a nonrandomised trial of patients with chronic atrophic gastritis. PLoS One 2013; 8:e76462. [PMID: 24098507 PMCID: PMC3788129 DOI: 10.1371/journal.pone.0076462] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Accepted: 08/19/2013] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION Autoimmune chronic atrophic gastritis (CAG) causes hypochlorhydria and hypergastrinaemia, which can lead to enterochromaffin-like (ECL) cell hyperplasia and gastric neuroendocrine tumours (type 1 gastric NETs). Most behave indolently, but some larger tumours metastasise. Antrectomy, which removes the source of the hypergastrinaemia, usually causes tumour regression. Non-clinical and healthy-subject studies have shown that netazepide (YF476) is a potent, highly selective and orally-active gastrin/CCK-2 receptor antagonist. Also, it is effective in animal models of ECL-cell tumours induced by hypergastrinaemia. AIM To assess the effect of netazepide on tumour biomarkers, number and size in patients with type I gastric NETs. METHODS We studied 8 patients with multiple tumours and raised circulating gastrin and chromogranin A (CgA) concentrations in an open trial of oral netazepide for 12 weeks, with follow-up 12 weeks later. At 0, 6, 12 and 24 weeks, we carried out gastroscopy, counted and measured tumours, and took biopsies to assess abundances of several ECL-cell constituents. At 0, 3, 6, 9, 12 and 24 weeks, we measured circulating gastrin and CgA and assessed safety and tolerability. RESULTS Netazepide was safe and well tolerated. Abundances of CgA (p<0.05), histidine decarboxylase (p<0.05) and matrix metalloproteinase-7(p<0.10) were reduced at 6 and 12 weeks, but were raised again at follow-up. Likewise, plasma CgA was reduced at 3 weeks (p<0.01), remained so until 12 weeks, but was raised again at follow-up. Tumours were fewer and the size of the largest one was smaller (p<0.05) at 12 weeks, and remained so at follow-up. Serum gastrin was unaffected. CONCLUSION The reduction in abundances, plasma CgA, and tumour number and size by netazepide show that type 1 NETs are gastrin-dependent tumours. Failure of netazepide to increase serum gastrin further is consistent with achlorhydria. Netazepide is a potential new treatment for type 1 NETs. Longer, controlled trials are justified. TRIAL REGISTRATION European Union EudraCT database 2007-002916-24 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2007-002916-24ClinicalTrials.gov NCT01339169 http://clinicaltrials.gov/ct2/show/NCT01339169?term=yf476&rank=5.
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Affiliation(s)
- Andrew R. Moore
- Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - Malcolm Boyce
- Hammersmith Medicines Research, London, United Kingdom
| | - Islay A. Steele
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - Fiona Campbell
- Department of Pathology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, United Kingdom
| | - Andrea Varro
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
| | - D. Mark Pritchard
- Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom
- * E-mail:
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Park MI. Endoscopic treatment for early foregut neuroendocrine tumors. Clin Endosc 2013; 46:450-5. [PMID: 24143301 PMCID: PMC3797924 DOI: 10.5946/ce.2013.46.5.450] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2013] [Revised: 06/28/2013] [Accepted: 07/01/2013] [Indexed: 12/04/2022] Open
Abstract
Foregut neuroendocrine tumors (NETs) include those arising in the esophagus, stomach, pancreas, and duodenum and seem to have a broad range of clinical behavior from benign to metastatic. Several factors including the advent of screening endoscopy may be related to increased incidence of gastrointestinal NETs; thus, many foregut NETs are diagnosed at an early stage. Early foregut NETs, such as those of the stomach and duodenum, can be managed with endoscopic treatment because of a low frequency of lymph node and distant metastases. However, controversy continues concerning the optimal management of early foregut NETs due to a lack of controlled prospective studies. Several issues such as indications, technical issues, and outcomes of endoscopic treatment for early foregut NETs are reviewed based on some published studies.
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Affiliation(s)
- Moo In Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
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30
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Kidd M, Gustafsson B, Modlin IM. Gastric carcinoids (neuroendocrine neoplasms). Gastroenterol Clin North Am 2013; 42:381-97. [PMID: 23639647 DOI: 10.1016/j.gtc.2013.01.009] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Gastric neuroendocrine neoplasms of the stomach can be divided into the usually well-differentiated, hypergastrinemia-dependent type I and II lesions and the more aggressively behaving gastrin-independent type III lesions. Studying menin and its complex interrelationship with gastrin may provide insight into tumor biology at the clinical level and in terms of basic cell biology (eg, the role of the epigenome in neuroendocrine cell proliferation), and lead to potential consideration of other targets that are known candidates for molecular-based therapies in other adenocarcinomas.
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Affiliation(s)
- Mark Kidd
- Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.
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Toumpanakis C, Caplin ME. Update on the role of somatostatin analogs for the treatment of patients with gastroenteropancreatic neuroendocrine tumors. Semin Oncol 2013; 40:56-68. [PMID: 23391113 DOI: 10.1053/j.seminoncol.2012.11.006] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Somatostatin analogs (SA) are the standard of care for controlling symptoms of patients with functional gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). SA control symptoms in more than 70% of patients with carcinoid syndrome. Similar results are obtained in patients with functional, hormone-secreting, pancreatic NETs. The use of SA as antiproliferative agents has been established only recently. Retrospective studies have shown stabilization of tumor growth in >50% of patients with progressive disease. The results of a recent randomized phase III trial (PROMID) demonstrated that the median time to progression in patients with midgut carcinoid tumors treated with octreotide LAR (Long-Acting-Repeatable, Novartis, Basel, Switzerland) was more than twice as long compared to that of patients treated with placebo. The results of a phase III study of lanreotide versus placebo in nonfunctional NETs are not yet available. More studies are needed to determine whether combining SA with novel targeted treatments will result in enhanced antiproliferative activity compared to treatment with a SA alone. Studies are ongoing using pan-receptor agonists (eg, pasireotide) and chimeric dimers, which possess features of somatostatin and dopamine agonists (dopastatins) and are thought to enhance symptom control by binding multiple receptors (somatostatin and dopamine receptors). Somatostatin receptor antagonists are also currently being developed for clinical use. Peptide receptor radionuclide therapy (PRRT), consisting of yttrium-90 and lutetium-177 isotopes conjugated with SA appear to be efficacious in advanced NETs. Randomized studies are needed to definitively establish the safety and efficacy of this strategy compared to other available treatments, and to determine which radiolabeled isotopes or combinations are most effective.
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Affiliation(s)
- Christos Toumpanakis
- Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK
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Abstract
"Carcinoids" are mostly slow-growing neuroendocrine neoplasms (NENs) with low proliferative activity. A wide range of therapeutic options with variable efficacy exist, including locoregional ablative strategies. Thereafter, some patients may not require medical therapy for years depending on the rate of progression or recurrence. However, the majority of patients require systemic treatment and therein lies the dilemma, since no antiproliferative agent is currently approved for carcinoids. Somatostatin analogs (SSAs), and to a lesser extent interferon-alpha, are standard therapy for carcinoids associated with the carcinoid syndrome. These drugs have some antiproliferative efficacy. SSAs rarely lead to tumor remission but may modestly prolong time to tumor progression. Chemotherapy is of limited value in carcinoids with low proliferation indices but may be useful in higher grade tumors. Peptide receptor-targeted radionuclide therapy may be of benefit and is mostly used after medical therapies fail. However, it is considered an investigational modality. More recently, targeted drugs such as mammalian target of rapamycin (mTOR) inhibitors and anti-angiogenics have been investigated. Objective remissions are rare. Their value remains to be rigorously elucidated. Increased efficacy requires a better understanding of the underlying tumor biology and identification of molecular pathological criteria to allow appropriate preselection of candidates for targeted therapies.
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Correlation between a short-term intravenous octreotide suppression test and response to antrectomy in patients with type-1 gastric neuroendocrine tumours. Eur J Gastroenterol Hepatol 2013; 25:474-81. [PMID: 23249603 DOI: 10.1097/meg.0b013e32835cec52] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Type-1 gastric neuroendocrine tumours (NETs) arise in some patients with chronic hypergastrinaemia secondary to autoimmune atrophic gastritis. Patients with small tumours are usually managed conservatively, because their prognosis is very good. However, larger tumours may require surgical intervention. Many type-1 gastric NETs regress following antrectomy because this removes the source of hypergastrinaemia. However, some tumours do not regress following antrectomy and additional surgery may be required. An octreotide suppression test has been previously suggested as a means to assess whether type-1 gastric NETs are likely to regress following antrectomy. AIM To prospectively examine the role of a short-term intravenous octreotide suppression test in predicting type-1 gastric NET regression in five patients who subsequently underwent antrectomy. MATERIALS AND METHODS Serum gastrin concentrations and gastric corpus and tumour histidine decarboxylase mRNA abundances were assessed in patients with type-1 gastric NETs before and 72 h after the administration of 25 µg/h intravenous octreotide. Gastric tumour response was assessed endoscopically following subsequent antrectomy. RESULTS All patients showed significant decreases in serum gastrin concentrations as well as corpus and tumour biopsy histidine decarboxylase mRNA abundance following octreotide infusion. All patients also showed resolution of hypergastrinaemia following subsequent antrectomy. However, tumour regression was only observed in four of the five patients. One patient had a persistent tumour 3 years after antrectomy and required additional surgical resection. CONCLUSION A positive octreotide suppression test result does not always predict response to antrectomy in patients with type-1 gastric NETs. Assessment of gastric mucosal responses to a gastrin/CCK-2 receptor antagonist may therefore also be helpful.
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Thomas D, Tsolakis AV, Grozinsky-Glasberg S, Fraenkel M, Alexandraki K, Sougioultzis S, Gross DJ, Kaltsas G. Long-term follow-up of a large series of patients with type 1 gastric carcinoid tumors: data from a multicenter study. Eur J Endocrinol 2013; 168:185-93. [PMID: 23132699 DOI: 10.1530/eje-12-0836] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To study the clinical presentation, diagnostic approach, response to treatment, and the presence of other pathologies in patients with gastric carcinoid type 1 (GC 1) tumors. DESIGN AND METHODS Retrospective analysis of 111 patients from four institutions and a mean follow-up of 76 months. RESULTS The main indications for gastroscopy were upper gastrointestinal tract symptoms. The mean number of lesions, maximum tumoral diameter, and percentage of cells expressing Ki-67 labeling index were 3.6±3.8, 8±12.1 mm and 1.9±2.4% respectively. Serum gastrin and chromogranin A (CgA) levels were elevated in 100/101 and 85/90 patients respectively. Conventional imaging studies demonstrated pathology in 9/111 patients. Scintigraphy with radiolabeled octreotide was positive in 6/60 without revealing any additional lesions. From the 59 patients who had been followed-up without any intervention, five developed tumor progression. Thirty-two patients were treated with long-acting somatostatin analogs (SSAs), leading to a significant reduction of gastrin and CgA levels, number of visible tumors, and CgA immune-reactive tumor cells in 28, 19, 27, and 23 treated patients respectively. Antrectomy and/or gastrectomy were initially performed in 20 patients and a complete response was achieved in 13 patients. The most common comorbidities were vitamin B12 deficiency, thyroiditis, and parathyroid adenomas. CONCLUSIONS Most GCs1 are grade 1 (82.7%) tumors presenting with stage I (73.9%) disease with no mortality after prolonged follow-up. Ocreoscan did not provide further information compared with conventional imaging techniques. Treatment with SSAs proved to be effective for the duration of administration.
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Affiliation(s)
- Dimitrios Thomas
- Department of Pathophysiology, National University of Athens, Mikras Asias 75, 11557 Athens, Greece.
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35
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Current concepts on gastric carcinoid tumors. Gastroenterol Res Pract 2012; 2012:287825. [PMID: 23316222 PMCID: PMC3534241 DOI: 10.1155/2012/287825] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2012] [Revised: 10/31/2012] [Accepted: 11/19/2012] [Indexed: 12/13/2022] Open
Abstract
Gastric carcinoid tumors (GCs) are rare lesions representing less than 10% of carcinoid tumors and less than 1% of all stomach neoplasms. There are three distinct types of gastric carcinoids; type I includes the vast majority (70–85%) of these neoplasms that are closely linked to chronic atrophic gastritis. Type II which accounts for 5–10 %, is associated with Zollinger-Ellison syndrome and often occurs in the context of multiple endocrine neoplasia type 1. Type III, finally, represents 15–25% of gastric carcinoids and is characterized by a far more aggressive course. The optimal clinical approach to GCs remains to be elucidated, depending upon type, size, and number of carcinoids. While there is universal agreement about the surgical treatment of type III GCs, current options for type I and II include simple surveillance, endoscopic polypectomy, surgical excision associated with or without surgical antrectomy, or total gastrectomy. Moreover, the introduction of somatostatin analogues could represent another therapeutic option.
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Abstract
Gastric neuroendocrine neoplasms of the stomach can be divided into the usually well-differentiated, hypergastrinemia-dependent type I and II lesions and the more aggressively behaving gastrin-independent type III lesions. Mainly due to better diagnostics and awareness of this tumor, the observed incidence has increased more than tenfold over the last 30 years. Small (<15-20 mm) localized type I and II lesions that are slowly proliferating (Ki67<2%) can usually be managed conservatively with endoscopic surveillance. Reducing hypergastrinemia by surgical removal of an underlying gastrinoma is important in inhibiting growth and induce reduction of type II lesions, while the specific gastrin receptor antagonist YF476 or gastrin antibodies may become useful for both type I and II lesions. Infiltrating and metastasized tumors and type III lesions require a more aggressive approach with surgical resection and consideration of modalities such as somatostatin analogs, cytotoxics, and peptide receptor targeted treatment.
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Affiliation(s)
- Mark Kidd
- Department of Surgery, Yale University School of Medicine, PO Box 208602, New Haven, CT, USA.
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Crosby DA, Donohoe CL, Fitzgerald L, Muldoon C, Hayes B, O'Toole D, Reynolds JV. Gastric neuroendocrine tumours. Dig Surg 2012; 29:331-48. [PMID: 23075625 DOI: 10.1159/000342988] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2012] [Accepted: 08/24/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Gastric neuroendocrine tumours (NETs) are increasingly recognised, and management decisions may be difficult due to an incomplete understanding of aetiology, natural history and optimum therapy. This article presents a current understanding based on recent advances in epidemiology, classification, molecular profiling, and treatment. METHODS Relevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance. RESULTS Gastric NETs may be divided into three clinical prognostic groups: type I is associated with autoimmune atrophic gastritis and hypergastrinaemia, type II is associated with Zollinger-Ellison syndrome, and type III lesions are gastrin-independent, have the greatest metastatic potential and poorest prognosis. There has been an increased frequency of gastric NETs reported. Management approaches have evolved in parallel with advances in endoscopic staging and surgery, as well as improved understanding of the biology and natural history of NETs. CONCLUSIONS Gastric NETs present a spectrum of activity from indolent tumours to metastatic malignancy. Treatment decisions for patients must be individualised and are best managed by a multidisciplinary team approach. The current evidence base is limited to small series and efforts to treat patients within clinical networks of expertise are warranted.
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Affiliation(s)
- David A Crosby
- Department of Surgery, Trinity Centre for Health Sciences, Trinity College Dublin/St James's Hospital, Dublin, Ireland
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Frilling A, Akerström G, Falconi M, Pavel M, Ramos J, Kidd M, Modlin IM. Neuroendocrine tumor disease: an evolving landscape. Endocr Relat Cancer 2012; 19:R163-85. [PMID: 22645227 DOI: 10.1530/erc-12-0024] [Citation(s) in RCA: 113] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) represent a heterogenous group of tumors arising from a variety of neuroendocrine cell types. The incidence and prevalence of GEP-NENs have markedly increased over the last three decades. Symptoms are often absent in early disease, or vague and nonspecific even in advanced disease. Delayed diagnosis is thus common. Chromogranin A is the most commonly used biomarker but has limitations as does the proliferative marker Ki-67%, which is often used for tumor grading and determination of therapy. The development of a multidimensional prognostic nomogram may be valuable in predicting tumor behavior and guiding therapy but requires validation. Identification of NENs that express somatostatin receptors (SSTR) allows for SSTR scintigraphy and positron emission tomography imaging using novel radiolabeled compounds. Complete surgical resection of limited disease or endoscopic ablation of small lesions localized in stomach or rectum can provide cure; however, the majority of GEP-NENs are metastatic (most frequently the liver and/or mesenteric lymph nodes) at diagnosis. Selected patients with metastatic disease may benefit from advanced surgical techniques including hepatic resection or liver transplantation. Somatostatin analogs are effective for symptomatic treatment and exhibit some degree of antiproliferative activity in small intestinal NENs. There is a place for streptozotocin, temozolomide, and capecitabine in the management of pancreatic NENs, while new agents targeting either mTOR (everolimus) or angiogenic (sunitinib) pathways have shown efficacy in these lesions.
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Affiliation(s)
- Andrea Frilling
- Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, London, UK
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Zorzetto V, Maddalo G, Basso D, Farinati F. Immunotherapy for gastric premalignant lesions and cancer. Immunotherapy 2012; 4:587-99. [PMID: 22788127 DOI: 10.2217/imt.12.50] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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40
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Delle Fave G, Kwekkeboom DJ, Van Cutsem E, Rindi G, Kos-Kudla B, Knigge U, Sasano H, Tomassetti P, Salazar R, Ruszniewski P. ENETS Consensus Guidelines for the management of patients with gastroduodenal neoplasms. Neuroendocrinology 2012; 95:74-87. [PMID: 22262004 DOI: 10.1159/000335595] [Citation(s) in RCA: 211] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Pavel M, Baudin E, Couvelard A, Krenning E, Öberg K, Steinmüller T, Anlauf M, Wiedenmann B, Salazar R. ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology 2012; 95:157-76. [PMID: 22262022 DOI: 10.1159/000335597] [Citation(s) in RCA: 592] [Impact Index Per Article: 45.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Marianne Pavel
- Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Berlin, Germany.
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Zhang L, Ozao J, Warner R, Divino C. Review of the pathogenesis, diagnosis, and management of type I gastric carcinoid tumor. World J Surg 2011; 35:1879-86. [PMID: 21559999 DOI: 10.1007/s00268-011-1137-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Gastric carcinoid tumors comprise 7% of all gastrointestinal carcinoids and have significantly increased in incidence over the past few decades. Seventy to 80% of gastric carcinoids are type I, which usually are clinically asymptomatic and found incidentally at endoscopic evaluation for abdominal pain or anemia. In this review, advances in understanding the pathophysiology of type I gastric carcinoid are highlighted. In addition, various current diagnostic and treatment options are discussed. Although type I carcinoids generally hold a benign course, rigorous investigation is needed to ensure accurate diagnosis and optimal treatment. This includes appropriate diagnostic procedures and imaging and accurate staging of tumor. Tumor size, depth of invasion, presence of metastasis, and the tumor's gastrin dependency dictate treatment options. Appropriate treatments can consist of endoscopic resection, antrectomy, medical management, or frequent follow-up. This article provides a systematic method of evaluating and treating type I gastric carcinoid.
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Affiliation(s)
- Linda Zhang
- Department of Surgery, Mount Sinai School of Medicine, 5 East 98th Street, 15th Floor, Box 1259, New York, NY 10029, USA
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Merola E, Sbrozzi-Vanni A, Panzuto F, D'Ambra G, Di Giulio E, Pilozzi E, Capurso G, Lahner E, Bordi C, Annibale B, Delle Fave G. Type I gastric carcinoids: a prospective study on endoscopic management and recurrence rate. Neuroendocrinology 2011; 95:207-213. [PMID: 21811050 DOI: 10.1159/000329043] [Citation(s) in RCA: 99] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2011] [Accepted: 05/05/2011] [Indexed: 02/05/2023]
Abstract
BACKGROUND Type I gastric carcinoids (TIGCs) are neuroendocrine neoplasms arising from enterochromaffin-like cells in atrophic body gastritis. Data regarding their evolution in prospective series are scarce, thus treatment and follow-up are not codified. Our aim was to evaluate clinical outcome and recurrence in TIGCs managed by endoscopic approach. METHODS 33 patients (24 females; median age 65 years, range 23-81) were included and managed through endoscopic follow-up every 6-12 months, with lesion removal and multiple gastric biopsies. Baseline clinical and histological features were analyzed as risk factors by Cox regression. RESULTS At diagnosis, 7 tumors were intramucosal carcinoids and 26 were polyps (median diameter 5 mm, range 2-20), multiple in 17 patients. Associated severe atrophy was present in 21 cases (63.6%), while mild atrophy was found in 6 cases (18.2%). During a 46-month median follow-up, survival was 100% and no metastases occurred. One patient developed a less-differentiated carcinoid that was radically treated by surgery. 21 patients (63.6%) had recurrence after a median of 8 months, 14 of these (66.6%) had a second recurrence after a median of 8 months following the previous carcinoid removal. Median recurrence-free survival was 24 months. Neither clinical nor biochemical recurrence-predicting factors were found. CONCLUSIONS Although about 60% of TIGCs had recurrence after endoscopic resection, endoscopic management may be considered safe and effective.
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Affiliation(s)
- Elettra Merola
- Department of Digestive and Liver Disease, Sant'Andrea Hospital, II Medical School, Sapienza University of Rome, Rome, Italy
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Abstract
Neuroendocrine tumors (NETs) of the stomach are the most frequent among all neuroendocrine neoplasms in the digestive tract. The diagnosis and classification are complicated by the fact that these tumors have to be categorized not only by common staging and grading but also according to their pathophysiological background (types). The types differ in their biological behaviour (aggressiveness) which influences therapeutic concepts. This article explains and summarizes the etiology and classification of gastric NETs and offers a precise concept for diagnosis and treatment to improve clinical outcome.
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45
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Histologic characterization and improved prognostic evaluation of 209 gastric neuroendocrine neoplasms. Hum Pathol 2011; 42:1373-84. [PMID: 21531442 DOI: 10.1016/j.humpath.2011.01.018] [Citation(s) in RCA: 137] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2010] [Revised: 01/22/2011] [Accepted: 01/28/2011] [Indexed: 12/13/2022]
Abstract
Gastric neuroendocrine neoplasms differ considerably in histology, clinicopathologic background, stage, and patient outcome, implying a wide spectrum of therapeutic options, hence the need for improved diagnostic and prognostic criteria to select appropriate therapy. Here, we tested the European NeuroEndocrine Tumor Society and the novel World Health Organization 2010 grade and stage classifications together with additional clinicopathologic and histologic parameters in a series of 209 gastric neuroendocrine neoplasms with a median follow-up of 89 months. Fifty-one grade 3 neuroendocrine carcinomas and 15 mixed endocrine-exocrine carcinomas of poor outcome were separated from 143 neuroendocrine tumors, including 132 G1 or G2 enterochromaffin-like (ECL) cell neoplasms and 11 G1 gastrin-cell, somatostatin-cell, or serotonin-cell tumors. Most G1 cases had excellent prognosis, even when metastatic, whereas G2 and G3 neoplasms had worse or very severe prognosis, respectively. The European NeuroEndocrine Tumor Society-World Health Organization 2010 proliferative grading system well correlated with patient survival. Structural histologic parameters were equally predictive and when combined with the European NeuroEndocrine Tumor Society-World Health Organization 2010 grading system in a "global grade" improved tumor prognostic stratification. The European NeuroEndocrine Tumor Society-World Health Organization 2010 staging system proved effective. Introduction of novel T (T(1a) and T(1b) or deep submucosal) and N categories (N(1), <3 nodes metastases; N(2), ≥3) allowed a simplified, equally informative 3-stage TNM system. Such improved diagnostic and prognostic criteria for gastric neuroendocrine neoplasms are proposed and discussed.
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Jianu CS, Fossmark R, Syversen U, Hauso Ø, Fykse V, Waldum HL. Five-year follow-up of patients treated for 1 year with octreotide long-acting release for enterochromaffin-like cell carcinoids. Scand J Gastroenterol 2011; 46:456-63. [PMID: 21133821 DOI: 10.3109/00365521.2010.539255] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Gastric carcinoids type 1 (GC1) are neuroendocrine tumors (NETs) arising from the enterochromaffin-like (ECL) cells in patients with chronic atrophic gastritis (CAG). The treatment of GC1 has been endoscopic polypectomy or surgical tumor excision and antrectomy. One year treatment with somatostatin analogs (SSAs) diminished tumor load and ECL cell density. The effect persisted 1 year after treatment was discontinued. However, the optimal SSA dose and treatment duration are unknown. OBJECTIVES The aim of the present work was to study macroscopic and histopathological changes in the stomach and serum markers gastrin and chromogranin A (CgA) in GC1 patients 5 years after 1 year of octreotide long-acting release (LAR) treatment. MATERIAL AND METHODS Five patients with GC1 were included 5 years after the initial year of octreotide LAR treatment. All patients underwent upper gastrointestinal endoscopy including tumor and mucosal biopsies from oxyntic mucosa, chest and abdominal computer tomography and octreotide scintigraphy. Fasting serum gastrin and CgA were also measured. RESULTS At 5 years, one patient had a highly malignant gastric tumor, one patient had an increased number of GCs, regional and distant metastases and three patients had an increased number of GCs. Serum gastrin and CgA increased to pre-treatment levels after 1 year of follow-up and were unchanged at the 5-year follow-up. CONCLUSIONS The disease had progressed in all five GCs patients treated with octreotide for 12 months at 5 years of follow-up. This suggests that, if started, octreotide treatment should not be discontinued in these patients.
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Affiliation(s)
- Constantin S Jianu
- Department of Gastroenterology and Hepatology, St. Olavs Hospital, Trondheim, Norway.
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Fendrich V, Bartsch DK. Surgical treatment of gastrointestinal neuroendocrine tumors. Langenbecks Arch Surg 2011; 396:299-311. [PMID: 21279821 DOI: 10.1007/s00423-011-0741-7] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2011] [Accepted: 01/17/2011] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are uncommon but clinically challenging and fascinating tumors. GEP-NETs present as either functional or as nonfunctional tumors. Functional tumors are commonly associated with a specific hormonal syndrome directly related to a hormone secreted by the tumor, like gastrinomas with a Zollinger-Ellison syndrome or carcinoid syndrome in patients with neuroendocrine tumors (NET) of the ileum. Nonfunctional tumors do not secrete a hormone resulting in a clinical syndrome. METHODS The natural course of GEP-NETs is highly variable. Small, benign neoplasms such as 90% of all insulinomas or gastric endocrine tumors type 1 are readily curable by surgical resection; however, most other GEP-NETs have a much less favorable prognosis. Patients with completely resected tumors generally have a good prognosis, and an aggressive surgical approach in patients with advanced disease may also prolong survival. CONCLUSIONS This review focuses on the current standards of surgical treatment of gastric endocrine tumors, NETs of the pancreas (PNET) and NETs of the ileum. Although the evidence level is low in many instances due to the lack of randomized controlled trials, important treatment recommendations can be given.
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Affiliation(s)
- Volker Fendrich
- Department of Surgery, Philipps University Marburg, Baldingerstrasse, Marburg, Germany.
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Lawrence B, Kidd M, Svejda B, Modlin I. A clinical perspective on gastric neuroendocrine neoplasia. Curr Gastroenterol Rep 2011; 13:101-109. [PMID: 21080245 DOI: 10.1007/s11894-010-0158-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
The incidence of gastric neuroendocrine tumors (NETs) has increased exponentially based on widespread use of endoscopy and a greater pathological awareness of the condition. A key concern is the potential association with hypergastrinemia induced by proton pump inhibitor administration. Previous confusion regarding diagnosis and therapy has been diminished by a series of international consensus statements defining the biology and management strategies for the disease. Overall, gastric NETs are categorized as well-differentiated or poorly differentiated neoplasms. Well-differentiated gastric NETs are enterochromaffin-like (ECL) cell tumors subclassified into three types based on their relationship to gastrin, a key regulator of ECL cell neoplastic transformation. The treatment of type 1 and type 2 tumors depends on the size and invasiveness of the tumor, whereas type 3 tumors and poorly differentiated neuroendocrine carcinomas warrant aggressive surgical resection. The disease-specific 5-year survival ranges from about 95% in type 1 gastric carcinoids to about 25% in poorly differentiated gastric NECs. Elucidation of the precise biology of a gastric NET is critical to diagnosis and delineation of a type-specific management strategy.
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Affiliation(s)
- Ben Lawrence
- Yale University School of Medicine, New Haven, CT 06520, USA.
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Gastric carcinoid with hypergastrinemia: report of three cases. Case Rep Med 2010; 2010. [PMID: 20885936 PMCID: PMC2946604 DOI: 10.1155/2010/348761] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2010] [Revised: 07/27/2010] [Accepted: 09/07/2010] [Indexed: 01/07/2023] Open
Abstract
We report 3 cases of gastric carcinoids with hypergastrinemia. Case 1: A 60-year-old man had a 2 cm carcinoid of the stomach and underwent partial resection. Involvement of the muscularis propria and lymph nodes metastasis were observed microscopically. Follow-up gastroscopy revealed another carcinoid lesion and total gastrectomy was performed. Case 2: A 67-year-old woman with multiple carcinoids of the entire stomach underwent antrectomy. No growth of residual tumors has been detected so far. Case 3: A 61-year-old man had a tumor near the esophagogastric junction and underwent total gastrectomy. Carcinoid component was diffusely intermingled with adenocarcinoma in the tumor and invaded into the subserosa. In all 3 cases, the serum gastrin level was high and atrophic gastritis was microscopically observed. Carcinoid tumor in Case 3 was different from those in Cases 1 and 2 and interestingly, gastric carcinoid with hypergastrinemia showed various types of appearance.
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Massironi S, Conte D, Sciola V, Spampatti MP, Ciafardini C, Valenti L, Rossi RE, Peracchi M. Plasma chromogranin A response to octreotide test: prognostic value for clinical outcome in endocrine digestive tumors. Am J Gastroenterol 2010; 105:2072-2078. [PMID: 20372113 DOI: 10.1038/ajg.2010.154] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) expressing somatostatin receptors may be treated with somatostatin analogs (SSAs). Selection criteria are a positive Octreoscan or a >50% hormone level decrease after octreotide subcutaneous (s.c.) injection (octreotide test) (OT). Plasma chromogranin A (CgA) is the best general GEP-NET marker, but data on CgA response to OT are scanty. Thus, we evaluated whether plasma CgA response to OT could predict the clinical response to SSAs. METHODS At diagnosis, 38 GEP-NET patients received octreotide 200 microg s.c., with plasma CgA determination at 0, 3, and 6 h. Long-term SSA treatment was then given by monitoring symptomatic, biochemical, and objective responses, and survival. RESULTS Basal plasma CgA levels were significantly higher in patients with functioning than non-functioning tumors (median (range): 220 (18-2,230) vs. 46 (25-8,610) U/l, P=0.03) and in those with than without metastases (171 (18-8,610) vs. 43 (28-220) U/l, P=0.04). CgA levels significantly correlated with WHO classification, clinical TNM staging, and Ki-67 proliferative index. After OT, CgA levels decreased from 146 (18-8,610) to 61 (10-8,535) U/l (basal and nadir values), P<0.001. In patients responsive to OT, a successful objective response occurred in 21/31 patients (68%). Successful symptomatic response occurred in 13/18 patients (72%), biochemical response in 25/31 (81%), and objective response in 21/31 (68%). In the remaining seven unresponsive cases, with CgA decrement <30%, disease progressed to death in six (86%). Median survival from enrollment was 48 months (6-138) in responsive and 6 (6-30) in unresponsive patients (P=0.0005). CONCLUSIONS In GEP-NETs, plasma CgA is a reliable marker, and a >30% decrease after OT has a relevant prognostic meaning allowing the identification of the subgroup of patients most likely to be responsive to chronic SSAs.
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Affiliation(s)
- Sara Massironi
- Gastroenterology Unit II, Fondazione IRCCS Policlinico, Mangiagalli e Regina Elena, Milan, Italy.
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