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Kővári B, Carneiro F, Lauwers GY. Epithelial tumours of the stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:227-286. [DOI: 10.1002/9781119423195.ch13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Köseoğlu H, Duzenli T, Sezikli M. Gastric neuroendocrine neoplasms: A review. World J Clin Cases 2021; 9:7973-7985. [PMID: 34621854 PMCID: PMC8462212 DOI: 10.12998/wjcc.v9.i27.7973] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 05/19/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric neuroendocrine neoplasms (g-NENs) or neuroendocrine tumors are generally slow-growing tumors with increasing incidence. They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features. Type 1 and 2 are gastrin dependent, whereas type 3 and 4 are sporadic. The reason for hypergastrinemia is atrophic gastritis in type 1, and gastrin releasing tumor (gastrinoma) in type 2 g-NEN. The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy. g-NENs are positively stained with chomogranin A and synaptophysin. Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis. It is crucial to discriminate between types of g-NENs, because the management, treatment and prognosis differ significantly between subtypes. Treatment options for g-NENs include endoscopic resection, surgical resection with or without antrectomy, medical treatment with somatostatin analogues, netazepide or chemotherapy regimens. Follow-up without excision is another option in appropriate cases. The prognosis of type 1 and 2 g-NENs are good, whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.
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Affiliation(s)
- Hüseyin Köseoğlu
- Department of Gastroenterology, Hitit University, Faculty of Medicine, Çorum 19200, Turkey
| | - Tolga Duzenli
- Department of Gastroenterology, Hitit University Erol Olçok Education and Research Hospital, Çorum 19200, Turkey
| | - Mesut Sezikli
- Department of Gastroenterology, Hitit University, Faculty of Medicine, Çorum 19200, Turkey
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Malczewska A, Procner A, Walter A, Kusnierz K, Zajecki W, Aslanian H, Kos-Kudla B. The NETest liquid biopsy is diagnostic for gastric neuroendocrine tumors: observations on the blood-based identification of microscopic and macroscopic residual diseaseOK. BMC Gastroenterol 2020; 20:235. [PMID: 32703157 PMCID: PMC7376918 DOI: 10.1186/s12876-020-01348-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 06/16/2020] [Indexed: 12/19/2022] Open
Abstract
Background NETest, a novel multi-gene liquid biopsy has utility in neuroendocrine tumor (NET) diagnosis and identification of residual disease. We independently assessed utility of the NETest to diagnose gastric neuroendocrine neoplasms (GNENs) and identify micro- and macroscopic residual disease. Methods Cohorts comprised histologically confirmed GNENs at biopsy, n = 46; GNETs Type 1: 42 (32 NET G1, 10 NET G2), a GNET Type 3: 1 well-differentiated NET G3, neuroendocrine carcinomas (NECs) (n = 3), and controls (n = 63). Disease status at sampling was assessed by gastroscopy, histology (resection margin [R] positivity of polypectomy or biopsy), EUS, CT or MRI, and/or 68Ga-DOTA-TATE PET/CT. Groups included image- (gastroscopy, EUS, and anatomical and/or functional imaging) positive or image negative disease. NETest assay by PCR (spotted plates, normal cut-off: 20). Data: mean ± SD. Results Disease extent: Image-negative (n = 30) (21 R0, 9 R1); Image-positive, n = 16. Diagnosis: NETest was increased in GNETs (23 ± 11) vs. controls (7 ± 4, p < 0.0001). In histology-positive, the NETest accuracy was 100% (25/25). Microscopic disease: In image-negative but R1, NETest was elevated in 100% (9/9; 28 ± 9). Levels were elevated vs. controls (7 ± 4, p < 0.0001), or R0 (16 ± 11, p = 0.02). Eight of 21 R0, exhibited positive NETest. Macroscopic disease: Gastric lesions were multiple: 38%, single: 62%, submucosal: 13%, or ulcerated: 13%. Lesions size was ≤5 mm (50%), > 5–9.9 mm (17%), 10–19.9 mm (17%), ≥20 mm (17%) [≥10 mm: 34%). The NETest accuracy was 100% (16/16). Levels (28 ± 7) were higher than controls (7 ± 4, p < 0.0001) or R0 (16 ± 11, p = 0.002) but not to R1 (28 ± 9, p = 0.5). Conclusions NETest is diagnostic for gastric NETs. Elevated levels identify both microscopic and macroscopic residual disease. In histology/image-negative disease, elevated NETest may reflect early evidence of increased neuroendocrine gene expression of hypergastrinemia-induced neoplastic transformation of enterochromaffin-like (ECL) cells to tumor status. A sensitive liquid biopsy has utility in the management and surveillance of gastric NET disease.
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Affiliation(s)
- A Malczewska
- Department of Endocrinology and Neuroendocrine Tumors, Medical University of Silesia, ul. Ceglana 35, 40-514, Katowice, Poland.
| | - A Procner
- Department of Endocrinology and Neuroendocrine Tumors, Medical University of Silesia, ul. Ceglana 35, 40-514, Katowice, Poland
| | - A Walter
- Department of Endocrinology and Neuroendocrine Tumors, Medical University of Silesia, ul. Ceglana 35, 40-514, Katowice, Poland
| | - K Kusnierz
- Department of Gastrointestinal Surgery, Medical University of Silesia, ul. Medykow 14, 40-752, Katowice, Poland
| | - W Zajecki
- Department of Pathology, Medical University of Silesia, ul. 3 Maja 13-15, 41-800, Zabrze, Poland
| | - H Aslanian
- Department of Digestive Diseases, Center for Advanced Endoscopy, Yale University School of Medicine, 310 Cedar Street, New Haven, CT, 06510, USA.
| | - B Kos-Kudla
- Department of Endocrinology and Neuroendocrine Tumors, Medical University of Silesia, ul. Ceglana 35, 40-514, Katowice, Poland
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Daskalakis K, Tsoli M, Karapanagioti A, Chrysochoou M, Thomas D, Sougioultzis S, Karoumpalis I, Kaltsas GA, Alexandraki KI. Recurrence and metastatic potential in Type 1 gastric neuroendocrine neoplasms. Clin Endocrinol (Oxf) 2019; 91:534-543. [PMID: 31254407 DOI: 10.1111/cen.14055] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 06/16/2019] [Accepted: 06/27/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND The aim of our study was to assess clinico-pathological and biochemical parameters of Type 1 Gastric Neuroendocrine Neoplasms (GNEN1) with respect to tumours propensity for recurrence and metastasis. METHODS Hospital charts of GNEN1 patients were reviewed at a single tertiary referral centre. RESULTS We included 114 consecutive patients (74 women; age at baseline 54.5 ± 12.7 years [mean ± SD]) with GNEN1. All tumours (n = 114) were well differentiated; Grade 1 (G1) accounted for 56 patients (49%), whereas 46 (40%) were Grade 2 (G2) and 12 (11%) of unknown Grade. Overall follow-up encompassed 45.3 ± 46 (mean ± SD) months in 84 patients who were subjected to annual surveillance; 44 (52%) developed recurrence in the stomach during follow-up with 22 experiencing multiple recurrences; three (2.6%) presented with metastases in locoregional lymph nodes (n = 3) and/or the liver (n = 2); No metastasis or death was reported during follow-up. Median recurrence-free survival (RFS) was 31 months (95% CI: 7.6-54.4). Among clinico-pathological and biochemical parameters investigated, endoscopic intervention compared with surgery (P-value = .009) and higher serum-gastrin levels (s-gastrin) at baseline and first-year follow-up were associated with recurrence (P-value = .022 and .003 respectively) and also shorter RFS (log-rank P = .009 for type of intervention and .014 for s-gastrin, respectively). Receiver Operator Curve analysis of s-gastrin levels at first-year follow-up for recurrence demonstrated an area under the curve of 0.702. CONCLUSION Despite the relatively high prevalence of G2 tumours, endoscopically and/or surgically treated GNEN1 remains an indolent disease with a low metastatic propensity and no disease-specific mortality reported in our series. Many patients though will experience local recurrence, warranting long-term endoscopic surveillance with s-gastrin biomarker being a complementary tool in recurrence prediction.
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Affiliation(s)
- Kosmas Daskalakis
- Endocrine Oncology Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Marina Tsoli
- Endocrine Oncology Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Angeliki Karapanagioti
- Endocrine Oncology Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Maria Chrysochoou
- Endocrine Oncology Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Dimitrios Thomas
- Endocrine Oncology Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Stavros Sougioultzis
- Gastroenterology Division, Department of Pathophysiology, Laikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis Karoumpalis
- Department of Gastroenterology, "G. Gennimatas" General Hospital, Athens, Greece
| | - Gregory A Kaltsas
- Endocrine Oncology Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Krystallenia I Alexandraki
- Endocrine Oncology Unit, 1st Department of Propaupedic Internal Medicine, Laiko Hospital, National and Kapodistrian University of Athens, Athens, Greece
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Abstract
Our group observed the first case of synchronous gastric neuroendocrine tumor (NET) and duodenal gastrinoma with autoimmune chronic atrophic gastritis (CAG), in the absence of Helicobacter pylori infection. Demographic, clinical, endoscopic, and pathologic data were abstracted from the electronic medical record at Mount Sinai Hospital from 2013 to 2015. The patient's anonymity was carefully protected, and informed consent was obtained for publication of protected health information. A 53-year-old woman with hypertension presented to Mount Sinai Hospital in June 2013 for a second opinion for management of gastric and duodenal NETs. After evaluation by gastroenterology and surgery, repeat upper endoscopy with ultrasound and fine-needle aspiration revealed multiple diminutive type I gastric NETs and 2 duodenal NETs, against a background of autoimmune CAG, with biopsy pathology negative for H. pylori. She subsequently underwent a transduodenal resection of the duodenal NETs, confirming low-grade, gastrin-positive, stage T2 duodenal NET. On routine follow-up over the next 2 years, clinical, radiographic, and endoscopic surveillance revealed no recurrent or metastatic gastric or duodenal disease. This first report of synchronous duodenal gastrinoma and gastric NET in the setting of autoimmune CAG can broaden our understanding of gastric NET pathophysiology.
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Grozinsky-Glasberg S, Alexandraki KI, Angelousi A, Chatzellis E, Sougioultzis S, Kaltsas G. Gastric Carcinoids. Endocrinol Metab Clin North Am 2018; 47:645-660. [PMID: 30098721 DOI: 10.1016/j.ecl.2018.04.013] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Gastric carcinoids, formally named gastric neuroendocrine neoplasms (NENs), are derived from enterochromaffin-like cells of the stomach and are increasingly diagnosed. A majority are designated as type I (related to autoimmune gastritis) and type II (related to gastrinoma) neoplasms that develop secondary to gastrin hypersecretion. Types I and II gastric carcinoids are mostly small-sized (1-2 cm), multiple, low-malignancy potential lesions mainly confined to the gastric mucosa/submucosa. These lesions have an indolent course and low metastatic potential. In contrast, type III gastric carcinoids are single, larger-sized (>2 cm), non-gastrin-related lesions that infiltrate the muscular layers associated with local and distant metastases.
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Affiliation(s)
- Simona Grozinsky-Glasberg
- Neuroendocrine Tumor Unit, Department of Endocrinology, Hadassah-Hebrew University Medical Center, P.O.B. 12000, Jerusalem 91120, Israel
| | - Krystallenia I Alexandraki
- 1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece
| | - Anna Angelousi
- 1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece
| | - Eleftherios Chatzellis
- 1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece
| | - Stavros Sougioultzis
- Department of Pathophysiology, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece
| | - Gregory Kaltsas
- 1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Mikras Asias 75, Athens 11527, Greece.
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Rossi RE, Rausa E, Cavalcoli F, Conte D, Massironi S. Duodenal neuroendocrine neoplasms: a still poorly recognized clinical entity. Scand J Gastroenterol 2018; 53:835-842. [PMID: 29726295 DOI: 10.1080/00365521.2018.1468479] [Citation(s) in RCA: 25] [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: 03/12/2018] [Revised: 04/16/2018] [Accepted: 04/16/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Duodenal neuroendocrine neoplasms (dNENs) are rare tumors, which usually show good prognosis. The optimal management of these tumors is still far from being clearly understood because of their rarity and the poor level of knowledge about their natural history. Herein, we have reviewed the literature on dNENs to collect and analyze the current data on epidemiology, diagnosis and management of these rare tumors. METHODS Bibliographical searches were performed in PubMed, using the following keywords: duodenal neuroendocrine neoplasm; duodenum; gastrinoma; diagnosis; therapy; guidelines. We searched for all relevant articles published over the last 15 years. Non-English language papers were excluded. RESULTS We reviewed the pertinent articles about dNENs. Upper gastrointestinal endoscopy with biopsy is the cornerstone of the dNENs diagnostic process. Endoscopic ultrasound with fine-needle aspiration/biopsy should be performed in order to locally stage the disease and in all cases of non-diagnostic endoscopy. Endoscopic or complete surgical removal of the primary lesion is the recommended treatment and is generally achievable for the majority of the patients. A less aggressive approach may be suggested for well-differentiated low-stage tumors. After NEN removal, patients should be closely followed-up especially during the first 3 years by endoscopic examination, imaging tests and CgA measurements. CONCLUSIONS The multi-disciplinary approach and the preservation of the quality of life of the patients play a key role in the therapeutic process for dNENs. Further studies are needed to better define standardized guidelines specific to dNENs, including optimal management approaches and follow-up intervals.
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Affiliation(s)
- Roberta Elisa Rossi
- a Department of Gastroenterology and Endoscopy , Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milan , Italy
- b Department of Pathophysiology and Organ Transplant , Università degli Studi di Milano , Milan , Italy
| | - Emanuele Rausa
- c General and Emergency Surgery Department , ASST Trauma Center "Papa Giovanni XXIII" Hospital , Bergamo , Italy
| | - Federica Cavalcoli
- a Department of Gastroenterology and Endoscopy , Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milan , Italy
- b Department of Pathophysiology and Organ Transplant , Università degli Studi di Milano , Milan , Italy
| | - Dario Conte
- a Department of Gastroenterology and Endoscopy , Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milan , Italy
- b Department of Pathophysiology and Organ Transplant , Università degli Studi di Milano , Milan , Italy
| | - Sara Massironi
- a Department of Gastroenterology and Endoscopy , Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico , Milan , Italy
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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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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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Kim HH, Kim GH, Kim JH, Choi MG, Song GA, Kim SE. The efficacy of endoscopic submucosal dissection of type I gastric carcinoid tumors compared with conventional endoscopic mucosal resection. Gastroenterol Res Pract 2014; 2014:253860. [PMID: 24693280 PMCID: PMC3947882 DOI: 10.1155/2014/253860] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Accepted: 01/09/2014] [Indexed: 12/13/2022] Open
Abstract
Background and Aims. Conventional endoscopic submucosal resection (EMR) of carcinoid tumors often involves the resection margin, which necessitates further intervention. Endoscopic submucosal dissection (ESD) is widely accepted for removing carcinoid tumors. We aimed to evaluate the clinical usefulness of ESD with that of EMR for resection of type I gastric carcinoid tumors. Patients and Methods. The study enrolled 62 patients (37 males, 25 females; median age, 50 years; range, 40-68 years) who were treated with EMR or ESD at three hospitals; the study group had 87 type I gastric carcinoid tumors with an estimated size of ≤10 mm. The complete resection rate and the complications associated with these two procedures were analyzed. Results. The overall ESD complete resection rate was higher than that of the EMR rate (94.9% versus 83.3%, P value = 0.174). A statistically lower vertical margin involvement rate was achieved when ESD was performed compared to when EMR was performed (2.6% versus 16.7%, P value = 0.038). The complication rate was not significantly different between the two groups. Conclusions. ESD showed a higher complete resection rate, particularly for the vertical margin, with a similar complication rate. We mildly recommend ESD rather than EMR for removing type I gastric carcinoid tumors.
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Affiliation(s)
- Hyung Hun Kim
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul 137-701, Republic of Korea
| | - Gwang Ha Kim
- Department of Internal Medicine, Pusan National University, School of Medicine, Busan 614-735, Republic of Korea
| | - Ji Hyun Kim
- Department of Internal Medicine, Inje University College of Medicine, Busan Paik Hospital, Gaegeum-dong, Busanjin-Gu, Busan 602-739, Republic of Korea
| | - Myung-Gyu Choi
- Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul 137-701, Republic of Korea
| | - Geun Am Song
- Department of Internal Medicine, Pusan National University, School of Medicine, Busan 614-735, Republic of Korea
| | - Sung Eun Kim
- Department of Internal Medicine, Kosin University College of Medicine, Busan 602-702, Republic of Korea
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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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Tüzün A, Keskin O, Yakut M, Kalkan C, Soykan I. The predictive value of mean platelet volume, plateletcrit and red cell distribution width in the differentiation of autoimmune gastritis patients with and without type I gastric carcinoid tumors. Platelets 2013; 25:363-6. [PMID: 24175991 DOI: 10.3109/09537104.2013.821607] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Autoimmune gastritis is an autoimmune and inflammatory condition that may predispose to gastric carcinoid tumors or adenocarcinomas. The early diagnosis of these tumors is important in order to decrease morbidity and mortality. Platelet indices such as mean platelet volume and plateletcrit levels increase in inflammatory, infectious and malign conditions. The primary aim of this study was to explore wheter platelet indices and red cell distribution width have any predictive role in the discrimination of autoimmune gastritis patients with and without gastric carcinoid tumors. Also secondary aim of this study was to investigate whether any changes exist betwenn autoimmune gastritis and functional dyspepsia patients by means of platelet indices. Plateletcrit (0.22 ± 0.06 vs. 0.20 ± 0.03%, p < 0.001) and red cell distribution width (16.11 ± 3.04 vs. 13.41 ± 0.95%, p < 0.001) were significantly higher in autoimmune gastritis patients compared to control group. Receiver operating curve analysis suggested that optimum plateletcrit cut-off point was 0.20% (AUC: 0.646), and 13.95% as the cut off value for red cell distribution width (AUC: 0.860). Although plateletcrit (0.22 ± 0.06 vs. 0.21 ± 0.04%, p = 0.220) and mean platelet volume (8.94 ± 1.44 vs. 8.68 ± 0.89 fl, p = 0.265) were higher in autoimmune gastritis patients without carcinoid tumor compared to patients with carcinoid tumors, these parameters were not statistically significant. Changes in plateletcrit and red cell distribution width values may be used as a marker in the discrimination of autoimmune gastritis and fucntional dyspepsia patients but not useful in patients with gastric carcinoid tumor type I.
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Affiliation(s)
- Ali Tüzün
- Division of Gastroenterology, Ibni Sina Hospital, Ankara University Faculty of Medicine , Ankara , Turkey
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13
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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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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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Carneiro F, Lauwers GY. Epithelial Tumours of the Stomach. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2013:180-222. [DOI: 10.1002/9781118399668.ch13] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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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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O'Toole D, Delle Fave G, Jensen RT. Gastric and duodenal neuroendocrine tumours. Best Pract Res Clin Gastroenterol 2012; 26:719-735. [PMID: 23582915 DOI: 10.1016/j.bpg.2013.01.002] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2013] [Accepted: 01/10/2013] [Indexed: 01/31/2023]
Abstract
Gastric neuroendocrine neoplasms (NENs) are increasing in frequency and have a varied spectrum with regard to histology, clinicopathologic background, stage, and prognosis. They are usually discovered incidentally, are for the most part benign and are associated with hypergastrinaemia (secondary either to chronic atrophic gastritis or rarely Zollinger-Ellison syndrome; types 1 and 2, respectively) or more rarely sporadic type 3. Applications of recent staging and grading systems - namely using Ki-67 proliferative indices - (from ENETS and WHO 2010) can be particularly helpful in further categorising these tumours. The natural history of Type 1 gastric carcinoids is generally (>95%) favourable and simple surveillance is usually recommended for small (<1 cm) T1 tumours, with local (endoscopic or surgical) resection for larger lesions. Other potential therapies such as somatostatin analogues and gastrin receptor antagonists may offer newer therapeutic possibilities. Rarely, gastric NENs have a malignant course and this is usually confined to Type 2 and especially Type 3 tumours; the latter mimic the biological course of gastric adenocarcinoma and require radical oncological therapies. Most duodenal NENs, apart from gastrinomas (that are not dealt with here) are sporadic and non functional. They are also increasing in frequency probably due to incidental discovery at endoscopy or imaging for other reasons and this may account for their overall good prognosis. Peri-ampullary and ampullary NENs may have a more aggressive outcome and should be carefully appraised and treated (often with surgical resection).
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Affiliation(s)
- Dermot O'Toole
- Department of Gastroenterology and Clinical Medicine, St James's Hospital and Trinity College, Dublin, Ireland.
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Dronamraju SS, Joypaul VB. Management of gastrointestinal carcinoid tumours - 10 years experience at a district general hospital. J Gastrointest Oncol 2012; 3:120-9. [PMID: 22811879 DOI: 10.3978/j.issn.2078-6891.2011.039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2011] [Accepted: 08/13/2011] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND There is paucity of guidelines regarding management of gastrointestinal carcinoid tumours in district hospitals. METHODS This study was undertaken at a district hospital to analyse the management pathway of gastrointestinal carcinoid tumours. RESULTS Over a period of 10 years there were 35 patients, with an estimated annual incidence of 2.5 per 100,000 population. After a median follow up of 24 months, 22 (63%) patients were alive and disease free. Only 56% patients were referred to the regional neuro-endocrine multidisciplinary team. CONCLUSIONS Management of patients with carcinoid tumours in district hospitals needs streamling with increased utilisation of regional neuroendocrine multidisciplinary teams.
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Affiliation(s)
- Shridhar S Dronamraju
- Department of General Surgery, South Tyneside District General Hospital, Harton Lane, South Shields, UK
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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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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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Hung CY, Chen MJ, Shih SC, Liu TP, Chan YJ, Wang TE, Chang WH. Gastric carcinoid tumor in a patient with a past history of gastrointestinal stromal tumor of the stomach. World J Gastroenterol 2008; 14:6884-6887. [PMID: 19058321 PMCID: PMC2773889 DOI: 10.3748/wjg.14.6884] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2008] [Revised: 11/07/2008] [Accepted: 11/14/2008] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal stromal tumor is the most common mesenchymal tumor in the gastrointestinal tract. It may coexist with other type of cancers, and if so, the tumors usually involve the stomach. The most common associated cancers are gastrointestinal carcinomas. We report a 65-year-old woman with a history of gastric gastrointestinal stromal tumor who had undergone subtotal segmental gastrectomy. New polypoid lesions were detected on a follow-up gastroscopy one year later. The lesions were biopsied and found to be carcinoid tumors. There was serum hypergastrinemia, and type 1 gastric carcinoid tumor was diagnosed. A total gastrectomy was performed. Pathologic examination revealed both carcinoid tumors and a recurrent gastrointestinal stromal tumor.
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Landry CS, Brock G, Scoggins CR, McMasters KM, Martin RCG. A proposed staging system for gastric carcinoid tumors based on an analysis of 1,543 patients. Ann Surg Oncol 2008; 16:51-60. [PMID: 18953609 DOI: 10.1245/s10434-008-0192-8] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2008] [Revised: 09/13/2008] [Accepted: 09/15/2008] [Indexed: 01/27/2023]
Abstract
The lack of a clinically relevant staging system for gastric carcinoid tumors creates a persistent challenge for clinicians trying to provide patients with meaningful prognostic information. The purpose of this study was to identify the clinicopathologic factors that affect survival for patients diagnosed with gastric carcinoid, and use this information to create a staging system. A search of 15,983 patients with carcinoid tumors from the Surveillance Epidemiology and End Results (SEER) database identified 1,543 patients with gastric carcinoid tumors from 1973 to 2004. Patients were analyzed according to various clinicopathologic factors, and a tumor (T1, T2, T3), lymph node (N0, N1), and metastasis (M0, M1) staging system was created according to these parameters. Gastric carcinoid was the only primary malignancy in 74% of patients; 24% presented with one additional primary malignancy, and 2.7% had two or more additional malignancies. On multivariate analysis, age and depth of invasion were significant for patients with one tumor. Four stages were created according to statistically significant prognostic factors: 60% of patients were classified into stage I, 7.6% into stage II, 6.5% into stage III, and 26% into stage IV. Five-year survival rates were 82, 63, 21, and 5.5% for stages I-IV, respectively. We conclude that this tumor-node-metastasis (TNM) staging system accurately discriminates prognosis for all types of gastric carcinoid tumors, with size, depth of invasion, lymph node involvement, and distant metastasis having the greatest impact on survival. Incorporation of this staging system into clinical practice will allow better study of outcomes and development of stage-specific treatment recommendations.
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Affiliation(s)
- Christine S Landry
- Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer Center, University of Louisville School of Medicine, 315 East Broadway, Room 313, Louisville, KY 40202, USA
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Abstract
BACKGROUND Long-term therapy with potent acid inhibitors is a common treatment for gastro-esophageal reflux disease. Administration of proton pump inhibitors (PPIs) causes profound and continuous hypochlorhydria by inhibition of the proton pump in gastric parietal cells. Long-term hypergastrinaemia increases mucosal thickness and enterochromaffin-like cell density in oxyntic mucosa. OBJECTIVE The aim of this study was to see whether this very common clinical intervention induces significant changes in the gastric mucosal gene expression pattern. METHODS Seven patients suffering from gastro-esophageal reflux disease were included in this study. Endoscopic biopsies were taken from the corpus mucosa before and toward the end of a 3-month treatment with the PPI esomeprazole. RESULTS Microarray analysis identified 186 differentially expressed genes. A high proportion of genes with changed gene expression levels during PPI treatment are involved in proliferation, apoptosis, and stress response. CONCLUSION This study identified many genes that were not previously known to be affected by inhibition of gastric acid secretion. Further characterization of the functional roles of genes whose expression is modulated by potent acid inhibition may give new insight into the biological responses to potent acid inhibition, including the mucosal response to the moderately increased gastrin levels encountered in clinical practice.
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Grozinsky-Glasberg S, Grossman AB, Korbonits M. The role of somatostatin analogues in the treatment of neuroendocrine tumours. Mol Cell Endocrinol 2008; 286:238-50. [PMID: 18037561 DOI: 10.1016/j.mce.2007.10.006] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2007] [Revised: 09/30/2007] [Accepted: 10/10/2007] [Indexed: 02/08/2023]
Abstract
Neuroendocrine tumours belong to a heterogeneous family of neoplasms, originating in endocrine glands (such as the pituitary, parathyroid or the neuroendocrine adrenal glands), in endocrine islets (within the thyroid or pancreas) as well as in endocrine cells dispersed between exocrine cells throughout the digestive or respiratory tracts. The clinical behaviour of neuroendocrine tumours is variable; they may be functioning or not functioning, ranging from well-differentiated slow growing neuroendocrine tumours to poorly differentiated neuroendocrine tumours, which are highly aggressive malignant tumours. The development of somatostatin analogues as important diagnostic and treatment tools have revolutionised the clinical management of patients with neuroendocrine tumours. However, although symptomatic relief and stabilisation of tumour growth for various periods of time are observed in many patients treated with somatostatin analogues, tumour regression is rare. Development of new somatostatin analogues and new drug combination therapies should further improve the clinical management of these patients.
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Affiliation(s)
- Simona Grozinsky-Glasberg
- Department of Endocrinology, William Harvey Research Institute, Barts and the London, Queen Mary School of Medicine, University of London, London, UK
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25
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De Block CEM, De Leeuw IH, Van Gaal LF. Autoimmune gastritis in type 1 diabetes: a clinically oriented review. J Clin Endocrinol Metab 2008; 93:363-71. [PMID: 18029461 DOI: 10.1210/jc.2007-2134] [Citation(s) in RCA: 128] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
CONTEXT Autoimmune gastritis and pernicious anemia are common autoimmune disorders, being present in up to 2% of the general population. In patients with type 1 diabetes or autoimmune thyroid disease, the prevalence is 3- to 5-fold increased. This review addresses the epidemiology, pathogenesis, diagnosis, clinical consequences, and management of autoimmune gastritis in type 1 diabetic patients. SYNTHESIS Autoimmune gastritis is characterized by: 1) atrophy of the corpus and fundus; 2) autoantibodies to the parietal cell and to intrinsic factor; 3) achlorhydria; 4) iron deficiency anemia; 5) hypergastrinemia; 6) pernicious anemia may result from vitamin B12 deficiency; and 7) in up to 10% of patients, autoimmune gastritis may predispose to gastric carcinoid tumors or adenocarcinomas. This provides a strong rationale for screening, early diagnosis, and treatment. The management of patients with autoimmune gastritis implies yearly determination of gastrin, iron, vitamin B12 levels, and a complete blood count. Iron or vitamin B12 should be supplemented in patients with iron deficiency or pernicious anemia. Whether regular gastroscopic surveillance, including biopsies, is needed in patients with autoimmune gastritis/pernicious anemia is controversial. The gastric carcinoids that occur in these patients generally do not pose a great threat to life, whereas the danger of developing carcinoma is controversial. Nevertheless, awaiting a consensus statement, we suggest performing gastroscopy and biopsy at least once in patients with autoantibodies to the parietal cell, iron-, or vitamin B12-deficiency anemia, or high gastrin levels. CONCLUSION The high prevalence of autoimmune gastritis in type 1 diabetic patients and its possible adverse impact on the health of the patient provide a strong rationale for screening, early diagnosis, periodic surveillance by gastroscopy, and treatment.
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MESH Headings
- Anemia, Pernicious/complications
- Anemia, Pernicious/immunology
- Anemia, Pernicious/pathology
- Anemia, Pernicious/therapy
- Autoantibodies/blood
- Diabetes Mellitus, Type 1/complications
- Diabetes Mellitus, Type 1/immunology
- Diabetes Mellitus, Type 1/pathology
- Diabetes Mellitus, Type 1/therapy
- Gastritis, Atrophic/complications
- Gastritis, Atrophic/immunology
- Gastritis, Atrophic/pathology
- Gastritis, Atrophic/therapy
- Humans
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Affiliation(s)
- Christophe E M De Block
- Department of Diabetology-Endocrinology, Antwerp University Hospital and University of Antwerp, Wilrijkstraat 10, B-2650 Edegem, Belgium.
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Neuroendocrine Tumors of the Pancreas and Gastrointestinal Tract and Carcinoid Disease. Surgery 2008. [DOI: 10.1007/978-0-387-68113-9_59] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Steigedal TS, Bruland T, Misund K, Thommesen L, Laegreid A. Inducible cAMP early repressor suppresses gastrin-mediated activation of cyclin D1 and c-fos gene expression. Am J Physiol Gastrointest Liver Physiol 2007; 292:G1062-9. [PMID: 17185632 DOI: 10.1152/ajpgi.00287.2006] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The gastric hormone gastrin and its precursors promote proliferation in several gastrointestinal cell types. Here we show that gastrin induces transcription of cell cycle gene cyclin D1 and protooncogene c-fos in the neuroendocrine pancreatic cell line AR42J and that this gastrin response is inhibited by endogenous inducible cAMP early repressor (ICER). The transcriptional repressor ICER is known to downregulate both its own expression and the expression of other genes containing cAMP-responsive elements (CREs). Using siRNA, we also show that CRE promoter elements are the targets of endogenous ICER in AR42J cells as well as in the neuroendocrine cell line RIN5F. Our results suggest that ICER plays an important role in molecular mechanisms governing gastrin-mediated growth by modulating gastrin's transcriptional activation of growth-related genes. Our finding that ICER modulates pituitary adenylate cyclase-activating polypeptide-activated gene expression also indicates a regulatory effect of ICER in the responses of neuroendocrine cells to peptides other than gastrin.
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Affiliation(s)
- Tonje S Steigedal
- Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway
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Ruszniewski P, Delle Fave G, Cadiot G, Komminoth P, Chung D, Kos-Kudla B, Kianmanesh R, Hochhauser D, Arnold R, Ahlman H, Pauwels S, Kwekkeboom DJ, Rindi G. Well-differentiated gastric tumors/carcinomas. Neuroendocrinology 2007; 84:158-164. [PMID: 17312375 DOI: 10.1159/000098007] [Citation(s) in RCA: 90] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Abstract
Cholecystokinin and gastrin receptors (CCK1R and CCK2R) are G protein-coupled receptors that have been the subject of intensive research in the last 10 years with corresponding advances in the understanding of their functioning and physiology. In this review, we first describe general properties of the receptors, such as the different signaling pathways used to exert short- and long-term effects and the structural data that explain their binding properties, activation, and regulation. We then focus on peripheral cholecystokinin receptors by describing their tissue distribution and physiological actions. Finally, pathophysiological peripheral actions of cholecystokinin receptors and their relevance in clinical disorders are reviewed.
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Affiliation(s)
- Marlène Dufresne
- Institut National de la Santé et de la Recherche Médicale U. 531, Institut Louis Bugnard, Centre Hospitalier Universitaire Rangueil, France
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Abstract
Dermatologists may also encounter patients presenting with skin lesions that reflect an underlying endocrine disorder not commonly seen in daily practice. Some of these endocrine disorders include glucagonoma, neurofibromatosis type 1, McCune-Albright syndrome, multiple endocrine neoplasia, the Carney complex, carcinoid tumors, and mastocytosis. The clinical syndrome classically associated with glucagonoma includes necrolytic migratory erythema, weight loss, diabetes mellitus, anemia, cheilitis, venous thrombosis, and neuropsychiatric symptoms. The hallmarks of neurofibromatosis type 1 are the multiple café-au-lait spots and associated cutaneous neurofibromas. Other presenting features include freckling, peripheral neurofibromas, Lisch nodules, bone abnormalities, tumors, neurologic abnormalities and hypertension. McCune-Albright syndrome is characterized by café-au-lait spots, polyostotic fibrous dysplasia, sexual precocity, and hyperfunction of multiple endocrine glands. Multiple endocrine neoplasia type 2A is characterized by medullary thyroid cancer, pheochromocytoma, and primary parathyroid hyperplasia. In some patients with multiple endocrine neoplasia type 2A, cutaneous lichen amyloidosis may also be present. Multiple endocrine neoplasia type 2B is characterized by medullary thyroid cancer and pheochromocytoma but not hyperparathyroidism. The syndrome also includes mucosal neuromas, typically involving the lips and tongue, intestinal ganglioneuromas and a marfanoid habitus. Multiple endocrine neoplasia type 1 is an autosomal dominant predisposition to tumors of the parathyroid glands (four-gland hyperplasia), anterior pituitary, and pancreatic islet cells; hence, the mnemonic device of the "3 Ps"; multiple cutaneous lesions (angiofibromas and collagenomas) are frequent in patients with multiple endocrine neoplasia type 1. Carney complex may be viewed as a form of multiple endocrine neoplasia because affected patients often have tumors of two or more endocrine glands, including primary pigmented nodular adrenocortical disease (some with Cushing's syndrome), pituitary adenoma, testicular neoplasms, thyroid adenoma or carcinoma, and ovarian cysts. Additional unusual manifestations include psammomatous melanotic schwannoma, breast ductal adenoma, and a rare bone tumor, osteochondromyxoma. Carcinoid syndrome is the term applied to a constellation of symptoms mediated by various humoral factors elaborated by some carcinoid tumors; the major manifestations are diarrhea, flushing, bronchospasm, and cardiac valvular lesions. Mast cell diseases include all disorders of mast cell proliferation. These diseases can be limited to the skin, referred to as "cutaneous mastocytosis," or involve extracutaneous tissues, called "systemic mastocytosis." Patients present with urticaria pigmentosa, mastocytoma, or diffuse cutaneous mastocytosis. Systemic involvement may be gastronintestinal, hematologic, neurologic, and skeletal.
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Affiliation(s)
- Serge A Jabbour
- Division of Endocrinology, Diabetes and Metabolic Diseases, Thomas Jefferson University, Philadelphia, PA 19107, USA.
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O'Toole D. [Current trend: endocrine tumors of the stomach, small bowel, colon and rectum]. ACTA ACUST UNITED AC 2006; 30:276-91. [PMID: 16565662 DOI: 10.1016/s0399-8320(06)73165-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Dermot O'Toole
- Service de Gastroentérologie-Pancréatologie, Pôle des Maladies de l'Appareil Digestif, Hôpital Beaujon, 92118 Clichy Cedex.
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Dakin GF, Warner RRP, Pomp A, Salky B, Inabnet WB. Presentation, treatment, and outcome of type 1 gastric carcinoid tumors. J Surg Oncol 2006; 93:368-72. [PMID: 16550587 DOI: 10.1002/jso.20468] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND OBJECTIVES The aim of this study was to review the presentation, treatment, and outcome of patients with Type 1 gastric carcinoid tumors. METHODS A retrospective review of 1,600 carcinoid patients was analyzed to identify patients with gastric carcinoid tumors. RESULTS Eighteen patients were found to have biopsy-confirmed Type 1 gastric carcinoid tumors on upper endoscopy. Reasons for endoscopy included abdominal pain (n = 4), gastrointestinal bleeding (n = 4), surveillance for pernicious anemia (n = 8), and other (n = 2). The mean pre-treatment serum gastrin and chromogranin A levels were 1,436 ng/ml (+/-771 ng/ml) and 91.6 ng/ml (+/-68.6 ng/ml), respectively. Imaging revealed evidence of gastric carcinoid in 4 of 10 patients undergoing CT scanning and 3 of 10 patients undergoing octreotide scintigraphy. Of the 18 patients, 8 were treated medically (acidification or octreotide) and 10 were treated with surgery (laparoscopic antrectomy or partial gastrectomy). Mean gastrin levels decreased by 37.2% in the medically treated group (median follow-up 6 months), versus 94.0% in the surgically treated patients (median follow-up 5 months). Mean chromogranin A levels decreased by 56.2% in patients undergoing surgery. CONCLUSIONS Gastric antrectomy is the most efficacious treatment for Type 1 gastric carcinoid, leading to a significant reduction in serum gastrin levels and regression of carcinoid tumors.
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Affiliation(s)
- Gregory F Dakin
- Department of Surgery, Weill Medical College of Cornell University, New York, NY, USA
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Jensen RT. Consequences of long-term proton pump blockade: insights from studies of patients with gastrinomas. Basic Clin Pharmacol Toxicol 2006; 98:4-19. [PMID: 16433886 DOI: 10.1111/j.1742-7843.2006.pto_378.x] [Citation(s) in RCA: 99] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Proton pump inhibitors are being increasingly used and for longer periods of time, especially in patients with gastroesophageal reflux disease. Each of these trends has led to numerous studies and reviews of the potential risk-benefit ratio of the long-term use of proton pump inhibitors. Both long-term effects of hypergastrinaemia due to the profound acid suppression caused by proton pump inhibitors as well as the effects of hypo-/achlorhydria per se have been raised and studied. Potential areas of concern that have been raised in the long-term use of proton pump inhibitors, which could alter this risk-benefit ratio include: gastric carcinoid formation; the development of rebound acid hypersecretion when proton pump inhibitor treatment is stopped; the development of tolerance; increased oxyntic gastritis in H. pylori patients and the possibility of increasing the risk of gastric cancer; the possible stimulation of growth of non-gastric tumours due to hypergastrinaemia; and the possible effect of the hypo/achlorhydria on nutrient absorption, particularly iron and vitamin B12. Because few patients with idiopathic gastro-oesophageal reflux disease/peptic ulcer disease have been treated long-term (i.e., >10 years), there is little known to address the above areas of potential concern. Most patients with gastrinomas with Zollinger-Ellison syndrome have life-long hypergastrinaemia, require continuous proton pump inhibitors treatment and a number of studies report results of >5-10 years of tratment and follow-up. Therefore, an analysis of Zollinger-Ellison syndrome patients can provide important insights into some of the safety concerns raised above. In this paper, results from studies of Zollinger-Ellison syndrome patients and other recent studies dealing with the safety concerns above, are briefly reviewed.
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Affiliation(s)
- Robert T Jensen
- Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1804, USA.
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Borch K, Ahrén B, Ahlman H, Falkmer S, Granérus G, Grimelius L. Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg 2005; 242:64-73. [PMID: 15973103 PMCID: PMC1357706 DOI: 10.1097/01.sla.0000167862.52309.7d] [Citation(s) in RCA: 189] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To analyze tumor biology and the outcome of differentiated treatment in relation to tumor subtype in patients with gastric carcinoid. BACKGROUND Gastric carcinoids may be subdivided into ECL cell carcinoids (type 1 associated with atrophic gastritis, type 2 associated with gastrinoma, type 3 without predisposing conditions) and miscellaneous types (type 4). The biologic behavior and prognosis vary considerably in relation to type. METHODS A total of 65 patients from 24 hospitals (51 type 1, 1 type 2, 4 type 3, and 9 type 4) were included. Management recommendations were issued for newly diagnosed cases, that is, endoscopic or surgical treatment of type 1 and 2 carcinoids (including antrectomy to abolish hypergastrinemia) and radical resection for type 3 and 4 carcinoids. RESULTS Infiltration beyond the submucosa occurred in 9 of 51 type 1, 4 of 4 type 3, and 7 of 9 type 4 carcinoids. Metastases occurred in 4 of 51 type 1 (3 regional lymph nodes, 1 liver), the single type 2 (regional lymph nodes), 3 of 4 type 3 (all liver), and 7 of 9 type 4 carcinoids (all liver). Of the patients with type 1 carcinoid, 3 had no specific treatment, 40 were treated with endoscopic or surgical excision (in 10 cases combined with antrectomy), 7 underwent total gastrectomy, and 1 underwent proximal gastric resection. Radical tumor removal was not possible in 2 of 4 patients with type 3 and 7 of 9 patients with type 4 carcinoid. Five- and 10-year crude survival rates were 96.1% and 73.9% for type 1 (not different from the general population), but only 33.3% and 22.2% for type 4 carcinoids. CONCLUSION Subtyping of gastric carcinoids is helpful in the prediction of malignant potential and long-term survival and is a guide to management. Long-term survival did not differ from that of the general population regarding type 1 carcinoids but was poor regarding type 4 carcinoids.
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Affiliation(s)
- Kurt Borch
- Department of Surgery, University Hospital of Linköping, Linköping, Sweden.
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Affiliation(s)
- L Kölby
- The Lundberg Laboratory for Cancer Research at Department of Surgery, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden
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37
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Guillem P. [Gastric carcinoid tumours. Is there a place for antrectomy?]. ACTA ACUST UNITED AC 2005; 130:323-6. [PMID: 15890310 DOI: 10.1016/j.anchir.2005.03.010] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2004] [Accepted: 03/24/2005] [Indexed: 12/18/2022]
Abstract
UNLABELLED Gastric carcinoid tumours are classified in 3 types depending on whether they are sporadic (type III), or they are associated with a chronic atrophic gastritis (type I) or a multiple endocrine neoplasia type I-associated Zollinger-Ellison syndrome (type II). For type I tumours, the role of antrectomy, which aims to suppress the causative hypergastrinemia, has not been determined. AIM To determine, from literature review the role of antrectomy in the management of type I gastric carcinoid tumours. METHODS Bibliographic study searching for published observations of antrectomy for type I gastric carcinoid tumours. Data regarding postoperative evolution of gastrinemia and carcinoid tumours were collected. RESULTS Thirty-eight published cases were identified. Preoperative gastrinemia was elevated in the 32 patients in whom it was measured. It came to normal ranges in the 19 patients in whom it was postoperatively assessed. With a mean follow-up of 34 months (1 to 120), disappearance of carcinoid tumours was observed in 27 of 38 patients (71%), the 11 others having tumour recurrence or persistence. When postoperatively assessed, hyperplasia of fundic enterochromaffine-like cells persisted in 7 patients, regressed in 4 and disappeared in the 6 others. No antrectomy-related complication was reported. CONCLUSION Antrectomy can be considered as a worthwhile alternative for the treatment of gastric carcinoid tumours related to chronic atrophic gastritis and hypergastrinemia.
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Affiliation(s)
- P Guillem
- Service de chirurgie digestive, hôpital Edouard Herriot, hospices civils de Lyon, Place d'Arsonval, CHU de Lyon, 69003 Lyon, France.
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Nørsett KG, Laegreid A, Langaas M, Wörlund S, Fossmark R, Waldum HL, Sandvik AK. Molecular characterization of rat gastric mucosal response to potent acid inhibition. Physiol Genomics 2005; 22:24-32. [PMID: 15827235 DOI: 10.1152/physiolgenomics.00245.2004] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Potent acid inhibition with proton pump inhibitors (PPIs) is widely used in clinical medicine, especially for gastroesophageal reflux disease. PPIs cause profound changes in the intragastric environment with near-neutral pH and increase serum concentration of the gastric secretagogue hormone gastrin. Long-term hypergastrinemia increases mucosal thickness and enterochromaffin-like cell density in gastric corpus mucosa and results in development of gastric carcinoids in experimental animals. Our aim was to study responses to potent acid inhibition by characterizing genome-wide gene expression changes in gastric corpus mucosa in rats dosed with the PPI omeprazole. Nine rats received 400 micromol/kg omeprazole daily for 10 wk. Seven rats received vehicle only. Analysis of gastric corpus with microarrays representing 11,848 genes identified 134 genes with changed gene expression levels in omeprazole-dosed rats. Several of the identified genes were previously known to be affected by potent acid inhibition. Of the 62 genes with known functions that changed gene expression levels after PPI dosing, 27 are known to be involved in proliferation and apoptosis and immune, inflammatory, and stress responses. Our study indicates that microarray analysis can detect relevant gene expression changes in the complex gastric tissue, and that cellular processes involved in cell growth and defense responses are strongly affected by PPI dosing. Many genes are identified that were not previously known to be affected by inhibition of gastric acid secretion or that have unknown biological functions. Characterization of the roles of these genes may give new insight into molecular responses to treatment with PPIs.
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Affiliation(s)
- Kristin G Nørsett
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
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Abstract
Neuroendocrine tumors (NETs) constitute a heterogeneous group of neoplasms that originate from endocrine glands such as the pituitary, the parathyroids, and the (neuroendocrine) adrenal, as well as endocrine islets within glandular tissue (thyroid or pancreatic) and cells dispersed between exocrine cells, such as endocrine cells of the digestive (gastroenteropancreatic) and respiratory tracts. Conventionally, NETs may present with a wide variety of functional or nonfunctional endocrine syndromes and may be familial and have other associated tumors. Assessment of specific or general tumor markers offers high sensitivity in establishing the diagnosis and can also have prognostic significance. Imaging modalities include endoscopic ultrasonography, computed tomography and magnetic resonance imaging, and particularly, scintigraphy with somatostatin analogs and metaiodobenzylguanidine. Successful treatment of disseminated NETs requires a multimodal approach; radical tumor surgery may be curative but is rarely possible. Well-differentiated and slow-growing gastroenteropancreatic tumors should be treated with somatostatin analogs or alpha-interferon, with chemotherapy being reserved for poorly differentiated and progressive tumors. Therapy with radionuclides may be used for tumors exhibiting uptake to a diagnostic scan, either after surgery to eradicate microscopic residual disease or later if conventional treatment or biotherapy fails. Maintenance of the quality of life should be a priority, particularly because patients with disseminated disease may experience prolonged survival.
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Affiliation(s)
- Gregory A Kaltsas
- Department of Endocrinology, St Bartholomew's Hospital, London EC1A 7BE, United Kingdom
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Abstract
Carcinoid tumors originate from the neuroendocrine cells throughout the body and are capable of producing various peptides. Their clinical course is often indolent but can also be aggressive and resistant to therapy. We examined all aspects of carcinoid tumors including the molecular biology oncogenesis, role of angiogenesis, recent advances in imaging, and therapy. The Medline and Cancerlit databases were searched using carcinoid as the keyword. English language manuscripts were reviewed and relevant references from a total of 7741 were found. All titles were screened and all the relevant manuscripts were analyzed; we found 307 references pertinent to the history, epidemiology, clinical behavior, pathology, pathophysiology, molecular biology, radiologic imaging, supportive care of carcinoid syndrome, and results of therapeutic clinical trials. Management of patients with carcinoid tumors requires an understanding of the disease process and a multimodality approach. Introduction of long-acting somatostatin analogues has resulted in significant advances in the palliative care of patients with carcinoid syndrome. However, advanced carcinoid tumor remains incurable. Existing therapies for advanced disease have low biologic activity, high toxicity, or both. Clearly, more research is necessary in the areas of molecular biology, targeted therapy, and development of new drugs Future advances in this field need to focus on clinical and biological predictors of outcome. Early works in the area of tumor biology such as the role of p53, bcl-2, bax, MEN1, FGF TGF PDGF and VEGF expression are of interest and need to be explored further.
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Affiliation(s)
- Isac I Schnirer
- Department of Gastrointestinal Oncology and Digestive Diseases, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77005-4341, USA
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Abstract
Neuroendocrine tumours often present a diagnostic and therapeutic challenge. They can arise almost anywhere in the body, and are therefore associated with a broad range of local symptoms. The systemic manifestations of neuroendocrine tumours are also diverse, and are related to the secretion of numerous hormones and biogenic amines. In recent years, improved diagnostic techniques, increased recognition of neuroendocrine tumour subtypes, and new therapeutic modalities have enhanced clinicians' ability to detect and appropriately treat these malignancies.
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Affiliation(s)
- Matthew H Kulke
- Dana-Farber Cancer Institute and Harvard Medical School, Department of Medical Oncology, Boston, MA 0215, USA.
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Abstract
Interest in gastric carcinoid tumors has in recent time amplified considerably as the understanding of both their biological background and clinical significance has developed. The increase in identification associated with the widespread availability of upper gastrointestinal endoscopy has facilitated diagnosis. In addition concern related to the consequences of long-standing hypergastrinemia generated by the use of potent acid-suppressive medications has augmented both clinical and scientific focus on gastric neuro endocrine issues. The elucidation of the regulatory mechanisms of the progenitor cell (ECL cell) of the gastric carcinoid tumor, the refinement of a pathological grading system for ECL cell proliferation, and the availability of specific immunohistologic identification techniques have further amplified the characterization of this lesion. Although the putative malignant potential of gastric carcinoids may ultimately be of only modest concern in a background of hypergastrinemia its relationship to gastric adenocarcinoma is still enigmatic and worthy of further consideration. This review will describe the molecular interrelationship between low-acid states, gastrin, and ECL cell proliferation and will discuss the pathological classification of the distinct types of gastric carcinoid tumors. In addition, the clinical rationale of current diagnostic and therapeutic strategies will be examined, providing a logical basis for the formulation of appropriate management strategies for patient care.
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Affiliation(s)
- Irvin M Modlin
- Gastrointestinal Surgical Pathobiology Research Group, Yale University School of Medicine, New Haven, CT 06520-8062, USA.
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Devarbhavi H, Alvares JF. Polypoid gastric carcinoid tumor presenting as hematemesis with prolapse into the duodenum. Gastrointest Endosc 2003; 57:618-20. [PMID: 12665788 DOI: 10.1067/mge.2003.151] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Affiliation(s)
- Harshad Devarbhavi
- Department of Gastroenterology, St. John's Medical College Hospital, Bangalore, India
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Papadimitraki E, Bree ED, Tzardi M, Skordilis P, Kofteridis D, Tsiftsis DD. Gastric Carcinoid in a Young Woman with Systemic Lupus Erythematosus and Atrophic Autoimmune Gastritis. Scand J Gastroenterol 2003; 38:477-481. [PMID: 28443773 DOI: 10.1080/00365520310001734] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Gastric carcinoid is a rare tumour that is associated with chronic atrophic gastritis in the majority of cases. It usually occurs in the 6th or 7th decade of life and is rarely diagnosed in patients under 30 years of age. METHODS We describe a case of multiple gastric carcinoids in a 23-year-old woman with systemic lupus erythematosus and atrophic autoimmune gastritis--an association that has not been reported previously. RESULTS The combination of atrophic autoimmune gastritis and gastric carcinoid with other autoimmune disorders has rarely been reported in the English medical literature. CONCLUSION The fact that it mostly concerns (relatively) young patients may suggest a potential causative relation between those autoimmune disorders and the early development of atrophic gastritis with hypergastrinaemia, which subsequently leads to the occurrence of gastric carcinoid tumours at a young age.
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Affiliation(s)
- E Papadimitraki
- a Depts. of Surgical Oncology, Pathology, Gastroenterology and Internal Medicine University Hospital Medical School of Crete Herakleion Greece
| | - E de Bree
- a Depts. of Surgical Oncology, Pathology, Gastroenterology and Internal Medicine University Hospital Medical School of Crete Herakleion Greece
| | - M Tzardi
- a Depts. of Surgical Oncology, Pathology, Gastroenterology and Internal Medicine University Hospital Medical School of Crete Herakleion Greece
| | - P Skordilis
- a Depts. of Surgical Oncology, Pathology, Gastroenterology and Internal Medicine University Hospital Medical School of Crete Herakleion Greece
| | - D Kofteridis
- a Depts. of Surgical Oncology, Pathology, Gastroenterology and Internal Medicine University Hospital Medical School of Crete Herakleion Greece
| | - D D Tsiftsis
- a Depts. of Surgical Oncology, Pathology, Gastroenterology and Internal Medicine University Hospital Medical School of Crete Herakleion Greece
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Dolan JP, Norton JA. Neuroendocrine Tumors of the Pancreas and Gastrointestinal Tract and Carcinoid Disease. Surgery 2001. [DOI: 10.1007/978-3-642-57282-1_41] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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Ho AC, Horton KM, Fishman EK. Gastric carcinoid tumors as a consequence of chronic hypergastrinemia: spiral CT findings. Clin Imaging 2000; 24:200-3. [PMID: 11274882 DOI: 10.1016/s0899-7071(00)00199-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The development of gastric carcinoid tumors is a rare but recognized complication of prolonged, severe hypergastrinemia. We present 2 patients with elevated gastrin levels who developed gastric carcinoid tumors and the CT findings are reviewed.
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Affiliation(s)
- A C Ho
- Department of Radiology, The Johns Hopkins Medical Institution, Room 3251, 601 North Caroline Street, Baltimore, MD 21287, USA.
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47
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Dickman R, Shaklai M, Lapidot M, Okon E, Zandbank J, Fraser GM, Niv Y. Pernicious anemia, gastric carcinoid, and autoimmune thrombocytopenia in a young woman. J Clin Gastroenterol 2000; 30:299-302. [PMID: 10777192 DOI: 10.1097/00004836-200004000-00019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The association between gastric carcinoid tumors and pernicious anemia is well recognized. Such tumors occur in the presence of achlorhydria, chronic atrophic gastritis, hypergastrinemia, and enterochromaffin-like cell hyperplasia. In this case report, a 29-year-old woman with pernicious anemia and autoimmune thrombocytopenia who developed gastric carcinoid tumors of the gastric body is described. This is the second description of pernicious anemia associated with autoimmune thrombocytopenia. This association in a young woman together with the therapeutic options and decisions that were taken in the treatment of the patient are discussed.
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Affiliation(s)
- R Dickman
- Department of Gastroenterology, Rabin Medical Center, Sackler School of Medicine, Tel Aviv University, Israel
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48
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De Block CE, De Leeuw IH, Pelckmans PA, Michielsen PP, Bogers JJ, Van Marck EA, Van Gaal LF. Autoimmune hepatitis, autoimmune gastritis, and gastric carcinoid in a type 1 diabetic patient: a case report. J Diabetes Complications 2000; 14:116-20. [PMID: 10959074 DOI: 10.1016/s1056-8727(00)00059-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The history of a 45-year-old male type 1 diabetic patient is presented. At the age of 29 years, he was diagnosed to have an autoimmune hepatitis with incipient liver cirrhosis. Five years later, a successful liver/pancreas transplantation was performed. Eighteen months later, however, pancreatic insufficiency occurred due to thrombosis of the pancreatic graft. Besides these conditions, iron deficiency, pernicious anemia, and autoimmune gastritis were also diagnosed. Serum parietal cell antibodies (PCA) and intrinsic factor antibodies (AIF) were positive. At 45, this patient was found to have a gastric carcinoid tumor. The clinical importance of PCA is discussed with regard to chronic atrophic gastritis and pernicious anemia, which both predispose toward gastric carcinoid tumors. Autoimmune type 1 diabetic patients who have a high prevalence of PCA should be screened for gastric autoimmune manifestations and tumors, as the history of this patient illustrates.
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Affiliation(s)
- C E De Block
- Department of Endocrinology-Diabetology, Faculty of Medicine, University of Antwerp (UA), University Hospital Antwerp, Edegem, Belgium.
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49
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Affiliation(s)
- M H Kulke
- Department of Adult Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
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50
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Lau CF, Hui PK, Mak KL, Wong AM, Yee KS, Loo CK, Lam KM. Gastric polypoid lesions--illustrative cases and literature review. Am J Gastroenterol 1998; 93:2559-64. [PMID: 9860427 DOI: 10.1111/j.1572-0241.1998.00719.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Currently, upper gastrointestinal endoscopies are frequently performed for patients with various gastrointestinal symptoms. From time to time, lumps and bumps in the stomach are encountered on endoscopy. Four cases of gastric polypoid lesions are presented. The classification, differentiation, and management approach to these lesions are discussed. Although there is consensus that all gastric adenomatous polyps should be removed, as should gastric hyperplastic polyps that are symptomatic and/or bear dysplastic foci on forceps biopsy, controversy still exists over the management of asymptomatic gastric hyperplastic polyps that do not bear any dysplastic focus on forceps biopsies. Endoscopic ultrasonography (EUS) has a promising role in the evaluation of gastric submucosal polypoid lesions.
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Affiliation(s)
- C F Lau
- Department of Medicine, Kwong Wah Hospital, Kowloon, Hong Kong
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