Multimodality treatment for gastric carcinoid tumor with liver metastases

Carcinoid tumors are the most common neuroendocrine tumors in the gastrointestinal tract, and between 10% and 30% of these tumors are gastric in origin. Three types of gastric carcinoid tumors are recognized: type I, associated with chronic atrophic gastritis type A; type II, associated with multiple endocrine neoplasia; and type III, sporadic and the most malignant. We present a patient with an aggressive, sporadic-type gastric carcinoid that metastasized to the liver. Her symptomatic treatment included the somatostatin analog octreotide. Octreotide scintigraphy demonstrated that this tumor avidly bound the peptide. The patient's gastric carcinoid (assessed by endoscopy and endoscopic ultrasound) regressed and she underwent hepatic artery embolization for her liver metastases. After initial partial CT resolution the tumor grew, compressing the inferior vena cava. The patient underwent orthotopic liver transplant with excellent recovery, although she was subsequently found to have two small lung metastases. She has responded well to adjuvant Indium-111 octreotide receptor targeted therapy. This case highlights the therapeutic options for metastatic neuroendocrine tumors, including liver transplantation and adjuvant receptor targeted therapy.     

Gastric Carcinoid Tumors: The Biology and Therapy of an Enigmatic and Controversial Lesion

Gastric carcinoid tumors were previously believed to be* rare lesions, representing less than 2% of all carcinoid tumors and less than 1 % of all stomach neoplasms. More recent studies have demonstrated that they may constitute as much as 10–30% of carcinoid tumors. Patients with conditions associated with hypergastrinemia, such as chronic atrophic gastritis. Zollinger-Ellison syndrome with multiple endocrine neoplasia type 1 (ZES-MEN-1), and pernicious anemia, display a markedly elevated incidence of gastric carcinoid tumor formation. A classification system distinguishing three types of gastric carcinoid tumor has been proposed: 1) tumors associated with chronic atrophic gastritis, 2) tumors associated with Zollinger-Ellison syndrome, and 3) sporadic lesions. Tumors that develop in association with hypergastrinemia are usually composed of entcrochroniaffinlike (ECL) cells, in contrast to sporadic lesions that contain a variety of endocrine cell types (enterochromaffin, ECL, X), In both intact animal models such as the rat and Praomys (mastomys) natalensis and in isolated purified ECL cell preparations, gastrin has been demonstrated to exert a powerful trophic effect on ECL cells, in addition to stimulating histamine secretion. It is apparent that hypergastrinemia-associated gastric carcinoids display relatively benign biological behavior. Sporadic lesions require aggressive surgical management on diagnosis. Type I and type II (hypergastrineoiia-aasoci-ated) lesions can be managed initially by endoscopic excision of accessible tumors, followed by endoscopic surveillance. If tumors recur, antrectomy and local excision may be used to remove the source gastrin, resulting in cure in the vast majority of patients.     

胃内分泌细胞瘤的免疫组化研究

日的:对胃内分泌细胞肿瘤及瘤旁粘膜的病理生物学行为进行探讨。方法:应用10种内分泌标记及激素抗体免疫组化方法对34例胃内分泌肿瘤及瘤旁粘膜进行观察。结果:发现胃内分泌瘤可以分为两个类型。一型为伴有慢性萎缩性胃炎A型(CAG-A)24例的瘤旁粘膜内分泌细胞增生及异型增生较重;肿瘤多位于粘膜内及粘膜下层。患者多伴有高胃泌素血症及胃窦G细胞增生。另一型为伴有慢性萎缩性胃炎B型(CAG—B)或不伴有萎缩性胃炎10例的内分泌瘤瘤旁粘膜内分泌变化较轻,肿瘤侵润性强。结论:不同类型的胃内分泌肿瘤生物学行为及治疗有所不同。     

Neuroendocrine gastric carcinoma. A case report and review of current management

Neuroendocrine or carcinoid tumors of the gastrointestinal tract considered previously extremely rare, are diagnosed at present with increased frequency due to the better capacity to identify neuroendocrine system cells in normal and pathologic conditions. Occasionally, these tumors secrete a great variety of vasoactive substances, producing the carcinoid syndrome. Gastric carcinoids are classified, according to their degree of differentiation into well differentiated and poorly differentiated tumors, also called neuroendocrine carcinomas. Neuroendocrine gastric carcinomas or poorly differentiated gastric carcinoids are seen in 5-15% of all gastric carcinoids, mainly in older male patients. Generally they are large, very aggressive tumors with extensive local infiltration. Due to poor differentiation, they are not frequently associated with an endocrine syndrome. They can be located in any part of the stomach but are mainly seen in antrum. These tumors have an aggressive behavior and must be treated in a radical manner; recurrences are not uncommon. We report the case of a patient with a neuroendocrine gastric carcinoma treated with an en bloc subtotal gastrectomy and colectomy.     

Gastrointestinal carcinoid tumors: cellular biology, molecular expression and physiopathological consequences of an enigmatic neoplasia

Gastrointestinal carcinoid tumors arise from cells of the diffuse neuroendocrine system localized in the digestive trace and represent more than 70% of all carcinoid tumors in humans. The present article reviews the following topics: 1) The biological profile of these tumors (histopathology, cytokine markers, metabolic alterations, storage of neuroamines and hormonal proteins, cytodynamic behavior, and biological behavior according to embryological origin). 2) The etiological circumstances (exceptional hereditary factors, association of gastric carcinoid tumors with autoimmune gastritis, little-known exogenous factors). 3) Pathogenic aspects (persistent mitogenesis of endocrine cells associated with hypergastrinemia, inactivation of some putative tumor suppressor genes, the doubtful participation of oncogenes, autocrine action of some cellular growth-stimulating proteins). 4) The repercussions of certain physiopathological events (peritumoral desmoplastic reaction causing the "mass effect" on the digestive tube, the "kidnapping" of dietary tryptophan by tumoral cells toward an abnormal metabolic pathway; the easy metastatic dissemination coexisting with low tumoral aggressivity, and the release into the bloodstream of stored secretory products leading to "carcinoid syndrome" and some endocrine hyperfunction syndromes. Finally, it should be remembered that gastrointestinal carcinoid tumors represent only a proportion of the neoplasms classified as neuroendocrine tumors.     

Gastric neuroendocrine tumors

Gastric carcinoids are rare neuroendocrine tumors, usually classified as type I, if associated with atrophic body gastritis; type II, if associated with Zollinger-Ellison syndrome and multiple endocrine neoplasia type I, and type III, in the absence of any gastric pathology (sporadic tumors). The pathological features, as well as the prognosis of the tumor and the patient's survival strictly depend on this classification. The correct management of the patient with gastric carcinoid can only be proposed when the tumor has been classified by an accurate pathological and clinical evaluation of the patient. While the therapeutic approach in types I and II is based on a conservative strategy, including endoscopic resection, an adequate follow-up program, and the possible use of somatostatin analogues, an aggressive surgical approach is required in type III.     

A Clinical Perspective on Gastric Neuroendocrine Neoplasia

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.     

Gastric neuroendocrine carcinoma associated with chronic atrophic gastritis type A

We report a case of gastric neuroendocrine (NE) carcinoma associated with chronic atrophic gastritis type A (CAG/A) or reversed atrophic type gastritis. A 9 × 6 cm tumor was resected from the stomach to control pain in a 55-year-old Japanese woman with peritoneal dissemination and metastatic tumors of the liver and ovary. Histologically, the tumor was NE carcinoma which showed an organoid structure, but consisted of NE Cells with overt cytological atypia and frequent mitotic activity. Multiple microcarcinoids and NE cell micronests (NECMs) were also observed in the atrophic non-neoplastic mucosa of the gastric body. CEA immunoreactivity and a high Ki-67 labeling index were characteristic features of the neoplastic NE cells of the carcinoma. Although most NE tumors arising from CAG/A are typical carcinoid tumors, the present case illustrates that a high-grade NE carcinoma can develop from diverse NE cell proliferation in association with CAG/A.     

Ghrelin immunoreactive cells in gastric endocrine tumors and their relation to plasma ghrelin concentration

GOALS: Our aim was to elucidate the incidence and distribution pattern of ghrelin-immunoreactive (IR) cells in various types of human gastric endocrine tumors, and their surrounding mucosa, and relate the findings to total ghrelin concentrations in plasma. BACKGROUND: It has been demonstrated previously, that ghrelin-IR cells are present not only in normal human gastric oxyntic mucosa, but also in all types of enterochromaffinlike (ECL) cell carcinoids (ECL-CCs), and in mucosal regions affected by ECL cell hyperplasia. STUDY: Forty-eight gastric endocrine tumors were included in the study: 32 type I ECL-CCs, 3 type II, 9 type III, 1 non-ECL-CC, and 3 poorly differentiated endocrine carcinomas. The tumors were analyzed immunohistochemically with antibodies raised versus chromogranin A, synaptophysin, serotonin, somatostatin, vesicular monoamine transporter 2 and ghrelin. Total ghrelin in plasma was measured in 20 patients, using a commercial radioimmunoassay kit. RESULTS: Ghrelin-IR cells were found in all types I and II ECL-CCs but in only a few cases of the other tumors. Ghrelin-IR cells were also found among the hyperplastic endocrine cells in the mucosa surrounding types I and II, where they showed diffuse, linear, nodular and adenomatoid hyperplasia patterns. In type III ECL-CCs and poorly differentiated endocrine carcinomas, only diffuse and linear ghrelin-IR cell hyperplasia was present in the oxyntic mucosa in about half of the cases, whereas the mucosa of the non-ECL-CC did not show this feature. CONCLUSIONS: Despite the frequent occurrence of ghrelin-IR cells in both the neoplastic parenchyma and the oxyntic mucosa, plasma total ghrelin concentrations remained within the reference range and can therefore not be used as a clinical marker to identify ghrelin expressing ECL-CCs or ghrelin cell hyperplasia.     

Fundic argyrophil carcinoid tumor in a patient with sporadic-type zollinger-ellison syndrome

Summary In the Zollinger-Ellison syndrome, fundic argyrophil carcinoid tumors occur almost exclusively in the small subgroup of patients who also have multiple endocrine neoplasia type 1. In these patients, tumor development seems related to the same genetic alterations as those observed in other endocrine tumors related to multiple endocrine neoplasia type 1. We report here the second detailed case of a patient with sporadic Zollinger-Ellison syndrome who developed an argyrophil carcinoid tumor in nonatrophic fundic mucosa, suggesting that chronic hypergastrinemia may lead to fundic carcinoid development in non-genetically predisposed patients.     

Gastric carcinoid tumor in a patient with a past history of gastrointestinal stromal tumor of the stomach

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.     

Carcinoid of the ampulla of Vater

Endocrine neoplasms only rarely occur at the ampulla of Vater, comprising mostly carcinoids and malignant carcinoids, as well as few cases of poorly differentiated endocrine carcinomas (small cell carcinomas). Only 105 cases are reported in the literature, most as single case reports. For many years, the neoplasms of the disseminated neuroendocrine cell system of the gastrointestinal tract have been subsumed as 'carcinoids'. Instead, in the latest World Health Organization (WHO) classification published in 2000, it is recommended to distinguish between (i) well-differentiated endocrine tumors (carcinoids); (ii) well-differentiated endocrine carcinomas (malignant carcinoids); and (iii) poorly differentiated endocrine carcinomas (small cell carcinomas). Patients with carcinoid tumors of the ampulla of Vater are very often free of clinical and laboratory findings that belong to the carcinoid syndrome. Approximately 26% of all patients with carcinoid tumor reported in the literature had neurofibromatosis. Besides endoscopic retrograde cholangiopancreatography, endosonography, computed tomography or magnetic resonance imaging may complete the staging approach of this tumor. The Kausch-Whipple procedure or pylorus-preserving pancreaticoduodenectomy is considered the treatment of choice for ampullary, well-differentiated carcinoids >2.0 cm and for ampullary neuroendocrine carcinomas. However, it should be considered that long-term survival of patients with ampullary carcinoids is also reported after local tumor excision (5-year survival rate of 90%). The dilemma is that the differentiation of neuroendocrine tumors cannot be assessed intraoperatively in most cases. Therefore, considering that the 5-year survival rate in patients with neuroendocrine carcinomas of the ampulla of Vater is very low without radical resection, neuroendocrine tumors of the ampulla of Vater without definite histological differentiation should undergo extended surgery.     

Treatment of gastric carcinoids

Gastric carcinoid tumors are uncommon, but their percentage among all gastric malignancies has increased to 1.8%. Although they are most often discovered incidentally during endoscopy, gastric carcinoids can present with abdominal pain, bleeding, or symptoms related to the secretion of bioactive substances, most commonly histamine. Gastric carcinoids originate from the foregut and are derived from histamine-containing enterochromaffin-like (ECL) cells. Type I gastric carcinoid, the most common, exhibits slow growth and benign behavior. It occurs within the setting of chronic atrophic gastritis with achlorhydria-induced hypergastrinemia. Gastrin acts directly on ECL cells to induce hyperplasia, dysplasia, and, eventually, neoplasia. Type II gastric carcinoid, the least common type, occurs in patients with gastrinoma-associated multiple endocrine neoplasia syndrome-type 1 (MEN-1). The overall survival is related more to the underlying MEN-1 syndrome than to the gastric carcinoid. Rodents readily develop gastric carcinoid tumors in response to hypergastrinemia. However, in humans, other factors in addition to hypergastrinemia, such as pernicious anemia or MEN-1, must be present, implying that a genetic predisposition is necessary for the development of these tumors. Type III or sporadic gastric carcinoids exhibit a more malignant behavior, with overall 5-year survival rates of less than 50% and normal serum gastrin concentrations. Treatment of all types of gastric carcinoids is predicated upon accurate classification and staging. Radiolabeled somatostatin analogues are superior to conventional radiologic imaging techniques in detecting both primary and metastatic lesions. Treatment of choice for localized disease is excision, either endoscopically or surgically. Antrectomy, by eliminating the trophic effect of gastrin, can be useful for select type I carcinoids. Long-acting somatostatin analogues are excellent palliative agents.     

Management of gastric and duodenal neuroendocrine tumors

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 followup, 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.     

Risk for gastric neoplasias in patients with chronic atrophic gastritis: a critical reappraisal

Chronic atrophic gastritis (CAG) is an inflammatory condition characterized by the loss of gastric glandular structures which are replaced by connective tissue (non-metaplastic atrophy) or by glandular structures inappropriate for location (metaplastic atrophy).Epidemiological data suggest that CAG is associated with two different types of tumors:Intestinal-type gastric cancer (GC) and type Ⅰ gastric carcinoid (TⅠGC).The pathophysiological mechanisms which lead to the development of these gastric tumors are different.It is accepted that a multistep process initiating from Helicobacter pylori-related chronic inflammation of the gastric mucosa progresses to CAG,intestinal metaplasia,dysplasia and,finally,leads to the development of GC.The TⅠGC is a gastrin-dependent tumor and the chronic elevation of gastrin,which is associated with CAG,stimulates the growth of enterochromaffin-like cells with their hyperplasia leading to the development of TⅠGC.Thus,several events occur in the gastric mucosa before the development of intestinal-type GC and/or TⅠGC and these take several years.Knowledge of CAG incidence from superficial gastritis,its prevalence in different clinical settings and possible risk factors associated with the progression of this condition to gastric neoplasias are important issues.This editorial intends to provide a brief review of the main studies regarding incidence and prevalence of CAG and risk factors for the development of gastric neoplasias.     

Carcinogenic hypergastrinemia: signet-ring cell carcinoma in a patient with multiple endocrine neoplasia type 1 with Zollinger-Ellison's syndrome

CONTEXT: Gastric neuroendocrine tumors are rare neoplasms that originate from gastric enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin and its derivates have been reported to regulate epithelial cell proliferation, migration, and differentiation. Mutations in the epithelial cadherin (E-cadherin) gene have been shown to be associated with the occurrence of diffuse gastric carcinomas in affected families. OBJECTIVE: In this study we investigated the histopathological and molecular findings in the gastrointestinal wall of a patient with multiple endocrine neoplasia type 1 with malignant duodenal gastrinoma and multiple gastric ECL cell tumors, who additionally developed a signet-ring cell carcinoma of the stomach. DESIGN AND PATIENT: Biopsies from the gastrointestinal tract of a patient with multiple endocrine neoplasia type 1 were immunostained for vesicular monoamine transporter-2 and E-cadherin. Nonamidated gastrin products were measured in the serum of the patient using antibodies that react with progastrin, Gly-extended, and amidated gastrins. Genetic analyses were performed to exclude germ-line mutations within the E-cadherin gene. RESULTS: Immunohistochemical studies of gastric ECL cell tumors showed a largely diminished E-cadherin expression in comparison to gastric surface mucosa cells and a loss of E-cadherin expression in the cells of the signet-ring carcinoma. Detailed biochemical measurements revealed progastrin concentrations that were approximately 20%, and Gly-gastrin concentrations that were approximately 10% the amidated gastrin concentrations in plasma. Molecular analyses revealed no E-cadherin germ-line mutation. CONCLUSION: Our immunohistochemical studies might suggest that the gastrinoma-associated excessive progastrin tissue concentrations led to diminished expression of E-cadherin within the gastric mucosa and promoted tumor development of a signet-ring cell carcinoma.     

BRAF and endocrine tumors: mutations are frequent in papillary thyroid carcinomas, rare in endocrine tumors of the gastrointestinal tract and not detected in other endocrine tumors

The tumorigenesis of sporadic endocrine tumors is still not fully understood. Activating point mutations of the serine/threonine kinase gene BRAF located on 7q34 are found in a wide range of malignancies, with the highest frequency (66%) occurring in malignant melanomas. Melanomas are tumors of neural-crest-derived cells as are medullary thyroid carcinomas, pheochromocytomas and paragangliomas. BRAF has not been examined in endocrine tumors of the diffuse neuroendocrine system or of neural-crest-derived cells. We examined 130 endocrine tumors of the pancreas, parathyroid gland, adrenal medulla, paraganglia, lung and gastrointestinal tract as well as follicular and c-cell-derived thyroid tumors. We found a high rate of V559E mutations in papillary thyroid carcinomas (47%), one V599E mutation in a well-differentiated gastric endocrine carcinoma (malignant carcinoid), but no activating BRAF mutations in all other endocrine tumors examined. These results point towards different pathways in tumorigenesis of endocrine tumors of various localizations and only rare involvement of the MAP kinase (MAPK) pathway in a subset of malignant neuroendocrine tumors.     

Somatostatin analogs for gastric carcinoids:for many,but not all

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 GC1 s 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.     

The effect of Zollinger-Ellison syndrome and omeprazole therapy on gastric oxyntic endocrine cells.

In 1983, all trials of omeprazole in humans were stopped because rats given the drug developed gastric endocrine cell hyperplasia and carcinoid tumors. Further studies in rats showed that drug-induced achlorhydria and hypergastrinemia caused these changes. Because data in humans are limited, we compared the numbers of endocrine cells, as judged by silver staining (argyrophilia), in the gastric mucosa of patients with Zollinger-Ellison syndrome, who are hypergastrinemic, and in normogastrinemic patients with idiopathic acid-peptic diseases. In addition, we analyzed the number of gastric endocrine cells in patients with Zollinger-Ellison syndrome given omeprazole for up to 3 years. Patients with Zollinger-Ellison syndrome had 15.7% +/- 6.9% argyrophil cells in biopsies of gastric oxyntic mucosa, and patients with idiopathic acid-peptic disease had 7.8% +/- 2.3% (P less than 0.01). In patients with Zollinger-Ellison syndrome, the percentage of argyrophil cells was not related to serum gastrin concentration, duration of symptoms, time since diagnosis, basal or maximal acid output, extent of tumor, or age. There was a tendency for patients with multiple endocrine neoplasia type 1 to have a greater percent of argyrophil cells than patients with sporadic Zollinger-Ellison syndrome. Considering the biopsies from both normogastrinemic and hypergastrinemic patients, there was a significant relationship between the percentage of argyrophil cells and the serum concentration of gastrin (P less than 0.01). Patients with Zollinger-Ellison syndrome given omeprazole for up to 3 years developed no significant changes in percentage of argyrophil cells, no carcinoid tumors, and no changes in serum concentrations of gastrin. The present study shows that patients with Zollinger-Ellison syndrome have an increased percentage of argyrophil cells in oxyntic mucosa and that omeprazole does not increase this percentage. In periods of up to 3 years, omeprazole had no effects on gastric morphology in patients with Zollinger-Ellison syndrome.     

Gastric Carcinoid Tumor Associated with Graves' Disease: A Case Report

Abstract: We report a patient with hyperthyroid Graves' disease associated with type A gastritis and a gastric carcinoid tumor. A 45-year-old female visited our hospital because of exophthalmos, and hyperthyroidism was found. TSH receptor antibody and anti-parietal cell antibody were positive in the patient's serum. An endoscopic examination revealed type A gastritis and a gastric carcinoid tumor. The diagnosis of type A gastritis was determined histologically. The gastric carcinoid tumor was solitary and small (less than 5 mm in diameter), and was removed by biopsy. The patient's hypergastrinemia continued after the thyroid function was normalized by treatment with methimazole. Endoscopic surveillance for metachronous gastric carcinoid tumors will therefore be required. The association of Graves' disease, type A gastritis and a gastric carcinoid tumor is discussed.