Gastric neuroendocrine tumor: review and update / Tumor neuroendócrino gástrico: revisão e atualização

ABSTRACT Introduction: The frequency of gastric neuroendocrine tumors is increasing. Reasons are the popularization of endoscopy and its technical refinements. Despite this, they are still poorly understood and have complex management. Aim: Update the knowledge on gastric neuroendocrine tumor and expose the future perspectives on the diagnosis and treatment of this disease. Method: Literature review using the following databases: Medline/PubMed, Cochrane Library and SciELO. Search terms were: gastric carcinoid, gastric neuroendocrine tumor, treatment. From the selected articles, 38 were included in this review. Results: Gastric neuroendocrine tumors are classified in four clinical types. Correct identification of the clinical type and histological grade is fundamental, since treatment varies accordingly and defines survival. Conclusion: Gastric neuroendocrine tumors comprise different subtypes with distinct management and prognosis. Correct identification allows for a tailored therapy. Further studies will clarify the diseases biology and improve its treatment.

RESUMO Introdução: A frequência de tumores neuroendócrinos gástricos está aumentando. As razões são a popularização da endoscopia e seus refinamentos técnicos. Apesar disso, os gástricos ainda são pouco compreendidos e têm manejo complexo. Objetivo: Atualizar os conhecimentos nos tumores neuroendócrinos gástricos e expor as perspectivas futuras no diagnóstico e tratamento. Método: Revisão da literatura utilizando as seguintes bases de dados: Medline/PubMed, Cochrane Library e SciELO. Os descritores da busca foram: carcinóide gástrico, tumor neuroendócrino gástrico, tratamento. Dos artigos selecionados, 38 foram incluídos nesta revisão. Resultados: Tumores neuroendócrinos gástricos são classificados em quatro tipos clínicos. A identificação correta do tipo clínico e grau histológico é fundamental, pois a conduta é variável e define a sobrevida. Conclusão: Tumor neuroendócrino gástrico possui diferentes subtipos com tratamento e prognóstico distintos. A identificação correta destes e seu entendimento permite o tratamento individualizado. Estudos futuros ajudarão a esclarecer a biologia desta doença e melhorar o tratamento.

Ghrelin and pre-proghrelin immunoreactive cells in gastric neuroendocrine tumors associated with atrophic body gastritis / Grelina e pré-progrelina em tumores neuroendócrinos do estômago associados à gastrite atrófica do corpo

INTRODUCTION: Ghrelin is a 28 amino acid peptide secreted mainly by endocrine cells present in the gastric mucosa and acknowledged as an endogenous releaser of growth hormone. The immunohistochemical expression of ghrelin has been described in neuroendocrine tumors, and it is believed that may exert modulating action related to the growth of these tumors. OBJECTIVE: To study the presence of ghrelin and preproghrelin immunoreactive cells in gastric neuroendocrine tumors associated with atrophic body gastritis. METHODS: Endoscopic biopsies from 15 patients with neuroendocrine tumor of the gastric mucosa associated with atrophic body gastritis were performed for immunohistochemistry, and specific chromogranin, ghrelin and preproghrelin antibodies were applied. The immunohistochemical expression was assessed in tumor cells and endocrine micronodular hyperplasia present in mucosa adjacent to the tumor, and it was classified in relation to the number of stained cells. RESULTS: Chromogranin was positive in 14 out of 15 tumors. Ghrelin and preproghrelin immunoreactive cells were detected in 11 (73 percent) and 13 (87 percent) tumors, respectively. There was a significant correlation between the immunohistochemical results of both antigen expressions (kappa = 81 percent). Ghrelin and preproghrelin expression was detected in hyperplastic nodules present in the mucosa adjacent to the tumor in seven and eight cases, respectively. There was no correlation between these results and those observed in neoplastic cells. CONCLUSION: Ghrelin and preproghrelin immunoreactive cells may be found in variable number in Type I neuroendocrine gastric tumors and in hyperplastic nodules associated with these tumors. However, it remains unclear what role these peptides play on the development of these tumors.

INTRODUÇÃO: Grelina é um peptídeo de 28 aminoácidos, reconhecido como liberador endógeno do hormônio do crescimento, sendo secretado principalmente por células endócrinas da mucosa gástrica. A expressão imuno-histoquímica da grelina tem sido descrita em tumores neuroendócrinos, acreditando-se que possa ter ação moduladora relacionada com o crescimento desses tumores. OBJETIVO: Estudar a presença de células imunorreativas a grelina e pré-progrelina em tumores neuroendócrinos gástricos associados à gastrite crônica atrófica do corpo. MÉTODOS: Biópsias endoscópicas de 15 pacientes portadores de tumor neuroendócrino da mucosa gástrica, associados à gastrite crônica atrófica do corpo, foram obtidas para as colorações imuno-histoquímicas, utilizando-se anticorpos contra cromogranina, grelina e pré-progrelina. A expressão imuno-histoquímica foi avaliada nas células tumorais e na hiperplasia endócrina micronodular presente na mucosa adjacente ao tumor e classificada em relação ao número de células coradas. RESULTADOS: A cromogranina foi positiva em 14 dos 15 tumores. Células imunorreativas à grelina foram detectadas em 11 (73 por cento) tumores e à pré-progrelina em 13 (87 por cento), ocorrendo excelente concordância (kappa = 81 por cento) entre os resultados imuno-histoquímicos dos dois antígenos. A expressão de grelina e pré-progrelina foi detectada em nódulos hiperplásicos presentes na mucosa adjacente ao tumor em sete e oito casos, respectivamente, não ocorrendo concordância entre esses resultados e aqueles observados nas células neoplásicas. CONCLUSÃO: Células imunorreativas a pré-progrelina e grelina podem ser encontradas em número variável nos tumores neuroendócrinos tipo I do estômago e nas lesões hiperplásicas associadas a esses tumores. Entretanto, permanece obscuro o papel desses peptídeos em relação ao desenvolvimento desses tumores.

Helicobacter pylori-induced carcinoids in glandular stomach of Mongolian gerbils / 中华微生物学和免疫学杂志

Objective To investigate the roles of infection of Helicobacter priori (Hp) and effects of Hp eradication in the development of gastric carcinoids in Mongolian gerbils. Methods A total of 100 an-imals were divided into seven groups: A, B without Hp were sacrificed after 50 and 100 weeks as controls, Hp was inoculated into group C, D, E, F, G. Group F and G received eradication of Hp after 75 weeks and 50 weeks, respectively. Results In control group A and B, no hyperplasia/dysplasia and carcinoids were ob-served. In Hp-infected groups (C, D, E,), Anti-Hp antibodies and serum gastrin levels significantly in-creased at 50 week,75 weeks and 100 weeks, and the incidences of hyperplasia/dysplasia and carcinoids were 27.8% (5/18), 31.2% (5/16), 58.3% (14/24) and 16.7% (3/18), 31.2% (5/16), 62.5% (15/24), respectively, and significantly higher than each control group(P< 0.01). The areas of carcinoids increased accordingly over the time(P < 0.01). After eradication of Hp in group F at 75 weeks and in group G at 50 weeks, values for anti-Hp IgG titer, gastrin levels decreased gradually. The frequencies of hyperpla-sia/dysplasiaand and carcinoids were 25.0% (4/16), 15.4% (2/13) and 37.5% (6/16), 23.1% (3/13), respectively. The incidences of hyperplasia/dysplasia and carcinoids in earlier Hp-eredicated group G were significantly lower than non-eradicated group E (P < 0.001). The areas of carcinoids also marked re-duced compared with non-eradicated group E(P <0.001). There were significant correlations between anti-Hp antibodies and serum gastrin levels(P <0.005), and between serum gastrin levels and carcinoids(P <0.001). Conclusion These results suggested that Hp infection plays a critical role in development of gas-tric carcinoids and eradication of Hp might be effective in preventing development of Hp-related gastric carci-noids in Mongolian gerbils.

A Case of Multiple Gastric Carcinoid in a Woman with Systemic Lupus Erythematosus / 대한류마티스학회지

Gastric carcinoid tumor is a rare neoplasm and it accounts for only 0.3% of all the gastric neoplasms. Gastric carcinoid tumor has high incidence in patients who are aged between 50 and 70 years, and it usually develops over a long period of time. Type I gastric carcinoid tumors are associated with autoimmune atrophic gastritis and pernicious anemia, and there are a few cases of gastric carcinoids in patients with other autoimmune diseases like Sjogren's syndrome and autoimmune thyroiditis. Here, we report on a case of recurrent type I gastric carcinoid tumors in a 42-years old woman who suffered with systemic lupus erythematosus.

The Clinicopathologic Characteristics of Patients with Gastric Carcinoid Tumor

PURPOSE: We wanted to analyze the clinicopathologic characteristics of patients with gastric carcinoid tumor, which is a rare gastric tumor (less than 2% of all gastric tumors). MATERIALS AND METHODS: We reviewed all the carcinoid patients who were treated from 1996 to 2006. The clinicopathologic characteristics, the treatment modalities and the survival rates were retrospectively analysed. RESULTS: There were 8 type I patients and 10 type III patients, but there were no type II patients. The mean age of onset for type I was 47.75 years and that for type III was 57.90 years. More type III patients were female, but the gender ratio of type I patients was equal at a ratio of 1:1. There were 4 cases of solitary tumor, which were all T1 except for one case, and there was neither distant metastasis nor lymph node involvement for the type T1 cases. In the 13 patients who had no metastasis, 5 underwent endoscopic mucosal resection and 8 underwent surgery, and their combined 5 year survival rate was 92.3%. For the 5 cases who had metastastses, their mean survival was 22 months and especially, 3 of them underwent palliative surgery and their median survival were 24 months (95%, +/-6.52). CONCLUSION: Higher incidence of type III gastric carcinoid tumor and less multiplicity in type I gastric tumor were identified in our study compared with previous reports. For the type III cases, there were some noteable differences compared with the Western country's survival rate for the patients who underwent palliative surgery, so physicians must pay close attention to the definite clinicopathologic characteristics of gastric carcinoid patients.

Operative Treatment of Gastric Carcinoid Tumor Presenting as Multiple Polyps: A Case Report

Gastric carcinoid tumor is a neoplasm that arises from enterochromaffine-like (ECL) cells in the gastric fundus. It is a rare disease that comprises less than 2% of all gastric neoplasms; however its incidence has been recently increasing. We experienced one case of gastric carcinoid tumor that was revealed to be multiple polypoid lesions. A 29-year-old female patient visited a hospital three years ago due to syncope. The blood hemoglobin was measured as 6.0 g/dl. Gastroscopy revealed multiple polypoid lesions with bleeding; therefore endoscopic clipping was performed. The polyps were diagnosed as carcinoid tumor via endoscopic biopsy. She was transferred to our hospital because of persistent iron deficiency anemia that was caused by bleeding at the gastric polyps. Gastroscopy revealed more than twenty various-sized polypoid lesions from the mid-body to the antrum. The blood hemoglobin level was 9.0g/dl. Total gastrectomy was performed under the diagnosis of gastric carcinoid tumor with bleeding. All of the gastric polyps were diagnosed as carcinoid tumors, and any metastasis to the regional lymph nodes was not found. Eighteen months after operation, the blood hemoglobin was increased to 12.8g/dl with no evidence of recurrence. Surgical resection should be considered for treating gastric carcinoid tumor with continuous bleeding.

A case of a minute gastric carcinoid tumor with regional lymph node metastasis that was misdiagnosed as an intraabdominal mass / 대한내과학회지

Gastric carcinoid tumors have been regarded as rare neoplasms, accounting for just 0.3% of all gastric tumors and fewer than 2% of all carcinoid tumors. Recently, there has been an increase in the number of reported studies of gastric carcinoid tumors with the widespread use of gastroscopy and improvements in immunohistochemical methods. Gastric carcinoid tumors are classified into three types. For type III gastric carcinoids not associated with hypergastrinemia, which tend to be larger and demonstrate a biologically more aggressive behavior with metastasis, and also for sporadic lesions, excision with regional lymph node clearance has been recommended. Tumors that are less than 1cm in size are called minute carcinoids, which seldom give rise to regional lymph node metastasis, except in rare cases. We report here a rare case of a minute gastric carcinoid tumor with regional lymph node metastasis that was misdiagnosed as an intraabdominal mass in a 42-year-old woman. Furthermore, we review the available literature on this entity.

Composite Tumor of Gastric Adenoma with Carcinoid Tumor / 대한소화기내시경학회지

A gastric carcinoid is a rare disease that accounts for only 0.3% of all primary gastric tumors. It can be multiple or occur with other types of tumor. However, there has been a recent increase in incidence. While carcinoids of the appendix and rectum are accompanied by adenoma or adenocarcinoma, a gastric carcinoid rarely occurs with an adenocarcinoma, particularly with a gastric adenoma. We encountered a case of a gastric adenoma and carcinoid mixed as a composite tumor, which became a lesion. The lesion resembled a type IIc early gastric cancer at the endoscopic examination and was removed by an endoscopic mucosal resection. We report a composite tumor of the gastric antrum composed of areas of adenoma and carcinoid, with an analysis of the histological components by immunohistochemical staining. Microscopically, the lesion was composed of a gastric adenoma and carcinoid as a composite tumor.

A Case of Multiple Pedunculated Polypoid Gastric Carcinoids / 대한소화기내시경학회지

Gastric carcinoids usually appear as a single polypoid tumor or yellowish rounded submucosal tumor in the fundus or body of the stomach. Multiple gastric carcinoids are associated with pernicious anemia, chronic atrophic gastritis and Zollinger-Ellison syndrome. These are believed to be due to hypergastrinemia. In Korea, carcinoids usually appear as single round-based submucosal tumor or sessile polyps. Multiple pedunculated polypoid carcinoids were rarely reported. A 27-year old woman was admitted to our hospital due to melena. The endoscopy revealed multiple pedunculated polypoid lesions in the fundus and body, predominantly in Yamada type III and IV. The histopathologic examination revealed the diagnosis of gastric carcinoid tumors. Serum fasting gastrin level was normal. We report a case of multiple pedunculated polypoid gastric carcinoids without atrophic gastritis or hypergastrinemia with a review of relevant literatures.

A Case of Gastric Carcinoid Tumor Accompanied with Bleeding / 대한소화기내시경학회지

Gastric carcinoid tumor is a rare neoplasm that occupies less than 1% of total gastric tumor. Especially, gastric carcinoid tumor with hemorrhage has been very rare. A sixty-three-year old male patient was admitted to the hospital because of hematemesis and melena. On the endoscopic examination, a 2 cm-long polypoid mass with central ulcer and hemorrhagic erosions was seen on the anterior wall of the mid-body without active bleeding. Endoscopic ultrasonography revealed that the lesion was limited to submucosa without evidence of metastasis to adjacent lymph node. We experienced a case of gastric carcinoid tumor accompanied with upper gastrointestinal bleeding. The patient underwent extended wedge resection and omentectomy under the diagnosis of type 3 carcinoid tumor. This tentative diagnosis was based on clinical and pathological findings. We report a case of gastric carcinoid with bleeding that is probably type 3.

Endoscopic features of gastric carcinoid tumors / 中华消化内镜杂志

Objective To investigate the endoscopic feat ures and endoscopical treatment of gastric carcinoid tumors.Methods The clinical and endoscopic materials of 18 patients w ith gastric carcinoid tumors was retrospectively reviewed.Results Five of the 18 patients were benign and 13 were maligna nt. Benign gastric carcinoid tumors were found by biopsy at endoscopy ,and were resected by endoscopic mucosal resection(EMR).Their endoscopic appearance was mu ltiple polypoid masses. 13 malignant patients were confirmed by surgery. Their e ndoscopic appearance was ulcerating and infiltrating lesions.Conclusion Gastroscopy remains to be valuable to set correct di agnosis of gastric carcinoid tumors. EMR may be the first choice for benign gast ric carcinoid tumors.

A Case with Gastric Carcinoid Tumor Removed by Endoscopical Procedure / 대한소화기내시경학회지

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 l0-30% of carcinoid tumors. We recently experienced a 35-years old businessman with gastric carcinoid tumor who camplained of postprandial epigastric discomfort. Gastrofiberscope showed protruding mass with central depression and erasion which was located on greater curvature of lower body and its size was 1 x 1 cm. Gastroendoscopic biopsy was per formed. It was identified to carcinoid tumor(Argyrophilic tumor). EUS(endoscopic ultrasonography) revealed that the lesion was limited to submucosa without evidence of any metastasis to adjacent lymph node. The carcinoid tumor was successfully removed by endoscopic polypectomy. Gastrofiberscope and EUS 9months after polypectomy showed that the lesion was nearly normal mucosa without submucosal thickening.

A Case of Gastric Carcinoid Tumor Simulating Early Gastric Cancer / 대한소화기내시경학회지

The endoscopic diagnosis of gastric carcinoid has been considered difficult. Reported cases of this tumor diagnosed by endoscopic examination are rare. And the gastric carcinoid with massive upper gastrointestinal bleeding is a rare disease entity. We experienced a case of gastric carcinoid admitted to the hospital because of hematemesis, melena and syncope. And it was diagnosed by endoscopic biopsy, although it resembled type IIa+IIc early gastric cancer at endoscopic examination. To our knowledge, this is the first case report of gastric carcinoid tumor mimicking early gastric cancer. So we report this case with a review of relevant literatures.