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Long-acting release octreotide induce complete response in type 1 gastric carcinoid tumors

#18

Introduction: Gastric endocrine tumors (GET) are increasingly recognized due to expanding indications of upper gastrointestinal endoscopy. Often silent and benign, GET may also be aggressive when sporadic and may sometimes mimic the course of gastric adenocarcinoma. Current incidence of GETs is estimated at around 8% of digestive endocrine tumors. Yearly age-adjusted incidence is around 0.2 per population of 100,000. Gastric carcinoids (ECLomas) develop from gastric enterochromaffin-like cells (ECL cells) in response to chronically elevated gastrin. Type 1 tumors (ECLomas in the course of atrophic gastritis) may occur in conditions of achlorhydria secondary to auto-immune atrophic fundic gastritis. It occurs mostly in women and they are non-functioning tumors, typically found during upper GI endoscopy performed for dyspepsia. ECLomas present frequently as multiple polyps, usually < 1 cm in diameter in the gastric fundus. Type 1 tumors are almost exclusively benign lesions with little risk of deep invasion of the gastric parietal wall. The neoplastic ECL cells become progressively dedifferentiated with an increasing number of Ki-67 immunoreactive (IR) cell nuclei. In addition, there is a substantial decrease in argynophil and IR NE cells that can be visualized by conventional methods. ECLomas secondary to hypergastrinemia should be closely followed for signs of clinical and histopathological tumor progression. Such ECLomas deserve early, active, radical surgical treatment. Traditionally, gastric carcinoid type 1 (GCA1s) are endoscopically or surgically removed, depending on the number, appearance and size of the tumors. Antrectomy, with surgical excision of the majority of the G cells, is thought to facilitate regression of these tumors by removing the source of excessive gastrin secretion; however, the long-term benefits of antrectomy still remain uncertain. Although proton pump inhibitors are effective in reducing hypergastrinemia-induced gastric acid hypersecretion in GCA2, they do not affect ECL-cell hyperplasia, and therefore their role in GCA1 is limited. Moreover, in selected cases, significant reduction of hypergastrinemia does not prevent development of ECL carcinoid, suggesting that, in addition to hypergastrinemia, other pathogenic or genetic factors may be involved. Treatment with somatostatin analogues (SSA) might impede ECL-cell hyperplasia by suppressing gastrin secretion and/or by a direct anti-proliferative effect on ECL cells. Treatment with SSAs in GCA1 leads to a substantial tumor load reduction, with a concomitant decrease of serum gastrin levels. Published data indicate an important anti-proliferative effect of SSA on ECL cells, providing clinical benefit and obviating, at least temporarily, the need for invasive therapies for GCA1. Morphometric studies demonstrated that, while antrectomy specifically decreased the volume of ECL cells versus the total volume of endocrine cells, octreotide reduces the overall endocrine cell volume. Although the number of treated patients is small, it has been suggested that SSA may exert important anti-proliferative effects either directly, by inhibiting ECL-cells proliferation, or indirectly through suppression of gastrin hypersecretion.

Aim(s): To demonstrate tumor regression in gastric enterochromaffin-like cell carcinoids treated with octreotide.

Materials and methods: We studied five patients, four women and one man, aged 32 to 64 years, with GCA1 treated with monthly long-acting release octreotide (LAR) (10 mg) for at least 6 months. Patients had serum gastrin and chromogranin A measurements performed and biopsies taken from tumors at diagnosis and at every three months following treatment. Sections were immunostained for neuroendocrine markers. The cell proliferation index Ki-67, intensity of staining before and after treatment and the degree of gastric wall invasion were also assessed.

Conference: 7th Annual ENETSConcerence (2010)

Presenting Author: Francis de Oliveira Alves

Authors: Caponero R, Francis de Oliveira Alves , Flávio Issao Sakamoto , Osmar Martins Cruz Jr. ,

Keywords: gastric carcinoid tumors type 1, octreotide LAR, ECLomas, neuroendocrine tumors,

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