Tatsuguchi Atsushi, Hoshino Shintaro, Kawami Noriyuki, Gudis Katya, Nomura Tsutomu, Shimizu Akira, Iwakiri Katsuhiko
Department of Gastroenterology Nippon Medical School, Tokyo, Japan; Department of Analytic Human Pathology, Nippon Medical School, Graduate School of Medicine Tokyo, Japan.
Department of Gastroenterology Nippon Medical School, Tokyo, Japan.
Pathol Res Pract. 2020 Oct;216(10):153113. doi: 10.1016/j.prp.2020.153113. Epub 2020 Jul 13.
Proton pump inhibitor (PPI) therapy causes hypergastrinemia, which could promote the development and progression of neuroendocrine tumors (NETs). Concerns have been raised about the safety of long-term PPI use due to a possible increased risk of NETs. This study aimed to investigate the association between hypergastrinemia and the risk of NETs. Twenty outpatients presenting with serum gastrin levels greater than 400 pg/mL after long-term PPI treatment were registered in this study. Immunohistochemical analyses for chromogranin A (CgA), Ki67, gastrin and CCK/B gastrin receptor (CCKBR) were performed, and positive cell numbers were counted. There were no NET or gastric epithelial neoplasia cases observed among any of the 20 patients examined throughout the PPI treatment period. Histologically, ECL cell hyperplasia were shown in all patients. However, no relationship was found between serum gastrin levels and the number of CgA positive ECL cells. There was also no relationship between serum gastrin levels and the proportion of Ki67 positive cells or the density of CCKBR positive cells. The data indicate no relationship may exist between NETs and hypergastrinemia secondary to PPI treatment in patients having no, or mild, atrophic gastritis.
质子泵抑制剂（PPI）治疗会导致高胃泌素血症，这可能会促进神经内分泌肿瘤（NETs）的发生和发展。由于NETs风险可能增加，长期使用PPI的安全性受到了关注。本研究旨在调查高胃泌素血症与NETs风险之间的关联。本研究纳入了20例长期接受PPI治疗后血清胃泌素水平高于400 pg/mL的门诊患者。对嗜铬粒蛋白A（CgA）、Ki67、胃泌素和CCK/B胃泌素受体（CCKBR）进行免疫组织化学分析，并对阳性细胞数进行计数。在整个PPI治疗期间检查的20例患者中，未观察到NET或胃上皮肿瘤病例。组织学上，所有患者均显示肠嗜铬样（ECL）细胞增生。然而，血清胃泌素水平与CgA阳性ECL细胞数量之间未发现相关性。血清胃泌素水平与Ki67阳性细胞比例或CCKBR阳性细胞密度之间也没有相关性。数据表明，在无萎缩性胃炎或轻度萎缩性胃炎的患者中，NETs与PPI治疗继发的高胃泌素血症之间可能不存在关联。
