Waldum Helge L, Sørdal Øystein, Fossmark Reidar
a Department of Clinical and Molecular Medicine, Faculty of Medicine , Norwegian University of Science and Technology , Trondheim , Norway.
b Department of Gastroenterology and Hepatology , St. Olav´s University Hospital , Trondheim , Norway.
Scand J Gastroenterol. 2018 Jun;53(6):639-642. doi: 10.1080/00365521.2018.1450442. Epub 2018 May 31.
Recently, two epidemiological studies showed that long-term treatment with proton pump inhibitors (PPIs) increased the risk of gastric cancer. It is well known that hypergastrinemia predisposes to gastric neoplasia in animals as well as man. Recently a study showed that hypergastrinemic patients had an increased risk of gastric cancer when followed for about 25 years. It is likely that hypergastrinemia is the pathogenic factor for gastric carcinogenesis due to PPI. PPI are the only group of drugs that causes long-term hypergastrinemia in the doses used in a clinical setting. Due to the likely carcinogenic effect, PPIs should be used carefully. Moreover, since the carcinogenic effect of Helicobacter pylori (Hp) infection also may be mediated by an increase in gastrin, Hp should be eradicated whenever treatment with PPI is initiated. In peptic ulcer disease Hp eradication is the treatment of choice. Gastro-oesophageal reflux disease (GERD) is the most prevalent condition leading to long-term use of inhibitors of gastric acid secretion. Only in severe oesophagitis should the treatment be initiated by PPIs, whereas histamine-2 (H-2) blockers ought to be the initial option in most cases of GERD particularly since PPI treatment induces tolerance to H-2 blockers. In the cases where long-term PPI treatment is necessary, the dose should be adjusted by the determination of chromogranin A, which in a way reflects 24-h gastrin exposure. Finally, due to latency of neoplasia, the use of PPI must be very restricted in children and young adults.
最近，两项流行病学研究表明，长期使用质子泵抑制剂（PPI）会增加患胃癌的风险。众所周知，高胃泌素血症在动物和人类中都易引发胃肿瘤形成。最近一项研究表明，高胃泌素血症患者在随访约25年后患胃癌的风险增加。高胃泌素血症很可能是PPI导致胃癌发生的致病因素。PPI是临床使用剂量下唯一能引起长期高胃泌素血症的一类药物。鉴于可能存在的致癌作用，应谨慎使用PPI。此外，由于幽门螺杆菌（Hp）感染的致癌作用也可能由胃泌素增加介导，因此在开始使用PPI治疗时应根除Hp。在消化性溃疡疾病中，根除Hp是首选治疗方法。胃食管反流病（GERD）是导致长期使用胃酸分泌抑制剂的最常见病症。仅在严重食管炎时才应由PPI开始治疗，而在大多数GERD病例中，组胺-2（H-2）受体阻滞剂应作为初始选择，特别是因为PPI治疗会诱导对H-2受体阻滞剂产生耐受性。在需要长期使用PPI治疗的情况下，应通过测定嗜铬粒蛋白A来调整剂量，嗜铬粒蛋白A在一定程度上反映24小时胃泌素暴露情况。最后，由于肿瘤形成具有潜伏期，儿童和年轻人必须非常谨慎地使用PPI。
