Jensen Robert T., Ito Tetsuhide
Chief, Cell Biology Section, Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases. National Institutes of Health, Bethesda, MD 20892
Professor, Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital, International University of Health, and Welfare, 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan
Gastrinomas are neuroendocrine neoplasms (NENs), that occur primarily in the duodenum and pancreas, which ectopically secrete gastrin, resulting in the Zollinger-Ellison syndrome (ZES), which is due to marked hypersecretion of gastric acid causing severe gastro-esophageal peptic disease. ZES patients have two management problems that must be dealt with: control of the acid hypersecretion and control of the gastrinoma, which is malignant in 60-90% of cases. Most gastrinomas are sporadic, but 20-25% of patients have it as part of the Multiple Endocrine Neoplasia-type 1 syndrome (MEN1), an autosomal dominant disorder characterized by endocrine tumors/hyperplasia of multiple endocrine organs (parathyroid> pancreatic islets>pituitary>adrenal). It is important to identify those with ZES/MEN1 as their management differs from those with sporadic disease. Acid hypersecretion is now controlled medically both acutely and long term, with proton pump inhibitors (PPI) the drugs of choice. In patients with sporadic ZES, after detailed imaging with cross-sectional imaging and somatostatin receptor imaging (SRI), resection of the gastrinomas should be considered whenever possible, with cures reported in 20-45% of patients. The role of surgical resection of the gastrinomas in MEN1/ZES is controversial and it is generally recommended it be reserved for patients with tumors>1.5/2 cm because of the multiplicity of small gastrinomas resulting in very low cure rates. The diagnosis of ZES requires demonstrating fasting hypergastrinemia in the presence of inappropriate acid secretion (pH<2), however, because of the widespread use of PPIs and the lack of gastric acid testing, the diagnosis of ZES is becoming more difficult and referral to a specialty group is frequently required. Patients with advanced metastatic disease are treated as other patients with advanced NENs including with somatostatin analogues, chemotherapy, everolimus, sunitinib, liver directed therapies, and peptide radio-receptor therapy (PRRT) with radiolabeled somatostatin analogues. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.
胃泌素瘤是一种神经内分泌肿瘤（NENs），主要发生在十二指肠和胰腺，可异位分泌胃泌素，导致卓-艾综合征（ZES），这是由于胃酸大量分泌引起严重的胃食管消化性疾病。ZES患者有两个必须解决的管理问题：控制胃酸过度分泌和控制胃泌素瘤，胃泌素瘤在60%-90%的病例中是恶性的。大多数胃泌素瘤是散发性的，但20%-25%的患者将其作为多发性内分泌肿瘤1型综合征（MEN1）的一部分，MEN1是一种常染色体显性疾病，其特征是多个内分泌器官（甲状旁腺>胰岛>垂体>肾上腺）出现内分泌肿瘤/增生。识别那些患有ZES/MEN1的患者很重要，因为他们的管理方式与散发性疾病患者不同。目前，无论是急性还是长期，胃酸过度分泌都可通过药物控制，质子泵抑制剂（PPI）是首选药物。对于散发性ZES患者，在进行详细的横断面成像和生长抑素受体成像（SRI）后，应尽可能考虑切除胃泌素瘤，据报道20%-45%的患者可治愈。胃泌素瘤手术切除在MEN1/ZES中的作用存在争议，由于胃泌素瘤数量众多且治愈率极低，一般建议仅对肿瘤>1.5/2 cm的患者进行手术。ZES的诊断需要在存在不适当的酸分泌（pH<2）的情况下证明空腹高胃泌素血症，然而，由于PPI的广泛使用以及缺乏胃酸检测，ZES的诊断变得更加困难，通常需要转诊至专科小组。晚期转移性疾病患者的治疗与其他晚期NENs患者相同，包括使用生长抑素类似物、化疗、依维莫司、舒尼替尼、肝脏定向治疗以及用放射性标记的生长抑素类似物进行肽受体放射性核素治疗（PRRT）。欲全面涵盖内分泌学的所有相关领域，请访问我们的在线免费网络文本，WWW.ENDOTEXT.ORG。
