Hirschowitz B I, Mohnen J, Shaw S
Department of Medicine, University of Alabama at Birmingham 35294, USA.
Aliment Pharmacol Ther. 1996 Aug;10(4):507-22. doi: 10.1046/j.1365-2036.1996.10152000.x.
Normalization of gastric secretion and cure of associated upper gastrointestinal lesions by resection of gastrinoma is possible in approximately 20% of patients with Zollinger-Ellison syndrome, leaving approximately 80% dependent on medical treatment with proton pump inhibitors for acid suppression.
Lansoprazole was given for 3-48 months (median 28 months) to 26 Zollinger-Ellison syndrome patients with peptic ulcer manifestations in all and oesophagitis in 13. Starting with 60 mg/day. the dose was individualized to lower basal acid output to less than 5 mmol/h for those with intact stomachs and less than 1 mmol/h in those who had prior gastrectomy or with oesophagitis. The patients were studied every 3 months for 1 year and then every 6 months with gastric analysis (basal and maximal acid and pepsin output) and endoscopy with biopsy for enterochromaffin-like (ECL) cells.
Lansoprazole inhibited basal acid output by 95%, pepsin output by 65% and remained effective at the initial mean (66 +/- 4.3 mg/day) or smaller doses (56 +/- 12 mg/day) at 48 months. Mucosal lesions healed and symptoms (ulcer-type pain, diarrhoea, heartburn, weight loss) resolved rapidly, usually within a few weeks. Serum gastrin and ECL cell populations, which were elevated before treatment, remained statistically unchanged but one of the three multiple endocrine neoplasia I (MEN-I) patients developed a small carcinoid. Of the three patients with metastatic gastrinoma at diagnosis one has died and one has progressed, while the third has had stable liver metastases for 26 years. Ulcer-type relapses occurred in three of the five post-gastrectomy patients, one with fatal jejunal ulcer perforation despite adequate acid suppression. No biochemical or clinical adverse events due to lansoprazole were encountered.
Lansoprazole effectively inhibits acid and pepsin secretion in Zollinger-Ellison syndrome patients without any demonstrated side-effects. Despite strict acid control, post-gastrectomy Zollinger-Ellison syndrome patients were more liable to ulcer relapse, while oesophagitis was not a marker for therapeutic difficulty.
对于约20%的佐林格-埃利森综合征患者,通过切除胃泌素瘤可实现胃酸分泌正常化并治愈相关上消化道病变,约80%的患者仍依赖质子泵抑制剂进行抑酸治疗。
对26例佐林格-埃利森综合征患者给予兰索拉唑治疗3 - 48个月(中位时间28个月),所有患者均有消化性溃疡表现,13例有食管炎。起始剂量为60毫克/天,对于胃完整的患者,将剂量个体化调整以使基础胃酸分泌量降至5毫摩尔/小时以下,对于既往接受过胃切除术或有食管炎的患者,基础胃酸分泌量降至1毫摩尔/小时以下。在1年的时间里,每3个月对患者进行一次研究,之后每6个月进行一次研究,检查项目包括胃分析(基础胃酸和最大胃酸及胃蛋白酶分泌量)以及对肠嗜铬样(ECL)细胞进行内镜活检。
兰索拉唑可使基础胃酸分泌量抑制95%,胃蛋白酶分泌量抑制65%,在48个月时,初始平均剂量(66±4.3毫克/天)或更小剂量(56±12毫克/天)时仍保持有效。黏膜病变愈合,症状(溃疡型疼痛、腹泻、烧心、体重减轻)通常在几周内迅速缓解。治疗前升高的血清胃泌素和ECL细胞数量在统计学上保持不变,但3例多发性内分泌肿瘤I型(MEN-I)患者中有1例发生了小的类癌。诊断时有转移性胃泌素瘤的3例患者中,1例死亡,1例病情进展,第3例患者肝脏转移灶稳定26年。5例胃切除术后患者中有3例发生溃疡型复发,其中1例尽管胃酸抑制充分仍发生致命的空肠溃疡穿孔。未发现因兰索拉唑导致的生化或临床不良事件。
兰索拉唑可有效抑制佐林格-埃利森综合征患者的胃酸和胃蛋白酶分泌,且未显示出任何副作用。尽管严格控制胃酸,但胃切除术后的佐林格-埃利森综合征患者更容易出现溃疡复发,而食管炎并非治疗困难的标志。