Bardhan K D, Nayyar A K, Royston C
Rotherham General Hospitals NHS Trust, Moorgate Road, Rotherham, South Yorkshire S60 2UD, UK.
Dig Liver Dis. 2003 Aug;35(8):529-36. doi: 10.1016/s1590-8658(03)00269-x.
This prospective cohort observational study, set in a district hospital, presents our experience (1976-1993) of duodenal ulcer refractory to histamine H2 receptor antagonists (defined as not healed after 3 months' treatment) and comments on onset, outcome and spontaneous decline.
Patients were treated mainly with cimetidine, the dose being titrated (up to 3.2 g daily) according to response, and followed by serial check endoscopy and clinical assessment.
A total of 782 of the 4032 duodenal ulcer patients seen (19%) were refractory; the incidence declined over time: 1976-1978: 124/379 (33%); 1979-1983: 390/1240 (31%); 1984-1988: 190/1295 (15%); 1989-1993: 78/1118 (7%). A total of 344 were refractory for the first time on their first healing course and 174 on their second. Healing was achieved in two-thirds after a mean of 7 months' treatment with cimetidine 1 g; treatment for 12-18 months with higher doses was needed in the remainder. Relapse occurred in up to three-quarters of patients despite maintenance cimetidine up to 3 g daily. Eventually 47 patients were operated upon but good results (i.e., no ulcer, no symptoms) were achieved in only 11.
Refractoriness was common until recently. Its incidence has declined dramatically, the fall preceding the newer more powerful treatment with proton pump inhibitors and with Helicobacter pylori eradication. We suggest this phenomenon is a modern example of a spontaneous change in the natural history of the disease.
这项前瞻性队列观察研究在一家地区医院开展，呈现了我们（1976 - 1993年）对组胺H2受体拮抗剂治疗无效的十二指肠溃疡（定义为治疗3个月后未愈合）的经验，并对其发病、结局及自然缓解情况进行了评论。
患者主要接受西咪替丁治疗，剂量根据反应进行滴定（每日最高达3.2 g），随后进行系列内镜检查和临床评估。
在4032例十二指肠溃疡患者中，共有782例（19%）治疗无效；其发病率随时间下降：1976 - 1978年：124/379（33%）；1979 - 1983年：390/1240（31%）；1984 - 1988年：190/1295（15%）；1989 - 1993年：78/1118（7%）。共有344例在首次愈合疗程中首次出现治疗无效，174例在第二次愈合疗程中出现。平均用1 g西咪替丁治疗7个月后，三分之二的患者实现愈合；其余患者需要用更高剂量治疗12 - 18个月。尽管维持每日最高3 g的西咪替丁治疗，仍有多达四分之三的患者复发。最终47例患者接受了手术，但仅有11例取得了良好效果（即无溃疡、无症状）。
直到最近，治疗无效仍很常见。其发病率已大幅下降，这一下降早于质子泵抑制剂和根除幽门螺杆菌等更新、更强效治疗方法的出现。我们认为这种现象是该疾病自然史中自发变化的一个现代实例。
