BACKGROUND Heartburn that persists despite proton-pump inhibitor (PPI) treatment is a frequent clinical problem with multiple potential causes. Treatments for PPI-refractory heartburn are of unproven efficacy and focus on controlling gastroesophageal reflux with reflux-reducing medication (e.g., baclofen) or antireflux surgery or on dampening visceral hypersensitivity with neuromodulators (e.g., desipramine). METHODS Patients who were referred to Veterans Affairs (VA) gastroenterology clinics for PPI-refractory heartburn received 20 mg of omeprazole twice daily for 2 weeks, and those with persistent heartburn underwent endoscopy, esophageal biopsy, esophageal manometry, and multichannel intraluminal impedance-pH monitoring. If patients were found to have reflux-related heartburn, we randomly assigned them to receive surgical treatment (laparoscopic Nissen fundoplication), active medical treatment (omeprazole plus baclofen, with desipramine added depending on symptoms), or control medical treatment (omeprazole plus placebo). The primary outcome was treatment success, defined as a decrease of 50% or more in the Gastroesophageal Reflux Disease (GERD)-Health Related Quality of Life score (range, 0 to 50, with higher scores indicating worse symptoms) at 1 year. RESULTS A total of 366 patients (mean age, 48.5 years; 280 men) were enrolled. Prerandomization procedures excluded 288 patients: 42 had relief of their heartburn during the 2-week omeprazole trial, 70 did not complete trial procedures, 54 were excluded for other reasons, 23 had non-GERD esophageal disorders, and 99 had functional heartburn (not due to GERD or other histopathologic, motility, or structural abnormality). The remaining 78 patients underwent randomization. The incidence of treatment success with surgery (18 of 27 patients, 67%) was significantly superior to that with active medical treatment (7 of 25 patients, 28%; P = 0.007) or control medical treatment (3 of 26 patients, 12%; P<0.001). The difference in the incidence of treatment success between the active medical group and the control medical group was 16 percentage points (95% confidence interval, -5 to 38; P = 0.17). CONCLUSIONS Among patients referred to VA gastroenterology clinics for PPI-refractory heartburn, systematic workup revealed truly PPI-refractory and reflux-related heartburn in a minority of patients. For that highly selected subgroup, surgery was superior to medical treatment. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT01265550.).

中文翻译：

---

难治性胃灼热的药物治疗与手术治疗的随机试验。

背景技术尽管进行质子泵抑制剂（PPI）治疗，仍会持续存在烧心，这是一个常见的临床问题，可能有多种潜在原因。PPI难治性胃灼热的疗效尚未得到证实，其重点在于通过减少反流的药物（例如巴氯芬）或抗反流手术控制胃食管反流，或通过神经调节剂（例如地昔帕明）抑制内脏超敏反应。方法转诊至退伍军人事务（VA）肠胃病门诊进行PPI难治性烧心的患者，每天两次接受20 mg奥美拉唑，持续2周，对持续烧心的患者进行内窥镜检查，食管活检，食管测压和多通道腔内阻抗-pH监测。如果发现患者有反流相关的胃灼热，我们随机分配他们接受手术治疗（腹腔镜Nissen胃底折叠术），积极的药物治疗（奥美拉唑加巴氯芬，根据症状加用地西拉明）或对照药物治疗（奥美拉唑加安慰剂）。主要结果是治疗成功，定义为1年时胃食管反流疾病（GERD）-健康相关的生活质量评分（范围为0到50，评分越高表示症状越差）降低50％或更多。结果共纳入366例患者（平均年龄48.5岁； 280例男性）。随机化前的程序排除了288例患者：在为期2周的奥美拉唑试验中，有42例缓解了烧心； 70例未完成试验程序； 54例因其他原因而被排除； 23例患有非GERD食管疾病；99例患有功能性烧心（不是由于GERD或其他组织病理学，运动或结构异常）。其余78例患者接受了随机分组。手术治疗成功的发生率（27例中的18例，占67％）明显优于主动药物治疗（25例中的7例，占28％； P = 0.007）或对照药物治疗（26例中的3例，占12％）。 ； P <0.001）。活跃医疗组与对照组的治疗成功率之差为16个百分点（95％置信区间，-5至38； P = 0.17）。结论在转诊至VA肠胃科门诊的PPI难治性胃灼热患者中，系统检查显示少数患者确实患有PPI难治性和反流相关的胃灼热。对于该高度选择的子组，手术优于药物治疗。（由退伍军人事务部合作研究计划部资助； ClinicalTrials.gov编号，NCT01265550。）。