美国贝勒大学医学中心Stuart J. Spechler研究组近日进行了一项内科与外科治疗难治性胃灼热的随机对照试验。2019年10月17日，国际知名医学期刊《新英格兰医学杂志》发表了这一成果。

即使采用质子泵抑制剂（PPI）进行治疗，患者依然有烧心症状，这在临床上很常见，有多种潜在原因。关于PPI难治性胃灼热的治疗方法尚未证实，但主要有抗反流药物、抗反流手术或神经调节剂等治疗方案。

研究组在退伍军人事务部胃肠科门诊收治PPI难治性胃灼热的患者，让其服用20mg奥美拉唑，每日两次，持续2周。仍持续性胃灼热的患者则接受内镜检查、食道活检等进一步检查。若发现患者有反流性胃灼热，则随机分配他们接受腹腔镜Nissen胃底折叠术（手术组）；积极的药物治疗，奥美拉唑+巴氯芬，根据症状添加地昔帕明（积极治疗组）；或对照药物进行治疗，即奥美拉唑+安慰剂（对照组）。

研究组共招募了366名患者，平均年龄48.5岁，280名为男性。但在分组前排除了288例患者：有42例在奥美拉唑治疗2周后缓解了胃灼热的症状，70例未完成试验，54例因其他原因被排除，23例患有非胃食管反流病，99例出现了功能性胃灼热。余下的78例患者接受了随机分组，其中手术组27例，积极治疗组25例，对照组26例。最终手术组的治疗成功率为67%，显著优于积极治疗组（28%）和对照组（12%）。

结果表明，对于PPI难治性胃灼热和反流性胃灼热的患者来说，手术效果优于药物治疗。

附：英文原文

Title: Randomized Trial of Medical versus Surgical Treatment for Refractory Heartburn

Author: Stuart J. Spechler, John G. Hunter, Karen M. Jones, Robert Lee, Brian R. Smith, Hiroshi Mashimo, Vivian M. Sanchez, Kerry B. Dunbar, Thai H. Pham, Uma K. Murthy, Taewan Kim, Christian S. Jackson, Jason M. Wallen, Erik C. von Rosenvinge, Jonathan P. Pearl, Loren Laine, Anthony W. Kim, Andrew M. Kaz, Roger P. Tatum, Ziad F. Gellad, Sandhya Lagoo-Deenadayalan, Joel H. Rubenstein, Amir A. Ghaferi, Wai-Kit Lo, Ronald S. Fernando, Bobby S. Chan, Shirley C. Paski, Dawn Provenzale, Donald O. Castell, David Lieberman, Rhonda F. Souza, William D. Chey, Stuart R. Warren, Anne Davis-Karim, Shelby D. Melton, Robert M. Genta, Tracey Serpi, Kousick Biswas, Grant D. Huang

Issue&Volume: 2019-10-16

Abstract: 

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. 

DOI: 10.1056/NEJMoa1811424

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1811424