内镜抗反流黏膜切除术治疗难治性胃食管反流病一例

胃食管反流病(GERD)是指胃或十二指肠内容物反流至食管引起不适症状和/或并发症的一种疾病,以烧心和反流为典型表现。大多数糜烂性胃食管反流病患者的病变程度为轻度（洛杉矶分级 A 级患者占 50-90%）,因此,目前对GERD的治疗主要依靠质子泵抑制剂（PPI）。但仍有一部分患者PPI治疗疗效甚微。目前亚太的共识认为：在常规PPI剂量治疗至少 8 周反流症状仍无缓解的 GERD 可以定义难治性胃食管反流病（Refractory GERD,RGERD）。对于RGERD的治疗,最近内镜下出现了一种新的治疗方法——抗反流黏膜切除术(ARMS),初步报导可以有效地重塑贲门抗反流屏障,改善患者症状。在这篇报告中,我们将介绍国内首例通过抗反流黏膜切除术(ARMS)治疗难治性胃食管反流病的病例。     

基于24 h多通道食管腔内阻抗-pH监测的难治性胃食管反流病诊治进展

难治性胃食管反流病（RGERD）的发病率呈逐年上升趋势,部分患者伴有烧心或食管外症状。24 h多通道食管腔内阻抗-pH监测技术可以较全面、客观地监测反流,有助于分析导致RGERD的原因。RGERD包括非糜烂性反流病（NERD）、反流高敏感（RH）、功能性烧心（FH）及伴有食管外症状的胃食管反流病（GERD）等,酸暴露异常、非酸反流、近端反流、气体反流等反流模式是其难治性的原因,临床可依据反流模式调整PPI的种类和剂量,辅以促动力药物、抗焦虑药物和中药治疗,或考虑转诊至精神科。     

难治性胃食管反流病的诊断进展

胃食管反流病(GERD)是临床常见疾病,其中约10%～40%对质子泵抑制剂(PPI)抵抗,即难治性胃食管反流病,临床诊治较为棘手,常因缺乏灵敏度高、特异性好的诊断方法,从而贻误病情。此文对目前常应用于辅助诊断难治性胃食管反流病(RGERD)的上消化道内镜、病理诊断、食管pH监测、食管腔内多通道阻抗pH技术和食管胆红素监测等技术的研究进展作一综述,有望为临床选择诊断方法提供参考。     

胃食管反流病诊断方法的临床价值

胃食管反流病（GERD）虽可根据反流症状群、上消化道内镜检查、24h食管pH监测、质子泵抑制剂（PPI）诊断性治疗等综合分析而作出诊断,但目前尚缺乏统一、明确的诊断流程和标准,因此GERD的诊断仍存在诸多争议。本文就GERD相关诊断方法的临床价值作一综述。     

难治性胃食管反流病的处理对策

难治性胃食管反流病（refractory gastroesophageal reflux disease,RGERD）是指胃食管反流病（gastroesophageal refluxdisease,GERD）患者对于标准质子泵抑制剂（proton pump inhibitor,PPI）治疗方案产生不完全或缺乏应答,持续表现严重而频繁的反流症状,故又称为“PPI治疗失败的GERD”。     

36例难治性胃食管反流病患者阻抗-pH监测结果分析

质子泵抑制剂（PPIs）广泛用于治疗胃食管反流病（GERD）,但部分患者对抑酸治疗的疗效不佳,称为难治性GERD。目的：研究难治性GERD患者食管内反流的严重程度和反流物性质,以探讨难治性GERD症状形成的因素。方法：选取2009年1月-2010年12月华东医院确诊的难治性GERD患者36例,以PPls治疗后症状得到缓解的12例GERD患者作为对照。行24h阻抗-pH监测,根据反流物pH值和阻抗值,分析比较两组的反流情况。结果：难治性GERD组24h总反流和弱酸反流次数的中位数（第25百分位数,第75百分位数）分别为98（58,136）和62（40,86）,均显著高于对照组（P〈0．001）;两组酸反流次数均控制在较低水平,且组问差异无统计学意义（P：0．423）。难治性GERD组的气体反流和液气混合反流次数分别为48（31,61）和41（22,58）,均显著高于对照组（P〈0．001,P=0．002）;液体反流次数无明显差异（P=0．757）。结论：弱酸反流在难治性GERD患者症状形成中起一定的作用,气体反流可能加重反流症状的感知。     

多通道腔内阻抗技术在胃食管反流病诊断中的应用

24h食管pH监测有助于诊断胃食管反流病（GERD）,但其只能发现pH〈4的酸反流。多通道腔内阻抗（MII）技术通过记录食管腔内食团通过所引起的阻抗值变化,可在多种食管水平上发现胃食管反流事件而不依赖于反流物的pH值,同步联合pH监测可明确反流物的酸度、反流持续和清除时间、反流到达近端食管的高度等。本文就MII技术及其在GERD诊断中的临床应用作一综述。     

非心源性胸痛的评估和处理

非心源性胸痛（NCCP）是指复发性心绞痛样胸痛,并除外心源性因素,是常见且具有挑战性的临床问题,需经过适当的评估,鉴别症状产生的原因。胃食管反流病（GERD）、食管动力异常和功能性胸痛是NCCP的三大主要病因,其中以GERD最为常见,应首先进行评估。质子泵抑制剂（PPI）试验、上消化道内镜检查、24 h食管pH-阻抗监测是评估GERD相关胸痛的常用方法,食管高分辨率测压是鉴别食管动力异常的主要工具,而诊断功能性胸痛需要心脏检查、PPI试验、上消化道内镜检查和活检病理、食管pH-阻抗监测和食管测压结果均阴性。NCCP的治疗应根据症状产生的机制选择个体化方案,PPI和平滑肌松弛剂分别是GERD和食管动力异常相关胸痛的常用药物,也可选择内镜和外科手术治疗,神经调节剂（主要为抗抑郁药）则是功能性胸痛的治疗基石。     

24h食管pH-阻抗联合监测评估以慢性咳嗽为表现的GERD患者的反流特征

背景：腔内阻抗技术与24h食管pH监测联用,可检出各种类型的胃食管反流事件,明确反流物的性质及其酸碱性。目的：应用24h食管pH-阻抗联合监测初步探讨以慢性咳嗽为表现的胃食管反流病（GERD）患者的反流特征。方法：连续纳入胸部X线检查无明显异常、无典型胃食管反流症状的不明原因慢性咳嗽患者73例,其中内镜检查无异常发现且DH-阻抗联合监测结果符合GERD诊断者定义为慢性咳嗽GERD组,21例健康志愿者作为正常对照组,比较两组pH-阻抗联合监测结果。结果：单纯根据pH监测结果,17例患者诊断为GERD。根据pH-阻抗联合监测结果,则有26例患者诊断为GERD。慢性咳嗽GERD组以气一液混合反流为主（46.3％）,正常对照组以气体反流为主（68．9％）,两组均以弱酸反流为主（59．9％和59．1％）。两组间DeMeester计分以及气体反流、酸反流、近端反流次数等差异有统计学意义（P〈0．05）。结论：以慢性咳嗽为表现的GERD患者以气．液混合反流和弱酸反流为主,无论是立位还是卧位时均存在明显的异常反流且近端反流较正常人多见。24h食管DH-阻抗联合监测对疑似GERD的慢性咳嗽患者有重要诊断价值。     

综述食管pH-阻抗监测在临床中的应用

食管pH-阻抗监测通过记录食管腔内食团通过所引起的阻抗变化反应食团的性质及运动情况。弥补了食管pH监测、无线pH胶囊检测不能检测到弱酸、非酸反流的弱点,从而提高了检测反流事件的灵敏度,增加了反流检测的价值。食管pH-阻抗监测在某些情况下允许不停用抑酸药的情况下进行监测。传统的指标,如酸暴露时间、DeMeester评分在诊断胃食管反流病（GERD）,特别是以酸反流为主的胃食管反流病中是主要指标。但食管pH-阻抗监测提高了反流症状关联、反流事件的检出率,提高了GERD的检出灵敏度。新的基于阻抗的指标如：反流后吞咽诱导蠕动波指数和食管基线阻抗提高了pH-阻抗监测在难治性胃食管反流病、功能性胃灼热、反流高敏感和GERD相关食管外症状等的临床诊断价值。本文描述了食管pH-阻抗监测在临床中应用,以期更好的利用食管pH-阻抗监测辅助诊断食管疾病。     

食管阻抗-pH监测在胃食管反流病诊断中的作用

阻抗-pH监测是目前监测胃食管反流病(GERD)的新技术,可通过对胃反流物的pH值和阻抗值进行检测,从而了解反流物为酸反流、弱酸反流或非腹反流,并可区分反流物的性状。阻抗-pH监测可应用于GERID的诊断,尤其适用于对弱酸反流或非酸反流的诊断、对难治性GERD的诊断以及非典型症状GERD的诊断。本文主要就阻抗-pH监测的机制和临床应用作一论述。     

Diagnostic options for patients with refractory GERD

Patients with refractory gastroesophageal reflux disease (GERD) are those who have persistent symptoms while being treated with proton pump inhibitors (PPIs). One third of GERD patients requiring a daily PPI are estimated to eventually experience treatment failure. These patients are usually referred for further investigation to confirm the presence of GERD or to identify other entities as the cause of symptoms. Tools that can be used in this diagnostic process include upper gastrointestinal endoscopy with analysis of esophageal biopsies, esophageal pH monitoring, impedance-pH monitoring, and esophageal bilirubin monitoring. The conventional diagnostic approach includes upper gastrointestinal endoscopy and ambulatory pH monitoring while receiving PPI therapy. New diagnostic techniques that may be useful with refractory GERD include impedance-pH monitoring, which is very sensitive in detecting persistent weakly acidic reflux, and bilirubin monitoring, which detects increased esophageal exposure to bile. Gastric pH monitoring should be reserved for patients in whom PPI resistance is suspected.     

Laparoscopic fundoplication for gastroesophageal reflux disease

Gastroesophageal reflux disease(GERD) is a condition that develops when the reflux of gastric contents into the esophagus leads to troublesome symptoms and/or complications. Heartburn is the cardinal symptom, often associated with regurgitation. In patients with endoscopy-negative heartburn refractory to proton pump inhibitor(PPI) therapy and when the diagnosis of GERD is in question, direct reflux testing by impedance-pH monitoring is warranted. Laparoscopic fundoplication is the standard surgical treatment for GERD. It is highly effective in curing GERD with a 80% success rate at 20-year follow-up. The Nissen fundoplication, consisting of a total(360°) wrap, is the most commonly performed antireflux operation. To reduce postoperative dysphagia and gas bloating, partial fundoplications are also used, including the posterior(Toupet) fundoplication, and the anterior(Dor) fundoplication. Currently, there is consensus to advise laparoscopic fundoplication in PPI-responsive GERD only for those patients who develop untoward side-effects or complications from PPI therapy. PPI resistance is the real challenge in GERD. There is consensus that carefully selected GERD patients refractory to PPI therapy are eligible for laparoscopic fundoplication, provided that objective evidence of reflux as the cause of ongoing symptoms has been obtained. For this purpose, impedance-pH monitoring is regarded as the diagnostic gold standard.     

Refractory GERD: What is it?

Refractory gastroesophageal reflux disease (GERD) is very common and may affect up to 40% of patients who use a proton pump inhibitor (PPI) once daily. Refractory GERD can present as incomplete or lack of response to PPI therapy. The disorder is clearly driven by patients, who present with a wide range of symptom severity and frequency while on PPI treatment. Poor compliance and improper timing of PPI consumption should always be excluded before further evaluation of this patient population. The putative mechanisms for refractory GERD include weakly acidic reflux, duodenogastroesophageal/bile reflux, visceral hypersensitivity, delayed gastric emptying, psychological comorbidity, and concomitant functional bowel disorders. Reduced PPI bioavailability, rapid PPI metabolism, PPI resistance, nocturnal reflux, and Helicobacter pylori infection status have very limited roles in refractory GERD. The contribution of eosinophilic esophagitis to refractory GERD is still unknown. Pill-induced esophagitis, Zollinger-Ellison syndrome, achalasia, and other disorders are rarely responsible for PPI failure and usually are not confused with GERD.     

Twice‐daily proton pump inhibitor therapy does not decrease the frequency of reflux episodes during nocturnal recumbency in patients with refractory GERD: analysis of 200 patients using multichannel intraluminal impedance–pH testing

Over half of patients with gastroesophageal reflux disease (GERD) report nocturnal symptoms. Proton pump inhibitors (PPIs) are the main medications used to treat GERD. Multichannel intraluminal impedance with pH (MII‐pH) monitoring is the most sensitive method for detection and characterization of GERD. The aim of this study was to assess and compare reflux frequency in patients with refractory GERD symptoms on and off PPI therapy during the nocturnal recumbent period, as assessed by MII‐pH testing. We analyzed 24‐hour MII‐pH studies performed in 200 patients monitored either on twice‐daily (n = 100) or off (n = 100) PPI therapy. Demographic analysis of the on‐therapy group revealed a mean age of 52 years (24–78 years) with 37% males, and the off‐therapy group revealed a mean age of 49 years (18–84 years) with 40% males. All studies were interpreted to assess and characterize the number of acid and nonacid reflux episodes in the nocturnal recumbent period identified by each patient on an overnight recorder (Zephyr, Sandhill Scientific, Inc., Highlands Ranch, CO, USA). The nocturnal recumbent period was the period documented by patients during which they lie in the recumbent period at night to sleep with average periods lasting 456 and 453 minutes for patients on and off PPI therapy. There were more mean recumbent reflux episodes in the on‐therapy group in comparison with the off‐therapy group (3.76 mean reflux episodes [mre] per patient in the recumbent vs. 2.82 mre); the difference was not statistically significant (P = 0.187). When the reflux events are classified into acid and non‐acid reflux episodes, the relative occurrence of acid reflux events is less in the on‐therapy group (P = 0.047), while the off‐therapy group have fewer nonacid reflux episodes (P = 0.003). PPIs decrease the acidity of esophageal refluxate but do not decrease the relative frequency of reflux episodes in the recumbent position in patients with refractory GERD despite twice‐a‐day treatment with PPI therapy. The explanation for the finding of numerically increased, although not statistically significant, amount of reflux episodes in the PPI treatment group in this study, and previous studies is unclear and warrants further evaluation.     

Extra-Esophageal Manifestations of Gerd: Who Responds to GERD Therapy?

Gastroesophageal reflux disease (GERD) is a common disease that is defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms. In addition to the esophageal manifestations of heartburn and regurgitation, the role of GERD in causing extra-esophageal symptoms, such as laryngitis, asthma, cough, chest pain, and dental erosions, is increasingly recognized with renewed interest. Due to the poor sensitivity of endoscopy and pH monitoring, and the poor specificity of laryngoscopy, empiric therapy with proton pump inhibitors (PPI) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. In those who are unresponsive to such therapy, other diagnostic testing such as impedance/pH monitoring may be reasonable in order to exclude continued acid or weakly acid reflux. Recent data suggest that patients with extra-esophageal symptoms who have concomitant typical symptoms, moderate-sized hiatal hernia and moderate reflux on pH testing may respond better to acid suppressive therapy. This group only accounts for 20?30 % of patients commonly referred for suspected GERD. PPI-unresponsive patients usually have causes other than GERD for their extra-esophageal signs and symptoms and continued PPI therapy in this group is not recommended.     

Yield of 24-Hour Esophageal pH and Bilitec Monitoring in Patients with Persisting Symptoms on PPI Therapy

Current management algorithms propose pH monitoring under proton pump inhibitors (PPIs) in suspected gastroesophageal reflux disease (GERD) with insufficient treatment response, but recent observations challenge this approach because of its low yield. AIM: To perform an audit of the outcomes of pH monitoring under PPI therapy in our unit, and to study the yield of additional nonacid reflux monitoring. METHODS: All pH monitoring studies under antireflux therapy since 1997, with or without simultaneous Bilitec monitoring, were analyzed. RESULTS: From 1997 to 2003, 347 patients (157 men, mean age 49.4 +/- 0.8 years) underwent pH studies on PPI therapy (28% half-, 67% full-, and 5% double-dose PPI) for persisting typical (53%) or atypical (75%) symptoms. In 184 patients, simultaneous Bilitec monitoring was performed. Esophageal pH monitoring on PPI was pathological in 105 (30%) patients. Pathological pH monitoring on PPI was associated with typical reflux symptoms (64 versus 52%, P = 0.03), and a higher prevalence of persisting esophagitis (54 versus 36%, P < 0.005) and of hiatal hernia (58 versus 27%, P < 0.005). Bilitec monitoring on PPI therapy was pathological in 114 (62%) patients, of which 74 (40%) had normal pH monitoring. Adding Bilitec increased the rate of abnormal results over pH monitoring alone, from 38% to 69% on half-dose, from 27% to 69% on full-dose, and from 0% to 38% on double-dose PPI. CONCLUSIONS: The rate of abnormal pH monitoring in symptomatic GERD patients while on PPI therapy is relatively low, especially in those on double-dose PPI. Combined pH and Bilitec monitoring significantly increased the rate of ongoing pathological reflux compared to pH alone in refractory to PPI therapy GERD patients.     

Reflux Parameters as Modified by Laparoscopic Fundoplication in 40 Patients with Heartburn/Regurgitation Persisting Despite PPI Therapy: A Study Using Impedance-pH Monitoring

Background  

Patients with typical reflux symptoms (heartburn/regurgitation) persisting despite proton pump inhibitor (PPI) therapy are not uncommon. Impedance-pH monitoring detects gastroesophageal reflux at all pH levels and may establish if ongoing symptoms on PPI therapy are associated with acid/nonacid reflux. Laparoscopic fundoplication is a therapeutic option in such patients but reflux parameters on PPI therapy and after intervention and their relationship with symptom persistence/remission have been scarcely studied.     

Extra-esophageal gastroesophageal reflux disease and asthma: understanding this interplay

Gastroesophageal reflux disease (GERD) is a condition that develops when there is reflux of stomach contents, which typically manifests as heartburn and regurgitation. These esophageal symptoms are well recognized; however, there are extra-esophageal manifestations of GERD, which include asthma, chronic cough, laryngitis and sinusitis. With the rising incidence of asthma, there is increasing interest in identifying how GERD impacts asthma development and therapy. Due to the poor sensitivity of endoscopy and pH monitoring, empiric therapy with proton pump inhibitors (PPIs) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. If unresponsive, diagnostic testing with pH monitoring off therapy and/or impedance/pH monitoring on therapy, may be reasonable in order to assess for baseline presence of reflux with the former and exclude continued acid or weakly acid reflux with the latter tests. PPI-unresponsive asthmatics, without overt regurgitation, usually have either no reflux or causes other than GERD. In this group, PPI therapy should be discontinued. In those with GERD as a contributing factor acid suppressive therapy should be continued as well as optimally treating other etiologies requiring concomitant treatment. Surgical fundoplication is rarely needed but in those with a large hiatal hernia, moderate-to-severe reflux by pH monitoring surgery might be helpful in eliminating the need for high-dose acid suppressive therapy.     

难治性胃食管反流病的诊疗

难治性胃食管反流病目前已成为临床上的棘手问题。其发生机制尚未完全阐明。上消化道内镜、食管内动态pH监测以及食管多通道腔内阻抗-pH值监测等技术能够对难治性胃食管反流病的诊断提供帮助。通过改善患者的服药依从性以及调整质子泵抑制剂的剂量、种类和服药时间,配合促胃肠动力药、一过性下食管括约肌松弛抑制剂、疼痛调节剂或抗反流手术均有助于改善患者的顽固症状。