Pathogenesis and treatment of refractory gastroesophageal reflux disease in Japanese patients

Prevalence of refractory gastroesophageal reflux disease (GERD) defined as a patient who have persistent GERD symptoms during treatment with proton pump inhibitor (PPI) is rare in Japanese patinets. Pathogenesis of refractory GERD is associated with several factors including dysfunction of esophageal motility, presence of severe hiatal hernia, complication such as stricture and short esophagus, extensive metabolizer of CYP2C19 genotype, nocturnal gastric acid breakthrough, absence of H. pylori infection, or bile reflux. Examination by 24 hr pH monitoring is necessary to assess refractory GERD and if acid suppression is insufficient, treatment with double doses of PPIs or combination of PPI and H2 blocker is effective. However, most cases of refractory GERD are required surgical treatment. Endoscopic therapy might be useful for refractory GERD in future.     

Gastroesophageal reflux disease in diabetic patients

Esophageal dysfunctions occur frequently in patients with diabetic autonomic neuropathy, and the complication of gastroesophageal reflux disease (GERD) has also been reported. However, the characteristics of the GERD complicated with diabetes are obscure, because no detail assessment was performed. We recorded esophageal motility and acid reflux simultaneously in diabetic patients, and the correlation between esophageal dysfunction and diabetic neuropathy was examined. Esophageal dysfunctions including GERD were significantly related to diabetic motor neuropathy. Although the GERD is frequently complicated with diabetes, the symptoms are not apparent in diabetic patients. Therefore, physicians treating diabetic patients should have GERD in mind regardless of the symptoms. We also examined the effect of aldose reductase inhibitor (ARI) on the esophageal dysfunction in diabetic patients. Significant improvement of gastroesophageal reflux and esophageal motility were observed in diabetic patients by ARI treatment. ARI may be useful for the treatment of GERD complicated with diabetes.     

Gastroesophageal reflux disease: presentation and assessment of a common, challenging disorder

Although gastroesophageal reflux disease (GERD) is frequently referred to as a continuous spectrum, it is more useful to consider GERD as 2 discrete entities with several subsets that differ in pathophysiology, clinical presentation, natural history, and therapy. One entity is classic severe acid reflux with erosive esophagitis and its complications. Barrett's esophagus is an important subset of this group, with markedly increased acid exposure and an increased risk of adenocarcinoma. The second entity is nonerosive reflux disease (NERD) with minimal or no esophagitis. Patients with NERD do not develop local mucosa complications, like stricture or Barrett's esophagus, but their symptom severity can equal that of erosive esophagitis. Acid is involved in the symptoms of many but not all NERD patients. This acid dependence is evident either as an increase in esophageal acid reflux or a hypersensitivity to acid, and both generally respond well to proton pump inhibitor (PPI) therapy. NERD patients who are not acid-dependent have what is called functional heartburn; GERD-like symptoms are present, but there is no obvious involvement of refluxed acid. An important subset of GERD is refractory GERD, which consists of patients who fail aggressive PPI therapy. Parallel findings with other refractory syndromes can be anticipated; however, there are indications that psychosocial factors play a major role in refractory GERD, and these patients may benefit more from an integrated biopsychosocial approach. Diagnosis of GERD is usually made on clinical grounds, often supplemented by a therapeutic trial with antisecretory agents. Endoscopy is reserved for patients with alarm symptoms, such as dysphagia, anemia, or weight loss, or to detect Barrett's esophagus. Endoscopy is not useful to exclude the diagnosis of GERD because it will be negative in 70% of cases in primary care. Ambulatory 24-hour esophageal pH monitoring is necessary only when the diagnosis is in doubt, the patient fails medical management, or surgery is contemplated.     

Gastroesophageal reflux disease in diabetic patients

Esophageal dysfunctions occur frequently in patients with diabetic neuropathy, and the complication of gastroesophageal reflux disease(GERD) has also been reported. However, the characteristics of GERD complicated with diabetes mellitus are obscure because no detailed assessment was performed. We performed long-term ambulatory esophageal pH and motility monitoring in diabetic patients, and analyzed the data in detail. Esophageal dysfunctions including GERD were significantly related to diabetic neuropathy and duration. Although GERD was frequently complicated with diabetes mellitus, the symptoms were not apparent in diabetic patients. The average score of a questionnaire was extremely low, and no significant difference in score was observed between patients with and without gastroesophageal reflux. We should keep in mind that diabetic patients have the abnormal gastroesophageal reflux even when they do not complain of the related symptoms.     

24h食管pH监测和食管测压及奥美拉唑治疗试验在食管原性胸痛中的应用

目的 :探讨 2 4 h食管 p H监测和食管测压及奥美拉唑治疗试验在食管原性胸痛中的诊断价值。方法 :对食管原性胸痛 6 8例行内镜、食管测压、2 4 h食管 p H监测及 7d的奥美拉唑 (2 0 mg,2次 / d)治疗试验 ,治疗后症状评分比治疗前降低超过 75 %者则为治疗试验阳性。结果 :食管原性胸痛 6 8例中 5 5例 (81% )符合胃食管反流病 (GERD) ,胡桃夹食管 2例 ,早期贲门失驰缓症 3例 ,弥漫性食管痉挛 3例 ,无效食管运动 (IEM) 5例。GERD5 2例测压分析 ,35例(6 7% )符合 IEM诊断标准。奥美拉唑治疗试验对诊断 GERD的敏感性为 93% ,特异性为 85 %。结论 :GERD是食管原性胸痛的主要原因。 2 4 h食管 p H监测和食管测压是诊断食管原性胸痛的主要检查手段 ,奥美拉唑治疗试验是临床诊断GERD简便而实用的方法。     

三种不同检查方法在胃食管反流病诊断中的应用比较

目的：探讨电子胃镜、24 h食管pH值监测及胃食管反流病（GERD）Q评分三种方法在GERD诊断中的临床应用价值。方法：将于2011年4月—2012年6月因烧心、反酸等症状就诊于消化科门诊的120例患者随机分为胃镜组、24 h食管pH值监测组及GERD Q评分组,每组40例,分别接受电子胃镜、24 h食管pH值监测及GERD Q问卷评分,比较分析各种方法对GERD的检出情况。结果：24 h食管pH值监测组40例患者中病理性反流者19例,生理性反流者5例,GERD阳性率显著高于胃镜组及GERD Q评分组,差异具有统计学意义（P〈0.05）;胃镜组与GERD Q评分组之间差异无统计学意义（P〉0.05）。结论：24 h食道pH值监测可以对食管内反流情况进行实时、动态监测,为GERD的临床诊断及不同类型的反流治疗方案提供客观、准确的依据。     

Esophageal pH monitoring

According to westernization of dairy life-style and aging, gastroesophageal reflux disease (GERD) with its physical symptoms such as heartburn is increasing in Japan. Although typical GERD has reflux esophagitis, GERD patients without abnormal endoscopic findings called non-erosive GERD (NERD) have been paid great attention. And more, the association between GERD and chronic respiratory diseases or laryngeal disease has been reported. To catch the more information about clinical questionnaire of GERD cases, esophageal pH monitoring is a useful method because of evaluating the direct condition of acid exposure of esophagus. Recently the new wireless pH monitoring system have been developed, this system is less stress than conventional method and has performance of pH recording for continuous 48 hours time. The widespread usage of pH monitoring system is expected to give us the new knowledge of GERD, NERD and GERD associated diseases.     

难治性胃食管反流病的反流危险因素调查

目的：收集胃食管反流病（gastroesophageaf reflux disease,GERD）患者的临床信息、胃镜表现以及24 h食管pH-阻抗监测结果,比较难治性GERD和非难治性GERD的反流特点,探讨难治性GERD的预测因素,为临床处理提供依据.方法：入选2008年10月-2012年12月因反酸、烧心、非心源性胸痛、咽痛等症状在复旦大学附属中山医院消化科疑诊为GERD的74例患者.记录患者的年龄、性别、身高、体质量、胃镜结果等.监测患者的食管下段pH和食管阻抗变化.难治性GERD诊断：符合GERD诊断标准,同时经过质子泵抑制剂（PPI）治疗4周（每天至少1次）无效或者deMeester评分下降少于50％;非难治性GERD诊断：符合GERD诊断标准,同时经过PPI治疗4周（每天至少1次）症状改善明显;非GERD诊断：内镜检查未见食管黏膜损害,且24 h食管pH-阻抗监测反流次数和deMeester评分不足以诊断GERD.计数资料正态分布者用r±s表示,菲正态分布者用中位数和百分位数（25th,75th）表示.采用SPSS 17.0软件进行统计学处理.按是否为GERD、是否为难治性GERD分组,比较患者的一般资料和反流特征性因素.结果：（1）难治性GERD患者与非难治性GERD患者的酸反流次数、总反流次数差异无统计学意义;难治性GERD患者的deMeester评分较非难活性GERD患者高,长酸反流次数较非难治GERD患者多（P=0.032,P=0.008）;（2）经Logistic多因素分析发现,难治性GERD与长酸反流次数、非糜烂性胃食管反流病（NERD）呈正相关（P值分别为0.01和0.045）.长酸反流次数增加1次,发生难治性GERD的危险增加36％;NERD患者发生难治性GERD的危险是反流性食管炎患者的4.54倍;（3）不同类型GERD的反流特征：NERD患者的近端反流次数大于反流性食管炎和Barrett食管患者,而近端反流百分比显著大于反流性食管炎患者和Barrett食管患者（P=0.006）.结论：（1）长酸反流次数多和NERD是难治性GERD的独立危险因素;（2）NERD患者比糜烂食管炎患者更容易发展为难治性GERD.NERD患者的近端反流百分比的升高可能与其对PPI的反应差有关.     

Diagnosing gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is a common condition with a variety of clinical manifestations and potentially serious complications. This article reviews available methods for diagnosing GERD. A clinical history of the classic symptoms of GERD, heartburn or acid regurgitation, is sensitive enough to establish the diagnosis in patients without other complications. Esophagogastroduodenoscopy is the best way to evaluate suspected complications of GERD, but endoscopic findings are insensitive for the presence of pathological reflux, and therefore they cannot reliably exclude GERD. The "gold standard" study for confirming or excluding the presence of abnormal gastroesophageal reflux is the 24-hour ambulatory esophageal pH monitoring test, and this study should be used for the evaluation of refractory symptoms and extraesophageal manifestations of GERD. A formal acid-suppression test is helpful in the evaluation of the atypical GERD symptom of noncardiac chest pain. Optimal use of currently available tests for GERD may allow for more efficient diagnosis and better characterization of the pathological manifestations associated with GERD.     

食管pH监测对内镜阴性胃食管反流病的诊断价值探讨

目的观察食管pH监测在内镜阴性胃食管反流病中的诊断价值。方法选择临床诊断胃食管反流病（GERD）而内镜检查阴性的42例患者作为研究组，选择无上消化道症状的10例体检者作为对照组．分别行食管24h pH监测检查，分析比较其结果。结果42例内镜阴性者经食管24h pH值监测检出36例（85.71％）符合GERD诊断标准，有反流症状患者酸反流次数、酸长反流次数、最长酸反流时间、pH值〈4 总百分比、pH值〈4 立位百分比、pH值〈 4卧住百分比均显著高于正常对照组，各指标比较有统计学意义（t分别=7.95、6.38、6.12、7.34、7.86、6.06，P均〈0.05）。老年患者24h pH监测GERD栓出率显著高于非老年患者（X^2=6.36，P〈0.05）。结论食管24h pH值监测是诊断内镜检查阴性的胃食管反流病的理想方法。     

Clinical significance of 24-hour intraesophageal pH monitoring in GERD patients

24-hour intraesophageal pH monitoring(24-pH-M) is a method of choice to measure the esophageal acid exposure, and evaluate a patient's lifestyle who has reflux symptoms. The 24-pH-M is indicated to the cases who have at least one of the following signs/symptoms; endoscopy negative GERD(gastroesophageal reflux disease), atypical clinical course for reflux disease, atypical symptoms of GERD, and those who are subjected to have surgical treatment. In the 24-pH-M, not only the duration of gastroesophageal reflux(GER), but also reflux and symptom association should be evaluated. The 24-pH-M is useful to investigate the diagnosis and treatment of GERD including reflux esophagitis.     

幽门螺杆菌感染对胃食管反流病患者食管酸暴露及食管动力的影响

目的分析幽门螺杆菌（helicobacterpylor,Hp）感染胃食管反流病（gastroesophagealrefluxdisease,GERD）患者食管远端酸暴露及食管动力变化特点,探讨Hp感染与GERD的关系。方法GERD患者80例,分为Hp阳性组30例,Hp阴性组50例,同期20例慢性浅表性胃炎患者为对照组,对3组进行食管动力学检测和食管24hpH监测。结果Hp阳性组与Hp阴性组DeMeester评分、食管下括约肌压力、24hpH监测各项指标及食管动力学各项指标比较差异均无统计学意义（P〉O．05）;2组DeMeester评分均高于对照组（P〈0．05）,食管下括约肌压力低于对照组（P〈0．05）。结论GERD患者食管下括约肌压力较正常人群低,且存在过量酸反流;Hp感染与GERD发生可能无明显关系。     

Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole

BACKGROUND AND OBJECTIVES: The acid-inhibitory effect of lansoprazole depends on differences in cytochrome P450 (CYP) 2C19 genotypes. We assessed whether therapeutic effects of lansoprazole on gastroesophageal reflux disease (GERD) depended on the CYP2C19 genotype status in relation to the grade of GERD. METHODS: A total of 65 patients with GERD (grades A-D) completed treatment with lansoprazole, by taking 30 mg orally once a day for 8 weeks. The CYP2C19 genotype status of patients was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. Before and after treatment, esophageal endoscopy was performed. GERD was considered to be cured on the basis of endoscopic findings at the end of treatment. Plasma lansoprazole levels could be determined at 3 hours after the last 30-mg dose of lansoprazole in the 27 genotyped patients. RESULTS: Cure rates for GERD depended significantly on the CYP2C19 genotype status, as well as the grade of GERD before treatment. Cure rates in the homozygous extensive, heterozygous extensive, and poor metabolizer groups were 45.8%, 67.9%, and 84.6%, respectively. Cure rates in the groups with GERD grade A, grade B, and grade C or D were 85.0%, 60.0%, and 45.0%, respectively. The cure rate in patients with the homozygous extensive metabolizer genotype of CYP2C19 with a GERD grade of C or D was very low (16.7%). Plasma lansoprazole levels in patients with the homozygous extensive metabolizer genotype were the lowest of the 3 groups. CONCLUSIONS: CYP2C19 genotype status, as well as the grade of GERD before treatment, is one of the determinants for the success or failure of treatment of GERD with lansoprazole. The low cure rate in patients with the homozygous extensive metabolizer genotype appeared to be a result of these patients having the lowest plasma lansoprazole levels among the 3 genotype groups.     

支气管哮喘患者24小时食管pH监测的分析

目的　许多研究发现支气管哮喘和胃食管酸反流有关 ,但是有关胃食管酸反流引起支气管哮喘的机制还并不是十分清楚 ,用 pH监测仪对支气管哮喘患者的胃食管酸反流进行监测 ,以进一步探讨哮喘病的发病机制。 方法　将 84例患者分为 3组 ,单纯反流组 (30例 ) ,哮喘组 (2 8例 ) ,哮喘伴反流组 (2 6例 )。应用敏感的 2 4小时食管 pH监测仪监测食管 pH的变化。 结果　伴有酸反流的哮喘患者的 2 4小时酸反流次数、超过 5分钟的反流次数和 pH <4的时间均明显高于无胃食管反流的支气管哮喘患者 ,但超过 5分钟的反流次数、最长反流时间和 pH <4的时间明显低于单纯有胃食管反流的患者。结论　伴有酸反流的支气管哮喘患者 ,其哮喘的发作与酸反流有密切的关系 ,但是其酸反流程度小于单纯有胃食管反流的患者。这说明此类患者的哮喘发作除与胃食管酸反流对食管下段的刺激有关外 ,对酸反应的高敏感性也是其发病的重要因素 ,因此与胃食管反流相关的支气管哮喘发作是这两方面作用的结果     

放大内镜下胃食管反流病患者食管乳头内毛细血管环形态学观察

目的探讨胃食管反流病（GERD）患者食管乳头内毛细血管环（IPCL）形态学检查在GERD诊断中的临床价值及护理。方法对非糜烂性食管炎（NERD）患者20例、糜烂性食管炎（EE）患者20例和10例健康志愿者行24h食管pH监测,采用白光和放大内镜窄波成像（NBI）模式观察食管下段黏膜IPCL形态并进行分型,同时配合有效的护理措施。结果3组受检者顺利完成内镜检查。NERD组患者24h食管pH监测阳性率为55％,EE组为90％,健康对照组均为阴性,NERD组低于EE组;放大内镜NBI模式下健康对照组食管IPCL呈茶色规律排列的卷发状、小螺旋状;NERD组85％及EE组100％食管IPCL形态为Ⅱ型,但仍排列规律,与健康对照组比较差异均有统计学意义（P〈0．05）。结论食管ICPL形态特异性改变有助于GERD的内镜诊断;高质量的护理配合对顺利完成内镜检查起到了重要的作用。     

Wireless pH capsule--yield in clinical practice

Wireless pH monitoring is one of the recent technologies that focus on improving the diagnosis of gastroesophageal reflux disease (GERD). The capsule, which is fixed within the esophagus, transmits data via telemetry to an external receiver. The capsule is usually inserted 6 cm above the squamocolumnar junction during an upper endoscopy. The standard recording duration is 48 hours but this can be extended to 96 hours. The wireless capsule has been shown to be at least as accurate as the conventional catheter for the monitoring of esophageal pH. Normal pH values have been established in three different series. The use of a wireless capsule provides an increased diagnostic yield for GERD compared with the conventional catheter. The increased yield is the result of higher sensitivity to detect both abnormal acid esophageal exposure and positive symptom-reflux association. This may be related both to the prolonged recording duration and to fewer dietary modifications and restrictions on activities. Several studies have shown that the pH capsule was better tolerated by patients than the conventional pH catheter. Mild-to-moderate chest pain represents the main side effect of the pH capsule: severe chest pain requiring endoscopic removal of the capsule is rare. The main indication for wireless capsule application is monitoring of distal esophageal pH for diagnostic purpose, particularly in patients with a normal endoscopic examination. The capsule technique has some limitations: costs are higher than conventional pH monitoring, misplacement may occur, and the sampling rate is lower. Finally, compared with pH-impedance monitoring, only acid reflux events can be evaluated.     

Long-term results of laparoscopic partial posterior fundoplication in patients with esophageal reflux and disorders of esophageal peristalsis

BACKGROUND: Gastrosophageal reflux disease (GERD) of long duration is frequently associated with impaired esophageal body motility. This condition has been considered unsuitable for antireflux surgery. METHODS: In order to investigate the outcome of antireflux surgery in the presence of impaired esophageal peristalsis, we studied 67 consecutive GERD patients with poor esophageal body function who underwent laparoscopic partial posterior fundoplication. A standardized questionnaire, upper GI endoscopy, esophageal manometry and 24-hour pH monitoring were performed preoperatively and at a median of 28 months (range, 6-54 months) postoperatively. Esophageal motility was analyzed for contraction amplitudes in the distal two thirds of the esophagus (level 3, 4, and 5), frequency of peristaltic, simultaneous and interrupted waves and total number of defective propagations. In addition, parameters defining the function of the lower esophageal sphincter (LES) were-evaluated. RESULTS: Following antireflux surgery 65 patients (97%) were free of heartburn and regurgitation and had no esophagitis on endoscopy, confirmed by histology. The rate of dysphagia was reduced from 49% preoperatively to 9% postoperatively (p < 0.001). There was significant improvement in esophageal peristalsis after the antireflux procedure. The median DeMeester reflux score was reduced from 33.3 to 1.1 (p < 0.001). Lower esophageal sphincter pressure and intra-abdominal length were normal after surgery. CONCLUSIONS: Partial posterior fundoplication provides an effective antireflux barrier in patients with impaired esophageal body motility in the long term. Postoperative dysphagia is avoided by improving esophageal body function.     

24小时食管PH监测对诊断胃食管反流的临床研究

目的:探索24h食管pH检测对胃食管反流和胃食管反流性疾病的诊断价值。 方法:采用携带式24h食管pH分析仪对37例具有胃食管反流症状患者作为疾病组在常态下进行24h食管pH监测,并以20名健康成人作为对照组进行比较。 结果:20名正常成人中平均97.7％的时间食管pH>4,观察6项食管pH测定指标,得出95％的正常值范围:pH<4的总时间百分率为4.97％;pH<4的立位时间百分率为3.82％;pH<4的卧位总时间百分率2.34％,反流持续≥5min的次数<2.57;最长反流持续时间<18.62min,pH<4的反流次数为25.69次。疾病组与对照组相比有显著差异(P<0.01),24h食管pH监测的阳性检出率为94.59％,明显高于食管钡餐X线检查(27.02％)、内镜检查(40.54％)及食管粘膜活检(51.35％)等方法。 结论:24h食管pH监测的指标对鉴别生理性与病理性GER,深入了解GER与食管炎的关系,特别对GERD的诊断和疗效判定,提供了可靠的依据。其诊断价值明显优于食管钡餐X线检查和内镜检查。     

Gastroesophageal reflux disease: clinical manifestations.

Gastroesophageal reflux disease (GERD) is generally a lifelong illness that affects many people, but its significance is often underestimated. Chronic abnormal gastric reflux results in erosive esophagitis in up to 60% of patients with GERD. Esophageal stricture, Barrett's esophagus, and esophageal adenocarcinoma are the most serious complications of GERD. Although heartburn and acid regurgitation are the most common complaints, extraesophageal symptoms such as noncardiac chest pain, laryngitis, coughing, and wheezing can be manifestations of GERD. Unfortunately, the severity of symptoms is not a reliable indicator of the severity of erosive esophagitis. Endoscopy is the preferred method to diagnose and grade erosive esophagitis, and various classification systems are used to grade disease severity. The Los Angeles Classification is a valid and widely accepted system to evaluate the severity of erosive esophagitis. The immediate goals of treatment are to provide effective symptomatic relief and to achieve healing in patients with esophageal damage. The treatment regimen often begins by prescribing a therapy to reduce gastric acid secretion. A proton pump inhibitor is the preferred agent for many patients. Because GERD is a chronic, relapsing disease, long-term maintenance therapy is usually necessary to relieve symptoms, prevent complications, and improve the quality of life in patients with GERD.     

Relief of reflux symptoms after endoscopic gastroplication may be associated with reduced esophageal Acid sensitivity: a pilot study

BACKGROUND AND STUDY AIMS: Although the new endoscopic techniques for the treatment of gastroesophageal reflux disease (GERD) lead to marked clinical benefit, the underlying mechanism of this is unknown. MATERIALS AND METHODS: In this prospective study, the effect of endoscopic gastroplication was investigated in six patients with GERD, who were assessed before and 4 weeks after treatment. The effect on reflux symptoms, quality of life, proton pump inhibitor (PPI) consumption, reflux esophagitis, acid exposure, esophageal motility, lower esophageal sphincter pressure (LESP), and gastric emptying was measured. Esophageal acid sensitivity before and after treatment was investigated using a standardized acid provocation test, and compared with that of six age- and sex-matched healthy controls. RESULTS: Significant clinical benefit and discontinuation of PPI consumption after gastroplication was seen. Among the objectively measured parameters, only acid exposure was significantly reduced and gastric emptying significantly delayed. However, acid exposure remained pathologically high. Esophageal acid sensitivity was significantly reduced. The induction of heartburn and/or pain was abolished in four patients after gastroplication. In two patients the intensity of heartburn/pain was significantly reduced by 40 % or 60 %, and the time to provoke heartburn/pain significantly prolonged by 40% or 100%. CONCLUSION: These preliminary data suggest that the decrease of esophageal sensitivity to acid after endoscopic gastroplication is part of the mechanism responsible for the reduction of reflux symptoms.