Use of an endoscopic suturing device (the "ESD") to treat patients with gastroesophageal reflux disease, after unsuccessful EndoCinch endoluminal gastroplication: another failure

BACKGROUND: Endoluminal gastroplication, using the EndoCinch procedure, has emerged as a potential endoscopic antireflux therapy. Although initial results have been promising, the long-term durability of the treatment is uncertain due to suture loss. A new endoscopic suturing device, the "ESD," has been developed that promises excellent visibility and endoscopic control. The aim of this study was to evaluate prospectively the feasibility and efficacy of the ESD method after EndoCinch failure. METHODS: The study involved 20 patients with gastroesophageal reflux disease (GERD), who had been initially treated with an EndoCinch procedure, but had relapsed after a median of 7.5 months, with lost or dysfunctional sutures and with reflux symptoms that required proton pump inhibitor (PPI) treatment. Using the ESD, at least three plications were created at the gastroesophageal junction. Patients underwent endoscopy, 24-hour pH monitoring and esophageal manometry before treatment and 6 months afterwards. In addition, reflux symptoms as well as quality-of-life scores were assessed (using the SF-6 and GERD-HRQL scales). RESULTS: The ESD procedure (median procedure time 45 min) was performed successfully in all patients without major complications. After 6 months only one patient (5 %) still had all sutures in situ, while no remaining sutures could be detected in 3/20 (15 %). No significant changes in reflux esophagitis; 24-hour pH monitoring results (median pH < 4/24 h9.9 % vs. 12.3 %; P = 0.60); manometry findings (median lower esophageal sphincter pressure 7.2 mm Hg vs. 9.9 mm Hg; P = 0.22); PPI use; or reflux esophagitis could be detected after 6 months. While reflux symptoms improved (heartburn severity score 30 vs. 48, P < 0,05), no changes in quality-of-life scores were detected. CONCLUSIONS: Endoluminal gastroplication using the ESD is an easy and safe, but unfortunately ineffective procedure for endoscopic GERD treatment. Endoluminal gastroplication techniques clearly need refinements before these therapies can evolve as a treatment option for GERD patients.     

从心身角度认识胃食管反流病

胃食管反流病(GERD)为一组疾病症候群,包括典型症状如反酸和烧心,以及不典型症状如胸痛、嗳气,还有食管外症状如咳嗽、哮喘等。其定义不断进行更新,最新定义为胃内容物反流入食管或口腔、咽喉、肺部引起的症状和并发症。GERD发病机制包括滑动性食管裂孔疝、一过性食管下括约肌松弛、酸囊、食管清除能力下降、胃排空延迟、十二指肠胃食管反流等。焦虑、抑郁等心理因素可导致食管的敏感性增高,而后者可产生GERD相关症状。心理应激对食管敏感性的影响主要通过外周及中枢机制,即外周致敏和中枢致敏,而后者起主要作用。对GERD患者的治疗中应根据每位患者的具体情况采取个体化原则,应重视心理因素。     

Endoscopic augmentation of the lower esophageal sphincter for the treatment of gastroesophageal reflux disease: multicenter study of the Gatekeeper Reflux Repair System

BACKGROUND AND STUDY AIMS: The safety and effectiveness of the Gatekeeper Reflux Repair System (Medtronic Europe, Tolochenaz, Switzerland) in the treatment of gastroesophageal reflux disease (GERD) was evaluated. This new, reversible treatment modality involves the endoscopic introduction of expandable polyacrylonitrile-based hydrogel prostheses into the esophageal submucosa to augment the lower esophageal sphincter (LES). PATIENTS AND METHODS: For this study, data from two prospective, nonrandomized European multicenter trials were pooled. Sixty-nine GERD patients with heartburn and regurgitation and abnormal esophageal acid exposure (24-h pH < 4.0 for > 4 % of the total time) who had responded to proton-pump inhibitor (PPI) therapy were recruited, and 68 were treated with up to six prostheses placed at the gastroesophageal junction. Patients underwent esophageal manometry, endoscopy, 24-h pH-metry, and symptom scoring at intake and 1, 3, and 6 months after the procedure. RESULTS: A total of 77 procedures were performed in 67 patients, and a total of 270 prostheses were placed (mean 4.3 per procedure). At 1 and 6 months, 80.4 % and 70.4 % of the prostheses were retained, respectively. At 6 months, 24-h pH-metry outcomes with pH < 4.0 for > 4.0 % of the time decreased from 9.1 % to 6.1 % (n = 45; P < 0.05). Median LES pressure increased significantly from 8.8 mmHg at baseline to 13.8 mmHg at 6 months (n = 42, P < 0.01). Median GERD heartburn-related quality-of-life scores improved significantly from 24.0 to 5.0 (n = 53, P < 0.01) in patients no longer receiving PPI therapy. Two serious adverse events (3.0 %) occurred. Both patients recovered uneventfully. Prostheses were endoscopically removed from one patient without any adverse events. CONCLUSIONS: The Gatekeeper Reflux Repair System is a safe endoscopic treatment modality that significantly improves GERD symptoms and has objective effects on acid reflux.     

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.     

Endoluminal gastroplication. A new therapeutic endoscopic procedure for gastroesophageal reflux disease.

It is estimated that more than 15 million Americans suffer daily from gastroesophageal reflux disease (GERD) (De Vault, 1995). The spectrum of symptoms for GERD ranges from simple heartburn and regurgitation to persistent esophageal tissue damage with subsequent development of serious complications. The frequent occurrence and intensity of GERD symptoms can severely impact a person's quality of life (Behar, 1990). Until recently, treatment options included a lifetime of drug therapy, disagreeable daily lifestyle changes, and the possibility of invasive surgery. In 2000, the Food and Drug Administration cleared a new endoscopic tool called the EndoCinch, a device that enables endoscopic endoluminal gastroplication as an outpatient procedure for the treatment of GERD. Endoscopic endoluminal gastroplication has been shown to be a safe and effective therapeutic outpatient procedure offering sustainable clinical benefits and cost savings to patients suffering with GERD (Patel, 2001; Raijman, 2001; Weiland, 2001). The purpose of this article is to present an overview of GERD with a particular focus on management of the disease using this new procedure.     

Pathogenesis of gastro-esophageal reflux disease

Gastro-esophageal reflux disease (GERD) refers a condition that develops when the reflux of stomach contents causes troublesome symptoms and/or complications. The disease was subclassified into esophageal and extraesophageal syndromes in the new Montreal Definition. Hiatal hernia, decreased lower esophageal sphincter, transient lower esophageal sphincter relaxation, esophageal acid clearance, and delayed gastric emptying might be implicated as the pathogenesis of esophageal syndrome. Although non-erosive reflux disease (NERD) is included in the esophageal syndrome, it might be different from reflux esophagitis because of the lower response rates to acid suppression with proton pump inhibitors. Esophageal visceral hypersensitivity, sustained esophageal contractions, and abnormal tissue resistance are thought to be the mechanisms of NERD. Further investigations for the pathogenesis of each classification are expected.     

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。     

Relationship between gastric motility and the pathophysiology of GERD

Various factors contribute to the reflux symptoms such as heartburn and regurgitation in patients with GERD. There have been some reports on delayed gastric emptying or impaired gastric myoelectrical activity in those with GERD. The reason for the direct relationship between reflux symptoms and gastric hypomotility in GERD patients is still unclear. Gastric distension and impaired fundic relaxation as a result of disturbed gastric motility might play a partial role in acid reflux to the esophagus. Gastric hypomotility appears to be an important causative factor in the reflux symptoms in some GERD patients.     

Test of refractory gastroesophageal reflux disease

It should be considered that the causes of refractory gastroesophageal reflux disease (GERD) are multifactorial. Esophageal manometry study is useful when we make distinguish patients with esophageal motility disorders from those with refractory GERD. Endoscopic ultrasonography is also performed to observe the thickness of esophageal wall which represents the disturbance of esophageal motor function. Esophageal pH monitoring is useful to detect the acid clearance disturbance and phenomenon of nocturnal acid breakthrough. Both are occurred at night, and are recently considered to be responsible for refractory GERD. Catheter-free pH monitoring system, Bravo, makes it possible to measure esophageal pH under quite physiological conditions. Genotype of CYP2C19 is sometimes checked in patients with PPI resistance GERD. Intra-gastric pH with omeprazole and lansoprazole depends on patient's genotype of CYP2C19. Monitoring of 24-hour bilirubin, Bilitec, is also useful to detect duodeno-gastro-esophageal reflux.     

Long-term failure of endoscopic suturing in the treatment of gastroesophageal reflux: a prospective follow-up study

BACKGROUND AND STUDY AIMS: Several endoscopic antireflux therapies have been marketed, but long-term data on their objective and clinical efficacy are sparse. This report presents prospective 1-year follow-up results, including technical, clinical, and functional success rates, for the first of these treatments to be developed, endoscopic gastroplication (EGP). PATIENTS AND METHODS: A total of 43 EGP procedures were carried out in 38 patients with gastroesophageal reflux disease (GERD). Two or three EndoCinch gastroplications were constructed at the level of the gastric cardia in each patient; five patients were treated twice within 6 - 12 months. Each endoscopic suture joined two gastric folds to each other as a double fold, known as a "gastroplication", in order to narrow the esophagogastric junction. Postprocedure data after 2 months and after 1 year were compared with preoperative data, focusing on symptoms, medication requirements, endoscopic findings, and pH-metry results. RESULTS: In contrast to the findings at 2 months (which showed that 72 % of the sutures were present and that there was a reduction in the percentage of time when the esophageal pH was < 4 from 15.4 % to 8.7 %), the results 1 year after EGP were considered to indicate failure of the treatment in all 38 patients because none of them still had all of the initially placed gastroplications in situ (90 % of gastroplications were lost). The percentage of patients who did not require proton pump inhibitor medication decreased from 52 % at 2 months to only 20 % at 1 year and even more patients had evidence of reflux esophagitis at 1 year (56 %) than had initially demonstrated signs of this (41 %). CONCLUSIONS: EGP has some short-term beneficial effects on clinical symptoms and pH-metry. However, mainly due to the loss of the endoscopically placed sutures, these effects were not maintained at the 1-year follow-up. EGP cannot therefore be recommended for routine clinical use. Better endoscopic methods need to be developed, and they should be adequately tested before being marketed.     

Clinical effect of proton pump inhibitors on reflux esophagitis]

The clinical efficacy of proton pump inhibitors (PPI, omeprazole 20 mg or lansoprazole 30 mg), once daily, after breakfast, was studied in patients with erosive/ulcerative reflux esophagitis. The following results were obtained. 1) Twenty-four hour esophageal pH monitoring was performed before treatment and on 7th day of PPI medications. Omeprazole reduced the percent time pH less than 4 from 29.1 to 1.2 and lansoprazole from 68.0 to 2.4. 2) The cumulative disappearance rate of overall symptom was 52% after 1 week and 62% after 2 weeks with omeprazole these were 66% and 91%, and with lansoprazole respectively 3) The endoscopic healing rate was 63% was after 2 weeks and 76% after 4 weeks with omeprazole medication, and 76% and 97% respectively with lansoprazole. These results indicate that PPI medication inhibits the acid reflux almost completely and is a more useful therapeutic agent for GERD than H2-antagonists.     

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.     

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.     

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.     

Maintenance therapy of mild form of GERD by H2 receptor antagonists

Because of high relapse rate after the healing by proton pump inhibitor(PPI) or H2 receptor antagonist(H2RA), GERD usually needs long time maintenance therapy. PPI is superior to H2RA in the first line as well as maintenance therapy. PPI is necessary for severe cases of GERD. However, H2RA is sufficient for milder form of GERD patients. Among the H2RA using in Japan, nizatidine has known to stimulate gastric emptying and elevate LES pressure. Nizatidine may be superior to other H2RAs in the treatment of GERD. Recently, nocturnal acid breakthrough which night time acid is secreted even PPI is administered twice daily has been documented. H2RAs are stronger than PPI to inhibit nocturnal acid breakthrough and may be better than night time acid reflux.     

Significance of PPI-test in the diagnosis of GERD

Gastroesophageal reflux disease (GERD) is defined as 'Chronic symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus'. Reflux esophagitis refers to a subgroup of GERD patients with histopathologically demonstrated characteristic changes in the esophageal mucosa. Besides, GERD includes symptoms without endoscopic findings (endoscopic negative GERD) and extra-esophageal symptoms. Therefore, GERD cannot be diagnosed only by endoscopy. Three methods are indispensable in the diagnosis of GERD; endoscopy, evaluation of patient symptoms and acid reflux. Since 'Symptom relief is well correlated with the degree or suppression of gastric acid secretion in GERD', symptom in relation to acid reflux can be evaluated by PPI-test. Characteristics of PPI-test including extra-esophageal GERD diagnosis are discussed in this review.     

Primary care for GEDR

Current approach for the treatment of gastroesopageal reflux disease (GERD) was reviewed. The most effective treatment of erosive esophagitis or symptomatic GERD is to reduce gastric acid secretion with either an H2 receptor antagonists (H2RA) or a proton pump inhibitor (PPI). The PPI lead to more rapid healing and symptom relief than H2RA. Despite treatment with PPI, some patients with GERD continue to have symptoms or endoscopic evidence of esophagitis. Nocturnal acid breakthrough may be one of the mechanisms responsible for the refractory GERD. There are two approaches to the initial medical treatment of gastroesophageal reflux disease ('step down' therapy or 'step up' approach). Although there are arguments in favour of both approaches, the former is considered to be preferable these days.     

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.     

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。     

The course of gastroesophageal reflux disease in elderly patients with concomitant ischemic heart disease

AIM: To study basic functional and pathogenetic features of the course of gastroesophageal reflux disease (GERD) in elderly patients with concomitant coronary heart disease (CHD). MATERIAL AND METHODS: Esophagogastroduodenoscopy, 24-h pH-metry, simultaneous 24-h pH- and ECG-monitoring, omeprasol test were made in 126 patients: 74 GERD patients with CHD and 52 patients with GERD alone. RESULTS: Mean number of refluxes for 24 hours in isolated GERD was maximal at stages IIa and IIb (74%). In CHD patients (77%) there was a trend to a rise in this number. Only patients with associated CHD demonstrated a clinically significant depression of ST segment related to reflux, a significantly more frequent occurrence of supraventricular and ventricular extrasystoles. CONCLUSION: The acid component of gastric content pushed into the esophagus is not a leading factor of esophageal mucosa lesion in GERD patients with CHD. Pathological gastroesophageal refluxes may trigger mechanisms provoking new attacks of angina pectoris.