The common denominator for virtually all episodes of gastroesophageal reflux in health and disease is the loss of the barrier that confines the distal esophagus to the stomach. Factors important in maintaining the function of the barrier are its pressure, length and position. In early reflux disease, overeating, gastric distention and delayed gastric emptying led to a transient loss of the barrier. A permanent loss of the barrier occurs from inflammatory injury to the muscle allowing free flow of gastric juice into the esophageal body. Corrective therapy requires augmentation or restoration of the barrier referred to more commonly as the lower esophageal sphincter.

With the advent of high-resolution esophageal manometry, it is recognized that the antireflux barrier receives a contribution from both the lower esophageal sphincter (intrinsic sphincter) and the muscle of the crural diaphragm (extrinsic sphincter). Further, an increased intra-abdominal pressure is a major force responsible for an adaptive response of a competent sphincter or the disruption of the esophagogastric junction resulting in gastroesophageal reflux, especially in the presence of a hiatal hernia. This review describes how the pressure dynamics in the lower esophageal sphincter were discovered and measured over time and how this has influenced the development of antireflux surgery.

Treatment of gastroesophageal reflux disease (GERD) has changed markedly over the last half-century. The introduction of H2 blockers followed by proton pump inhibitors (PPIs) provided much more effective medical therapy for GERD symptoms, and although antireflux surgery had progressed to being done in a minimally invasive fashion, the number of patients referred or considered for antireflux surgery was on the decline by the end of the twentieth century. The traditional surgical procedure for GERD is a fundoplication, which takes the mobilized fundus of the stomach and wraps (or plicates; ergo fundoplication) it to various degrees around the distal esophagus. Patients with Barrett's esophagus (BE) typically have advanced reflux disease. This is logical since BE develops in the setting of more advanced GERD. Further, in patients with early reflux disease and no hiatal hernia, the TIF procedure offers an endoscopic option to relieve GERD symptoms.

BACKGROUND:Many factors may play a role in the severity and progression of gastroesophageal reflux disease (GERD) since pathophysiology is multifactorial. Data regarding the progression of GERD are controversial: some reports of increased esophageal acid exposure (EAE) and mucosal damage were considered as evidence for a stable disease course, while others interprete these findings as disease progression. The aim of this study is to analyze a large patient-population with persisting symptoms indicative of GERD under protonpumpinhibitor-therapy and identify components characterizing disease severity and progression.METHODS:Patients with symptoms indicative of GERD were included in the study in a tertiary referral center (Frankfurt, Germany). All selected patients were under long-term protonpumpinhibitor-therapy with persistant symptoms. All patients underwent investigations to collect data on their physical status, EAE, severity of esophagitis, anatomical changes, and esophageal functional defects as well as their relation to the duration of the disease. Incidence over time was plotted as survival curves and tested with Log-rank tests for the four main disease markers. Multivariate modeling with COX-regression model was used to estimate the general impact of the four main disease markers on the time course of the disease. In order to elucidate possible causal relationships over time, a path analysis (structural equation model) was calculated.RESULTS:From the database with 1480 data sets, 972 patients were evaluated (542 males, 430 females). The mean age was 50.5 years (range18-89). The mean body mass index was 27.2(19-48). The mean time between the onset of symptoms and the diagnostic investigations was 8.2 years (1-50). A longer disease history for GERD was significantly associated with a higher risk for LES-incompetence. The mean duration from symptom onset to the time of clinical investigation was 9 years for patients with LES-incompetence (n = 563), compared to a mean of 6 years for those with mechanically intact LES (n = 95). A longer period from symptom onset to diagnostics was significantly associated with higher acid exposure. The pathway analysis was significant for the following model: 'history' (P < 0.001➔LES-incompetence & Hiatal Hernia➔(p < 0,001)➔pH-score (P < 0.001).Conclusion: LES-incompetence, the functional deterioration of the LES, and the anatomical alteration at the esophagogastric junction (Hiatal Hernia) as well as an increased EAE were associated with a long history of suffering from GERD. Path modeling suggests a causal sequence overtime of the main disease-parameters, tentatively allowing for a prediction of the course of the disease.

Introduction: The detailed process of a gastroesophageal reflux event is still under controversial discussion. Gastroenterologists have developed and favor the concept of Transient Lower esophageal Sphincter Relaxations (TLESR`s) as the major cause of gastroesophageal reflux episodes. TLESR`s are related with reflux episodes both in healthy individuals and patients with GERD. Another concept around the functional mechanism of the antirefluxbarrier is a more mechanical interpretation of the Lower Esophageal Sphincter (LES), developed by surgeons. The aim of this study is to investigate this relationship between TLESR`s and the mechanical failure of the LES by investigating these criteria in the same individuals. Methods: In a referral center for esophageal and gastric functional disease at the University Hospital in Würzburg, Germany, we investigated healthy volunteers and patients with proven GERD. The assessment of the LES consisted of the overall length, the intraabdominal length, and the end-expiratory pressure of the LES. The manometry was performed in a station-to-station-pull-through technique. The changing LES pressure and the TLESRs were measured with a sleeve catheter according to the protocol published by Dent and Schoeman. The presence of pathologic reflux in patients was evaluated by 24h pH monitoring. Results: In total, 8 healthy volunteers were investigated (median age: 26 years (22-34)). In addition, 21 patients with GERD were evaluated (median age: 49 years (25-68)). The frequency of TLESR´s was quite low in volunteers and patients with 0,4 TLESR`s/h and 0,6 TLESR`s/h respectively. While the frequency of TLESR`s was not different between volunteers and GERD-patients, the percentage of reflux-associated TLESR`s was significantly higher in GERD-patients with mechanically incompetent LES (20,8%), compared to the percentage in GERD-patients with intact LES (6,8%) and also compared to the percentage in healthy volunteers (7,8%) (p<0,001). Conclusion: The present analysis shows a relationship between a mechanically incompetent LES and an increased number of reflux-associated TLESR`s, suggesting that the two mechanisms are not mutually exclusive, but may be instead different measurements of the same condition - a functionally and mechanically defective LES.

This study compared the outcome between patients who had an open and those who had a hybrid esophagectomy for T1 or T3 esophageal adenocarcinoma (eAC). No clear data are available concerning this question based on T-category. Two groups of patients with esophagectomy and high intrathoracic esophagogastrostomy for eAC were analyzed: hybrid (laparoscopy + right thoracotomy) (n = 835) and open (laparotomy + right thoracotomy) (n = 188). Outcome criteria were 30- and 90-day mortality, R0-resection rate (R0), number of resected lymph nodes (rLNs), and 5-year survival rate (5y-SR). For each type of surgery, three patient groups were analyzed: pT1-carcinoma (group-1), cT3Nx and neoadjuvant chemoradiation (group-2), and pT3N0-3 without neoadjuvant therapy (group-3). The comparison was based on a propensity score matching in relation of 1:2 for open versus hybrid. In group-1 (38 open vs 76 hybrid) R0-resection (100%), 30-day mortality (0%), 90-day mortality (2.6% vs 0%), and rLNs (median 29.5 vs 28.5) were not significantly different. The pN0-rate was 76% in the open and 92% in the hybrid group (p = 0.036). Accordingly, the 5y-SR was 69% and 87% (p = 0.016), but the prognosis of the subgroups pT1pN0 or pT1pN+ was not significantly different between open or hybrid. In group-2 (68 open vs 135 hybrid) R0-resection (97%), 30-day (0% vs 0.7%) and 90-day (4%) mortality, rLNs (28.5 vs 26), and 5y-SR (36% vs 41%) were not significantly different. In group-3 (37 open vs 75 hybrid) R0, postoperative mortality, rLNs, and 5y-SR were not significantly different. In a propensity score–matched comparison of patients with an open or hybrid esophagectomy for esophageal adenocarcinoma the quality of oncologic resection, postoperative mortality and prognosis are not different.

BACKGROUND: Attention has been focused on the amplitude of esophageal body contraction to avoid persistent dysphagia after a Nissen fundoplication. The current recommended level is a contraction amplitude in the distal third of esophagus above the fifth percentile. We hypothesized that a more physiologic approach is to measure outflow resistance imposed by a fundoplication, which needs to be overcome by the esophageal contraction amplitude. STUDY DESIGN: The esophageal outflow resistance, as reflected by the intra-bolus pressure (iBP) measured 5 cm above the lower esophageal sphincter (LES), was measured in 53 normal subjects and 37 reflux patients with normal esophageal contraction amplitude, before and after a standardized Nissen fundoplication. All were free of postoperative dysphagia. A test population of 100 patients who had a Nissen fundoplication was used to validate the threshold of outflow resistance to avoid persistent postoperative dysphagia. RESULTS: The mean (SD) amplitude of the iBP in normal subjects was 6.8 (3.7) mmHg and in patients before fundoplication was 3.6 (7.0) mmHg (p = 0.003). After Nissen fundoplication, the mean (SD) amplitude of the iBP increased to 12.0 (3.2) mmHg (p < 0.0001 vs normal subjects or preoperative values). The 95th percentile value for iBP after a Nissen fundoplication was 20.0 mmHg and was exceeded by esophageal contraction in all patients in the validation population, and 97% of these patients were free of persistent postoperative dysphagia at a median 50-month follow-up. CONCLUSIONS: Nissen fundoplication increases the outflow resistance of the esophagus and should be constructed to avoid an iBP > 20 mmHg. Patients whose distal third esophageal contraction amplitude is > 20 mmHg have a minimal risk of dysphagia after a tension-free Nissen fundoplication. ((C) by the American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective and background: The etiology and natural history of gastroesophageal reflux disease (GERD) is discussed in regard to the reported progression of GERD in patients while on proton pump inhibitor (PPI) therapy. The probability of this occurring has led to concern that PPI therapy does not address all aspects of the disease and suggests that in selected patients a minimally invasive surgical procedure may be required for complete therapeutic control of the disease. Study design and methods: Review the literature on GERD and its progression under PPI therapy. If verified, design a plan to prevent progression. Results: Existing literature supports that GERD can progress under PPI therapy and is likely caused by inflammatory injury to the lower esophageal sphincter (LES). Current treatment of progression is elevation of the PPI dose without investigating the condition of the LES. Further, endoscopic biopsies of the squamocolumnar junction (SCJ) within the LES can show microscopic intestinalized metaplastic cardiac mucosa produced by reflux-induced inflammatory injury of the original squamous mucosa. This finding is predictive of future endoscopically visible Barrett esophagus—the precursor of esophageal adenocarcinoma. A proposed algorithm to avoid progression of GERD under therapy using LES augmentation is presented. Conclusions: Patients who partially respond or fail to respond to PPI therapy should undergo biopsies of the SCJ to identify histologic changes predictive of future development of visible Barrett esophagus. Intervention using an LES augmentation procedure is a potential form of effective therapy.

The aim of this study was to investigate influence of delayed gastric emptying on postprandial reflux in esophageal pH. SixtyLnine consecutive patients underwent 24 hour (h) esophageal pH monitoring ancl gastric emptying. In 24 h esophageal pH monitoring, % postprandial reflux pH<4 for 2 h after each meal (% PRI) was extracted from the 24 h pH profile. After solid test meal (1 mCi, Tb99m) was given, gastric emptying was measured with a gamma detector placed transnasally 5 cm below lower esophageal sphincter. % PIU' was similar among the 34 normal, 26 delayed and 9 rapid gastric emptying rate patients. Thirty-five with a positive pH study and 34 with a negative had a similar prevalence of gastric emptying disorder. In the positive pH study group, patients with norrnal gastric emptying had significantly higher % Pl(I' than those with delayed gasnic emptying (22.0 vs 12,1%, P<O.05). In the same population, patients with a normal %PIU' had a significantly higher prevalence of delayed gastric emptying compared with those with a positive % PiU' (618 vs 9127, P<O,05), In patient with abnormal acid exposure but normal % PIrr en 24 h esophageal pH monitoring, gastric emptying may be delayed,

The progression of gastroesophageal reflux disease (GERD) in patients who are taking proton pump inhibitors (PPIs) has been reported by several investigators, leading to concerns that PPI therapy does not address all aspects of the disease. Patients who are at risk of progression need to be identified early in the course of their disease in order to receive preventive treatment. A review of the literature on GERD progression to Barrett's esophagus and the associated physiological and pathological changes was performed and risk factors for progression were identified. In addition, a potential approach to the prevention of progression is discussed. Current evidence shows that GERD can progress; however, patients at risk of progression may not be identified early enough for it to be prevented. Biopsies of the squamocolumnar junction that show microscopic intestinalization of metaplastic cardiac mucosa in endoscopically normal patients are predictive of future visible Barrett's esophagus, and an indicator of GERD progression. Such changes can be identified only through biopsy, which is not currently recommended for endoscopically normal patients. GERD treatment should aim to prevent progression. We propose that endoscopically normal patients who partially respond or do not respond to PPI therapy undergo routine biopsies at the squamocolumnar junction to identify histological changes that may predict future progression. This will allow earlier intervention, aimed at preventing Barrett's esophagus.

Esophageal cancer poses an interesting challenge for oncologists. Esophageal squamous cell cancer has the most varied geographical incidence of any cancer, suggesting the existence of critically important environmental and molecular epidemiologic factors. These factors remain largely unrecognized. Equally puzzling is the dramatic increase in the incidence of adenocarcinomas of the esophagus and gastro-esophageal junction or cardia that has occurred in western societies during the past 3 decades.[1,2] This increase in incidence is particularly disturbing in view of the highly lethal nature of esophageal cancer. For the year 2000, the estimated number of new cases of esophageal cancer in the United States is 12,300 and the estimated number of deaths due to this cancer is 12,100.[3] In response to these challenges, there has been a great increase in the amount of research and the number of publications on malignant and premalignant esophageal diseases. In the 2-week period following January 26, 2000, for example, 136 new English language entries using any of the key words “esophageal neoplasms, Barrett’s esophagus, gastric cardia, and gastro-esophageal reflux” were added on Medline. Many readers of Oncology are thus likely to welcome the efforts by Forastiere et al to review this increasing mass of information. Barrett’s Esophagus and Esophageal Adenocarcinoma The main risk factor for esophageal adenocarcinoma is the presence of Barrett’s esophagus. This is currently defined by most investigators as the replacement of the normal squamous epithelium of the distal esophagus by a visible segment of columnar mucosa containing intestinal metaplasia on microscopic examination. Similar to adenocarcinoma, the incidence of Barrett’s esophagus has been rising rapidly,[4,5] suggesting that the increase in esophageal adenocarcinoma incidence is explained, at least in part, by this increase in Barrett’s. However, another possible explanation is that the proportion of patients with Barrett’s who progress to malignancy has increased. The latter explanation is not supported by recent prospective analyses of the risk of cancer developing in patients with Barrett’s,[6,7] but large population-based studies are needed to properly evaluate this possibility. It may be that the incidence of nonvisible intestinal metaplasia, termed either “ultra-short segment Barrett’s esophagus” or “cardiac mucosa with intestinal metaplasia,” is increasing. Indeed, recent studies have found intestinal metaplasia at the gastroesophageal junction in 9% to 36% of individuals undergoing endoscopy.[8-10] The normal-appearing gastroesophageal junction was rarely studied prior to the mid-1990s. Consequently, a rise in intestinal metaplasia at this site cannot be confirmed. It has been hypothesized that the increasing incidence of adenocarcinoma at the gastroesophageal junction or cardia is a consequence of this putative increase in the incidence of nonvisible areas of intestinal metaplasia. As Forastiere et al note, there is considerable variability in the reported risk of developing adenocarcinoma within a segment of Barrett’s esophagus. In part, this reflects the fact that none of the reported prospective studies has included sufficient numbers of patients to make definitive estimates, and that the size of a study required to provide these estimates is prohibitively large. Furthermore, because only a small proportion of Barrett’s mucosa is usually biopsied at endoscopy, there is considerable risk that patients with Barrett’s are staged incorrectly for the presence and grade of dysplasia, thus confounding estimates of the cancer risk in supposedly nondysplastic Barrett’s epithelium. Even when Barrett’s segments are carefully evaluated histologically, with a large number of biopsies taken throughout the Barrett’s segment, conventional examination of the

The increasing incidence of adenocarcinoma of the lower esophagus and cardia arising in Barrett's metaplastic epithelium continues to be of great concern because medical and surgical efforts to reverse the process have been disappointing. A potential answer to the problem is removal of the metaplastic epithelium. Modern technology has introduced physical and chemical modalities which facilitate ablation of the neo-epithelium endoscopically. These techniques have been used in several centers, and preliminary results are encouraging. This report summarizes the proceedings of an international symposium on ablative therapy held in Brittany, France in August 1997. Twenty-eight speakers contributed to the talks on the pathology, pathogenesis, current therapy experimental studies and clinical experience of ablation of Barrett's esophagus.

Diagnosis of gastroesophageal reflux disease (GORD) is delayed by the lack of uniform histopathologic criteria for diagnosis. The only practical value of pathology is the assessment of columnar lined esophagus (CLO). As a result, GORD is treated with acid suppressive drug therapy until there is a failure to control symptoms and/or advanced adenocarcinoma develops. The reasons why there is a failure of pathologic diagnosis are two false dogmas that result in two widely believed fundamental errors. These are the belief that cardiac epithelium normally lines the proximal stomach (1) and that the gastroesophageal junction (GOJ) is defined by the proximal limit of rugal folds (2). When these false dogmas are eradicated by existing powerful evidence, the pathology of GERD falls into the following stages, all defined by histology: (a) The normal state where the esophageal squamous epithelium transitions at the GOJ to gastric oxyntic epithelium with no intervening cardiac epithelium; (b) cardiac metaplasia of the squamous epithelium due to exposure to gastric juice results in cephalad movement of the squamo-columnar junction (SCJ). This creates the squamo-oxyntic gap and the dilated distal esophagus, which is distal to the endoscopic GOJ. The length of the squamo-oxyntic gap in the dilated distal esophagus is concordant with the shortening of the abdominal segment of the lower esophageal sphincter (LOS); (c) in the early stages, the gap is <5 mm and the LOS retains its competence. Reflux is uncommon and patients are asymptomatic; (d) the squamo-oxyntic gap increases in length, concordant with the amount of shortening of the LOS, which becomes increasingly incompetent. At a gap length of 5-15 mm, reflux is sufficient to cause symptoms, but in most patients, symptoms are controllable and the patients are normal at endoscopy. The gap is entirely within the dilated distal esophagus, which is mistaken by present criteria for proximal stomach. (e) The last stage of GORD is when the squamo-oxyntic gap is >15 mm. In these patients, reflux is severe with increasingly uncontrollable symptoms and columnar lined esophagus, both irreversible states.Understanding this pathophysiology of GORD by these new histologic criteria will allow diagnosis at the earliest and eminently reversible stages of the disease. This can open the door to new methods of treatment that will have the potential to prevent progression to the irreversible phase of GORD, including columnar lined esophagus. If successful, this will effectively prevent progression to adenocarcinoma.

Endoscopic therapy has revolutionized the treatment of Barrett’s esophagus with high-grade dysplasia (HGD) or intramucosal adenocarcinoma by allowing preservation of the esophagus in many patients who would previously have had an esophagectomy. This paradigm shift initially occurred at high-volume centers in North America and Europe but now is becoming mainstream therapy. There is a lack of uniform guidelines and algorithms for the management of these patients. Our aim was to review important concepts and pitfalls in the endoscopic management of superficial esophageal adenocarcinoma.

Journal of Laparoendoscopic & Advanced Surgical TechniquesVol. 25, No. 9 Interview25th Anniversary State-of-the-Art Expert Discussion With Tom R. DeMeester, MD, on GERDInterview by C. Daniel SmithInterview by C. Daniel SmithSearch for more papers by this authorPublished Online:16 Sep 2015https://doi.org/10.1089/lap.2015.29003.trdAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited byMagnetic Sphincter Augmentation and Postoperative Dysphagia: Characterization, Clinical Risk Factors, and Management6 August 2019 | Journal of Gastrointestinal Surgery, Vol. 24, No. 1Perspectives on the interlinked nature of systemic sclerosis and reflux disease4 January 2019 | Expert Review of Gastroenterology & Hepatology, Vol. 13, No. 3 Volume 25Issue 9Sep 2015 InformationCopyright 2015, Mary Ann Liebert, Inc.To cite this article:Interview by and C. Daniel Smith.25th Anniversary State-of-the-Art Expert Discussion With Tom R. DeMeester, MD, on GERD.Journal of Laparoendoscopic & Advanced Surgical Techniques.Sep 2015.695-701.http://doi.org/10.1089/lap.2015.29003.trdPublished in Volume: 25 Issue 9: September 16, 2015PDF download

I read with interest the report by Rodriquez et al 1 Rodriguez L. Rodriquez P. Gomez B. Ayala J. Oxenberg D. Perez-Castilla A. et al. Two-year results of intermittent electrical stimulation of the lower esophageal sphincter treatment of gastroesophageal reflux disease. Surgery. 2015; 157: 556-567 Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar and the editorial by Attwood 2 Attwood S.E. Electrical stimulation for gastroesophageal reflux disease: formal randomized clinical trials are needed. Surgery. 2015; 157: 568-569 Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar on the electrical stimulation of the lower esophageal sphincter (LES) for the therapy of gastroesophageal reflux disease (GERD). Attwood acknowledges the ongoing existence of a gap in our therapeutic armamentarium for the treatment of GERD and explains the unique benefits of electrical LES modulation as a solution to the problem. I was impressed by the 2-year sustained decrease in esophageal acid exposure obtained with the device and concur with Dr Attwood's comment that “there is no other therapy that has this magnitude of effect and lack of side effects.” Reply “Electrical stimulation for GERD: The need for controlled clinical trials”SurgeryVol. 158Issue 5PreviewI appreciate the comments and constructive criticism by Dr Tom DeMeester in his letter.1 He states correctly that the placebo effect of a sham procedure on esophageal acid reduction is small or nonexistent and this, together with the encouraging safety results and side effect profile of this therapy, provides a rationale for using the system in a group of well-selected patients. However, the impact of a sham procedure on symptoms is evident, and there would be value in running a sham-controlled clinical trial. Full-Text PDF