Complications Of Gastroesophageal Reflux Disease Research Articles

The Pathophysiological Mechanisms of GERD in the Obese Patient

Obesity has increased dramatically in the last 30 years, affecting 33% of the adult population in the United States. Increase in body mass index has been shown to be associated with the increase in the prevalence of gastroesophageal reflux disease (GERD) symptoms, esophageal mucosal injury, and GERD complications. The putative mechanisms responsible for the close relationship between GERD and increased body mass index include increased intragastric pressure, increased gastroesophageal pressure gradient, esophageal motor and sensory abnormalities, increase in prevalence of hiatal hernia, increase in serum female hormonal levels, diet, and increase in comorbidities. Whilst the current efforts are to focus on one major underlying mechanism, it is highly likely that multiple factors contribute to the increased prevalence of GERD in the obese patient.

Confronto tra il color Doppler con MdC ecografico e pH-metria nella diagnosi del reflusso gastro-esofageo nei bambini

The aim of this study was to evaluate the accuracy of contrast-enhanced colour-Doppler ultrasound (CDUS) in the diagnosis of gastro-oesophageal reflux in children. One hundred and twenty children (68 boys and 52 girls aged between 1 month and two years) with a clinical suspicion of gastro-oesophageal reflux (postprandial vomiting, weight loss, failure to thrive, anaemia, night-time coughing and crying, regurgitation, etc.) were studied by contrast-enhanced CDUS and subsequently by 24-hour pH-metry. Results of the two techniques were compared using the McNemar test. Gastro-oesophageal reflux was detected on CDUS in 84 patients and with 24-h pH-metry in 86. In all cases of reflux, CDUS visualised the passage of contrast material from the stomach into the abdominal and middle and distal third of the thoracic oesophagus, enabling assessment of the segment of oesophagus involved by the reflux. Compared with pH-metry, CDUS had a sensitivity of 98% (p<0.0001 with McNemar's test). In consideration of the results obtained and particularly of the low level of invasiveness, contrast-enhanced CDUS could be used to monitor children undergoing medical or surgical treatment for the complications of gastro-oesophageal reflux disease.

Gastro-oesophageal reflux symptoms, oesophagitis and Barrett’s oesophagus in the general population: the Loiano–Monghidoro study

Objective:Existing endoscopy-based data on gastro-oesophageal reflux disease (GORD) in the general population are scarce. This study aimed to evaluate typical symptoms and complications of GORD, and their associated risk factors,...

Proton pump inhibitors in Barrett's esophagus: Pluripotent but controversial

BACKGROUND: Barrett's esophagus (BE), a significant complication of gastro-esophageal reflux disease (GERD), is the single most important risk factor for esophageal adenocarcinoma. The strong association between BE and chronic GERD suggests that abnormal esophageal acid exposure plays a vital role in this condition. METHODS: Review on PPI treatment for Barrett's esophagus. RESULTS: The progression of BE from specialized intestinal metaplasia to dysplasia and finally invasive carcinoma is incompletely understood, but increased and disordered proliferation is a key cellular event. In both ex vivo experiments and clinical trials in humans, effective acid suppression scales down the proliferative activity of Barrett's metaplasia and the likelihood of dysplasia as well. Today, proton pump inhibitors (PPIs) are almost universally used for the management of reflux symptoms in patients with BE while they may offer many other benefits when used as single agents or in conjunction with pharmacologic or endoscopic therapies. Yet, acid suppression with these drugs may be suboptimal in many patients and their ultimate role in preventing cancer formation has not yet been proven. Because PPIs are life-long therapy for patients with BE, their potential drawbacks need to be reviewed and their relative value need to be balanced when compared to laparoscopic fundoplication. CONCLUSIONS: The ability of PPIs to suppress acid profoundly and consistently may be crucial in the long-term management of BE and esophageal cancer chemoprevention.

Prevalence of Complicated Gastroesophageal Reflux Disease and Barrett's Esophagus Among Racial Groups in a Multi-Center Consortium

Prevalence of Complicated Gastroesophageal Reflux Disease and Barrett's Esophagus Among Racial Groups in a Multi-Center Consortium

Nighttime Heartburn in Patients with Gastroesophageal Reflux Disease under Routine Care

Background: Gastroesophageal reflux disease (GERD) is a common disorder. The aim of our study was to describe the prevalence of nighttime heartburn and its associations with esophagitis, Barrett’s esophagus, and extra-esophageal symptoms. Methods: Data were collected as part of the ongoing Progression of Gastroesophageal Reflux Disease (ProGERD) study. Based on endoscopy results, patients were categorized as having nonerosive GERD, erosive GERD, or Barrett’s esophagus. ORs and 95% CIs derived from logistic regression analysis were calculated for the association between nighttime heartburn and GERD complications. Results: The overall prevalence of nighttime heartburn for at least 1 of 3 years was 49%, and 21% of patients reported nighttime heartburn in all 3 years. According to multivariate analysis, chronic nighttime heartburn was associated with globus sensation (OR 1.79, 95% CI 1.29–2.47) and erosive GERD (OR 1.67, 95% CI 1.29–2.15). Compared to continuous proton pump inhibitor (PPI) intake, noncontinuous PPI therapy (OR 2.26, 95% CI 1.73–2.96) and medication other than PPIs (OR 2.46, 95% CI 1.67–3.62) were also associated with chronic nighttime heartburn. Conclusions: The prevalence of nighttime heartburn in GERD patients under routine care was high, even in patients on continuous PPI therapy. Nighttime heartburn was not associated with Barrett’s esophagus or most extra-esophageal symptoms.

Gastro-Oesophageal Reflux Disease in Asia

Gastro-oesophageal reflux disease (GORD) is one of the most common gastrointestinal diseases in the Western world and imposes a heavy burden on society. Although its prevalence in Asia is much lower, there is evidence that this is rapidly rising in Asia. The reported population prevalence of GORD in Eastern Asia ranges from 2.5% to 6.7% for at least weekly symptoms of heartburn and/or acid regurgitation. In general, Asians tend to have a milder spectrum of the disease. Most Asian patients have non-erosive GORD; erosive oesophagitis is less commonly seen than in the Western population. Complicated GORD, such as oesophageal stricture and Barrett's oesophagus, is seldom encountered. The mechanisms of GORD may be different in the Chinese population compared with the Western population. Chest pain is the most predominant extra-oesophageal manifestation of GORD in China, whereas an association with asthma has been shown in Japanese patients. The prevalence of GORD appears to be increasing and possible factors for GORD in Asian populations include Helicobacterpylori infection, obesity and increasing dietary fat intake. The adoption of a Western lifestyle in many developing Asian countries may account for the increasing prevalence of GORD. Proton pump inhibitors remain the most effective medical treatment for GORD. GORD will undoubtedly be a great challenge to clinicians both in primary care and in gastroenterology practice in the Asia-Pacific region in the coming years.

Barrett's Esophagus: Diagnosis, Screening, Surveillance, and Controversies.

Barrett's esophagus (BE) is a frequent complication of gastroesophageal reflux disease, an acquired condition resulting from persistent mucosal injury to the esophagus. The incidence of Barrett's metaplasia and Barrett's adenocarcinoma has been increasing, but the prognosis of Barrett's adenocarcinoma is worse because individuals present at a late stage. Attempts have been made to intervene at early stage using surveillance programmes, although proof of efficacy of endoscopic surveillance is lacking. There is much to be learned about BE. Whether adequate control of gastroesophageal reflux early in the disease alters the natural history of Barrett's change once it has developed remains unanswered. Thus there is great need for carefully designed large randomised controlled trials to address these issues in order to determine how best to manage patients with BE. The AspECT and BOSS clinical trials proride this basis.

Epidemiology of oesophagogastric cancer

Oesophagogastric cancer occurs in the oesophagus, the oesophagogastric region and the stomach, including the proximal and distal stomach. In 2005, the worldwide burden of oesophagogastric cancer was estimated to be 1,500,000 new cases (500,000 oesophagus and 1,000,000 stomach). Squamous cell cancer is linked with alcohol and tobacco consumption in Western countries. Its incidence is much higher in regions of Asia with a low-socio-economic status, nutritional deficiencies, poor oral status, carcinogens absorbed with smoked meat, fat-cooked foodstuffs, vegetables containing toxic alkaloids or mycotoxins, and water containing nitrites, nitrates and nitrosamines. Adenocarcinoma develops in the columnar lined oesophagus. Its incidence is still low but there is an increasing trend. The incidence of stomach cancer is decreasing worldwide, but is still high in Japan. Causal factors include Helicobacter pylori infection with atrophic gastritis and a diet poor in fruit and vegetables. Preneoplastic conditions of the oesophagogastric mucosa include erosive oesophagitis in alcoholics, columnar lined oesophagus as a complication of gastro-oesophageal reflux disease, and atrophic gastritis following H. pylori infection.

Body mass index and GERD: Is the association that huge?

Body mass has been proposed as a modifiable risk factor for gastroesophageal reflux disease (GERD). Although this association makes intuitive sense, study results conflict. This article critically reviews the epidemiologic and mechanistic data surrounding the relationship between body mass index (BMI) and GERD, evaluates how the relationship may depend upon abdominal size, and explores potential alternative mechanisms through which body mass may influence the risk of GERD complications.

GERD und Komplikationen: Wann ist der Chirurg gefragt?

Esophagitis, ulcer with potential for bleeding and peptic stenosis are typical complications of gastroesophageal reflux disease (GERD). Whereas GERD is frequent with symptom prevalence of 30 % in the normal population, ulcer and peptic stenosis have become very rare. Consequently surgical interventions due to these complications are only necessary in exceptional cases. After successful bougienage and response to adequate medical treatment, surgical indications for peptic stenosis or ulcer are not different to those for other forms of reflux disease. GERD patients with a "short esophagus" and axial hiatal hernia are difficult to treat either by medication or surgery. However, intrathoracic fundoplication may lead to acceptable results. Extraesophageal manifestations of GERD are caused by a severe reflux up to the cervical esophagus. The resulting laryngitis or pulmonary problems require antireflux surgery more often than in the absence of these symptoms. Long-standing reflux can lead to the development of Barrett mucosa, which represents a precancerous for esophageal adenocarcinoma and can be considered as a special complication of GERD. Retrospective data show that progression of Barrett mucosa or its malignant degeneration cannot be prevented by fundoplication. However, in a comparative study concerning low-grade neoplasia fundoplication leads to significantly more cases with regression than medication. High-grade neoplasia has to be removed in all cases. With regard to the prerequisite for correct indications the long-term results of endoscopic or surgical procedures are equal, but endoscopic mucosectomy is favoured due to its lower invasiveness. Indications for surgery by limited or radical esophagectomy are incomplete removal of neoplasia after mucosectomy, long Barrett's esophagus with multifocal lesions or suspicion of submucosal carcinoma.

Effects of Age on the Gastroesophageal Junction, Esophageal Motility, and Reflux Disease

The prevalence of complicated gastroesophageal reflux disease (GERD) increases with age; however, the mechanism by which this occurs is uncertain. This study assessed (1) whether physiologic degradation of the gastroesophageal junction and esophageal motility occurs with aging, and (2) whether these effects are associated with increased esophageal acid exposure and reflux symptoms in the elderly. Retrospective study of 1307 patients referred for investigations of reflux symptoms (median age, 49 years; range, 15-92 years) was conducted. Manometry assessed LES pressure, LES length, and esophageal peristalsis. Ambulatory pH studies assessed esophageal acid exposure (% time pH <4) during a period of 24 hours; reflux symptoms were assessed by validated questionnaire. On multivariate regression, esophageal acid exposure was associated independently with decreasing LES pressure (P < .0001) and abdominal LES length (P < .0004). Dysmotility exacerbated reflux in the recumbent position (P < .004). Acid exposure increased with age (P < .0001), a 1.1%/24 hours (95% confidence interval, 0.4%-1.4%) increase in acid exposure every decade (more pronounced in the recumbent position). The age-related increase in acid exposure was associated independently with decreasing abdominal LES length (P < .001) and increasing dysmotility (P < 0.01). Reflux symptoms increased with acid exposure (P < .001); however, at any given level of exposure, symptom severity was less in the elderly (P < .006). Age was associated with an increase in esophageal acid exposure; however, the severity of reflux symptoms reduced with age. These changes were associated with progressive decrease in abdominal LES length and esophageal motility. Increasing GERD severity in the elderly is related to degradation of the gastroesophageal junction and impaired esophageal clearance.

Pediatric and adolescent GERD

Gastroesophageal reflux (GER) and GER disease (GERD) are common problems in children and adults. Most infants with GER achieve symptomatic resolution by 1 year of age and are not thought to develop GERD later in life; most adults tolerate intermittent symptoms of heart-burn and nerve develop complications of GERD. Recent data suggest that some children who have persistent GER in infancy may develop symptoms of reflux in preadolescence. Similarly, when symptoms of reflux begin after the age of 2 years, concerns are raised that these symptoms could be early manifestations of GERD later in childhood, adolescence, or as an adult. Identification of children and adolescents with GERD, who may become adults with GERD or experience complications of GERD, is a significant challenge for practitioners. Implementation of safe and effective therapies is essential for not only improving symptoms and quality of life but also preventing long-term complications of GERD in adulthood.

Role of gastroscopy in gastro-oesophageal reflux disease (GORD)

AbstractBackgroundThis two-year study is a retrospective analysis of records of patients diagnosed with gastro-oesophageal reflux disease (GORD) at a private medical aid society for the period January 2002 to December 2003. In this study of GORD and its complications, the use of gastroscopy as a staging criteria and the cost of treatment were evaluated. Patients with alarming symptoms (chronic gastrointestinal bleeding, progressive unintentional weight loss, progressive difficulty in swallowing, persistent vomiting, iron deficiency anaemia, epigastric mass or suspicious barium meal), those with complications of GORD (erosive oesophagitis, ulcerative oesophagitis, oesophageal strictures, Barrett's oesophagus and oesophageal adenocarcinoma), and patients in whom symptoms have not resolved need to have a gastroscopy performed. If left untreated, some of these symptoms could lead to more severe and serious complications. Accurate recognition of these symptoms will help to identify, evaluate and treat patients...

Value of a Novel Multi-Factorial Scoring System as a Diagnostic Aid in the Prospective Evaluation of Patients with Reflux-Like Dyspepsia

Purpose: Reflux-like dyspepsia (RLD), where predominant epigastric pain is associated with heartburn and/or regurgitation, is quite prevalent and has variable response to proton pump inhibition (PPI) therapy. Since symptom frequency and severity vary, there is frequent overlap among gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD) and RLD. We assessed the potential of an algorithm and a multi-factorial scoring system in discriminating patients presenting with RLD from those with true GERD or NERD. Methods: We prospectively evaluated an outpatient, community-based, cohort presenting with RLD using the following algorithm: After an initial symptom evaluation (epigastric pain, heartburn, regurgitation, dysphagia), endoscopy and distal esophageal biopsies were performed to evaluate the structure of the esophagus, stomach and duodenum, followed by esophageal motility and 24-hr ambulatory pH monitoring to assess esophageal function and pathologic acid exposure. Results: 110 patients (35 men, 75 women) were evaluated. Endoscopy showed erosive or complicated GERD in 33 patients (30%) and it was normal in 77 patients (70%). Of this latter group, 62 (56%) had abnormal pH and motility studies and were classified as patients with NERD. The remaining 15 (14%) had normal functional studies and were classified as patients with RLD. A disease severity score was then applied (Table). The scoring system effectively distinguished patients with GERD (mean score 8.69, range 5–15), NERD (mean score 6.22, range 3–10) and RLD (mean score 3.27, range 2–4). A score higher than 4 excludes RLD; a score higher than 10 excludes NERD. Conclusion: An algorithmic evaluation and scoring of patients presenting with RLD effectively distinguishes patients with NERD and GERD from those with functional RLD, facilitates long-term management and defines the need for continuous PPI therapy.Table: Components of disease severity score.

The association of gastric leptin with oesophageal inflammation and metaplasia

Background:Gastro-oesophageal reflux disease complications may reflect imbalances between protective and injurious factors. Through its effects on cell growth, leptin may influence oesophageal mucosal homeostasis.Aims:To determine whether leptin receptors are present...

Nissen versus Toupet fundoplication: Results of a randomized and multicenter trial

Laparoscopic Toupet fundoplication (TF) is reported to be as effective as Nissen (NF), but to be associated with fewer unfavorable postoperative side-effects. This study evaluates the one- and three-year clinical outcome of 140 randomized patients after a laparoscopic NF or TF. Inclusion criteria included patients over 16 years old with complications of gastro-oesophageal reflux disease (GORD) and persistence or recurrence of symptoms after three months of treatment. Subjects with a previous history of gastric surgery or repeated fundoplication, brachy-oesophagus or severe abnormal manometry results were excluded. Seventy-seven NF and 63 TF were performed. The severity of symptoms was assessed before and after the procedure. One hundred and twenty-one of the 140 patients after one year, and 118 after three years, were evaluated and no statistically significant clinical difference was observed. The level of satisfaction concerning the outcome of the operation remained high after one or three years regardless of the type of fundoplication performed. Functional complications after NF are not avoided with TF.

GERD

Gastroesophageal reflux disease (GERD) is a common acid-related disorder presenting with a broad spectrum of symptoms with or without esophageal mucosal damage and/or complications. In general, the frequency and severity of symptoms and esophagitis correlate with the severity and duration of acid exposure, particularly during the nighttime. Acid suppression, with proton pump inhibitors (PPIs), is the mainstay of acute and maintenance treatment of GERD. Optimizing the choice of PPI and dose is essential for controlling GERD symptoms, accelerating healing of esophagitis, and preventing the long-term complications. Postprandial acid control is needed during the day particularly to control the symptoms. Additionally, acid control especially in those with nighttime symptoms or severe mucosal injury is important for preventing complicated GERD. However, there is a substantial proportion of patients who do not respond to routine PPI therapy probably because of inadequate acid suppression or nonacid-related problems. Failure to respond to twice daily PPIs can be partly explained by the short half-lives of currently available PPIs that may fail to adequately control acid secretion after midnight, even if given before the evening meal. There has been considerable discussion in recent years over nocturnal acid breakthrough, which is really a misnomer, as this represents the pattern of acid secretion when there is no drug available to inhibit secretion. Several approaches to properly controlling acid secretion have included b.i.d. dosing of PPIs, adding an H2-receptor antagonist at night and the development of an instant release PPI. The former approaches have not been universally effective and clinical studies not yet performed with the latter. There are several new acid suppressing drugs in development and these include PPIs with longer half-lives, which give more prolonged acid suppression. In addition, there are drugs which block the potassium channel (potassium competitive acid blockers) of the proton pump and which have a rapid onset of action. These drugs are under investigation and some may require more than 1 dose daily to adequately control acid secretion. In this review, we further explore different aspects of the need for new PPIs for the optimal management of GERD.

Polymorphisms of glutathione S-transferase M1, T1 and P1 in patients with reflux esophagitis and Barrett’s esophagus

Reflux esophagitis (RE) and Barrett's esophagus (BE) belong to the most common esophageal complications of gastroesophageal reflux disease. Glutathione S-transferase (GST) enzymes play an important role in cellular protection against oxidative stress and toxic foreign chemicals. Therefore, we investigated the hypothesis that polymorphisms in genes for these detoxifying enzymes could influence susceptibility to RE and BE. GSTM1, GSTT1 and GSTP1 loci were analyzed by PCR-based methods in 64 patients with RE (and an additional group of 22 subjects with BE as the fourth grade of esophagitis) and 173 unrelated controls. There were no significant differences in the distributions of GSTM1 and GSTT1 genotypes between the controls and patients with RE or BE. Similarly, frequencies of GSTP1 alleles were non-significantly different between the control and RE groups. However, GSTP1 B allele carriers were more frequent among the patients with BE compared to those in the reflux esophagitis group (P=0.04, OR=2.10, 95% CI 0.99-4.44) and most significantly when compared to the controls (P=0.0067, Pcorr<0.05, OR=2.56, 95%CI 1.30-5.05). Although the GSTM1 and GSTT1 genes did not show any relationship with reflux disease, the GSTP1 gene might be one of the risk factors associated with susceptibility to RE, especially to BE.

The prevalence of Helicobacter pylori infection and the status of gastric acid secretion in patients with gastroesophageal junction adenocarcinoma in Japan

We have previously reported that H. pylori infection prevents reflux esophagitis (RE) and Barrett's esophagus (BE) by decreasing gastric acid secretion. Gastroesophageal (GE) junction adenocarcinoma, including Barrett's adenocarcinoma, has been thought to be a complication of gastroesophageal reflux disease. However, the relationship between H. pylori infection, gastric acid secretion and GE junction adenocarcinoma had not yet been investigated in Japan. We demonstrated that the status of gastric acid secretion was higher in patients with GE junction adenocarcinoma than in patients with early gastric cancer (EGC), and that the level was the same in patients with RE and those with BE. We also found that the prevalence of H. pylori infection in patients with GE junction adenocarcinoma was significantly lower than that in patients with EGC, although not as low as that in patients with RE and BE, suggesting that preservation of gastric acid secretion may be important for the development of GE junction adenocarcinoma in Japanese people, regardless of the presence of H. pylori infection.