Development Of Gastroesophageal Reflux Disease Research Articles

Enfermedades relacionadas con Helicobacter pylori: dispepsia, úlcera y cáncer gástrico

This article summarizes the main conclusions drawn from the presentations on Helicobacter pylori infection at Digestive Disease Week 2011. In developed countries, the prevalence of H. pylori infection has decreased, but seems to have reached a plateau at a fairly high level. Antibiotic resistance is increasing in several countries. H. pylori eradication does not contribute to the development of gastroesophageal reflux disease or worsen its course. The frequency of idiopathic peptic ulcers seems to be increasing. H. pylori eradication eliminates almost all episodes of peptic ulcer rebleeding; nevertheless, the use of non-steroidal anti-inflammatory drugs or H. pylori reinfection can lead to bleeding recurrence. H. pylori-negative patients with peptic ulcer bleeding more frequently have bleeding recurrences and higher mortality. In each particular population, there is a close correlation between the prevalence of H. pylori infection and the incidence of gastric cancer. H. pylori eradication is associated with a higher and faster healing rate of ulcerous lesions caused by endoscopic submucosal dissection. In patients undergoing endoscopic submucosal dissection for early gastric cancer, H. pylori eradication decreases the incidence of metachronous tumors. In a high proportion of cases, H. pylori eradication induces MALT lymphoma regression, and long-term tumoral recurrences are exceptional. Narrow-band imaging allows visualization of the mucous and vascular pattern in H. pylori-infected patients during the endoscopic examination. The electrochemical properties of H. pylori allow these lesions to be rapidly and accurately detected in gastric biopsies. The efficacy of “traditional” triple therapies currently leaves much to be desired. The superiority of “sequential” therapy over the standard triple therapy should be confirmed in distinct environments. The “concomitant” quadruple therapy seems to be as effective as “sequential” therapy, but with the advantage of being simpler. Both the “sequential” and the “concomitant” regimens are relatively effective even when clarithromycin resistance is present. Second-line rescue therapy with levofloxacin for 10 days is effective and is simpler and better tolerated than quadruple therapy. In patients allergic to penicillin, a combination with levofloxacin and clarithromycin is a promising rescue alternative. The new-generation quinolones, such as moxifloxacin and sitafloxacin, could be useful as eradication treatment. After two eradication treatment failures, an empirical third-line rescue therapy may be a valid option in clinical practice. Even after three previous H. pylori eradication failures, an empirical fourth-line rescue treatment with rifabutin may be effective.

Dietary nitrate may have a role in development of gastro-esophageal reflux disease.

Gastro-esophageal reflux disease (GERD) has become very common in the past three decades. The reason for this, as well as its exact pathophysiologic mechanisms are yet unknown. In this ecologic study we assessed the relation between water nitrate content and prevalence of GERD in Tehran, Iran. We determined the prevalence of acid regurgitation, heartburn or any of them occurring on a frequent (at least weekly) or infrequent basis in areas with different water nitrate. The areas for nitrate were defined as below: <50 mg nitrate/L, 50-74 mg/L, 75-100 mg/L, and >100 mg/L. Frequency of each symptom was assessed in each area and compared. Adjustment for age, sex, education, NSAID-consumption, BMI, smoking, history of GERD in first degree relatives and spouse was done in a multivariate model. People living in areas with water nitrate content more than 100mg/L had a higher chance of suffering from frequent AR than those living in areas with water nitrate less than 100mg/L (25.5% vs. 12.0%, OR: 2.53, 95% CI: 1.36-4.73, P=0.006). After adjustment for the named factors, the relationship remained significant (OR: 3.65, 95% CI: 1.32-10.09). The relation for frequent heartburn or infrequent symptoms was not significant. In this ecologic study, we found a relation between experiencing frequent AR and drinking or cooking with water containing more than 100mg nitrate/L. Considering our current knowledge, if we put dietary nitrate into the puzzle of increased prevalence and/or pathophysiology of GERD, it can theoretically answer several questions. Hence we propose a nitrate-hypothesis for GERD pathogenesis.

What is the Incidence of Barrett's and Gastric Metaplasia in Esophageal Atresia/Tracheoesophageal Fistula (EA/TEF) Patients?

Aim of the study was to document the incidence of gastric and intestinal metaplasia (Barrett's esophagus) in a closely followed group with EA/TEF, determine the efficacy of pH probe studies in diagnosing reflux and, moreover, to determine the lag period between the development of gastroesophageal reflux disease (GERD) and metaplasia. Patients who underwent EA/TEF correction were followed up over an 18-year period (1990-2009) with regular pH probe and endoscopy investigations. Biopsies were performed at 3 year intervals to evaluate for metaplastic changes in the esophageal epithelium. The interval between esophageal atresia correction and the development of erosive esophagitis, gastric metaplasia and Barrett's esophagus was determined. The development of complicated GERD was statistically correlated to age at detection. 51 patients (28 male) underwent EA/TEF correction during the study period. The ages of the children followed up ranged from 7 months to 19 years. There were 5 Type A, 44 Type C and 2 Type D fistulas. 37 patients (5 Type A, 31 Type C, 1 Type D) had documented reflux and 14 did not. 17 (46%) of the patients with reflux underwent an anti-reflux operation. 4 of the 17 underwent 2 or more anti-reflux procedures. 21 patients had pH probe studies positive for reflux, 3 had negative pH probe studies after an anti-reflux operation. 18 of the 37 patients with reflux (about 50%) needed esophageal dilatation for either anastamotic or non-anastamotic strictures. Only 4/14 (28.5%) patients without reflux underwent dilatations and only in their first year of life (p=NS). 15 patients had mucosal abnormalities in endoscopic biopsies. 8 patients had gastric metaplasia and 1 patient had Barrett's esophagus. The mean age in the group with metaplasia (gastric and intestinal) was 13 years, which was significantly different from the mean age of the group (5.2 years) without mucosal changes (p<0.001). 2 patients with normal pH probe studies had metaplasia on biopsies. Metaplasia arises in about 15% of patients with EA/TEF. The lag time to developing metaplasia from the time of initial surgical correction is about 10 years. Endoscopy and biopsies are the best way of detecting mucosal changes.

Platelet 12-lipoxygenase and stem cells in Barrett’s esophagus

Esophageal adenocarcinoma has shown a significant increase in incidence in recent years. It is thought that the development of gastroesophageal reflux disease (GERD), followed by columnar-lined esophagus and the development of dysplasia, leads to invasive adenocarcinoma. The exact pathogenesis of this process, the diagnosis and differentiation of the metaplastic and dysplastic esophageal lesions have yet to be determined. The purpose of this immunohistochemical study was to investigate the expression of pro-tumorigenic enzyme platelet 12-lipoxygenase (p12LOX) using two new available antibodies in non-dysplastic and dysplastic Barrett's esophagus. The stem cell markers nestin, CD117 and CD44, were then evaluated. The comparative group included GERD carditis, gastric intestinal metaplasia and colorectal adenoma. The overexpression of p12LOX detected by two specific antibodies in the non-dysplastic and dysplastic Barrett's mucosa clearly demonstrated that this enzyme plays an important role in the development of esophageal adenocarcinoma.

Helicobacter pylori infection and Nonmalignant Diseases

Several interesting studies have been published on nonmalignant Helicobacter pylori-related conditions over the past year, which are reviewed in this article. A revival of interest in the histologic classification of gastritis has led to grading of gastritis into stages correlating with risk of neoplastic progression, new data to improve this concept have been published. Unselected prescription of proton-pump inhibitors in patients with dyspepsia has been questioned by the finding that withdrawal of proton-pump inhibitors induces acid-related symptoms in healthy volunteers, probably by the mechanism of rebound gastric acid hypersecretion. Additional data on the rationale of tapering proton-pump inhibitor therapy are therefore awaited. Moreover, new data on peptic ulcer disease and its complications provide clear recommendations for daily clinical practice. Testing and eradication of H.pylori in patients with peptic ulcer bleeding is essential. However, in H.pylori-negative peptic ulcer disease, high overall patient mortality should be acknowledged, and this should guide considering continuation of nonsteroidal anti-inflammatory drugs. The role of H.pylori in the pathogenesis of gastroesophageal reflux disease is still unclear. An association has been described by several studies; however, it cannot be translated to individual risks for development of gastroesophageal reflux disease after H.pylori eradication. Possibly, additional data on subgroups, such as gastric ulcer, duodenal ulcer patients, and associated gastric mucosal changes, will solve this issue.

Short Segment Hiatal Hernia - The Long and the Short of It

The role of hiatal hernias (HH) has traveled through the full swing of the pendulum. Initially thought to be necessary for gastro-esophageal reflux, subsequently HH as a pathologic entity fell out of favour and was considered an incidental finding of no real consequence. In the last decade, HH have found favour again and are now established risk factors for the development of gastro-esophageal reflux disease (GERD), non-erosive reflux disease (NERD), Barrett's oesophagus, and oesophageal adenocarcinoma. Moreover HH have now been demonstrated impair the effect of proton pump inhibitors (PPI).1-9 To date most authors would consider a hiatus hernia, referred to Hyun et al. as long segment hiatus hernia (LSHH), to be present if the diaphragmatic indentation (diaphragmatic crus) is seen 2 cm or more distal to the Z-line and the top of the stomach mucosal folds.10,11 The manuscript by Hyun et al. is the first to suggest that hiatal hernias between 0.5-2 cm are significantly associated with columnar lined epithelium (CLE) and Los Angeles grade A reflux oesophagitis. Here the rates of CLE and grade A oesophagitis was greater or on par with patients who had LSHH. Moreover the study found that HH was present in 9.3% of patients with SSHH comprising the majority (5.6%) dwarfing the rate of LSHH (3.8%). HH can be of three types, with type 1 (sliding) HH the type in question in this study which accounts for about 90% of all HH.12 Type I (sliding) HH results from laxity and loss of elasticity of the phreno-oesophageal ligament. Currently HH is regarded as present if greater than 2 cm difference is detected because of the inherent margin of error, as the gastro-oesophageal junction (GOJ, recognized as the Z line) moves physiologically proximally during swallowing in relation to the diaphragmatic crus.2,13 The GOJ moves in relation to the diaphragmatic crus in a number of situations including respiration, oesophageal insufflation, and gastric insufflation, moving from the supine to the upright position.2,13 Moreover conditions including Barrett's epithelium or a patulous hernial orifice can make determination of the GOJ and diaphragmatic crus respectively, difficult to accurately determine. While large HH are easily identified in radiological, endoscopic and manometric studies, the diagnosis of a small hiatus hernia is not well-standardized. The current practice of diagnosing a hiatus hernia and measuring its size using the centimetre markings on the endoscope is inaccurate. There is no standardization regarding the degree of air insufflation or which phase of respiration the measurement is made at.11 It is also difficult to be certain that the tip of the endoscope is precisely at the Z-line or diaphragmatic crus, and the distance to the incisors is often obscured by the bite block. Presently the margin of error related to the above factors is considered to be 2 cm, hence the entity of short segment HH has not been considered in previously published papers. Recently developments in oesophageal manometry have suggested a method by which SSHH could be diagnosed with accuracy given the inherent inaccuracy of endoscopy, barium studies and traditional manometry in the sub group of HH under 2 cm in length. High resolution endoclip manometry studies although not practical for routine clinical assessment can be used to confirm the presence or absence of endoscopically determined SSHH. It is beyond the scope of this editorial to describe the method in detail, suffice to say that a major limitation of Hyun et al.'s study is the absence of reproducibility of the demonstration of SSHH, and this method may be a means by which this criticisms of the study may be circumvented. This is especially importantly as the published data relating to reproducibility of 'standard' or LSHH is scant, and the reproducibility of SSHH would be even more controversial. There are few published data on the correlation between different diagnostic modalities in the diagnosis of HH. One study demonstrated significant disagreement between the two diagnostic modalities for the diagnosis of HH when using both upper GI endoscopy and barium studies.14 In summary, the study by Hyun et al. raises the intriguing concept of SSHH. It is tempting to postulate that by detecting even mild grades of HH we may be able to manage a risk factor for diseases including reflux oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma or at the very least prognosticate for our patients. However the long of it is, more work needs to be done, the reproducibility of the measurements needs to verified, a protocol developed for measuring HH length which may possibly include the use of other diagnostic modalities and the short of it is, if SSHH is indeed an entity, it clearly deserves more attention given its association with CLE and reflux oesophagitis, and it's relative prevalence to LSHH as demonstrated in this paper.

Neither genotype nor the gastric colonization site of Helicobacter pylori are predictive factors for the development of erosive esophagitis in patients with peptic ulcer disease, 1 year after eradication

Whether Helicobacter pylori infection is a protective or predisposing factor for the development of gastroesophageal reflux disease remains controversial. The most virulent strains, such as those expressing the cytotoxin-associated gene A (CagA), and the site of gastric colonization have been correlated with the prevention or development of esophagitis. To determine the incidence of erosive esophagitis following eradication of H. pylori in patients with peptic ulcer disease and to evaluate the association of erosive esophagitis with virulent strains of H. pylori and the site of gastric colonization. Triple therapy with lansoprazole, amoxicillin and clarithromycin was administered to 159 patients with peptic ulcer disease. Endoscopy, histopathology, urease and carbon-14 urea breath tests were performed prior to treatment, at 3 months and 1 year following treatment. Genotyping of H. pylori strains using polymerase chain reaction was performed separately on samples from the corpus and antrum. One year after treatment, 148 successfully treated patients were reevaluated. Twenty-eight patients (19%) had erosive esophagitis, classified as Los Angeles grade A in 24 and B in 4. The samples taken from the corpus were CagA-positive in 18 patients (64%), while the samples taken from the antrum were CagA-positive in 21 patients (75%). The incidence of erosive esophagitis in peptic ulcer patients who had their H. pylori eradicated was 19%. No correlation was found between the gastric site colonized by H. pylori or strains expressing CagA and the prevention or development of erosive esophagitis in patients with peptic ulcer disease, 1 year after infection eradication.

Gastroesophageal reflux disease after Helicobacter pylori eradication in gastric ulcer patients: A one-year follow-up study

The aim of this study was to evaluate the course of gastroesophageal reflux disease in gastric ulcer patients after successful Helicobacter pylori eradication (group A), in patients with persistent infection after attempt to eradicate Helicobacter pylori (group B), and in control group without Helicobacter pylori eradication treatment (group C). Gastric ulcer patients (n=88) were assigned either to the group receiving Helicobacter pylori eradication treatment (54 patients) or to the control group (34 patients; omeprazole treatment for 4 weeks) and were followed up for 1-year or until gastric ulcer relapsed. Gastroesophageal reflux disease was diagnosed in patients who had erosive esophagitis and/or without esophagitis if they experienced heartburn and/or regurgitation at least 2 times a week and it was associated with impairment of daily activities (Genval consensus). The study was completed by 69 patients: 25 in group A, 19 in group B, and 25 in group C. At the beginning and at the end of the follow-up, gastroesophageal reflux disease was diagnosed in 10 (40%) and 9 (36%) group A patients, respectively (P>0.05); in 12 (63%) and 8 (42%) group B patients, respectively (P>0.05); and in 9 (36%) and 5 (20%) group C patients, respectively (P>0.05). At the beginning and at the end of the follow-up, reflux esophagitis was found in 3 (12%) and 5 (20%) group A patients, respectively (P>0.05); in 5 (26%) and 5 (26%) group B patients (P>0.05); in 4 (16%) and 3 (12%) group C patients (P>0.05). There was no statistically significant difference regarding the development of gastroesophageal reflux disease in gastric ulcer patients after Helicobacter pylori eradication, in the patients with persistent infection after attempt to eradicate, and in the control group without Helicobacter pylori eradication treatment.

A comprehensive review of gastroesophageal reflux disease and obesity

Obesity has been implicated as an important risk factor for the development of gastroesophageal reflux disease (GERD). A variety of physiological abnormalities have been described which likely contribute to the association of GERD and obesity. These abnormalities involve the oesophageal body, lower oesophageal sphincter and stomach. For obese patients with GERD, weight loss in conjunction with anti-secretory medications is first-line therapy. For those with severe obesity who fail medical weight loss treatment, bariatric surgery has been shown to be beneficial. On balance, Roux-en-Y gastric bypass is probably the most efficacious surgery for patients with morbid obesity suffering from concomitant GERD.

Inflammation and Oxidative Stress in Gastroesophageal Reflux Disease

The etiology of esophageal mucosal injury is complex, since it may involve the reflux of gastric acid, bile acid, and pancreatic juice, external factors such as drugs and alcohol, or functional factors such as esophagogastric motility. The mechanism of esophageal mucosal injury has gradually been understood at the molecular biological level. It is particularly important that pro-inflammatory factors, such as inflammatory cytokines (interleukin-6 and -8), leukocytes and oxidative stress, have been demonstrated to be involved in the development of gastroesophageal reflux disease (GERD) including nonerosive reflux disease (NERD). In addition, nociceptors such as acid-sensitive vanilloid receptors, protease-activated receptors and substance P have also been implicated in the pathogenesis of neurogenic inflammation in NERD patients with esophageal hypersensitivity. The development of new therapy with anti-inflammatory and anti-oxidant effects is expected to assist in the treatment of intractable NERD/GERD and the prevention of carcinogenesis.

Helicobacter pylori Extract Induces Nuclear Factor-kappa B, Activator Protein-1, and Cyclooxygenase-2 in Esophageal Epithelial Cells

Helicobacter pylori infection is recognized as the major cause of gastritis and gastric cancer; however, its role in the development of gastroesophageal reflux disease and Barrett's adenocarcinoma is unclear. The expression of NF-kappaB, AP-1, and COX-2 may be important in inflammation and tumorigenesis in the esophagus. The aim of this study was to examine the effect of live H pylori or H pylori extract (HPE) on these factors in the esophageal epithelial cell lines SKGT-4 and OE33. NF-kappaB and AP-1 activity were assessed by gel shift assay and COX-2 by Western blotting. Coculture of SKGT-4 and OE33 with live H pylori and HPE induced NF-kappaB and AP-1 DNA-binding activity, and also decreased IkappaB-alpha levels. Treatment with the specific MEK1/2 MAPK inhibitor PD98059, but not the p38 MAPK inhibitor SB203580, inhibited NF-kappaB and AP-1 activity. The antioxidant vitamin C inhibited H pylori-induced NF-kappaB activation, but increased AP-1 expression. Moreover, HPE induced COX-2 expression and IL-8 production, and PD98059 inhibited COX-2 expression, ERK1/2 phosphorylation, and IL-8 production. These data demonstrate that both live H pylori and HPE induce NF-kappaB and AP-1 expression in esophageal epithelial cells. The induction of such transcription factors may play a role in the specific immune response within Barrett's mucosa and may indirectly cause inflammation of the gastric cardia and the distal esophagus.

Lower Prevalence of Helicobacter pylori Infection with vacAs1a, cagA‐Positive, and babA2‐Positive Genotype in Erosive Reflux Esophagitis Disease

Increased prevalence of esophagitis has been recognized in the West. Helicobacter pylori infection, particularly virulent strains, is proposed as a protective factor against the development of gastroesophageal reflux disease. To evaluate the relationship of reflux esophagitis with virulent H. pylori infection, we studied the prevalence of reflux esophagitis among H. pylori-infected and -uninfected patients and the genotype of isolates in Taiwan. Patients who had routine physical examination were investigated. The severity of esophagitis was evaluated using the Los Angeles grading system. H. pylori status was assessed by histology, rapid urease test, and bacterial culture. Genotyping of vacA, cagA, and babA2 was determined by polymerase chain reaction (PCR). Risk factors for severe esophagitis were evaluated. Reflux esophagitis was found in 21.2% of 1622 patients. The prevalence of H. pylori infection was found in 33.0% of 276 patients with reflux esophagitis compared with 67.5% of 378 patients with normal esophagus (p < .001). Esophagitis occurred in a significantly lower rate among H. pylori-positive patients with peptic ulcer than those without peptic ulcer. cagA, babA2, and vacAs1a were detected in 100% of 143 isolates. Factors that predicted severe esophagitis included age, gender, and hiatus hernia but not H. pylori infection. Our study suggests significantly lower incidence of H. pylori infection with the triple-positive virulent genotype in patients with reflux esophagitis in Taiwan.

Delayed gastric emptying in gastroesophageal reflux disease: the role of malrotation

The association between gastroesophageal reflux (GER) and intestinal malrotation (IM) has been well described. Delayed or impaired gastric emptying in IM is thought to be a contributing factor in the development of gastroesophageal reflux disease (GERD). The current study assessed the role of malrotation in delayed gastric emptying in children with GERD. We also evaluated the interactions between GERD, malrotation, gastric pH abnormalities, and gastric dysmotility. Sixty-seven patients between 1 and 5 years of age (mean 3.08+/-1.2) and with symptoms of GER, such as emesis, reactive or recurrent lung disease, and/or growth retardation, were studied in 2001-2005. Upper and lower gastrointestinal contrast studies were performed for the diagnosis of malrotation. Gastric motility was evaluated with a liquid gastric emptying protocol. GER was documented by upper gastrointestinal studies, scintigraphy, and/or 24-h pH monitoring. In our series of 44 children with GERD, there was an unexpectedly high incidence of IM: 54.5% (24/44). IM has previously been known to occur in 25% of patients with GERD. GERD was found in 24 (82.7%) of 29 patients with IM. Mean nuclear gastric emptying (MNGE) was 51.6+/-8.04 min in patients with isolated GERD and 96.6+/-20.5 min in children with IM and GERD. There was a statistically significant difference in MNGE time (p<0.05) between children with primary GERD and in those with GERD and IM. Esophageal pH monitoring showed that mean fraction time below pH 4 was 7.06+/-1.1% in patients with isolated GERD and 14.7+/-4.1% in patients with IM and GERD. GERD is common in children between 1 and 5 years old. Using gastric emptying studies and esophageal pH monitoring, we have shown that gastric dysmotility and esophageal pH abnormalities are highly prevalent, especially in children with malrotation compared with children with isolated GERD. These findings suggest that malrotation is an important factor responsible for delayed gastric emptying in GERD. Hence, we recommend that all infants and children with GERD and delayed gastric emptying undergo careful evaluation for malrotation.

Delayed gastric emptying predisposes to non-acid reflux

Background: Delayed gastric emptying (DGE) was proved to play role in the development of gastroesophageal reflux disease (GERD), but the prevalence of gastric emptying disorder varies in different studies. Early GERD was identified by an abnormal postprandial response to a standardized test meal in symptomatic patients.1

Treatment of Epiphrenic and Mid-esophageal Diverticula.

Thoracic esophageal diverticula are uncommon. They account for less than 30% of esophageal diverticula. The majority of patients are asymptomatic or have minimal symptoms. About one third of patients present with severe symptoms. Occasionally, pulmonary symptoms can be the sole manifestation of the disease and can be life threatening. Dysphagia, food regurgitation, chest pain, weight loss, and reflux symptoms are the most commonly encountered gastrointestinal symptoms. Malignancy is a rare complication of esophageal diverticula; therefore, patients should be educated regarding this complication. Appropriate diagnostic tests should be arranged promptly if alarming symptoms develop. Esophageal motor disorders are found in the majority of patients and need to be taken into account when planning therapy. Medical and endoscopic therapies have limited roles in treatment. Surgery is the standard of care for patients with pulmonary or incapacitating symptoms related to an epiphrenic diverticulum, and myotomy is the cornerstone of surgery. To ensure complete relief of the obstruction, the myotomy should extend distally at least 1.5 to 2 cm into the stomach and proximally at least to the neck of diverticulum. Adding a nonobstructing entireflux procedure is recommended to prevent the development of gastroesophageal reflux disease. Occasionally, a specific treatment such as a diverticulectomy or diverticulopexy needs to be directed to the diverticulum. Preliminary treatment results from minimally invasive surgery, especially laparoscopy, have been promising. In the future with increased experience, minimally invasive surgery may become the standard of care.

Effect of Helicobacter pylori eradication on development of erosive esophagitis and gastroesophageal reflux disease symptoms: a post hoc analysis of eight double blind prospective studies

OBJECTIVES: The aim of this study was to assess the development of erosive esophagitis, the development of gastroesophageal reflux disease (GERD) symptoms in patients without prior symptomatic or endoscopic GERD, and the worsening of GERD symptoms in patients with prior symptomatic GERD in a post hoc analysis of eight double-blind prospective trials of Helicobacter pylori ( H. pylori) therapy in 1165 patients. METHODS: Patients with active or past duodenal ulcer and without baseline erosive esophagitis had end of study endoscopies 4–30 wk after completion of therapy. A total of 533 patients had heartburn and regurgitation scores assessed at baseline and 4 wk after end of therapy, and were divided into two groups: 1) no prior GERD symptoms (N = 127) and 2) prior GERD symptoms (N = 406). H. pylori was assessed at baseline and ≥4 wk after therapy by rapid urease test, histology, and culture. RESULTS: Erosive esophagitis developed in 24 (4%) of 621 patients with cure versus 14 (3%) of 544 with persistent H. pylori (OR = 1.52, 95% CI = 0.78–2.97). In the longest study (28–30-wk follow-up), esophagitis developed in two (7%) of 28 patients with cure versus five (7%) of 76 with persistent infection. New GERD symptoms developed in 13 (14%) of 92 patients with cure versus seven (20%) of 35 with persistent infection (OR = 0.66, 95% CI = 0.24–1.82). GERD worsened in 20 (7%) of 269 with cure vs 20 (15%) of 137 with persistent H. pylori (OR = 0.47, 95% CI = 0.24–0.91; p = 0.02). CONCLUSIONS: Our results do not support the hypothesis that H. pylori eradication in patients with duodenal ulcer disease leads to the development of erosive esophagitis, the development of new symptomatic GERD, or worsening of symptoms in patients with pre-existing GERD.

Effect of Helicobacter pylori eradication on development of erosive esophagitis and gastroesophageal reflux disease symptoms: a post hoc analysis of eight double blind prospective studies.

The aim of this study was to assess the development of erosive esophagitis, the development of gastroesophageal reflux disease (GERD) symptoms in patients without prior symptomatic or endoscopic GERD, and the worsening of GERD symptoms in patients with prior symptomatic GERD in a post hoc analysis of eight double-blind prospective trials of Helicobacter pylori (H. pylori) therapy in 1165 patients. Patients with active or past duodenal ulcer and without baseline erosive esophagitis had end of study endoscopies 4-30 wk after completion of therapy. A total of 533 patients had heartburn and regurgitation scores assessed at baseline and 4 wk after end of therapy, and were divided into two groups: 1) no prior GERD symptoms (N = 127) and 2) prior GERD symptoms (N = 406). H. pylori was assessed at baseline and > or = 4 wk after therapy by rapid urease test, histology, and culture. Erosive esophagitis developed in 24 (4%) of 621 patients with cure versus 14 (3%) of 544 with persistent H. pylori (OR = 1.52, 95% CI = 0.78-2.97). In the longest study (28-30-wk follow-up), esophagitis developed in two (7%) of 28 patients with cure versus five (7%) of 76 with persistent infection. New GERD symptoms developed in 13 (14%) of 92 patients with cure versus seven (20%) of 35 with persistent infection (OR = 0.66,95% CI = 0.24-1.82). GERD worsened in 20 (7%) of 269 with cure vs 20 (15%) of 137 with persistent H. pylori (OR = 0.47, 95% CI = 0.24-0.91; p = 0.02). Our results do not support the hypothesis that H. pylori eradication in patients with duodenal ulcer disease leads to the development of erosive esophagitis, the development of new symptomatic GERD, or worsening of symptoms in patients with pre-existing GERD.

Gastroesophageal reflux disease in chronic renal failure patients with upper GI symptoms: multivariate analysis of pathogenetic factors

OBJECTIVE: The association between gastroesophageal reflux disease and end-stage renal disease remains unclear. We aimed to assess the prevalence of gastroesophageal reflux disease and also to identify possible pathogenetic factors in the development of reflux in symptomatic end-stage renal disease patients. METHODS: The study involved 42 end-stage renal disease patients with upper GI symptoms (group I) and 46 age- and sex-matched controls who did not have renal disease but had the same symptoms (group II). Endoscopy, endoscopic biopsies, and 24-h esophageal pH studies were used to diagnose gastroesophageal reflux disease. Subjects were also investigated for Helicobacter pylori gastritis and GI amyloidosis. RESULTS: The prevalences of gastroesophageal reflux disease in the two groups were similar (81% vs 84.8%, p = 0.423). The prevalence of H. pylori infection was significantly lower in group I than in group II (38.1% vs 67.4%, p = 0.01). There were 11 cases of GI amyloidosis in group I. Multivariate logistic regression analysis in group I showed that GI amyloidosis (OR = 7.28, 95% CI = 1.13–46.93), chronic ambulatory peritoneal dialysis treatment (OR = 5.54, 95% CI = 1.01–30.43), and absence of H. pylori infection (OR = 3.75, 95% CI = 1.01–13.9) were significantly associated with reflux esophagitis. CONCLUSIONS: Upper GI symptoms are important in predicting gastroesophageal reflux disease in end-stage renal disease patients. Chronic ambulatory peritoneal dialysis, GI amyloidosis, and absence of H. pylori infection seem to be risk factors for the development of gastroesophageal reflux disease in end-stage renal disease patients.

Gastroesophageal reflux disease in chronic renal failure patients with upper GI symptoms: multivariate analysis of pathogenetic factors.

The association between gastroesophageal reflux disease and end-stage renal disease remains unclear. We aimed to assess the prevalence of gastroesophageal reflux disease and also to identify possible pathogenetic factors in the development of reflux in symptomatic end-stage renal disease patients. The study involved 42 end-stage renal disease patients with upper GI symptoms (group I) and 46 age- and sex-matched controls who did not have renal disease but had the same symptoms (group II). Endoscopy, endoscopic biopsies, and 24-h esophageal pH studies were used to diagnose gastroesophageal reflux disease. Subjects were also investigated for Helicobacter pylori gastritis and GI amyloidosis. The prevalences of gastroesophageal reflux disease in the two groups were similar (81% vs 84.8%, p = 0.423). The prevalence of H. pylori infection was significantly lower in group I than in group II (38.1% vs 67.4%, p = 0.01). There were II cases of GI amyloidosis in group I. Multivariate logistic regression analysis in group I showed that GI amyloidosis (OR = 7.28, 95% CI = 1.13-46.93), chronic ambulatory peritoneal dialysis treatment (OR = 5.54, 95% CI = 1.01-30.43), and absence of H. pylori infection (OR = 3.75, 95% CI = 1.01-13.9) were significantly associated with reflux esophagitis. Upper GI symptoms are important in predicting gastroesophageal reflux disease in end-stage renal disease patients. Chronic ambulatory peritoneal dialysis, GI amyloidosis, and absence of H. pylori infection seem to be risk factors for the development of gastroesophageal reflux disease in end-stage renal disease patients.

No association between gallstones and gastroesophageal reflux disease.

Gallstones and hiatal hernia reportedly have been linked to similar dietary factors prevalent in western countries, and patients with cholelithiasis or previous cholecystectomy have been reported to have more duodenogastric reflux than healthy controls. Nonetheless, the contribution of duodenogastric reflux to the development of gastroesophageal reflux disease (GERD) remains controversial. The present study was aimed to assess the association between gallstone disease and GERD. Outpatients from general medical clinics who underwent upper GI endoscopy and abdominal ultrasonography were recruited into a case-control study. A case population of 790 patients with various grades of GERD was compared to a control population of 407 patients without GERD. In a multivariate logistic regression, the presence of GERD served as the outcome variable, whereas the presence of gallstones, hiatal hernia, social habits, and demographic characteristics served as predictor variables. No associations were found between the presence of cholelithiasis or previous cholecystectomy and GERD or between the presence of cholelithiasis or previous cholecystectomy and hiatal hernia. The severity of GERD also remained unaffected by the presence of gallstones. The occurrence of GERD was influenced only by hiatal hernia (odds ratio [OR] = 3.15, 95% CI = 2.44-4.08), alcohol consumption (OR = 1.47, CI = 1.08-1.99), and not by cholelithiasis (OR = 1.02, CI = 0.68-1.51), or cholecystectomy (OR = 0.90, CI = 0.64-1.28). The frequency of GERD among hiatus hernia patients with gallstones (437/592 = 74%) was similar to the frequency of GERD among hiatus hernia patients without gallstones (168/220 = 76%, p = 0.516). Neither cholelithiasis nor cholecystectomy poses a risk for the occurrence of GERD or hiatal hernia. Gallstone disease does not seem to influence the integrity of the esophageal mucosa through GERD.