Negative Reflux Research Articles

The Significance of 99mTechnetium Dimercapto-Succinic Acid Renal Scan in Children With Spina Bifida During Long-Term Followup

(99m)Technetium dimercapto-succinic acid renal scans are ideal for demonstrating renal scarring in children with spina bifida. However, doubt persists about the need for routine application. We assessed the associations among abnormal (99m)technetium dimercapto-succinic acid renal scans, vesicoureteral reflux and urodynamic findings in patients with spina bifida during long-term followup. We retrospectively reviewed the records of 64 patients with spina bifida followed at our center. All patients were older than 10 years (mean 15.8, range 10 to 23). Dimercapto-succinic acid renal scans were considered abnormal with differential function of less than 40% or focal defects. Patient age, gender, previous febrile urinary tract infections, positive vesicoureteral reflux history, timing of clean intermittent catheterization initiation and the latest urodynamic findings were noted. Patients were grouped based on normal/abnormal scan results. Statistical analysis included univariate and multivariate regression analyses and chi-square tests. A total of 16 patients (25%) had abnormal scans. Mean patient age, male-to-female ratio, leak point pressure, bladder compliance and timing of clean intermittent catheterization initiation did not differ between groups. Rates of previous febrile urinary tract infections differed significantly (11 of 16 in the abnormal group vs 9 of 48 in the normal group, p <0.01), as did positive reflux history (100% vs 31%, p <0.01). No patient with a negative reflux history had an abnormal dimercapto-succinic acid renal scan. Multivariate analysis identified previous febrile urinary tract infections as a significant risk factor for an abnormal scan. A positive vesicoureteral reflux history and febrile urinary tract infections were associated with abnormal dimercapto-succinic acid renal scan in followup of patients older than 10 years with spina bifida. Thus, these factors are indicators of proactive evaluation of renal function using dimercapto-succinic acid renal scanning.

American Gastroenterological Association Institute Technical Review on the Management of Gastroesophageal Reflux Disease

American Gastroenterological Association Institute Technical Review on the Management of Gastroesophageal Reflux Disease

Role of positional instillation of contrast cystography in the algorithm for evaluating children with confirmed pyelonephritis

Objectives To assess the utility of positional instillation of contrast (PIC) cystography in detecting vesicoureteral reflux (VUR) in patients with renal scarring from recurrent febrile urinary tract infections that standard voiding cystourethrography and nuclear cystogram imaging failed to reveal. Methods Between June 2004 and November 2004, a total of 5 pediatric patients with recurrent febrile urinary tract infections and radiologic evidence of upper tract involvement were examined with PIC cystography. All patients had at least one previous negative standard reflux study (voiding cystourethrography or nuclear cystography). Results All 5 patients showed VUR on PIC cystography. Unilateral reflux was detected in 3 patients, and 2 patients had bilateral VUR. Conclusions The PIC cystogram should be integrated into the algorithm for diagnosing patients with recurrent febrile urinary tract infection, who do not exhibit VUR on standard imaging modalities. The morbidity associated with undiagnosed VUR, as demonstrated by this group of patients, suggests that permanent renal damage may be prevented by early diagnosis and treatment.

Prevalence of endoscopically negative and positive gastroesophageal reflux disease in the Japanese

Objective. The frequency of gastroesophageal reflux disease (GERD) has not been fully investigated in the Asian population. The aim of this study was to investigate the prevalence of GERD, endoscopy-negative GERD (NERD), and erosive GERD in Japan, and the factors influencing disease prevalence. Material and methods. A total of 2760 subjects (mean age 50.4 years, range 24–84 years) were prospectively enrolled in this multicenter study. GERD symptoms were assessed with the Japanese version of the Carlsson-Dent self-administered questionnaire (QUEST) and upper gastrointestinal endoscopy was performed on all study participants. Results. A total of 495 (17.9%) individuals were diagnosed with GERD by the presence of erosive esophagitis at endoscopy and/or by the presence of GERD symptoms. Erosive esophagitis was diagnosed endoscopically in 195 (7.1%), and symptomatic GERD was diagnosed in 351 (12.7%) based on a QUEST score of over 6. Of these 351 subjects, 300 (10.9%) were considered to have NERD. Male gender, hiatal hernia, and mild gastric mucosal atrophy were significant positive predictive factors of erosive esophagitis by multiple regression analysis. Hiatal hernia was the only significant predictor of GERD symptoms. Traditional Japanese foods, such as sweet cakes and rice cake, frequently exacerbated GERD symptoms. Conclusions. The prevalence of GERD in the Japanese was 17.9% and the prevalence rates of NERD and erosive esophagitis were 10.9% and 8.6%, respectively. The majority of symptomatic patients did not have endoscopically proven esophagitis. Hiatal hernia is the only important predictor of the presence of GERD symptoms.

Dichotomies and directions in acid‐related disorders

Presentations by international experts from old and new worlds bordering the Atlantic Ocean revealed surprising similarities with respect to the diagnosis and management of patients with upper gastrointestinal disorders. It was agreed that Helicobacter pylori infection continues to play a key role in gastroduodenal disease and has a great impact on clinical management. However, testing and treatment strategies vary in patients affected by functional dyspepsia and those receiving nonsteroidal anti-inflammatory drug (NSAID) therapy including aspirin. Among patients with gastro-oesophageal reflux disease (GERD), it was clear that we need to re-evaluate the validity of the classical concept of GERD as a progressive spectrum and instead focus on the pathophysiologic mechanisms responsible for producing the common symptom of heartburn and complications that occur in the three principle subsets of GERD patients: those with endoscopic negative reflux disease, erosive oesophagitis and Barrett's oesophagus. In addition, we need to be increasingly aware of the concept of extra-oesophageal manifestations of gastro-oesophageal reflux and the fact that GERD in adults often originates in childhood. In all these gastrointestinal disorders, proton pump inhibitor therapy has become the common thread either as a diagnostic tool or an effective short-term or long-term management strategy.

Interleukin‐8 expression in the esophageal mucosa of patients with gastroesophageal reflux disease

Background: It has been reported that inflammatory cell infiltration can be detected in patients with endoscopically negative gastroesophageal reflux disease (GERD) as well as those with erosive reflux esophagitis. In this study, we examined the expression of mRNA for interleukin (IL)‐8, a potent chemokine for neutrophils, in the esophageal mucosa of patients with GERD and compared the results with their endoscopic findings and symptoms. Methods: Biopsy samples were obtained from 80 patients. Endoscopic diagnosis was performed according to the Los Angeles classification. Patients with typical symptoms such as heartburn despite normal endoscopic findings were classified as the non‐erosive GERD group. Total cellular RNA was extracted from the biopsy samples and IL‐8 mRNA was quantified by real‐time polymerase chain reaction (PCR). Localization of IL‐8 protein in the esophageal mucosa was done by immunostaining. Results: Expression of IL‐8 mRNA was correlated with the endoscopic grade of esophagitis or with inflammatory cell infiltration, but not with the symptoms of the patients. Expression of IL‐8 mRNA was also detected in all patients with non‐erosive GERD. The level of IL‐8 expression in non‐erosive GERD was low compared with that in erosive GERD, but was higher than that in normal controls. IL‐8 immunostaining was found in the basal layers of the esophageal mucosa. Administration of lansoprazole, a proton‐pump inhibitor, decreased both IL‐8 mRNA and protein levels in the esophageal mucosa. Conclusion: These results suggest that IL‐8 in the esophageal mucosa may be involved in the pathogenesis of esophageal inflammation, including non‐erosive GERD.

Dyspepsia

Dyspepsia

Review article: test and treat or treat and test in reflux disease?

The role of diagnostic testing in reflux disease is in evolution. There is little question that patients with dysphagia, bleeding or other 'alarm' symptoms, should undergo early endoscopy. A substantial proportion of patients presenting with reflux symptoms have endoscopy negative reflux disease. pH testing is both inconvenient and lacks the sensitivity and specificity required for a 'gold standard'. Empirical trials of therapy using proton pump inhibitors have shown that a trial of treatment may be the most accurate way of diagnosing gastro-oesophageal reflux disease (GERD) and may the optimal strategy from a cost-effectiveness standpoint. On the other hand, the increasing rate of oesophageal adenocarcinoma has raised questions about the possible value of screening endoscopy to determine if Barrett's oesophagus is present. The role of endoscopic testing in the average patient is therefore shifting from a diagnostic modality to one that helps manage risk by identifying Barrett's oesophagus.

Are endoscopy negative GERD and reflux esophagitis different diseases? Baseline histology in GERD patients off-therapy ȁ the CHEER study

Are endoscopy negative GERD and reflux esophagitis different diseases? Baseline histology in GERD patients off-therapy ȁ the CHEER study

Gastroesophageal reflux pattern in patients with endoscopy negative and endoscopy positive gastroesophageal reflux disease

Gastroesophageal reflux pattern in patients with endoscopy negative and endoscopy positive gastroesophageal reflux disease

Clinical analysis of endoscopy negative gastroesophageal reflux disease in the elderly

Clinical analysis of endoscopy negative gastroesophageal reflux disease in the elderly

Medical management of nocturnal symptoms of gastro-oesophageal reflux disease in the elderly.

Elderly patients with nocturnal symptoms of gastro-oesophageal reflux disease (GORD) usually experience a more aggressive and complicated disease course compared with younger patients, resulting in impaired quality of life. The severity of disease and possible complications should be evaluated with upper endoscopy once the diagnosis is suspected. Elderly patients with nocturnal symptoms of GORD and evidence of endoscopic complications (oesophagitis, Barrett's oesophagus, etc.) and those with severe endoscopically negative reflux disease (ENRD) should be treated with proton pump inhibitors. Histamine H(2) receptor antagonists are suitable for mild-to-moderate ENRD. Antacids and lifestyle modifications may be incorporated into the management as adjuncts to more potent and durable therapeutic agents. Effective treatment of nocturnal GORD symptoms in the elderly will result in relief of symptoms, healing of oesophagitis and improved quality of life, and should be maintained indefinitely to prevent relapses of the disease.

Risk Factors for the Severity of Erosive Esophagitis in Helicobacter pylori -Negative Patients with Gastroesophageal Reflux Disease

Background: The risk factors for the varying grades of erosive esophagitis (EE) severity could be better understood. For that reason, we evaluated the risk factors associated with EE in patients with gastroesophageal reflux disease. Methods: We determined the presence and severity of EE (using the Los Angeles Classification) in patients with negative serology Helicobacter pylori who underwent esophago-gastroduodenoscopy as part of screening in four prospective, multicenter, randomized, double-blind comparative trials of once-daily esomeprazole and omeprazole for the acute healing of erosive esophagitis. We also examined the baseline characteristics of enrolled patients, and identified risk factors for severe disease using a multivariable logistic regression model. Results: Erosive esophagitis was documented in 6709 patients of a total of 10,294 patients who underwent endoscopy; of these, 34% had grade A, 39% had grade B, 20% had grade C, and 7% had grade D disease. The majority of patients were male (61%) and Caucasian (93%) with a mean age of 46 years. In the regression model, the following were significant independent risk factors for severe (grades C and D) versus mild erosive esophagitis (grades A and B): severe heartburn (adjusted odds ratio 1.79); prolonged heartburn >5 years in duration (1.16); obesity (1.21); the presence of hiatus hernia (2.13); male gender (1.97); and Caucasian ethnicity (1.53). Conclusion: In this large sample of patients with predominantly H. pylori -negative gastroesophageal reflux disease, risk factors for severe erosive esophagitis were the duration and severity of heartburn, and obesity.

Pathological issues of gastric and lower esophageal cancer: helicobacter pylori infection and its eradication.

Gastric carcinoma is thought to develop via the actions of inducers and promoters of carcinogenesis. Tryptophan in charred fish or animal meat, ultraviolet rays, and irradiation, which damage genes of normal cells, have long been regarded as inducers of carcinoma, and agents such as alcohol, tobacco, aflatoxin, and nitrosoamine as promoters, with tobacco having both activities. The interaction between these environmental factors, principally diet, and Helicobacter pylori (Hp) is important in the genesis of gastric carcinoma. In this report, the histopathological feature of the Hp gastritis-carcinoma sequence is outlined, and the pathological characteristics of gastroesophageal reflux disease (GERD) and endoscopically negative reflux disease (ENRD) and the risk factors for lower esophageal carcinoma after Hp eradicated status in particular are discussed regarding aspects of cell cycle-associated factors. We conclude that (1) Infection with Hp increases the risk of gastric cancer in two histological phenotypes (i.e., diffuse undifferentiated type and intestinal differentiated type). Excessive cell replication and interrupting the mucus secretion mechanism may result in a large proportion of cells with genetic abnormalities. (2) Genetic alterations in gastric carcinogenesis may differ from those in colonic carcinogenesis. (3) The degree of GERD in Japanese patients is milder than that in patients from Western countries, although the incidence of GERD increases the status after successful eradication of Hp. It is also possible that accumulation of genetic abnormalities increases the number of cardiac and lower esophageal cancers. Investigation of cell cycle factors in GERD including ENRD can be expected to reveal the risk of carcinogenesis.

Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease.

Heartburn affects 25% of the adult population on a monthly basis and represents the core symptom of gastro-oesophageal reflux disease (GORD). Treatment is readily available and puts a large demand on healthcare budgets. Research in the past has focused largely on the treatment of oesophagitis. A majority of GORD patients show no endoscopic abnormalities and in daily practice most patients are treated empirically. Summarise, quantify and compare the efficacy of the short-term use of proton pump inhibitors (PPI), H2-receptor antagonists (H2RA) and prokinetics in the empirical treatment of GORD and the treatment of endoscopy negative reflux disease (ENRD). Electronic searches were performed of the Cochrane Controlled Trials Register, MEDLINE and EMBASE. Bibliographies were screened. Included were randomised controlled trials focussing on symptomatic outcome after short-term treatment for GORD using proton pump inhibitors, H2-receptor antagonists or prokinetic agents. Participants had to be classifiable in the empirical treatment group (no endoscopy used in treatment allocation) or in the endoscopy negative reflux disease group (no endoscopic signs of erosive oesophagitis). Data from included trials were extracted by two reviewers independently. The impact of interventions was expressed as relative risks (RR) together with 95% confidence intervals (95% CI). Meta-analysis was only performed if there were sufficient trials of similar comparisons reporting the same outcomes. Relative risks were combined for binary outcomes. Twenty-three trials were included: eleven in the empirical treatment group, nine in the ENRD group and three in both. In empirical treatment of GORD the RR for heartburn remission in placebo-controlled trials for PPI was 0.35 (1 trial, 95% CI 0.26 to 0.46), for H2RAs 0.77 (2 trials, 95% CI 0.60 to 0.99) and for prokinetics 0.86 (1 trial, 95% CI 0.73 to 1.01). In a direct comparison PPIs were significantly (p<0.05) more effective than H2RAs (3 trials, RR 0.67, 95% CI 0.57 to 0.80) and prokinetic's (2 trials, RR 0.53, 95% CI 0.32 to 0.87). In treatment of ENRD, RR for heartburn remission for PPI versus placebo was 0.66 (5 trials, 95% CI 0.55 to 0.80) and for H2RA versus placebo was 0.84 (2 trials, 95% CI 0.74 to 0.95). The RR for PPI versus H2RA was 0.69 (2 trials, 95% CI 0.39 to 1.20) and for PPI versus prokinetic 0.72 (1 trial, 95% CI 0.56 to 0.92). The findings in this review suggest that antisecretory drugs are effective in the empirical treatment of complaints likely to originate from GORD and in treatment of ENRD and furthermore that PPIs are superior to H2RAs in empirical treatment of typical GORD symptoms, but not in treatment of ENRD.

Antacids and lifestyle advice for reflux oesophagitis and Endoscopy Negative Reflux Disease

Antacids and lifestyle advice for reflux oesophagitis and Endoscopy Negative Reflux Disease

Counting the cost of proton pump inhibitors

See article on page 488 Proton pump inhibitors (PPIs) have become an indispensable part of the armoury of treating gastro-oesophageal reflux disease (GORD). They are more effective than H2 receptor...

Mechanisms of oesophageal mucosal defence

The integrity of the oesophageal mucosa depends upon an equilibrium between aggressive factors, predominantly acid and pepsin, and protective mechanisms. Protective mechanisms operate within the oesophageal mucosa as pre-epithelial, epithelial and post-epithelial defences. Only the protective components of the oesophageal pre-epithelial defence can be tested in vivo in humans. It has been recently demonstrated that human oesophageal submucosal glands elaborate mucous secretion rich in bicarbonate and non-bicarbonate buffers, mucin, prostaglandin E2, epidermal growth factor (EGF) and transforming growth factor α (TGFα). This oesophageal secretion, accompanied by similarly protective factors within the swallowed saliva, defines the protective potential of the oesophageal pre-epithelial defence that exists in the form of a mucus-buffer layer covering the oesophageal mucosa and which retards the back-diffusion of hydrogen ions. It has also been demonstrated that patients with severe erosive reflux oesophagitis exhibit qualitative impairment in both the salivary and oesophageal components of the oesophageal pre-epithelial defence. Furthermore, patients with endoscopically negative gastro-oesophageal reflux disease have a significantly stronger oesophageal pre-epithelial defence than patients with erosive reflux oesophagitis. On the other hand, African–Americans, who are less likely to develop erosive reflux oesophagitis, have a stronger oesophageal pre-epithelial defence than do Caucasians. The salivary component of the oesophageal pre-epithelial defence can be enhanced by mastication and the administration of cisapride, whereas oesophageal secretion can only be significantly augmented by cisapride.

Symptom relief in gastroesophageal reflux disease (GERD): pantoprazole V nizatidine in a mixed patient population with endoscopy negative reflux disease (ENRD) and erosive esophagitis (EE)

Symptom relief in gastroesophageal reflux disease (GERD): pantoprazole V nizatidine in a mixed patient population with endoscopy negative reflux disease (ENRD) and erosive esophagitis (EE)

Symptom relief in gastroesophageal reflux disease (GERD): pantoprazole V nizatidine in a mixed patient population with endoscopy negative reflux disease (ENRD) and erosive esophagitis (EE)

Symptom relief in gastroesophageal reflux disease (GERD): pantoprazole V nizatidine in a mixed patient population with endoscopy negative reflux disease (ENRD) and erosive esophagitis (EE)