Long-term management of patients with symptoms of gastro-oesophageal reflux disease -- a Norwegian randomised prospective study comparing the effects of esomeprazole and ranitidine treatment strategies on health-related quality of life in a general practitioners setting

This article reports quality of life (QoL) aspects of a study that investigated the efficacy of three treatment regimens in gastro-oesophageal reflux disease patients. Following a 4-week symptom-control phase (esomeprazole 40 mg once daily), patients were randomised to 6 months' esomeprazole 20 mg once daily continuously (n = 658), on-demand (n = 634) or ranitidine 150 mg twice daily continuously (n = 610). Esomeprazole 40 mg once daily improved QoL during the symptom-control phase. At 6 months, both esomeprazole regimens were more effective than ranitidine in all dimensions of the Quality of Life in Reflux and Dyspepsia questionnaire (p < 0.0001). Esomeprazole continuous and on-demand led to a significant improvement in symptoms (Overall Treatment Evaluation questionnaire) compared with ranitidine (continuous: 80.2%, on-demand: 77.8%, vs. ranitidine 47.0%; p < 0.001). Esomeprazole once daily continuously maintained QoL better than esomeprazole on-demand and was associated with greater patient satisfaction. In conclusion, esomeprazole 20 mg once daily continuously and on-demand were more effective than ranitidine continuously for maintaining QoL.     

Rapid onset of effect of sodium alginate on gastro-oesophageal reflux compared with ranitidine and omeprazole, and relationship between symptoms and reflux episodes

The objective of the open, randomised, four-period crossover study was to compare the time of onset of effect of sodium alginate (SA), omeprazole, ranitidine and control, based on oesophageal and intragastric pH and to determine any correlation between reflux symptoms and episodes in volunteers suffering from occasional gastro-oesophageal reflux. SA showed extensive prevention of acid exposure in the oesophagus compared with other treatments during the first hour. Overall, SA was more effective than control or omeprazole and comparable with ranitidine. There was little evidence of association between 'oesophageal' symptoms and reflux episodes, but associations between 'gastric' symptoms and acidity in the oesophagus, fundus and corpus were apparent. For an immediate reduction in gastro-oesophageal reflux into the oesophagus and gastric acidity during the first hour, SA was significantly superior to control, ranitidine and omeprazole. Ranitidine showed a superior effect from 2 h, consistent with its pharmacological mode of action.     

Accuracy of the water‐siphon test associated to barium study in a high prevalence gastro‐oesophageal reflux disease population: a novel statistical approach

Rationale, aims and objectives Gastro‐oesophageal reflux disease (GORD) is ‘a condition which develops when the reflux of gastric content causes troublesome symptoms or complications’. Instrumental diagnostic tests generally used for GORD are 24‐hour pH‐metry and upper gastrointestinal (GI) endoscopy but barium study associated with provocative manoeuvres such as the water‐siphon test (WST), has also been used for GORD. The aim of this paper was to estimate the accuracy of several tests in patients with GORD in a tertiary care setting, focusing on WST, which is rapid and non‐invasive, simple to perform and well‐tolerated by patients. Method A total of 172 consecutive patients, symptomatic for reflux referred to a tertiary medical centre, were considered and data regarding the WST, 24‐hour pH‐metry, upper GI endoscopy with histology were analysed using latent class analysis, a multivariable statistical method for estimating the accuracy of tests when a gold standard is not available. Results The overall proportion of GORD in the sample was estimated at 0.664 [95% confidence interval (CI) = (0.589; 0.731)]. WST proved to be the most sensitive [Se = 0.886; 95% CI = (0.688; 1.000)] compared with pH‐metry [Se = 0.620; 95% CI = (0.493; 0.745)] and endoscopy with histology [Se = 0.534; 95% CI = (0.273; 0.789)]. It was less specific [Sp = 0.537; 95% CI = (0.003; 1.000)] than pH‐metry [Sp = 0.547; 95% CI = (0.281; 0.813)], and even less than endoscopy with histology [Sp = 0.862; 95% CI = (0.495; 1.00)]. Positive predictive values were estimated at 0.792 [95% CI = (0.721; 0.862)] for WST, 0.731 [95% CI = (0.643; 0.819)] for pH‐metry and 0.886 [95% CI = (0.811; 0.961)] for endoscopy with histology. Negative predictive values were estimated at 0.707 [95% CI = (0.573; 0.841)] for WST, 0.422 [95% CI = (0.310; 0.534)] for pH‐metry and 0.484 [95% CI = (0.387; 0.581)] for endoscopy with histology. Conclusion Water‐siphon test might possibly be useful in patients with suspected GORD because it is highly sensitive and predictive. A positive outcome of the WST associated with a barium study can certainly justify upper GI endoscopy and support any pharmacological treatment of GORD.     

Esomeprazole in acute and maintenance treatment of reflux oesophagitis: a multicentre prospective study

INTRODUCTION: The aim of this study was to assess the efficacy and safety of esomeprazole 40 mg once daily (q.d.) in healing reflux oesophagitis at 4 and 8 weeks, and the efficacy of esomeprazole 20 mg q.d. for 12 weeks in the maintenance of remission. METHODS: A total of 235 patients with endoscopically proven reflux oesophagitis were enrolled in this study, which consisted of two phases (healing and maintenance therapy). Patients who showed complete endoscopic and symptomatic healing at the end of 4 or 8 weeks were switched to maintenance treatment with esomeprazole 20 mg q.d. for 12 weeks. The primary efficacy endpoint was healing of reflux oesophagitis at week 8. Secondary assessments included the proportion of patients with symptomatic relapse in the maintenance phase. RESULTS: At the end of week 8, 88% (95% life-table confidence intervals [CI]: 84%, 92%) of patients were healed endoscopically and 90.6% of the patients were asymptomatic. Patient age, gender and Helicobacter pylori status had no effect on the efficacy of treatment. During the 12-week maintenance treatment phase, symptomatic relapse ratios were 0.5%, 2.2%, and 0%, for the first, second, and third 4-week periods, respectively. The proportions of patients satisfied with treatment were 95% and 99.4% at the end of acute and maintenance treatment, respectively. The most common adverse effects were headache, upper respiratory tract infection and abdominal pain. CONCLUSIONS: Esomeprazole is effective in the healing of reflux oesophagitis, the resolution of heartburn, and in maintaining symptomatic remission. The effectiveness of esomeprazole in patients with gastroesophageal reflux disease is not affected by the presence of H. pylori.     

Chronic aspiration shifts the immune response from Th1 to Th2 in a murine model of asthma

Background   Chronic aspiration associated with gastro oesophageal reflux disease (GERD) is thought to play a substantial role in the development of asthma, the incidence of which is dramatically increasing in industrially developed countries. The majority of data examining the association between aspiration and asthma has been obtained from epidemiological studies, which show that between 50 and 90% of individuals with asthma experience some element of GERD. This study describes the effect of chronic aspiration on a model of experimentally induced airway hypersensitivity in Balb/c mice.
Materials and methods   Four experimental groups were utilized: Aspiration/Asthma, Sham/Asthma, Aspiration/Sham and Sham/Sham. Mice were sensitized with aerosolized 1% ovalbumin on days 1 to 10 (sensitization phase), followed by repeated exposure on days 31 to 40 (challenge phase). Aspiration events occurred on days 1, 8,15, 22, 29, 36, 43 and 50. Animals were sacrificed on days 56 and 57.
Results   Chronic aspiration of 10 µL of murine gastric fluid per week for eight weeks produced an injury pattern distinct from that of acute aspiration, with lung injury characterized by hyperplasia, neutrophil infiltration of the bronchioles and relative parenchymal sparing. Aspiration during induction of ovalbumin-induced airway hypersensitivity was associated with a trend toward decreased production of antiovalbumin IgG, antiovalbumin IgE, and total IgE. Further, aspiration induced a substantial and significant increase in antiovalbumin IgG1/IgG2a ratios, consistent with a shift toward a predominantly Th2 response.
Conclusion   These findings indicate that chronic aspiration has a profound effect on the nature of the immune response to aerosolized allergens in a model of experimentally induced airway hypersensitivity.     

Computer analysis of upper gastrointestinal endoscope images

Gastro‐oesophageal reflux disease (GORD) occurs in up to 40% of adults in the West. Oesophagitis is a major determinant in the treatment of GORD but its current classification systems are subjective. In order to help to provide objective interpretation of upper gastro‐intestinal (GI) endoscope examination and reduce inter‐observer variability, we developed a computer image analysis system. Digital video recordings were made on patients with clinical evidence of reflux oesophagitis. Cross‐sectional profiles of hue and saturation data were analysed on images from seven patients with grade B or C oesophagitis (LA grading). This analysis showed clear changes in hue (p?=?0.01) and saturation (p?=?0.001). These results suggest that quantification of upper GI endoscopic images is feasible and may help in objective assessment.     

Clinical manifestations and complications of gastroesophageal reflux disease (GERD)

Gastroesophageal reflux-induced diseases are among the most common disorders and are associated with classical oesophageal manifestations of gastroesophageal reflux disease (GERD) including a range of symptoms such as heartburn, acid regurgitation and chest pain, and also organic manifestations such as oesophagitis, oesophageal strictures and ulcerations, Barrett's oesophagus and oesophageal adenocarcinoma. Recognition of its impact on other organ systems, extra-oesophageal reflux diseases, such as the ear, nose and throat (ENT) region and the bronchopulmonary system, as well as its contribution to symptoms such as chest pain and sleep disturbances, is also increasing. This paper addresses the symptoms, diseases and complications in which the abnormal reflux of gastric content to the oesophagus and adjacent organ systems is believed to be a frequent contributory factor.     

Upper aerodigestive tract disorders and gastro-oesophageal reflux disease

A wide variety of symptoms and diseases of the upper aerodigestive tract are associated to gastro-oesophageal reflux disease (GORD). These disorders comprise a large variety of conditions such as asthma, chronic otitis media and sinusitis, chronic cough, and laryngeal disorders including paroxysmal laryngospasm. Laryngo-pharyngeal reflux disease is an extraoesophageal variant of GORD that can affect the larynx and pharynx. Despite numerous research efforts, the diagnosis of laryngopharyngeal reflux often remains elusive, unproven and controversial, and its treatment is then still empiric. Aim of this paper is to review the current literature on upper aerodigestive tract disorders in relation to pathologic gastro-oesophageal reflux, focusing in particular on the pathophysiology base and results of the surgical treatment of GORD.     

Endoluminal fundoplication (ELF) – evolution of EsophyX™, a new surgical device for transoral surgery

A novel endoluminal fundoplication (ELF) technique using a trans‐oral and fastener‐deploying device (EsophyX?, EndoGastric Solutions) was developed and evaluated for feasibility, safety and the treatment of gastroesophageal reflux disease (GERD) in a series of bench, animal, human (phase 1, phase 2, commercial registry) studies. The studies verified biological compatibility, durability and non‐toxicity of the polypropylene fasteners as well as the feasibility of the ELF technique. The results of the preclinical testing indicated that the EsophyX? device was shown to be safe, and capable of deploying fasteners directly into tissue and forming an interrupted suture line at the base of the gastro‐esophageal valve (GEV). Moreover, the studies demonstrated that the ELF technique performed using the EsophyX? device resulted in the creation of new GEVs of 3–5?cm in length and a circumference of 200°–310°, which maintained their anatomical aspects at six months. The ELF‐created GEVs appeared similar to those created by laparoscopic anti‐reflux surgery (LARS). The ELF procedure also resulted in reduction of all small hiatal hernias (?2?cm in size) and restoration of the angle of His. The ELF procedure provides an anatomical approach similar to that of LARS for the treatment of GERD.     

Abdominal actinomycosis masquerading as an omental tumor in a 12-year-old female

We herein report a case of abdominal actinomycosis in a 12-year-old girl in whom an omental primary tumor was suspected before surgery. The patient began to experience intermittent lower left abdominal pain. Abdominal computed tomography (CT) scans were inconclusive at this time, but 6 months later, CT and magnetic resonance imaging (MRI) examinations showed a 7-cm, tumor-like lesion in the left abdominal cavity; malignancy could not be ruled out. The tumor, which originated in the omentum and adhered strongly to the left abdominal wall, was resected along with approximately 90 % of the omentum, the peritoneum in contact with the mass, and the posterior layer of the rectus abdominal sheath, under suspicion of a malignant tumor. However, omental actinomycosis was the final pathological diagnosis. The patient’s antibiotic treatment was changed to a penicillin-series oral antibiotic to prevent recurrence of the actinomycosis. The patient was discharged from our hospital 16 days after the first surgery, but she developed three episodes of ileus; the first two required surgery. The patient has had no further recurrences of actinomycosis or postoperative ileus 20 months after discharge.     

Detection of reflux esophagitis on double-contrast esophagrams and endoscopy using the histologic findings as the gold standard

The purpose of our study was to determine the accuracy of double-contrast barium studies and endoscopy for detecting reflux esophagitis, using the endoscopic biopsy findings as the gold standard. A review of radiology, endoscopy, and pathology files showed 37 patients with reflux symptoms who underwent double-contrast barium studies and endoscopy with biopsy specimens from the esophagus. The radiographic images were reviewed in a blinded fashion and correlated with the endoscopic and histologic findings to determine the radiographic and endoscopic accuracies for detecting reflux esophagitis, using the endoscopic biopsy specimens as the gold standard. Double-contrast barium studies and endoscopy had low but comparable accuracies for detecting reflux esophagitis, with sensitivities of 35% and 39%, specificities of 79% and 71%, positive predictive values of 73% and 69%, and negative predictive values of 42% and 41%, respectively. When mucosa granularity was evaluated as an individual sign of esophagitis on double-contrast studies, this finding had a sensitivity of 35%, a specificity of 93%, a positive predictive value of 89%, and a negative predictive value of 46% for detecting reflux esophagitis. Our experience suggests that double-contrast barium studies and endoscopy have limited ability to detect reflux esophagitis, in particular mild esophagitis, when using the histologic findings as the gold standard. When radiographic abnormalities are detected, however, mucosal granularity is the single best sign of reflux esophagitis on double-contrast studies.     

Prediction of post‐operative glomerular filtration rate after nephrectomy for renal malignancy

The importance of a correct estimation of contralateral renal function in cases of renal malignancy is obvious, necessitating a conservative approach to tumour resection when function of the contralateral kidney is markedly reduced. The aim of the present study was to determine the accuracy of preoperative gamma camera renography and ⁵¹Cr‐EDTA clearance to predict the glomerular filtration rate (GFR) early and up to 6 months after nephrectomy for renal malignancy. Patients (n=40) underwent both gamma camera renography (^99mTC‐DTPA) and ⁵¹Cr‐EDTA clearance preoperatively, whereas ⁵¹Cr‐EDTA clearance was measured within 1 week and up to 6 months after nephrectomy. The single kidney GFR values of the contralateral kidneys were estimated preoperatively and then compared with the post‐operative ⁵¹Cr‐EDTA clearance values. The predicted GFR values were lower compared with the measured post‐operative ⁵¹Cr‐EDTA clearance values (45 ± 2 vs. 54 ± 3 ml min^–1 1 week after nephrectomy and 53 ± 3 ml min^–1 6 months later, P<0·01, respectively). The difference between the measured and predicted GFR was larger in patients below the median age of 60 years (P<0·05) and confined to patients with a relative uptake of >30% by the tumour affected kidney. Prediction of post‐operative GFR by non‐invasive renal function tests performed prior to surgery for renal malignancy underestimate post‐operative GFR when the function of the tumour affected kidney is preserved, indicating an adaptive GFR increase in these cases.     

Sonographic appearance of a migrated Angelchik anti‐reflux prosthesis in the pelvis

Surgical implantation of Angelchik prosthesis around the distal esophagus was a popular treatment for gastroesophageal reflux in the 1980s. However, because of frequent complications, this surgical technique was abandoned. We report a case of a migrated Angelchik prosthesis in a 56‐year‐old woman in whom the prosthesis was found in the pelvic cavity 20 years after the initial surgery. The plain radiographic and ultrasound findings are described. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound 2009     

Relation between D‐dimer level,venous valvular reflux and the development of post‐thrombotic syndrome after deep vein thrombosis

Summary. Background: The pathophysiology of post‐thrombotic syndrome (PTS) is postulated to involve persistent venous obstruction and venous valvular reflux. Objective: To study the association between D‐dimer level, valvular reflux and the PTS in a well‐defined cohort of deep vein thrombosis (DVT) patients. Methods: Consecutive patients with acute symptomatic DVT were recruited at eight centers and were followed for 24 months. D‐dimer was measured at 4 months. A standardized ultrasound assessment for popliteal valvular reflux was performed at 12 months. Using the Villalta scale, patients were assessed for PTS during follow‐up by evaluators who were unaware of D‐dimer or reflux results. Results: Three hundred and eighty‐seven patients were recruited; of these, 305 provided blood samples for D‐dimer and 233 had a 12‐month reflux assessment. PTS developed in 45.1% of subjects. Mean D‐dimer was significantly higher in patients with vs. without PTS (712.0 vs. 444.0 μg L^?1; P = 0.02). In logistic regression analyses adjusted for warfarin use at the time of D‐dimer determination and risk factors for PTS, D‐dimer level significantly predicted PTS (P = 0.03); when stratifying for warfarin use at the time of blood draw, adjusted odds ratio (OR) for developing PTS per unit difference in log D‐dimer was 2.33 (95% CI 0.89, 6.10) in those not on warfarin vs. 1.25 (95% CI 0.87, 1.79) in those on warfarin. Ipsilateral reflux was more frequent in patients with moderate‐to‐severe PTS than in patients with mild PTS (65% vs. 40%, respectively; P = 0.01) and was independently associated with moderate‐to‐severe PTS in logistic regression analyses (P = 0.01). Conclusion: D‐dimer levels, measured 4 months after DVT in patients not on warfarin, are associated with subsequent development of PTS. Venous valvular reflux is associated with moderate‐to‐severe PTS.