Rabeprazole vs esomeprazole in non-erosive gastro-esophageal reflux disease: A randomized, double-blind study in urban Asia

AIM：Gastro-esophageal reflux disease (GERD) is becoming increasingly common in Asia. Data on the efficacy of proton pump inhibitors in patients with non-erosive GERD (NERD)in Asia is lacking. This double-blind study compared the efficacy and safety of rabeprazole with esomeprazole in relief of symptoms in patients with NERD.METHODS: One hundred and thirty-four patients with reflux symptoms of NERD and normal endoscopy were randomized to receive rabeprazole 10 mg or esomeprazole 20 mg once daily for 4 wk. Symptoms were recorded in a diary and changes in severity of symptoms noted.RESULTS: At 4 wk of treatment, rabeprazole 10 mg and esomeprazole 20 mg were comparable with regards to the primary endpoint of time to achieve 24-h symptomfree interval for heartburn 8.5 d vs9 d and regurgitation 6 d vs 7.5 d. Rabeprazole and esomeprazole were also similarly efficacious in term of patient's global evaluation with 96% of patients on rabeprazole and 87.9% of patients on esomeprazole, reporting that symptoms improved(P=NS). Satisfactory relief of day- and night-time symptoms was achieved in 98% of patients receiving rabeprazole and 81.4% of patients receiving esomeprazole. Adverse events were comparable in both groups (P = NS).CONCLUSION: Rabeprazole 10 mg has a similar efficacy and safety profile in Asians with NERD as esomeprazole 20 mg. Further study is necessary to investigate whether the small differences between the two drugs seen in this study are related to the improved pharmacodynamicpro perties of rabeprazole. Both drugs were well tolerated.

Diagnosis of gastroesophageal reflux disease in elderly subjects using 24-houres ophageal pH monitoring

Objective To evaluate the relationship between the parameters of 24 hour esophageal pH monitoring and gastroesophageal reflux disease (GERD) among elderly subjects. Methods Twenty four hour esophageal pH monitoring was carried out in 20 elderly subjects without apparent GERD symptoms (controls) and 69 suspected GERD subjects.Results Normal values of the parameters from 20 elderly controls were obtained. Percent of total time, percent of supine time and percent of upright time in which the pH was <4 (indicating reflux) were less than 3.3%, 1.4%, 5.5%, respectively. The number of reflux episodes and episodes lasting longer than 5 minutes were less than 65 and 2 times respectively. The values obtained in 66 GERD suspected subjects were significantly different from those in norrmal controls. The differences of reflux parameters between the esophagitis group and non esophagitis group, such as percent of total time with pH<4, percent of supine time with pH<4 and number of reflux lasting longer than 5 minutes were also significant. Conclusions About 51.6% patients (34/66) with reflux symptoms but without endoscopic evidence of esophagitis were definitely diagnosed as GERD by esophageal pH monitoring. Duration of esophageal acid exposure correlated with the severity of GERD.

Alginate controls heartburn in patients with erosive and nonerosive reflux disease

AIM:To evaluate the effect of a novel alginate-based compound,Faringel,in modifying reflux characteristics and controlling symptoms.METHODS:In this prospective,open-label study,40 patients reporting heartburn and regurgitation with proven reflux disease(i.e.,positive impedance-pH test/evidence of erosive esophagitis at upper endoscopy) underwent 2 h impedance-pH testing after eating a refluxogenic meal.They were studied for 1 h under basal conditions and 1 h after taking 10 mL Faringel.In both sessions,measurements were obtained in right lateral and supine decubitus positions.Patients also completed a validated questionnaire consisting of a 2-item 5-point(0-4) Likert scale and a 10-cm visual analogue scale(VAS) in order to evaluate the efficacy of Faringel in symptom relief.Tolerability of the treatment was assessed using a 6-point Likert scale ranging from very good(1) to very poor(6).RESULTS:Faringel decreased significantly(P < 0.001),in both the right lateral and supine decubitus positions,esophageal acid exposure time [median 10(25th75th percentil 6-16) vs 5.8(4-10) and 16(11-19) vs 7.5(5-11),respectively] and acid refluxes [5(3-8) vs 1(1-1) and 6(4-8) vs 2(1-2),respectively],but increased significantly(P < 0.01) the number of nonacid reflux events compared with baseline [2(1-3)vs 3(2-5) and 3(2-4) vs 6(3-8),respectively].Percentage of proximal migration decreased in both decubitus positions(60% vs 32% and 64% vs 35%,respectively;P < 0.001).Faringel was significantly effective in controlling heartburn,based on both the Likert scale [3.1(range 1-4) vs 0.9(0-2);P < 0.001] and VAS score [7.1(3-9.8) vs 2(0.1-4.8);P < 0.001],but it had less success against regurgitation,based on both the Likert scale [2.6(1-4) vs 2.2(1-4);P = not significant(NS)] and VAS score [5.6(2-9.6) vs 3.9(1-8.8);P = NS].Overall,the tolerability of Faringel was very good 5(2-6),with only two patients reporting modest adverse events(i.e.,nausea and bloating).CONCLUSION:Our findings demonstrate that Faringel is well-tolerated and effective in reducing heartburn by modifying esophageal acid exposure time,number of acid refluxes and their proximal migration.

In vitro effect of pantoprazole on lower esophageal sphincter tone in rats

AIM:To investigate the in vitro effects of pantoprazole on rat lower esophageal sphincter(LES)tone.METHODS:Rats weighing 250-300 g,provided by the Yeditepe University Experimental Research Center(Yü-DETAM),were used throughout the study.They were anesthetized before decapitation.LES tissues whose mucosal lining were removed were placed in a stan-dard 30-mL organ bath with a modif ied Krebs solution and continuously aerated with 95% oxygen-5% carbon dioxide gas mixture and kept at room temperature.The tissues were allowed to stabilize for 60 min.Sub-sequently,the contractile response to 10-6 mol/L carba-chol was obtained.Different concentrations of freshly prepared pantoprazole were added directly to the tis-sue bath to generate cumulative concentrations of 5×10-6 mol/L,5×10-5 mol/L,and 1.5×10-4 mol/L.Activi-ties were recorded on an online computer via a 4-channeltransducer data acquisition system using the software BSL PRO v 3.7,which also analyzed the data.RESULTS:Pantoprazole at 5×10-6 mol/L caused a small,but statistically insignif icant,relaxation in the car-bachol-contracted LES(2.23% vs 3.95%).The 5×10-5 mol/L concentration,however,caused a signif icant relax-ation of 10.47% compared with the control.1.5×10-4 mol/L concentration of pantoprazol caused a 19.89% relaxation in the carbachol contracted LES(P<0.001).CONCLUSION:This is the fi rst study to demonstrate that pantoprazole has a relaxing effect in isolated LESs.These results might have signif icant clinical implications for the subset of patients using proton pump inhibitors who do not receive full symptomatic alleviation from gastroesophageal reflux disease.

Circular smooth muscle contributes to esophageal shortening during peristalsis

AIM:To study the angle between the circular smooth muscle(CSM) and longitudinal smooth muscle(LSM) fibers in the distal esophagus.METHODS:In order to identify possible mechanisms for greater shortening in the distal compared to proximal esophagus during peristalsis,the angles between the LSM and CSM layers were measured in 9 cadavers.The outer longitudinal layer of the muscularis propria was exposed after stripping the outer serosa.The inner circular layer of the muscularis propria was then revealed after dissection of the esophageal mucosa and the underlying muscularis mucosa.Photographs of each specimen were taken with half of the open esophagus folded back showing both the outer longitudinal and inner circular muscle layers.Angles were measured every one cm for 10 cm proximal to the squamocolumnar junction(SCJ) by two independent investigators.Two human esophagi were obtained from organ transplant donors and the angles between the circular and longitudinal smooth muscle layers were measured using micro-computed tomography(micro CT) and Image J software.RESULTS:All data are presented as mean ± SE.The CSM to LSM angle at the SCJ and 1 cm proximal to SCJ on the autopsy specimens was 69.3 ± 4.62 degrees vs 74.9 ± 3.09 degrees,P = 0.32.The CSM to LSM angle at SCJ were statistically significantly lower than at 2,3,4 and 5 cm proximal to the SCJ,69.3 ± 4.62 degrees vs 82.58 ± 1.34 degrees,84.04 ± 1.64 degrees,84.87 ± 1.04 degrees and 83.72 ± 1.42 degrees,P = 0.013,P = 0.008,P = 0.004,P = 0.009 respectively.The CSM to LSM angle at SCJ was also statistically significantly lower than the angles at 6,7 and 8 cm proximal to the SCJ,69.3 ± 4.62 degrees vs 80.18 ± 2.09 degrees,81.81 ± 1.75 degrees and 80.96 ± 2.04 degrees,P = 0.05,P = 0.02,P = 0.03 respectively.The CSM to LSM angle at 1 cm proximal to SCJ was statistically significantly lower than at 3,4 and 5 cm proximal to the SCJ,74.94 ± 3.09 degrees vs 84.04 ± 1.64 degrees,84.87 ± 1.04 degrees and 83.72 ± 1.42 degrees,P = 0.019,P = 0.008,P = 0.02 respectively.At 10 cm above SCJ the angle was 80.06 ± 2.13 degrees which is close to being perpendicular but less than 90 degrees.The CSM to LSM angles measured on virtual dissection of the esophagus and the stomach on micro CT at the SCJ and 1 cm proximal to the SCJ were 48.39 ± 0.72 degrees and 50.81 ± 1.59 degrees.Rather than the angle of the CSM and LSM being perpendicular in the esophagus we found an acute angulation between these two muscle groups throughout the lower 10 cm of the esophagus.CONCLUSION:The oblique angulation of the CSM may contribute to the significantly greater shortening of distal esophagus when compared to the mid and proximal esophagus during peristalsis.

Impact of minimally invasive surgery on the treatment of benign esophageal disorders

Thanks to the development of minimally invasive surgery, the last 20 years have witnessed a change in the treatment algorithm of benign esophageal disorders. Today a laparoscopic operation is the treatment of choice for esophageal achalasia and for most patients with gastroesophageal reflux disease. Because the pathogenesis of achalasia is unknown, treatment is palliative and aims to improve esophageal emptying by decreasing the functional obstruction at the level of the gastro-esophageal junction. The refinement of minimally invasive techniques accompanied by large, multiple randomized control trials with long-term outcome has allowed the laparoscopic Heller myotomy and partial fundoplication to become the treatment of choice for achalasia compared to endoscopic procedures, including endoscopic botulinum toxin injection and pneumatic dilatation. Patients with suspected gastroesophageal reflux need to undergo a thorough preoperative workup. After establishing diagnosis, treatment for gastroesophageal reflux should be individualized to patient characteristics and a decision about an operation made jointly between surgeon and patient. The indications for surgery have changed in the last twenty years. In the past, surgery was often considered for patients who did not respond well to acid reducing medications. Today, the best candidate for surgery is the patient who has excellent control of symptoms with proton pump inhibitors. The minimally invasive approach to antireflux surgery has allowed surgeons to control reflux in a safe manner, with excellent long term outcomes. Like achalasia and gastroesophageal reflux, the treatment of patients with paraesophageal hernias has also seen a major evolution. The laparoscopic approach has been shown to be safe, and durable, with good relief of symptoms over the long-term. The most significant controversy with laparoscopic paraesophageal hernia repair is the optimal crural repair. This manuscript reviews the evolution of these techniques.

Eosinophilic esophagitis-endoscopic distinguishing findings

Eosinophilic esophagitis （EE） is the most frequent con- dition found in a group of gastrointestinal disorders called eosinophilic gastrointestinal diseases. The hypo- thetical pathophysiological mechanism is related to a hypersensitivity reaction. Gastroesophageal reflux dis- ease-like complaints not ameliorated by acid blockade or occasional symptoms of dysphagia or food impac- tion are likely presentations of EE. Due to its unclear pathogenesis and unspecific symptoms, it is difficult to diagnose EE without a strong suspicion. Although histo- togical criteria are necessary to diagnosis EE, there are some characteristic endoscopic features. We present the case of a healthy 55-year-old woman with dyspha- gia and several episodes of esophageal food impaction over the last six months. This case report stresses the most distinguishing endoscopic findings-mucosa rings, white exudative plaques and linear furrows-that can help in the prompt recognition of this condition.

Temporal trends in the relative prevalence of dysphagia etiologies from 1999-2009

AIM:To examine the relative prevalence and temporal variation of dysphagia etiologies in patients undergoing upper endoscopy(EGD) over the past decade.METHODS:EGDs with the indication of dysphagia at an urban,university medical center in 1999,2004 and 2009 were retrospectively identified from the electronic medical record.The entire patient chart,including EGD,pathology,manometry,radiographic and clinician reports,was reviewed for demographic and clinical data and to determine the etiology of dysphagia.The number of EGDs in which an esophageal biopsy was performed was also noted.Gastroesophageal reflux disease(GERD) as a cause of dysphagia independent of peptic stricture was defined by symptoms with erosive esophagitis or symptom response to proton pump inhibition(PPI).Cases of eosinophilic esophagitis(EoE) were defined by an appropriate clinical history and histological criteria of ≥ 15 eosinophils per high powered field.PPI-responsive esophageal eosinophilia was not routinely reported prior to 2008.Statistical analysis was performed using one-way analysis of variance to analyze for trends between 1999,2004 and 2009 and a post-hoc Tukey analysis was performed following a significant main effect.RESULTS:A total of 1371 cases(mean age 54 years,43% male) met pre-specified inclusion criteria with 191,504 and 675 cases in 1999,2004 and 2009,respectively.Patients were older in 2004 compared to 2009(mean ± SD,54.0 ± 15.7 years vs 52.3 ± 16.8 years,P = 0.02) and there were more males in 1999 compared to 2004(57.5% vs 40.8%,P = 0.005).Overall,GERD(27.6%) and EoE(7.7%) were the most common identifiable causes of dysphagia.An unspecified diagnosis accounted for 21% of overall cases.There were no significant differences in the relative prevalence of achalasia or other motility disorders,peptic stricture,Schatzki's ring,esophageal cancer or unspecified diagnoses over the 10-year time period.There was,however,a decrease in the relative prevalence of GERD(39.3% vs 24.1%,P < 0.001) and increases in the relative prevalence of EoE(1.6% vs 11.2%,P < 0.001) and oropharyngeal disorders(1.6% vs 4.2%,P = 0.02) from 1999 to 2009.Post-hoc analyses determined that the increase in relative prevalence of EoE was significant between 1999 and 2009 as well as 2004 and 2009(5.4% vs 11.6%,P < 0.001),but not between 1999 and 2004(1.6% P 5.4%,P = 0.21).On the other hand,the decrease in relative prevalence of GERD was significant between 1999 and 2009 and 1999 and 2004(39.3% vs 27.7%,P = 0.006),but not between 2004 and 2009(27.7% vs 24.1%,P = 0.36).There were also significantly more EGDs in which a biopsy was obtained in 1999 compared to 2009(36.7% vs 68.7%,P < 0.001) as well as between 2004 and 2009(37.5% vs 68.7%,P < 0.001).While total EGD volume did increase over the 10-year time period,the percentage of EGDs for the indication of dysphagia remained stable making increasing upper endoscopy an unlikely reason for the observed increased prevalence of EoE.CONCLUSION:EoE has emerged as a dominant cause of dysphagia in adults.Whether this was due to a rise in disease incidence or increased recognition is unclear.