Risk factors for proton pump inhibitor refractoriness in Chinese patients with non-erosive reflux disease

AIM:To analyze risk factors for refractoriness to proton pump inhibitors(PPIs) in patients with non-erosive reflux disease(NERD).METHODS:A total of 256 NERD patients treated with the PPI esomeprazole were enrolled.They were classified into symptom-free and residual symptoms groups according to Quality of Life in Reflux and Dyspepsia(QolRad) scale.All subjects completed questionnaires on psychological status(self-rating anxiety scale;selfrating depression scale) and quality of life scale(Short Form 36).Multivariate analysis was used to determine the predictive factors for PPI responses.RESULTS:According to QolRad,97 patients were confirmed to have residual reflux symptoms,and the remaining 159 patients were considered symptom free.There were no significant differences between the two groups in lifestyle factors(smoking and alcohol consumption),age,Helicobacter pylori infection,and hiatal hernia.There were significant differences between the two groups in relation to sex,psychological distress including anxiety and depression,body mass index(BMI),and irritable bowel syndrome(IBS)(P < 0.05).Logistic regression analysis found that BMI < 23,comorbid IBS,anxiety,and depression were major risk factors for PPI resistance.Symptomatic patients had a lower quality of life compared with symptom-free patients.CONCLUSION:Some NERD patients are refractory to PPIs and have lower quality of life.Residual symptoms are associated with psychological distress,intestinal disorders,and low BMI.

Risk factors for gastroesophageal reflux disease,reflux esophagitis and non-erosive reflux disease among Chinese patients undergoing upper gastrointestinal endoscopic examination

AIM: To analyze the spectrum and risk factors of gastroesophageal reflux disease (GERD) based on presenting symptoms and endoscopic f indings. METHODS: A cross-sectional survey in a cluster random sample was conducted from November 2004 to June 2005 using a validated Chinese version Reflux Disease Questionnaire (RDQ) and other items recording the demographic characteristics and potential risk factors for GERD. Subjects were def ined as having GERD symptoms according to the RDQ score (> 12). All subjects were endoscopied and the def inition and severity of erosive esophagitis were evaluated by Los Angeles classif ication. The statistical analysis was performed with SPSS13.0 programs. RESULTS: Of 2231 recruited participants, 701 (31.40%) patients were diagnosed as having GERD while 464 (20.80%) patients had objective findings of reflux esophagitis (RE). Of those 464 patients, only 291 (13.00%) were reported as subjects with GERD symptoms. A total of 528 (23.70%) patients were found to have GERD symptoms, including 19.50% patients with grade A or B reflux esophagitis, 0.90% with grade C and 0.40% with grade D. On multivariate analysis, old age, male, moderate working burden, divorced/widowed and strong tea drinking remained as signif icant independent risk factors for erosive esophagitis. Meanwhile, routine usage of greasy food and constipation were considered as significant independent risk factors for non-erosive reflux disease (NERD). CONCLUSION: GERD is one of the common GI diseaseswith a high occurrence rate in China and its main associated factors include sex, anthropometrical variables and sociopsychological characteristics.

Fiber-enriched diet helps to control symptoms and improves esophageal motility in patients with non-erosive gastroesophageal reflux disease

AIM To investigate the effect of dietary fiber on symptoms and esophageal function testing parameters in nonerosive gastroesophageal reflux disease(GERD)(NERD) patients.METHODS Thirty-six NERD patients with low(< 20 g/d) dietary fiber intake were enrolled in the study. They were examined with the use of symptom questionnaire(GERD-Q), highresolution esophageal manometry, 24-h esophageal p Himpedance examinations, and food frequency questionnaire before and after 10 d of usual diet supplemented by psyllium 5.0 g TID. Complete data of 30 patients were available to the final analysis. The obtained results were analyzed with the use of non-parametric statistics(Wilcoxon matched pairs test). RESULTS The number of patients experiencing heartburn was less(93.3% at baseline vs 40% at the end of the study, P < 0.001) and the GERD-Q score decreased(mean ± SD: 10.9 ± 1.7 vs 6.0 ± 2.3, P < 0.001) after the treatment period. Minimal resting lower esophageal sphincter(LES) pressure increased from 5.41 ± 10.1 to 11.3 ± 9.4 mm Hg(P = 0.023), but no change in residual LES pressure and mean resting pressure was found. Total number of gastroesophageal refluxes(GER) decreased from 67.9 ± 17.7 to 42.4 ± 13.5(P < 0.001) predominantly by acid and weak acid types of GERs. No significant change in mean esophageal p H and % of time p H < 4 was registered. Maximal reflux time decreased from 10.6 ± 12.0 min to 5.3 ± 3.7 min(P < 0.05). CONCLUSION Fiber-enriched diet led to a significant increase of minimal lower esophageal sphincter resting pressure, a decrease of number of gastroesophageal refluxes, and a decrease of heartburn frequency per week in NERD.

Proton pump inhibitor for non-erosive reflux disease:A meta-analysis

AIM:To evaluate the efficacy,safety and influential factors of proton pump inhibitor(PPI)treatment for non-erosive reflux disease(NERD).METHODS:PubMed,MEDLINE,EMBASE and the Cochrane Library were searched up to April 2013 to identify eligible randomized controlled trials(RCTs)that probed into the efficacy,safety and influential factors of PPI treatment for NERD.The rates of symptomatic relief and adverse events were measured as the outcomes.After RCT selection,assessment and data collection,the pooled RRs and 95%CI were calculated.This meta-analysis was performed using the Stata 12.0 software(Stata Corporation,College Station,Texas,United States).The level of evidence was estimated by the Grading of Recommendations Assessment,Development and Evaluation system.RESULTS:Seventeen RCTs including 6072 patients met the inclusion criteria.The results of the metaanalysis showed that PPI treatment was significantly superior to H2receptor antagonists(H2RA)treatment(RR=1.629,95%CI:1.422-1.867,P=0.000)and placebo(RR=1.903,95%CI:1.573-2.302,P=0.000)for the symptomatic relief of NERD.However,there were no obvious differences between PPI and H2RA(RR=0.928,95%CI:0.776-1.110,P=0.414)or PPI and the placebo(RR=1.000,95%CI:0.896-1.116,P=0.997)regarding the rate of adverse events.The overall rate of symptomatic relief of PPI against NERD was 51.4%(95%CI:0.433-0.595,P=0.000),and relief was influenced by hiatal hernia(P=0.030).The adverse rate of PPI against NERD was 21.0%(95%CI:0.152-0.208,P=0.000),and was affected by hiatal hernia(P=0.081)and drinking(P=0.053).CONCLUSION:PPI overmatched H2RA on symptomatic relief rate but not on adverse rate for NERD.Its relief rate and adverse rate were influenced by hiatal hernia and drinking.

Characteristics of non-erosive gastroesophageal reflux disease refractory to proton pump inhibitor therapy

AIM:To investigate whether potent acid inhibition is effective in non-erosive reflux disease (NERD) refractory to standard rabeprazole (RPZ) treatment. METHODS:We treated 10 Japanese patients with NERD resistant to standard dosages of RPZ:10 mg or 20 mg od,20 mg bid,or 10 mg qid for 14 d. All patients completed a frequency scale for symptoms of gastroesophageal reflux disease questionnaire frequency scale for the symptoms of GERD (FSSG); and underwent 24 h pH monitoring on day 14. RESULTS:With increased dosages and frequency of administration of RPZ,median intragastric pH significantly increased,and FSSG scores significantly decreased. With RPZ 10 mg qid,potent acid inhibition was attained throughout 24 h. However,five subjects were refractory to RPZ 10 mg qid,although the median intragastric pH in these subjects (6.6,range:6.2-7.1) was similar to that in the remaining five responsive subjects (6.5,range:5.3-7.3). With baseline RPZ 10 mg od,FSSG scores in responsive patients improved by > 30%,whereas there was no significant decrease in the resistant group. CONCLUSION:NERD patients whose FSSG score fails to decrease by > 30% after treatment with RPZ 10 mg od for 14 d are refractory to higher dosage.

Characteristics of symptomatic reflux episodes in Japanese proton pump inhibitor-refractory non-erosive reflux disease patients

AIM: To clarify the pathogenesis of gastroesophageal reflux disease symptoms in non-erosive reflux disease(NERD) patients.METHODS: Thirty-five NERD patients with persistent symptoms, despite taking rabeprazole 10 mg twice daily for at least 8 wk, were included in this study. All patients underwent 24 h combined impedance- p H on rabeprazole. The symptom index(SI) was considered to be positive if ≥ 50%, and proximal reflux episodes were determined when reflux reached 15 cm above the proximal margin of the lower esophageal sphincter.RESULTS: In 14(40%) SI-positive patients, with liquid weakly acid reflux, the occurrence rate of reflux symptoms was significantly more frequent in proximal reflux episodes(46.7%) than in distal ones(5.7%)(P < 0.001). With liquid acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes(38.5%) and distal ones(20.5%)(NS). With mixed liquid-gas weakly acid reflux, the occurrence rate of reflux symptoms in proximal reflux episodes was significantly more frequent(31.0%) than in distal reflux ones(3.3%)(P < 0.001). With mixed liquid-gas acid reflux, there were no significant differences in the occurrence rate of reflux symptoms between proximal reflux episodes(29.4%) and distal ones(14.3%)(NS).CONCLUSION: The proximal extent of weakly acidic liquid and mixed liquid-gas reflux is a major factor associated with reflux perception in SI-positive patients on proton pump inhibitor therapy.

Efficacy of endoluminal gastroplication in Japanese patients with proton pump inhibitor-resistant,non-erosive esophagitis

AIM： To evaluate the efficacy, safety, and long-term outcomes of endoluminal gastroplication （ELGP） in pa- tients with proton pump inhibitor （PPI）-resistant, non- erosive reflux disease （NERD）. METHODS： The subjects were NERD patients, diag- nosed by upper endoscopy before PPI use, who had symptoms such as heartburn or reflux sensations two or more times a week even after 8 wk of full-dose PPI treatment. Prior to ELGP, while continuing full-dose PPImedication, patients＇ symptoms and quality of life （QOL） were assessed using the questionnaire for the diagno- sis of reflux disease, the frequency scale for symptoms of gastro-esophageal reflux disease （FSSG）, gastroin- testinal symptoms rating scale, a 36-item short-form. In addition, 24-h esophageal pH monitoring or 24-h in- traesophageal pH/impedance （MII-pH） monitoring was performed. The Bard EndoCinchTM was used for ELGP, and 2 or 3 plications were made. After ELGP, all acid reducers were temporarily discontinued, and medica- tion was resumed depending on the development and severity of symptoms. Three mo after ELGP, symptoms, QOL, pH or MII-pH monitoring, number of plications, and PPI medication were evaluated. Further, symptoms, number of plications, and PPI medication were evalu- ated 12 mo after ELGP to investigate long-term effects. RESULTS： The mean FSSG score decreased signifi- cantly from before ELGP to 3 and 12 mo after ELGP （19.1 ：k 10.5 to 10.3 ＋ 7.4 and 9.3 ＋ 9.9, P 〈 0.05, respectively）. The total number of plications decreased gradually at 3 and 12 mo after ELGP （2.4 ＋ 0.8 to 1.2 ：l： 0.8 and 0.8 ：l： 1.0, P 〈 0.05, respectively）. The FSSG scores in cases with no remaining plications and in cases with one or more remaining plications were 4.4 and 2.7, respectively, after 3 too, and 2.0 and 2.8, respectively, after 12 mo, showing no correlation to plication loss. On pH monitoring, there was no differ- ence in the percent time pH 〈 4 from before ELGP to 3 mo after. Impedance monitoring revealed no changes in the number of reflux episodes or the symptom index for reflux events from before ELGP to 3 mo after, but the symptom sensitivity index decreased significantly 3 mo after ELGP （16.1：1：12.9 to 3.9 ~ 8.3, P 〈 0.01）. At 3 mo after ELGP, 6 patients （31.6%） had reduced their PPI medication by 50% or more, and 11 patients （57.9%） were able to discontinue PPI medication alto- gether. After 12 mo, 3 patients （16.7%） were able toreduce the amount of PPI medication by 50% or more, and 22 patients （66.7%） were able to discontinue PPI medication altogether. A high percentage of cases with remaining plications had discontinued PPIs medication after 3 mo, but there was no difference after 12 mo. No serious complications were observed in this study. CONCLUSION： ELGP was safe, resulted in significant improvement in subjective symptoms, and allowed less medication to be used over the long term in patients with PPI-refractory NERD.

A randomized open-label trial of on-demand rabeprazole vs ranitidine for patients with non-erosive reflux disease

AIM： To compare the efficacy of the proton-pump inhibitor, rabeprazole, with that of the H2-receptor antagonist, ranitidine, as on-demand therapy for relieving symptoms associated with non-erosive reflux disease （NEED）.METHODS： This is a single center, prospective, randomized, open-label trial of on-demand therapy with rabeprazole （group A） vs ranitidine （group B） for 4 wk. Eighty-three patients who presented to the American University of Beirut Medical Center with persistent gas- troesophageal reflux disease （GERD） symptoms and a normal upper gastrointestinal endoscopy were eligible for the study. Patients in group A （n = 44） were al-lowed a maximum rabeprazole dose of 20 mg twice daily, while those in group B （n = 39） were allowed a maximum ranitidine dose of 300 mg twice daily. Ef- ficacy was assessed by patient evaluation of global symptom relief, scores of the SF-36 quality of life （QoL） questionnaires, total number of pills used, and number of medication-free days.RESULTS： Among the 83 patients who were enrolled in the study, 76 patients （40 in the rabeprazole group and 36 in the ranitidine group） completed the 4-wk trial. Baseline characteristics were comparable between both groups. After 4 wk, there was no significant difference in the subjective global symptom relief between the rabeprazole and the ranitidine groups （71.4% vs 65.4%, respectively; P = 0.9）. There were no statistically significant differences between mean cumulative scores of the SF-36 QoL questionnaire for the two study groups （rabeprazole 22.40±27.53 vs ranitidine 17.28 ± 37.06; P = 0.582）. There was no significant difference in the mean number of pills used （rabeprazole 35.70±29.75 vs ranitidine 32.86±26.98; P = 0.66）. There was also no statistically significant difference in the mean number of medication-free days between both groups.CONCLUSION： Rabeprazole has a comparable efficacy compared to ranitidine when given on-demand for the treatment of NERD. Both medications were associated with improved quality of life.

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.

Non-erosive and uncomplicated erosive reflux diseases:Difference in physiopathological and symptom pattern

AIM:To investigate differences in the physiopathological findings(manometry and pH monitoring) and symptoms between cases of non-erosive reflux disease(NERD) and erosive reflux disease(ERD) found positive at 24 h pH monitoring. METHODS:For a total of 670 patients who underwent 24 h pH monitoring,esophageal manometry and upper endoscopy were retrospectively evaluated,assessing the reflux symptoms,manometric characteristics of the lower esophageal sphincter(LES) and esophageal body and the presence or absence of esophagitis and hiatal hernia. Typical and atypical symptoms were also evaluated. For inclusion in the study,patients had to have NERD or ERD and be found positive on pH monitoring(NERD+) . Patients with Gastroesophageal reflux disease(GERD) complicated by stenosis,ulcers or Barrett's esophagus were ruled out. RESULTS:214 patients were involved in the study,i.e. 107 cases of NERD+ and 107 of ERD. There were no significant gender-or age-related differences between the two groups. The ERD group had more cases of hiatal hernia(P = 0.02) and more acid reflux,both in terms of number of reflux episodes(P = 0.01) and as a percentage of the total time with a pH < 4(P = 0.00) ,when upright(P = 0.007) and supine(P = 0.00) . The NERD+ cases had more reflux episodes while upright(P = 0.02) and the ERD cases while supine(P = 0.01) . The LES pressure was higher in cases of NERD+(P = 0.03) while the amplitude and duration of their esophageal peristaltic waves tended to be better than in the ERD group(P >0.05) . The NERD+ patients presented more often with atypical symptoms(P = 0.01) . CONCLUSION:The NERD+ patients' fewer reflux episodes and the fact that they occurred mainly while in the upright position(unlike the cases of ERD) may be two factors that do not favor the onset of esophagitis. The frequently atypical symptoms seen in patients with NERD+ need to be accurately evaluated for therapeutic purposes because patients with GERD and atypical symptoms generally respond only partially to medical and surgical treatments.

Cell proliferation of esophageal squamous epithelium in erosive and non-erosive reflux disease

AIM： To elucidate cell proliferation in erosive reflux disease （ERD） and non-erosive reflux disease （NERD）, we evaluated markers in squamous epithelial cells.METHODS： Thirty-four consecutive patients with gas- troesophageal-reflux-disease-related symptoms （21 NERD and 13 ERD） were evaluated for the enrolment into the study. All patients underwent 24-h pH moni- toring, standard endoscopy, and biopsy for histological evaluation. The expression of cyclins D and A was eval- uated by real-time reverse transcription polymerase chain reaction （RT-PCR） from isolated epithelial cells. In all samples, analysis of the isolated cell population revealed the presence of epithelial cells only.RESULTS： Real-time RT-PCR showed that, in patientswith ERD, the relative expression of cyclin D1 mRNA in esophageal epithelium was strongly decreased in comparison with NERD patients. The mean value of relative expression of cyclin D1 mRNA in NERD patients was 3.44 ± 1.9, whereas in ERD patients, it was 1.32 ± 0.87 （P = 0.011）. Real-time RT-PCR showed that, in patients with ERD, relative expression of cyclin A mRNA in esophageal epithelium was decreased in comparison with that in NERD patients （2.31 ± 2.87 vs 0.66 ± 1.11）. The mean bromodeoxyuridine labeling index in the NERD patients was 5.42% ± 1.68%, whereas in ERD patients, it was 4.3% ± 1.59%.

Autofluorescence imaging endoscopy can distinguish non-erosive reflux disease from functional heartburn: A pilot study

AIM: To investigate whether autofluorescence imaging (AFI) endoscopy can distinguish non-erosive reflux disease (NERD) from functional heartburn (FH).METHODS: In this prospective observational trial, 127 patients presenting with typical reflux symptoms for &#x0003e; 6 mo were screened. All the participants underwent endoscopy, during which white light imaging (WLI) was followed by AFI. Finally 84 patients with normal esophageal appearance on WLI were enrolled. It was defined as being suggestive of NERD if one or more longitudinal purple lines longer than one centimeter were visualized in the distal part of the esophagus during AFI endoscopy. Ambulatory 24-h multichannel intraluminal impedance and pH monitoring was also performed. After standard proton-pump inhibitor (PPI) tests, subjects were divided into an NERD group and an FH group and the diagnostic performance of AFI endoscopy to differentiate NERD from FH was evaluated.RESULTS: Of 84 endoscopy-negative patients, 36 (42.9%) had a normal pH/impedance test. Of these, 26 patients with favorable responses to PPI tests were classified as having NERD. Finally 10 patients were diagnosed with FH and the others with NERD. Altogether, 68 (81.0%) of the 84 patients were positive on AFI endoscopy. In the NERD group, there were 67 (90.5%) patients with abnormal esophageal findings on AFI endoscopy while only 1 (10%) patient was positive on AFI endoscopy in the FH group. The sensitivity and specificity of AFI in differentiating NERD from FH were 90.5% (95%CI: 81.5%-96.1%) and 90.0% (95%CI: 55.5%-99.7%), respectively. Meanwhile, the accuracy, positive predictive value and negative predictive value of AFI in differentiating between NERD and FH were 90.5% (95%CI: 84.2%-96.8%), 98.5% (95%CI: 92.1%-99.9%) and 56.3% (95%CI: 30.0%-80.2%), respectively.CONCLUSION: Autofluorescence imaging may serve as a complementary method in evaluating patients with NERD and FH.

Hewei Jiangni granule alleviates visceral hypersensitivity in a rat model of non-erosive reflux disease via transient receptor potential channel signaling

Objective:To uncover the underlying mechanism of Hewei Jiangni granule(HWJNG)on non-erosive reflux disease(NERD)treatment by examining histological changes,gastrointestinal neurochemicals release and visceral hypersensitivity-related receptor expression in NERD model rats.Methods:A NERD rat model was established via a combination of basal sensitization and acid perfusion.HWJNG treatments at different doses were then administered.Pathological changes to tissues,mast cell(MC)activation,serum levels of esophageal visceral hypersensitivity-related neurochemicals,and transient receptor potential(TRP)receptor mRNA and protein levels were investigated.Results:Compared with the control group,the expression of tryptase in MCs,the changes of intercellular space,and the serum levels of substance P(SP),calcitonin gene-related peptides(CGRP)and proteinaseactivated receptor 2(PAR2)increased in the model group(all P<.05).The expression of TRP vanilloid 1(Trpv1)mRNA decreased in esophagus and dorsal root ganglia(DRG)of the model group(P=.030&P=.013),and the expression of TRP melastatin channel subfamily member 8(Trpm8)mRNA decreased in the esophagus of model group(P<.01).The level of esophageal TRPV1 protein increased in the model group(P<.01)and the level of TRPM8 protein decreased in esophagus and DRG of the model group(both P<.05).Compared with the model group,the serum levels of SP,CGRP,and PAR2 in the mediumdose HWJNG group showed significant decreases(all P<.05).The expression of Trpv1 mRNA in esophagus and DRG of the HWJNG groups and the Omeprazole group remarkably decreased(all P<.05),as was the expression of Trpm8 mRNA in esophagus of the HWJNG groups(all P<.05).Conclusion:HWJNG alleviated visceral hypersensitivity in NERD model rats by regulating TRP-mediated signaling.Our results indicate that HWJNG has potential as a therapeutic agent for NERD.

Therapeutic Advantages of Traditional Chinese Medicine in Non-erosive Reflux Disease

The incidence of gastroesophageal reflux disease(GERD) is increasing year by year. Non-erosive reflux disease(NERD) is not only the most common subtype of GERD, but also has the highest proportion of refractory GERD. The pathogenesis may be closely related to mixed reflux, non-acid reflux, esophageal hypersensitivity, psychology and so forth. On the one hand, the treatment with acid suppression drugs alone has a high recurrence rate, and the maintenance treatment continues to be controversial. On the other hand, the comprehensive treatment with the traditional Chinese medicine(TCM), which is based on a number of hybrid mechanisms, is more prominent in individualization with more advantages in long-term efficacy and improvement of quality of life for the patient. The authors conduct a comprehensive analysis on characteristics of NERD and advantages of TCM in treatment, in order to provide more ideas for clinical treatment.

Efficacy and safety of Amla(Phyllanthus emblica L.) in non-erosive reflux disease:a double-blind,randomized,placebo-controlled clinical trial

Background： Gastroesophageal reflux disease （GERD） is one of the most common gastrointestinal com- plaints. GERD, caused by the reflux of stomach contents into the esophagus, leads to troublesome symptoms such as heartburn and regurgitation. It is classified into two types： erosive esophagitis, characterized by visible esophageal mucosa erosion in endoscopy, and non-erosive reflux disease （NERD）. GERD is a chronic and recurrent disease that impairs the quality of life and imposes socioeco- nomic and therapeutic burdens to both patients and society. Objective： Due to the failure of the conventional treatments for GERD and to the traditional use of Amla （Phyllanthus emblica L.）, in addition to beneficial effects shown in recent studies, we evaluated the safety and efficacy of Amla tablet for improvement of symptoms of patients with NERD. Design, setting, participants and interventions： We designed a double-arm, randomized, double-blind, placebo-controlled clinical trial. Sixty-eight patients who had classic symptoms of GERD （heartburn, regurgitation and epigastralgia） for at least three months before the start of the trial were randomized in two parallel groups. Patients in the Amla group received two 500 mg Amla tablets twice a day, after meals, for 4 weeks. In the control group, patients received placebo tablets similar to the Amla prescription. Main outcome measures： The patients were visited at baseline, and at the end of the 2nd and 4th weeks of intervention; their symptoms were measured on a frequency and severity scale for the symptoms of NERD, according to the quality of life in reflux-associated disease questionnaire. Results： Frequencies of heartburn and regurgitation in both groups of the study were significantly reduced after intervention （P 〈 0.001）. Repeated measures logistic regression analysis showed that, in the Amla group, there was a more significant reduction in regurgitation frequency, heartburn frequency, regurgita- tion severity and heartburn severity during the study period, compared with the placebo group （P 〈 0.001 ）. Conclusion： This randomized double-blind, placebo-controlled clinical trial demonstrated that Amla could reduce frequencies of heartburn and regurgitation and improve heartburn and regurgitation severity in patients with NERD.

胃食管返流病患者应用黛力新疗效观察

目的观察胃食管返流病(GERD:NERD,RE)患者在对症治疗3月以上效果不佳的同时加用氟哌噻吨美利曲辛(商品名:黛力新)10.5mg,2次/d,口服治疗的疗效。方法 A组:GERD患者123例(NERD患者82例,RE患者41例)在对症治疗3月以上(平均5.6±1.9月)效果不佳的患者;B组:A组患者在原治疗不变的基础上同时加用黛力新10.5mg,2次/d,口服治疗2月(或症状消失2周以上停药)的两组疗效观察。结果统一用STATA10.0分析。结果B组患者中9例脱离治疗,114例患者完成治疗,起效从3～30d,平均(15.6±10.8)d,101例患者治疗有效(101/114,88.6%),13(13/114,11.4%)例患者2月疗程结束无效,治疗有效率的95%可信度区间:81.29%,93.79%。结论 GERD患者在对症治疗效果不佳的同时加用黛力新10.5mg,2次/d,口服治疗有较好的临床疗效,副作用少,GERD患者加用氟哌噻吨美利曲辛可以缩短治疗周期有良好的社会效益和经济效益,在临床上有一定的推广价值。

Heartburn and regurgitation have different impacts on life quality of patients with gastroesophageal reflux disease

AIM: To investigate the impact of heartburn and regurgitation on the quality of life among patients with gastroesophageal reflux disease (GERD).

Local inflammatory response to gastroesophageal reflux:Association of gene expression of inflammatory cytokines with esophageal multichannel intraluminal impedance-pH data

BACKGROUND Gene expression of inflammatory cytokines may take part in the pathophysiology of different forms of gastroesophageal reflux disease(GERD).AIM To explore gene expression of inflammatory cytokines in esophageal mucosa in patients with erosive esophagitis(EE)and non-erosive forms of GERD(NERD)and its association with data of esophageal multichannel intraluminal impedancepH(MII-pH)measurements.METHODS This was a single-center prospective study.Esophageal mucosa samples were taken from the lower part of the esophagus during endoscopy.Expression of interleukin(IL)-1β,IL-10,IL-18,tumor necrosis factorα(TNFA),toll-like receptor 4(TLR4),GATA binding protein 3(GATA3),differentiation cluster 68(CD68)andβ-2 microglobulin genes in esophageal mucosa was assessed with ImmunoQuantex assays.MII-pH measurements were performed on all the participants.Diagnosis of GERD was confirmed by the results of the MII-pH data.Based on the endoscopy,patients were allocated to the groups of EE and NERD.The control group consisted of non-symptomatic subjects with normal endoscopy and MII-pH results.We used nonparametric statistics to compare the differences between the groups.Association of expression of the mentioned genes with the results of the MII-pH data was assessed with Spearman’s rank method.RESULTS Data from 60 patients with GERD and 10 subjects of the control group were available for the analysis.Higher expression of IL-18(5.89±0.4 vs 5.28±1.1,P=0.04)and GATA3(2.92±0.86 vs 2.23±0.96,P=0.03)was found in the EE group compared to NERD.Expression of IL-1β,IL-18,TNFA,and TLR4 was lower(P<0.05)in the control group compared to EE and NERD.Esophageal acid exposure correlated with the expression of IL-1β(Spearman’s rank r=0.29),IL-18(r=0.31),TNFA(r=0.35),GATA3(r=0.34),TLR4(r=0.29),and CD68(r=0.37).Mean esophagealрНcorrelated inversely with the expression of IL-18,TNFA,GATA3,TLR4,and CD68.No association of gene expression with the number of gastroesophageal refluxes was found.CONCLUSION In patients with EE,local expression of IL-18 and GATA3 was higher compared to subjects with NERD.Esophageal acid exposure correlated directly with expression of IL-1β,IL-18,TNFA,TLR4,CD68,andβ-2 microglobulin genes.Inverse correlation was revealed between expression of IL-18,TNFA,GATA3,TLR4,and CD68 and mean esophageal pH.

Effect of omeprazole on symptoms and ultrastructural esophageal damage in acid bile reflux

AIM: To value whether omeprazole could induce the healing of DIS and regression of symptoms in patients with DGER. METHODS: We enrolled 15 symptomatic patients with a pathological esophageal 24-h pH-metry and bilimetry. Patients underwent endoscopy and biopsies were taken from the distal esophagus. Specimens were analyzed at histology and transmission electron microscopy (TEM). Patients were treated with omeprazole 40 mg/d for 3 mo and then endoscopy with biopsies was repeated. Patients with persistent heartburn and/or with an incomplete recovery of DIS were treated for 3 more months and endoscopy with biopsies was performed. RESULTS: Nine patients had a non-erosive reflux disease at endoscopy (NERD) while 6 had erosive esophagitis (ERD). At histology, of the 6 patients with erosive esophagitis, 5 had mild esophagitis and 1 moderate esophagitis. No patients with NERD showed histological signs of esophagitis. After 3 mo of therapy, 13/15 patients (86.7%,P<0.01) showed a complete recovery of DIS and disappearance of heartburn. Of the 2 patients treated for 3 more months, complete recovery of DIS and heartburn were achieved in one. CONCLUSION: Three or 6 mo of omeprazole therapy led to a complete regression of the ultrastructural esophageal damage in 86.7% and in 93% of patients with DGER, NERD and ERD respectively. The ultrastructural recovery of the epithelium was accompanied by regression of heartburn in all cases.

Heterogeneity of endoscopy negative heartburn:Epidemiology and natural history

It has now become clear that only about 40% or less of patients with heartburn and/or regurgitation have esophagitis, and that the majority of them lack visible distal esophageal mucosa breaks. These subjects are referred to as non-erosive gastroesophageal reflux disease (NERD) patients. It has been estimated that in the Western world at least one tenth of the general population has at least weekly heartburn. This proportion seems to be lower in Asia, while prevalence is rapidly increasing. Although it would be extremely useful to have prospective information regarding the fate of such patients, the natural history of NERD is largely unknown, and very few studies in the literature have addressed this issue. These studies are for the greater part old, not well conducted, and suffer from methodological drawbacks including ill-defined entry criteria. However, a review of these studies indicates that a consistent minority of NERD patients may develop erosive disease at an approximate rate of about 10% per year.