Clinical Efficacy And Effect To LES Pressure Of Gastric Electrical Stimulation For Non-erosive Reflux Disease

Non-erosive reflux disease (NERD) is defined by the presence of esophageal or extra-esophageal manifestations or by the occurrence of reflux induced symptoms severe enough to impair quality of life, without having either Barrett's esophagus or definite endoscopic esophageal mucosal breaks. It is also called endoscopic-negative reflux disease or symptomatic gastro-esophageal reflux disease. In west countries, about 50%～70% of patients with gastro-esophageal reflux disease (GERD) are NERD. Now, it lacks studies on the epidemiology of NERD in China. According to the investigation reports in Beijing and Shanghai, 67% of patients with GERD are NERD.NERD is a heterogenous disease with complicated pathogeny and pathogenesis, which is not very clear now. Dysfunction of lower esophageal sphincter (LES) is thought to be one of the main reasons of NERD, which happened in more than 50% NERD patients. Adjusting the function of LES was considered as a new approach to the treatment of NERD. Pharmacologic intervention of low LES pressure (LESP) including cholecystokinin-A (CCK-A) antagonists was shown to reduce the rate of transient lower esophageal sphincter relaxation (TLESR), but none of these agents has hand clinical application in NERD therapy. Although Endoscopic approaches and antireflux surgery to the treatment of NERD are evolving rapidly, these treatments still have limitations. Long term therapy to control low LESP and reflux symptoms should concern about patients' compliance and long term safety. In addition, the increasing cost and mutual influence of medicines is not only aggravating the economic burden of patients, but also arousing the anxiety to the side-effect and security of drugs. So it is very importantto find a new therapy, which is practical, economical, safe and efficient.Due to the obvious dysfuction of gastric myoelectrical activity, gastric dysrhythmias was considered as the significant cause of post-meal regurgitation. With the consideration, gastric electrical stimulation is proposed to simulate the electrophysiological process of normal gastric emptying in this paper. The site of gastric packer is stimulated, and the slow wave produced can be driven by the electric current outside. With this effort, the gastric myoelectrical activity can be normal again and the symptoms of NERD will be relieved or eliminated.In the present study, the clinical efficacy of gastric electrical stimulation for NERD was evaluated and the mechanism was explored.Materials and Methods Materials75 patients were recruited from December 2004 to December 2005 in five hospitals. All adult patients fulfilled the eligibility criteria, having two or more typical symptoms (heartburn, sour reflux, regurgitation) or atypical symptoms (chest pain, belching, nausea and vomiting). Patients with atypical symptoms should be approved that LESP<15mmHg and DeMeester score< 14.72. The main exclusion criteria was the presence of reflux esophagitis, hiatal hernias, Barrett's esophagus, systemic diseases (severe renal, cardiac, pulmonary, hepatic disease etc), the pregnant woman, the person older than 60 years old or younger than 18 years old and the person using drugs of H2RA, PPIs or prokinectics in last week. Methods20 patients with low LESP were monitored the changing of LESP when accepting the gastric electrical stimulation. 75 NERD patients were distributed into three groups based on different therapies. Group A used gastric electrical stimulation (once daily) plus rabeprazole (lOmg once daily). Group B adopted mosapride (5mg three times daily) plus rabeprazole (lOmg once daily). Group C was given rabeprazole (lOmg once daily). The period of treatment in three groups were all two weeks. Assessments on all groups included the initial recurred time and LESP, 24h pH, symptomatic scores at baseline and two weeks. Symptom efficacy was evaluated by the change of symptomscale score: remission was defined as score decrease not less than 80% of baseline, improvement as score decrease not less than 50% of baseline, ineffectiveness as score decrease less than 50% of baseline.Results1. The LESP of 20 patients with low LESP increased after lOmin's stimulation, and it was much higher after both 30min's and 40min's stimulation than lOmin's (both p values<0.05). But there was no difference in 30min's and 40min's (p>0.05). The result showed that the best time for stimulation was 30 minutes.2. The LESP of group A was (9.72+2.73) mmHg before treatment , and it increased to (18.67±3.13) mmHg after two weeks' therapy. The difference was evident (p<0.01). Also it was higher than both group B and C (both p values<0.01).3. The percent of PH<4.0 and DeMeester score (p<0.01) of A, B and C all decreased after two weeks' therapy, but group B's ability of controlling sour reflux was superior to group C and inferior to group A (p<0.05).4. Clinical efficacy of different groups can be evaluated by symptomatic scores and efficiency.1) There were no difference in the symptomatic scores of all three groups before treatment (p>0.05). The scores of all 3 groups were decreased obviously (p<0.01) at the first and second week. At the first week, the decrease of group B was inferior to group A and superior to group C (p<0.05) . At the second week, the decrease of both group A and B were superior to group C.2) At the first week, the remission rate was achieved by 50%, 24% and 10.71% in group A, B and C respectively. The total improvement rate was 81.83%, 44% and 28.57% respectively. Compared with both group B and C, the total improvement rate in group A had significant improvement (both p values<0.05). The remission rate of group A was higher than group C (p<0.05), but there was no difference between group A and B (p>0.05). At the second week, the remission and improvement rate were achieved by 68.18% and 90.91% in group A respectively, 52% and 76% in group B, 17.96% and 39.29% in group C. The remission rate and improvement rate ofgroup A, B were superior to group C respectively (p<0.05). 5. The initial recurred time of group A, B and C was (63.20+31.40) days, (37.11 ± 13.26) days and (21.09 + 8.76) days respectively. The recurred time of group A was longer than both group B and C (both p values<0.05), while group B was longer than group C (p<0.05).ConclusionGastric electrical stimulation could be a new therapy for NERD, which increased the LES pressure, reduced the abnormal acid reflux, relieved the symptoms of NERD ahead of schedule and delayed the recurrence.