Efficacy Of Endoscopic Radiofrequency For Treatment Of Esophageal Reflux Associated Disease

Part Ⅰ.Efficacy of endoscopic radiofrequency ablation for proton pump inhibitor dependent gastroesophageal reflux disease: A multicenter prospective cohort study ObjectiveProton pump inhibitor(PPI)is the main treatment for Gastroesophageal reflux disease(GERD),but some patients can’t stop taking medicine and need long-term maintenance treatment,which will reduce the quality of life and may have drug-related adverse effects.Endoscopic radiofrequency ablation is probably effective on PPI dependent GERD,but there are few studies in China,and most of them are single center with small sample.Meanwhile,the objective outcomes,such as acid exposure time(AET)and lower esophageal sphincter(LES)pressure,have an inconsistent effect,the specific mechanism of radiofrequency ablation is not clear.This study intends to conduct a prospective multicenter cohort study to evaluate the efficacy of endoscopic radiofrequency ablation on PPI dependent GERD,and to explore its mechanisms such as nerve injury.MethodsThis study was carried out in Tongji Hospital Affiliated to Tongji University,The First Affiliated Hospital of Naval Military Medical University(Changhai Hospital)and Renji Hospital Affiliated to Medical College of Shanghai Jiaotong University.Patients with PPI dependent GERD who could not stop taking PPI for at least 6 months were recruited.Endoscopic radiofrequency ablation was delivered to the gastroesophageal junction.Data were collected by questionnaire using a 6-point Likert scale.The primary outcome measure was GERD health related quality of life(GERD-HRQL).The secondary outcomes were effect on symptoms including heartburn,regurgitation,chest pain,pharyngalgia and cough,degree of satisfaction,medication use,AET,De Meester score,LES pressure,total reflux episodes and esophagitis.Meanwhile,the positive cell density of transient receptor potential vanilloid type-1 receptor(TRPV1)and calcitonin gene-related peptide(CGRP)in the distal esophagus and their correlation with symptoms were evaluated,both of which are biomarkers of afferent fibers.ResultsA total of 64 PPI dependent GERD patients were enrolled.A significant improvement in GERD-HRQL and symptom scores was noted at 3 mo(mean decrease in GERD-HRQL,-13.5±6.9,P<0.001;mean decrease in heartburn,-2.7±1.3,P<0.001;mean decrease in regurgitation,-3.8±1.8,P<0.001;mean decrease in chest pain,-2.2±1.1,P<0.001;mean decrease in pharyngalgia,-2.9±0.9,P<0.001;mean decrease in cough,-2.7±1.1,P<0.001),at 6 mo(mean decrease in GERD-HRQL,-14.5±6.7,P<0.001;mean decrease in heartburn,-2.9±1.3,P<0.001;mean decrease in regurgitation,-3.8±1.5,P<0.001;mean decrease in chest pain,-2.4±1.2,P<0.001;mean decrease in pharyngalgia,-2.9±1.1,P<0.001;mean decrease in cough,-3.0±1.5,P<0.001),at 12 mo(mean decrease in GERD-HRQL,-14.7 ± 7.0,P<0.001;mean decrease in heartburn,-2.9±1.2,P<0.001;mean decrease in regurgitation,-4.2±1.6,P<0.001;mean decrease in chest pain,-2.3±1.2,P=0.002;mean decrease in pharyngalgia,-3.5±1.3,P<0.001;mean decrease in cough,-3.1±1.6,P<0.001),at24mo(mean decrease in GERD-HRQL,-16.5 ± 6.8,P<0.001;mean decrease in heartburn,-3.5±1.5,P<0.001;mean decrease in regurgitation,-4.1±2.0,P<0.001;mean decrease in pharyngalgia,-4.3±1.5,P=0.039;mean decrease in cough,-3.4±1.6,P=0.001)and at 36mo(mean decrease in GERD-HRQL,-15.6±7.4,P<0.001;mean decrease in heartburn,-3.5±1.6,P<0.001;mean decrease in regurgitation,-4.5±1.6,P<0.001;mean decrease in cough,-3.5±1.7,P=0.005),except pharyngalgia at36mo(-4.0±1.7,P=0.057).Satisfaction with life increased to 66.1%,77.6%,87.8%,76.2%,76.9% at 3,6,12,24 and 36 mo,respectively,compared with baseline(P<0.001),meanwhile,37.1%,56.9%,59.2%,61.9%,53.8% subjects stopped their medication use.AET,De Meester scores and total reflux episodes were significantly lower than those pre-operation(P < 0.05),but 32.4% patients did not return to normal.No statistical difference was noted in LES pressure(P=0.072).The positive cell density of TRPV1 had a positive correlation with heartburn(r=0.63,P<0.01)and regurgitation(r=0.68,P<0.01),after treatment,TRPV1 decreased significantly(P<0.001),and the degree had a positive correlation with the change of heartburn(r=0.76,P < 0.01)and regurgitation(r=0.44,P=0.05).CGRP had no correlation with symptoms.ConclusionEndoscopic radiofrequency ablation can significantly improve subjective and objective clinical endpoints,except esophagitis and LES pressure.Radiofrequency ablation can reduce AET and total reflux episodes,it can also damage TRPV1 positive nerve fibers in the distal esophagus,which both responsible for improving patients’ symptoms.Part Ⅲ.Efficacy of endoscopic radiofrequency ablation for treatment of refractory gastroesophageal reflux disease: a meta-analysis ObjectiveEndoscopic radiofrenquency ablation is effective in PPI dependent GERD,but the efficacy is still controversial in refractory GERD.The aim of this study is to determine the efficacy of endoscopic radiofrenquency ablation in patients with refractory GERD.MethodsPapers published in Medline,Embase,Cochrane library,Elsevier,wanfang,VIP and CNKI were searched for the studies evaluating the efficacy of endoscopic radiofrenquency ablation for treatment of refractory GERD.Statistic analyses were performed using Rev Man 5.3 software.ResultsA total of 9 studies(all were cohort studies)were enrolled.The pooled results showed that the endoscopic radiofrenquency ablation reduced(improved)the heartburn standardized score by-2.21(P<0.00001),regurgitation score by-3.85(P<0.00001),chest pain score by-2.92(P<0.00001),cough score by-3.87(P<0.00001)and asthma score by-4.15(P < 0.00001).The prodecure also reduced(improved)GERD-health related quality of life by-19.84(P<0.00001).After the treatment,only41.2% of the patients using proton pump inhibitor(PPI)(P<0.00001),and the erosive esophagitis was remarkably alleviated(62.3% vs.34.0%,P<0.00001).The treatment also improved patient satisfaction score by 2.46(P<0.00001)and the proportion of patients who satisfied with GERD(20.0% vs.87.9%,P=0.28).ConclusionEndoscopic radiofrenquency ablation significantly improves the symptoms and the quality of life,reduces the use of PPI and alleviates erosive esophagitis in patients with refractory GERD.Part Ⅲ.Efficacy of endoscopic radiofrequency ablation for treatment of reflux hypersensitivityObjectiveEffective therapies for reflux hypersensitivity are lacking.Endoscopic radiofrequency ablation may reduce the sensitivity of the distal esophagus through direct interference with nociceptors or vagal afferent fibers,and thus may be useful in reflux hypersensitivity.The aim of this study is to assess the effectiveness and possible mechanisms of endoscopic radiofrequency ablation in reflux hypersensitivity patients.MethodsPatients with reflux hypersensitivity who fulfilled the Rome Ⅳ criteria and who wished to receive further treatment were recruited.Endoscopic radiofrequency ablation was delivered to the gastroesophageal junction.Data were collected by questionnaire using a 6-point Likert scale.The primary outcome measure was effect on symptoms including heartburn,regurgitation and chest pain.The secondary outcomes were degree of satisfaction,medication use,acid exposure time(AET),LES pressure and total reflux episodes.We also assessed positive cell density of TRPV1 and CGRP,both of which are biomarkers of afferent fibers,and their correlation with symptoms.These scales will be administered at baseline,3-month follow-up,6-month follow-up and 12-month follow-up.ResultsA total of 22 reflux hypersensitivity patients were enrolled.A significant improvement in symptom scores was noted at 3 mo(mean decrease in heartburn,-5.3±1.1,P<0.001;mean decrease in regurgitation,-4.4±1.2,P<0.001;mean decrease in chest pain,-3.5 ± 1.1,P<0.001),at 6 mo(mean decrease in heartburn,-5.6 ± 1.3,P<0.001;mean decrease in regurgitation,-4.8±1.5,P<0.001;mean decrease in chest pain,-3.7 ± 1.4,P<0.001)and at 12 mo(mean decrease in heartburn,-5.3 ± 1.3,P<0.001;mean decrease in regurgitation,-4.9±1.4,P<0.001;mean decrease in chest pain,-3.5±1.0,P<0.001).Satisfaction with life increased to 72.7%(16/22),72.7%(16/22)and 68.2%(15/22)at 3,6 and 12 mo,respectively,compared with baseline(P<0.001).Nineteen patients reduced their medication use after treatment.Of these,22.7%(5/22),31.8%(7/22)and 40.9%(9/22)subjects stopped medication use at 3 mo,6 mo and 12 mo,respectively.No statistical differences were noted in AET,LES pressure or total reflux episodes from pre-operation to 12 mo post-operation.The positive cell density of TRPV1 had a positive correlation with heartburn(r=0.51,P=0.03)and chest pain(r=0.77,P<0.01),after treatment,TRPV1 decreased significantly(P<0.001),and the degree had a positive correlation with the change of heartburn(r=0.72,P < 0.01)and chest pain(r=0.86,P < 0.01).CGRP had no correlation with symptoms.ConclusionEndoscopic radiofrequency ablation was an effective and safe therapeutic option in reflux hypersensitivity patients.TRPV1 positive afferent fibers may play an important role in the generation and treatment of symptoms.