Basic And Clinicl Research Of Peroral Endoscopic Cardial Constriction(PECC) In Gastroesophageal Reflux Diseases

Background and AimsGastroesophageal reflux disease(GERD)is a highly prevalent problem in the world,and its incidence rate is on the rise with the increasing prevalence of obesity.The treatment of GERD has been focused on medical tre,atment with proton pump inhibitors(PPIs)for suppression of gastric acidity,and surgical fundoplication to enhance the anatomic barrier at gastroesophageal junction(GEJ).However,some patients with PPIs have poor response,or recurrence after stopping the medicine.Laparoscopic fundoplication can solve the recurrence,but is received in less than 5%of the patients because of the adverse events and is not superior to drug therapy over a long period of observation.Approximately 25%to 30%of GERD patients have a poor response to medicine or are unable to tolerate long-term medicine,but also are reluctant to undergo surgical treatment.Therefore,the new treatment for GERD is necessary.Several endoscopic techniques,such as endoscopic radiofrequency ablation(Stretta),endoluminal folds and suturing,injection and implantation of bulking agents,had been developed to treat GERD patients.However,those methods cannot replace those traditional medicine or surgical treatment due to their efficacy and safety.Therefore,onesimple,safe and effective treatment method remains to be explored.Peroral endoscopic cardial constriction(PECC),a new technique,appears to be effective and safe in short-term study with a small number of cases,but large clinical study with long-term follow-up is still needed to confirm the results.There are four parts in this study.The first part is to explore PECC for GERD.The second part is to investigate the PECC ligation depth in animal experiment.The third part is to confirm the effect of PECC in clinical study.The fourth part is to establish the animal model of GERD through endoscopic submucosal tunnel technique.The aim of this study is to evaluate the safety and efficacy of PECC for GERD for further clinical application.MethodsPart Ⅰ:Professor Enqiang Linghu proposed PECC for GERD based on rich clinical and endoscopic operation experience,and performed this technique for one case.The treatment outcomes were recorded.Part Ⅱ:Six fresh pig cadavers were used in this part.The operation were conducted as followings steps:(1)The pigs taking left lateral position were fixed on the operating bed.(2)The band ligation device was attached at the front of the endoscope.(3)The endoscope was placed to the lower esophagus above the dentate line,and then the ligation ring was released after extensive suction.(4)The snare was placed at the root of the ligation ring through endoscopic biopsy channel,and closed with application of electrocautery to remove the specimen.(5)The diameter of the specimen was calculated after the specimen was stretched and fixed.(7)HE staining was performed after 10%formalin fixation,and then the thickness of the specimen was measured under microscopic observation.Part Ⅲ:The eligible patients was enrolled in this part.The PECC operation procedures included the following steps:(1)The patients were fasted without water intaking for 6 hours before the operation,and then performed under intavenous anesthesia with fentanyl,midazolem and propofol.(2)Two single-band ligation devices were fixed at the front of the endoscope,and placed at the greater curvature and lesser curvature about 1cm above the GEJ,respectively.(3)Two portions of the ligation root was fixed with clips.(4)The patients were fasted without water for 3 days routinely,and were given anti-acid,rehydration and nutritional support under close observation after the procedures.Then the oral PPIs were administrated for 2 weeks.The effect evaluation included the following parameters:GERD health-related quality of life(GERD-HRQL)and GERD-Q score,the grade of reflux esophagitis under endoscope according to Los Angeles grade A-D,24-hour PH monitoring and the changes of esophageal kinetics before and after the operation.Part Ⅳ:Six fresh pig cadavers were used in this part to expand the study.The operation procedures were described below.(1)The pigs with supine position and the upper body elevated 30 degrees were fixed on the radiographic bed.(2)The diameters of the lower esophagus above the GEJ and GEJ were measured under 20%diatrizoate meglumine esophagram.(3)The position of the pigs was changed to left lateral position.(4)The submucosal was preformed using 1:10000 methylene blue mixed with normal saline to elevate the mucosa at 10cm proximal to the GEJ.(5)Then inverted "T" shaped incision was made,and submucosal tunnel was created to 3 cm distal to the GEJ with triangular knife.(6)Endoscopic myotomy of the full muscularis propria was begun at 8cm proximal to the GEJ to 3cm distal to the GEJ.(7)The positon of the pigs was changed to the primary position,and then the diameters above were measured again.ResultsPart I:The PECC was operated successfully without complications.At 2-month follow-up after the operation,the reflux and heartburn relieved,the cardia was narrowed obviously under endoscopy,and the DeMeester score decreased 157.3 points compared with preoperational score form 24-hour monitoring results.Part II:13 ligations were performed in total,and 11 ones(84.6%)were successfully.The diameter of specimen resected from the successful ligation was 17cm to 20cm,After pathological evaluation,there were 9 ones(81.8%)with depth to the muscularis propria,and the other 2 ones(18.2%)limited to mucosa.Part III:The follow-up after the operation was 3-month,6-month and 12-month.①The scores of GERD-HRQL and GERD-Q during the follow-up had decreased obviously compared with the preoperational scores.② Curative rate,response rate and non-response rate had no significant differences among the three follow-up time points.The reflux,heartburn and chest pain improved after PECC.③ There was 33%patients presented normal DeMeester score at 3-month follow-up and 27%patients presented normal DeMeester score.The proportion of patients with DeMeester score 100 was decreased from 39%to 15%.The DeMeester score had significant differences among preoperational score and the above follow-up scores(p<0.01).The esophagitis also improved significantly.④ Form the 24-hour monitoring results,the DeMeester score,percentage of pH<4,reflux times,reflux times with longer than 5 minutes and reflux duration were also had significant differences at the follow-up times compared with preoperational ones(p<0.01).⑤The resting and residual pressure of lower esophageal sphincter were slightly increased,but there were no significant differences.⑥The patient satisfaction was significantly higher than that before the operation.Part IV:From the esophagram before and after the tunnel technique,the cardia was obviously relaxed,the contrast agent past smoothly,and the diameters of the lower esophagus above the GEJ and GEJ had no significant changes.Conclusions(1)PECC,as one minimally invasive technique,is sample,feasible,safe and effective for GERD from the short-term observation.(2)PECC is a new method for GERD by cardial ligation and fixation.The ligation depth may change the lower esophageal sphincter pressure and then clinical outcomes were improved.(3)The GERD animal model can be established through the submucosal tunnel technique,which is helpful for subsequent studies.