Simultaneous Endoscopic Submucosal Dissection For Multiple Early Gastric Cancers And The Role Of LINC00511 In Gastric Cancer

Part 1 Safety and feasibility of simultaneous endoscopic submucosal dissection for multiple early gastric cancersBackground and objectives:Gastric cancer is one of the most common digestive cancer in the world.The annual incidence of gastric cancer is the second highest in China.Early gastric cancer(EGC)has a better prognosis and less cost than advanced gastric cancer.The diagnosis of EGC has been improved remarkably due to all kinds of new endoscopic imaging techniques.Reports regarding multiple early gastric cancers are increasing as well.Endoscopic resection as a minimally invasive therapy has been widely accepted in Asian countries,for cases of early gastric cancer that have little evidence of lymph node metastasis.Synchronous multiple early gastric cancers are not frequently detected,thus there have been few investigations of the safety and feasibility of simultaneous ESD for multiple early gastric cancers in our country.This study aims to evaluate the safety and feasibility of simultaneous ESD for multiple early gastric cancers.Methods:We retrospectively reviewed the medical records of patients who underwent ESD to treat EGC between January 2014 and December 2017 at The Second Hospital of Shandong University.Clinical data included patient demographics,endoscopic and histologic data,results of endoscopic resection and procedure-related adverse events including bleeding and perforation.A total of 21 patients underwent simultaneous ESD for a total of 44 synchronous EGCs(multiple group).They were compared to 137 patients who underwent ESD for single early gastric cancer(single group).Results:The median patient age was significantly older in the multiple group than in the single group(67.7±6.4 years old vs.62.8±10.0 years old,respectively,P=0.005).The lesions of EGC were mainly located at lower third of the stomach in both groups.As for macroscopic types,the superficial elevated type and mixed type were most seen in both groups.Procedure time was significantly longer in the simultaneous resection group than in the single resection group(94.9±38.8 min vs.56.7±38.3 min,respectively,P<0.001).The rate of delayed bleeding was 9.5%(2/21)in multiple group and 5.8%(8/137)in single group,respectively.However,the difference was not significant(P=0.623).All the lesions in multiple group were differentiated adenocarcinoma,while 12 cases were mixed histological type in single group.And the difference was significant(P=0.041).The rate of curative resection was comparable between the two groups(multiple group 95.5%vs.single group 86.9%,respectively,P=0.457).Conclusions:Simultaneous ESD for multiple early gastric cancers is safe and feasible compared to single ESD.Part 2 Clinical analysis of synchronous and metachronous lesions after endoscopic submucosal dissection of early gastric cancerBackground and objectives:Endoscopic resection which preserves the stomach has been widely accepted as the standard treatment for EGC without the risk of regional lymph node metastasis,because it has the advantages of being less invasive,and comparable with surgery.Despite its convenience,there is a major concern about the high rate of newly developed neoplasms after endoscopic resection in the remaining gastric mucosa.Synchronous leison was classified as a newly developed high-grade dysplasia or adenocarcinoma at another site in the stomach within 1 year after initial ESD.Metachronous lesion was defined as a tumor which had developed more than 1 year after the primary procedure.The risk of metachronous gastric cancer after endoscopic resection is gradually increased with the prolongation of follow-up time The aim of this study is to analyze the distribution characteristic,background mucosa and Helicobacter pylori(HP)status between synchronous and metachronous early gastric cancer.This study also aims to identify the causes of synchronous early gastric cancer and the risk factors of metachronous early gastric cancer.Methods:Patients with early gastric tumors who were treated by ESD from January 2014 to December 2017 and followed up with endoscopic examination periodically for at least 2 year were enrolled(same as part 1).A total of 13 patients were included in this study,6 patients with synchronous early gastric cancer and 7 patients with metachronous early gastric cancer,respectively.Results:The incidence rate of synchronous early gastric cancer was 3.8%(6/158),and the time interval was 5.3±3.6 months(range from 3 to 12 months).The incidence rate of metachronous early gastric cancer was 4.4%(7/158),and the time interval was 24.4±9.1 months(range from 15 to 36 months).The incidence rate of synchronous and metachronous early gastric cancer was 2.9%(4/137)and 4.4%(6/137)in single group,respectively.In multiple group,it was 9.5%(2/21)and 4.8%(1/21),respectively.Seven synchronous lesions were detected in the 6 patients,and mostly located at the upper third of the stomach(42.9%,3/7).Most of the metachronous lesions were located at the lower third of the stomach(57.1%,4/7).As for Paris classification,mixed type and superficial depressed type was most seen in synchronous and metachronous early gastric cancer,respectively(both 42.9%).Regarding the concept of histologic features of background mucosa,all the 13 patients had severe intestinal metaplasia during initial ESD.The status of Hp infection was confirmed in 10 patients,and 9 patients were Hp negative.The causes for missed lesions were classified into three groups:group1,the synchronous lesion was small and not obvious in the previous images(2 patients);group 2,no images of the location of synchronous lesions were taken(2 patients);and group3,synchronous lesions were visible in the earlier images but a biopsy was not performed(2 patients).Multivariate analysis using the logistic regression model revealed that superficial depressed type was independent risk factor for metachronous early gastric cancer.Conclusions:Considerable attention should be paid to detect synchronous and metachronous lesion when the early gastric cancer is accompanied by severe intestinal metaplasia.Endoscopists should meticulously evaluate the entire gastric mucosa during endoscopic examination or resection.Periodic endoscopic follow-up after endoscopic resection is recommended.Part 3 The role of LINC00511 in gastric cancerBackground and objectives:Gastric cancer(GC)is a common-sighted cancer which is hard to cure over the world.Substantial researches revealed that long non-coding RNAs(lncRNAs)were fundamental regulators in the process of cancers.Nevertheless,the biological function of LINC00511 and how LINC00511 was involved in the regulatory system in GC remained unclear.Methods:RIP assays and luciferase reporter assays were performed to illustrate combination between LINC00511 and miR-625-5p.Loss-of-function assays were applied for identifying LINC00511 function in GC.Results:In our study,LINC00511 was discovered significantly high in expression in GC tissues and cell lines.Moreover,LINC00511 showed a strong expression in ?/?and III/IV stage.Knockdown of LINC00511 could inhibit the cell proliferation while enhanced cell apoptosis rate in GC.We used nuclear-cytoplasmic fractionation to judge the subcellular localization of LINC00511.Furthermore,miR-625-5p was found to have binding sites for LINC00511 and negatively regulated by LINC00511.Overexpression of miR-625-5p repressed the course of GC.And knockdown of miR-625-5p could recover the effects of LINC00511 silence.Besides,NFIX was discovered as a downstream target of miR-625-5p and overexpression of NFIX could offset the influence of LINC00511 silence.The results of vivo studies manifested that down-regulation of LINC00511 could reduce the Ki67 expression and NFIX while lifted the expression of miR-625-5p.Conclusions:Overall,the results from our study demonstrated that LINC00511 could function as a tumor promoter by targeting miR-625-5p NFIX axis,suggesting LINC00511 could be considered as a target for GC treatment.