Folic Acid And Risk For Esophageal Intraepithelial Neoplasia

BackgroundEsophageal cancer greatly affects the health of people,especially in China with its ranking the fifthin the mortality of malignant tumors.Two methods are available to prevent esophageal cancers thatare endoscopic resection and chemical prevention.And therefore,we designed this study includingtwo aspect,one is endoscopic resection of intraepithelial neoplasia (IEN),the other is folic acid andrisk of esophageal IEN.EMR or ESD has become the primary therapy for resectable IEN)andtunnel technique has made it more convenient to resect lesions of larger sizes by ESD. However,stenosis is a very frequent complication after resection of long circumferential or large-sizelesions.Dilation and metal stent placement are common treatments for stenosis after ESD.Althoughfolic acid has been proved effective in prevention of several epithelial lesions like cervical IEN andbronchal squamous metaplasia,it is by now not clear whether folic acid could or not reverseesophageal IEN.Aim1.To determine the safety and efficacy of Endoscopic submucosal tunnel dissection (ESTD) foresophageal long circumferential IEN and large-size IEN.2.To determine the correlation betweenfolic acid and risk for esophageal IEN by meta-analysis.3.To determine the correlation betweenserum folic acid and risk for esophageal IEN.4. To determine the correlation between methylationrate of p16gene and risk for esophageal IEN.Methods1.Clinical data of patients with esophageal long circumferential IEN or large-size IEN undergoingESD was analysed to evaluate safety and efficacy of ESTD.2.Original articles were searched indatabases including Pubmed,CNKI and WanFang using key words of folic acid andesophageal cancer. All studies included into the final meta-analysis must reported OR valuewith95%CI.3.Patients diagnosed with esophageal IEN from December2011to September2012were included,and control group was matched at1:4and selected from concurrent patients withoutesophageal diseases or malignant tumors.4. Patients diagnosed with esophageal IEN from October 2012to March2013were included,and control group was matched at1:4and selected fromconcurrent patients without esophageal diseases or malignant tumors.Under guidance of iodinechromoscopy,mucosal tissues were obtained and methylation rates of p16gene were tested by MSP.Results1.All patients underwent ESTD successfully in patients with esophageal long circumferentialIEN.Minor intraoperative bleeding occurred in2patients;perforation with subcutaneousemphysema occurred in1patient and stenosis persisted in2patients after follow up for an averageof26mons.No recurrence of IEN was observed,but metachronous EIN was observed in2patientsduring follow up.2.All patients underwent ESTD successfully in patients with esophageal large-sizeIEN.No bleeding or perforation occurred.After follow up for14mons, neither recurrences normetachronous IEN were observed.3.Fourteen original articles met the inclusion criteria and themeta-analyzed OR was0.60with P<0.00001.4.The average concentration of serum folic acid was8.75±2.21ng/ml and9.97±4.55ng/ml in IEN group and control group,respectively (p<0.05).TheOR was1.66withou statistical significance between the IEN group and the control group.5.Themethylation rate was0%（0/15）in the IEN group and0%(0/15) in the control group.Nodifference was observed between the two groups.Conclusions1.ESTD was safe and effective to treat esophageal long circumferential IEN,and retrievablefull-covered metal stents were effective to prevent stenosis after ESTD for esophageal longcircumferential IEN.2.ESTD was safe and effective to treat esophageal large-size IEN withou post-ESTD stenosis.3.Dietary folic acid was negatively correlated with the risk of esophageal cancer.4.Concentration of serum folic acid was lower in the IEN group than the control group.Thedifference of risk of esophageal IEN between the lower and the higher serum folic acid group wasnot statistically significant.5.No difference of methylation rate of p16gene was detected between the normal mucosa of theIEN group and that of the control group.