Clinical comparison of antrum-preserving double tract reconstruction vs roux-en-Y reconstruction after gastrectomy for Siewert types Ⅱ and Ⅲ adenocarcinoma of the esophagogastric junction

AIM:To explore a reasonable method of digestive tract reconstruction,namely,antrum-preserving double-tract reconstruction(ADTR),for patients with adenocarcinoma of the esophagogastric junction(AEG) and to assess its efficacy and safety in terms of longterm survival,complications,morbidity and mortality.METHODS:A total of 55 cases were retrospectively collected,including 18 cases undergoing ADTR and 37 cases of Roux-en-Y reconstruction(RY) for AEG(Siewert types Ⅱ and Ⅲ) at North Sichuan Medical College. The cases were divided into two groups. The clinicopathological characteristics,perioperative outcomes,postoperative complications,morbidity and overall survival(OS) were compared for the two different reconstruction methods.RESULTS:Basic characteristics including sex,age,body mass index(BMI),Siewert type,p T status,p N stage,and lymph node metastasis were similar in the two groups. No significant differences were found between the two groups in terms of perioperative outcomes(including the length of postoperative hospital stay,operating time,and intraoperative blood loss) and postoperative complications(consisting of anastomosis-related complications,wound infection,respiratory infection,pleural effusion,lymphorrhagia,and cholelithiasis). For the ADTR group,perioperativerecovery indexes such as time to first flatus(P = 0.002) and time to resuming a liquid diet(P = 0.001) were faster than those for the RY group. Moreover,the incidence of reflux esophagitis was significantly decreased compared with the RY group(P = 0.048). The postoperative morbidity and mortality rates for overall postoperative complications and the rates of tumor recurrence and metastasis were not significantly different between the two groups. Survival curves plotted using the Kaplan-Meier method and compared by log-rank test demonstrated similar outcomes for the ADTR and RY groups. Multivariate analysis of significantly different factors that presented as covariates on Cox regression analysis to assess the survival and recurrence among AEG patients showed that age,gender,BMI,pleural effusion,time to resuming a liquid diet,lymphorrhagia and tumor-nodemetastasis stage were important prognostic factors for OS of AEG patients,whereas the selection of surgical method between ADTR and RY was shown to be a similar prognostic factor for OS of AEG patients.CONCLUSION:ADTR by jejunal interposition presents similar rates of tumor recurrence,metastasis and longterm survival compared with classical reconstruction with RY esophagojejunostomy; however,it offers considerably improved near-term quality of life,especially in terms of early recovery and decreased reflux esophagitis. Thus,ADTR is recommended as a worthwhile digestive tract reconstruction method for Siewert types Ⅱ and Ⅲ AEG.

Non-coding RNA in drug resistance of gastric cancer

Gastric cancer(GC)is the third leading cause of cancer-related mortality worldwide.The poorly prognosis and survival of GC are due to diagnose in an advanced,non-curable stage and with a limited response to chemotherapy.The acquisition of drug resistance accounts for the majority of therapy failure of chemotherapy in GC patients.Although the mechanisms of anticancer drug resistance have been broadly studied,the regulation of these mechanisms has not been completely understood.Accumulating evidence has recently highlighted the role of non-coding RNAs(ncRNAs),including long non-coding RNAs and microRNAs,in the development and maintenance of drug resistance due to their regulatory features in specific genes involved in the chemoresistant phenotype of GC.We review the literature on ncRNAs in drug resistance of GC.This review summarizes the current knowledge about the ncRNAs’characteristics,their regulation of the genes involved in chemoresistance and their potential as targeted therapies for personalized treatment in resistant GC.

Decreased expression of the long non-coding RNA HOXD-AS2 promotes gastric cancer progression by targeting HOXD8 and activating PI3K/Akt signaling pathway

BACKGROUND Long non-coding RNAs(lncRNAs) have been shown to be associated with many tumors. However, the specific mechanism of lncRNAs in the occurrence and development of gastric cancer(GC) has not been fully elucidated.AIM To explore the expression level and molecular mechanism of HOXD-AS2 in GC tissues and cells, and analyze its significance in the prognosis of GC.METHODS Real-time quantitative PCR was used to detect the expression of HOXD-AS2 in 79 pairs of GC tissues and five cell lines. The pc HOXD-AS2 plasmid vector was constructed and transfected into SGC-7901 and SNU-1 GC cells. Matrigel Transwell and wound healing assays were used to confirm the effect of HOXDAS2 on invasion and migration of GC cells. Cell counting kit-8 assay and flow cytometry were used to verify the effect of HOXD-AS2 on the proliferation, cell cycle, and apoptosis of GC cells. The relevant regulatory mechanism between HOXD-AS2 and HOXD8 and PI3K/Akt signaling pathway was verified by Western blot analysis.RESULTS The low expression of lncRNA HOXD-AS2 was associated with lymph node metastasis and tumor-node-metastasis stage in GC. In vitro functional experiments demonstrated that overexpression of HOXD-AS2 inhibited GC cell progression. Mechanistic studies revealed that HOXD-AS2 regulated the expression of its nearby gene HOXD8 and inhibited the activity of the PI3K/Akt signaling pathway.CONCLUSION These results indicate that downregulation of HOXD-AS2 significantly promotes the progression of GC cells by regulating HOXD8 expression and activating the PI3K/Akt signaling pathway. HOXD-AS2 may be a novel diagnostic biomarker and effective therapeutic target for GC.

Prognostic impact of at least 12 lymph nodes after neoadjuvant therapy in rectal cancer: A meta-analysis

BACKGROUND The number of dissected lymph nodes(LNs)in rectal cancer after neoadjuvant therapy has a controversial effect on the prognosis.AIM To investigate the prognostic impact of the number of LN dissected in rectal cancer patients after neoadjuvant therapy.METHODS We performed a systematic review and searched Pub Med,Embase(Ovid),MEDLINE(Ovid),Web of Science,and Cochrane Library from January 1,2000 until January 1,2020.Two reviewers examined all the publications independently and extracted the relevant data.Articles were eligible for inclusion if they compared the number of LNs in rectal cancer specimens resected after neoadjuvant treatment(LNs≥12 vs LNs<12).The primary endpoints were the overall survival(OS)and disease-free survival(DFS).RESULTS Nine articles were included in the meta-analyses.Statistical analysis revealed a statistically significant difference in OS[hazard ratio(HR)=0.76,95%confidence interval(CI):0.66-0.88,I2=12.2%,P=0.336],DFS(HR=0.76,95%CI:0.63-0.92,I2=68.4%,P=0.013),and distant recurrence(DR)(HR=0.63,95%CI:0.48-0.93,I2=30.5%,P=0.237)between the LNs≥12 and LNs<12 groups,but local recurrence(HR=0.67,95%CI:0.38-1.16,I2=0%,P=0.348)showed no statistical difference.Moreover,subgroup analysis of LN negative patients revealed a statistically significant difference in DFS(HR=0.67,95%CI:0.52-0.88,I2=0%,P=0.565)between the LNs≥12 and LNs<12 groups.CONCLUSION Although neoadjuvant therapy reduces LN production in rectal cancer,our data indicate that dissecting at least 12 LNs after neoadjuvant therapy may improve the patients’OS,DFS,and DR.

Prognostic impact of number of examined lymph nodes on survival of patients with appendiceal neuroendocrine tumors

BACKGROUND The prognosis of patients with appendiceal neuroendocrine tumors(ANETs) is related to lymph node(LN) metastasis and other factors.However,it is unclear how the number of examined LNs(ELNs) impact on survival.AIM To determine the factors affecting the cancer-specific survival(CSS) of patients with ANET and to evaluate the impact of the number of ELNs on survival.METHODS A total of 4583 ANET patients were analyzed in the Surveillance,Epidemiology,and End Results database.Univariate survival analysis was used to identify factors related to survival and the optimal number of ELNs and lymph node ratio(LNR) were determined by the Kaplan–Meier method.The survival difference was determined by CSS.RESULTS Except for sex,the other factors,such as age,year,race,grade,histological type,stage,tumor size,ELNs,LNR,and surgery type,were associated with prognosis.The 3-,5-,and 10-year CSS rates of ANET patients were 91.2%,87.5,and 81.7%,respectively(median follow-up period of 31 mo and range of 0-499 mo).There was no survival difference between the two surgery types,namely,local resection and colectomy or greater,in both stratifications of tumor size ≥ 2 cm(P = 0.523)and < 2 cm(P = 0.068).In contrast to patients with a tumor size < 2 cm,those with a tumor size ≥ 2 cm were more likely to have LN metastasis(χ~2 = 378.16,P < 0.001).The optimal number of ELNs was more than 11,7,and 18 for all patients,nodenegative patients,and node-positive patients,respectively.CSS rates of patients with a larger number of ELNs were significantly improved(≤ 10 vs ≥ 11,χ~2 =20.303,P < 0.001;≤ 6 vs ≥ 7,χ~2 = 11.569,P < 0.001;≤ 17 vs ≥ 18,χ~2 = 21.990,P < 0.001;respectively).ANET patients with an LNR value ≤ 0.16 were more likely to have better survival than those with values of 0.17-0.48(χ~2 = 48.243,P < 0.001) and 0.49-1(χ~2 = 168.485,P < 0.001).CONCLUSION ANET ≥ 2 cm are more likely to develop LN metastasis.At least 11 ELNs are required to better evaluate the prognosis.For patients with positive LN metastasis,18 or more LNs need to be detected and lower LNR values(LNR ≤ 0.16) indicate a better survival prognosis.

LINC01268 promotes epithelial-mesenchymal transition,invasion and metastasis of gastric cancer via the PI3K/Akt signaling pathway and targeting MARCKS

BACKGROUND Long non-coding RNAs(lncRNAs)with differential expression characteristics have been found to be closely related to the tumorigenesis and development of gastric cancer(GC),but their specific mechanisms and roles still need to be further elucidated.AIM To investigate the expression of LINC01268 in GC and its mechanism of affecting GC progression.METHODS Real-time quantitative polymerase chain reaction was used to detect the expression of LINC01268 in GC tissues,cell lines and plasma.The Kaplan-Meier method was used to evaluate the value of LINC01268 in the prognostication of GC patients.An receiver operating characteristic curve was constructed to evaluate the value of LINC01268 in the diagnosis of GC.Transwell migration and invasion assays and wound healing assays were used to confirm the effect of LINC01268 on the invasion and migration of GC cells.The regulatory relationship between LINC01268 and myristoylated alanine rich protein kinase C substrate(MARCKS),the PI3K/Akt signaling pathway,and the epithelial-mesenchymal transition(EMT)process in GC was demonstrated by western blot analysis.RESULTS The expression of LINC01268 was increased in GC tissues and cell lines.The expression level of LINC01268 was significantly correlated with lymph node metastasis,TNM stage,and tumor differentiation in patients with GC.Over-expression of LINC01268 indicated a poor prognosis for patients with GC,and it had a certain auxiliary diagnostic value for GC.In vitro functional experiments proved that the abnormal expression of LINC01268 further activated the PI3K/Akt signaling pathway and promoted EMT by targeting and regulating MARCKS and ultimately promoted the invasion and metastasis of GC.CONCLUSION This study elucidates that LINC01268 in GC may be an oncogene that further activates the PI3K/Akt signaling pathway and EMT by targeting and regulating MARCKS,and ultimately promotes the invasion and metastasis of GC.LINC01268 may be a potential effective target for the treatment of GC.