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The incidence of proximal gastric cancer has shown a rising trend in recent years. Surgery is still the main way to cure proximal gastric cancer. Total gastrectomy with D2 lymph node dissection was considered to be the standard procedure for proximal gastric cancer in the past several decades. However, in recent years, many studies have confirmed that proximal gastrectomy can preserve part of the stomach function and can result in a better quality of life of the patient than total gastrectomy. Therefore, proximal gastrectomy is increasingly used in patients with proximal gastric cancer. Unfortunately, there are some concerns after proximal gastrectomy with traditional esophagogastrostomy. For example, the incidence of reflux esophagitis in patients who underwent proximal gastrectomy with traditional esophagogastrostomy is significantly higher than those patients who underwent total gastrectomy. To solve those problems, various functional digestive tract reconstruction methods after proximal gastrectomy have been proposed gradually. In order to provide some help for clinical treatment, in this article, we reviewed relevant literature and new clinical developments to compare various kinds of functional digestive tract reconstruction methods after proximal gastrectomy mainly from perioperative outcomes, postoperative quality of life and survival outcomes aspects. After comparison and discussion, we drew the conclusion that various functional reconstruction methods have their own advantages and disadvantages; large scale high-level clinical studies are needed to choose an ideal reconstruction method in the future. Besides, in clinical practice, surgeons should consider the condition of the patient for individualized selection of the most appropriate reconstruction method. [ABSTRACT FROM AUTHOR]

Abstract The role of thymidylate synthase (TS) is essential as a key rate-limiting enzyme in DNA synthesis. It is the primary target of fluorouracil and its derivates in colorectal cancer. In this study, TS mRNA expression was examined in primary tumor and normal tissues from 76 patients with high- risk stage II/III colorectal cancer by laser capture microdissection and polymerase chain reaction. Thirty (39.47%) patients were found to have higher TS expression in primary tumors with earlier stage (P = 0.018), lower histological grades (P = 0.001) and high frequency microsatellite instability (P = 0.000). Multivariate analysis showed that microsatellite instability, histological grade and number of lymph nodes examined are independent prognostic markers.

Long non-coding RNAs (lncRNAs) regulate a series of biological processes, and their anomalous expression exerts critical roles in progression of multiple malignancies, including colorectal cancer (CRC). The present study was designed to provide new ideas and perspectives for the role of lncRNA MCF2L-AS1 and disclose the underlying mechanism in CRC. Herein, we observed that MCF2L-AS1 expression was enriched in CRC tissues and cell lines. Additionally, silencing of MCF2L-AS1 dramatically impeded cell proliferation, invasion and migration capacities of CRC, and distinctly attenuated the expression of invasion associated targets MMP-2 and MMP-9. Moreover, depletion of MCF2L-AS1 apparently restricted the glucose consumption and lactate production, and downregulated GLUT1 and LDHA expression. More importantly, we predicted and verified that MCF2L-AS1 acted as a molecular sponge for miR-874-3p and inversely regulated miR-874-3p expression. Interesting, FOXM1 was identified as direct target of miR-874-3p, and positively modulated by MCF2L-AS1 through sponging miR-874-3p. Mechanistically, MCF2L-AS1 accelerated cell proliferation, invasion and glycolysis through competitively binding to miR-874-3p, leading to enhance FOXM1 expression. Collectively, these outcomes highlighted that MCF2L-AS1 acted as a motivator by modulating the miR-874-3p/FOXM1 axis, thereby aggravating tumorigenesis and glycolysis progress of CRC, disclosing that MCF2L-AS1 may serve as a valuable and promising therapeutic strategy for CRC. [ABSTRACT FROM AUTHOR]

Hypoxic microenvironment commonly occurred in the solid tumors considerably decreases the chemosensitivity of cancer cells. Salidroside (Sal), the main active ingredient of Rhodiola rosea, was shown to be able of regulating the tumor hypoxia micro-environment and enhancing the chemotherapeutic efficacy of drug-resistant cancer. Therefore, in this study, the Sal was co-loaded with Apatinib (Apa) by the PLGA-based nanoparticles (NPs) to improve the chemosensitivity of gastric cancer cells. Additionally, to improve the drug delivery efficacy, the tumor-homing peptide (iVR1 peptides) was further decorated on the surface of NPs. The tumor targeting ability of the peptides-functionalized nanoparticles (iVR1-NPs-Apa/Sal) was evaluated by in vitro and in vivo experiments. As the obtained results revealed that the iVR1-NPs-Apa/Sal displayed excellent tumor affinity than the unmodified ones (NPs-Apa/Sal), which in turn resulted in more efficient of anti-proliferation of gastric cancer cells and anti-tumor effect in vivo. In addition, compared with the cells or tumor-bearing mice only treaded by monotherapy of Apa, the cells or mice received combinational treatment of Apa and Sal showed obvious lower rate of growth, invasion, and migration or tumor growth and progress. Underlying mechanisms were further investigated and it was revealed that the anti-gastric cancer effect of Apa was signally improved by Sal through down-regulation the proliferation factors and increase the pro-apoptotic genes, as well as reprograming the tumor hypoxia micro-environment. In a word, the study showed that the Sal was able of improving the chemosensitivity of gastric cancer to Apa and the iVR1-NPs-Apa/Sal was capable of realizing highly efficient of tumor-targeting drug delivery. [ABSTRACT FROM AUTHOR]

Background: The objective of this study is to identify independent risks and protective factors and to construct a mortality prediction model for gastrectomy in the Chinese population. Study design: This is a population-based prospective cohort at an institutional level. Seventy-two participating hospitals reported their annual gastrectomy data between 2014 and 2016, while 44 variables covering the institution and surgical information were included in the analysis. We used R software to encode and complete data pre-processing. The first difference model was applied to build the risk model. Data from 2014 and 2015 were assigned to risk model development, while data from 2016 was used for validation. Results: In the included centers with 94,277 gastric cancer cases, the in-hospital mortality rate was 0.32%. The regression model revealed that provinces with low-middle GDP, hospitals with annual gastrectomy volume between 100 and 500, greater volume of urgent surgeries performed, larger proportion of males, and a higher proportion of liver metastasis were independent risk factors for mortality following gastric surgeries, while higher laparoscopic resection volume, greater volume of distal gastrectomy with B2 reconstruction, and larger proportion of palliative surgery were independent protective factors (p < 0.05, respectively). In the prediction test, the mean square error of the training set was 0.948, while that of the test set was 0.728, demonstrating the effectiveness of this model. Conclusions: We constructed the first mortality risk prediction model for gastric cancer surgery in the Chinese population. The identified risk factors will help with the therapy selection, while further informing Chinese medical policy decision-makers. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the most prevalent types of cancer worldwide. Cisplatin based chemotherapy is the primary strategy implemented for the treatment of G; however, chemoresistance is a major problem. Previous studies have indicated that microRNAs (miRs) are associated with chemoresistance in various types of cancer and that miR-218 specifically, serves important roles in the growth of GC cells. The present study assessed the potential biological roles of miR-218 in GC cell cisplatin (DDP) resistance. The results obtained from a polymerase chain reaction assay indicated that the expression of miR-218 was decreased in cisplatin resistant SGC7901/DDP cells compared with SGC7901 cells. Furthermore, MTT results indicated that the upregulation of miR-218 expression significantly enhanced SGC7901/DDP cell sensitivity to DDP. The results of a dual-luciferase assay indicated that survivin was a direct target gene of miR-218. Results also demonstrated that miR-218 was overexpressed in SGC7901/DDP cells and that the downregulation of survivin expression enhanced SGC7901/DDP cell sensitivity to DDP. Further study demonstrated that the upregulation of miR-218 decreased the expression of survivin in SGC7901/DDP cells and induced apoptosis. The findings of the present study indicated that the induction of miR-218 enhanced GC cell DDP resistance via the regulation of survivin, which may potentially benefit the clinical treatment of GC in the future. [ABSTRACT FROM AUTHOR]

Urban areas are the areas that are most strongly affected by human activities, which presents many challenges to the ecosystem and human well-being. Ecosystem services (ES) are a comprehensive indicator to measure the ecological effects of urbanization. To effectively identify and evaluate the impact of urbanization on ES, the spatial-temporal pattern of ES should be considered. According to the level of urbanization, Xi'an city is divided into four regions: the urban core area, the urban extended area, the rural area, and the ecological conservation area, then, five comprehensive ecosystem services (CES) are evaluated by In VEST model. The results showed the following: (1) There is an obvious spatial heterogeneity in the distribution of ES. The ecological conservation area is the hot spot of ES supply, and the low value is mostly distributed in the urban core area. (2) The CES in the urban extended area that has undergone the greatest change between 2000 and 2015, and the rates of change in the ecological conservation area are the smallest. (3) There is a significant correlation between urbanization and ES, and the correction between landscape urbanization and ES is the most significant. (4) The agglomeration relationship between urbanization and ES in different regions is not consistent. Regional division provides a new way to understand the interaction between urbanization and ES in time and space, so as to provide better guidance for policy makers in formulating sustainable development policies to alleviate the loss of ES caused by the process of urbanization. [ABSTRACT FROM AUTHOR]

• ES types were selected through the government policy and public preference. • The trade-offs/synergies among ES are Spatiotemporal dependent. • Public perception, ERL and trade-off were integrated into a management framwork. • Corresponding measures for improving ES are proposed in differnt ecological function areas. Ecosystem services (ES) are used as a tool for eco-environment management, and this study establishes a framework that integrates ecological red line (ERL), public perceptions of ES and trade-offs among ES into regional eco-environment management. The public perceptions of ES are assessed using questionnaires and statistical analyses. Three models (InVEST, i-Tree Eco, ROS), a food supply calculation method and GIS are used to quantify eight ecological indicators (water yield, soil retention, water purification, biodiversity conservation, atmospheric regulation, outdoor recreation, food supply, and prohibited development zones) in the Fenghe River watershed (FRW). Three ecological function areas are delineated via the ERL standard, and the trade-offs among ES are assessed via correlation analysis. The results show the following: 1) the top five preferred ES by the public are atmospheric regulation, water purification, food supply, freshwater supply and outdoor recreation, and the local environment and individual demands are the main factors that affect preferences; 2) from 2000 to 2015, the quantity of the water yield, soil retention, Nitrogen output and biodiversity index slightly decreases, and the amount of the NO 2 removal, food supply and outdoor recreation index slightly increases; 3) based on the "Delimitation scheme for ERL of Xi'an", the FRW is divided into ecological redline zone (ERZ), ecological function important zone and ecological function general zone, and the ERZ accounts for the largest proportion (55.7%); and 4) inconsistent trade-offs/ synergies among ES are observed in different ecological function areas. Based on these results, we establish a management framework and propose corresponding measures to improve ES for different ecological function areas. This multi-dimensional composite management framework can be used for planning or environmental management. [ABSTRACT FROM AUTHOR]

Background: Colon cancer (CC) is the second most common gastrointestinal malignancy. About one in five patients have already developed distant metastases at the time of initial diagnosis, and up to half of patients develop distant metastases from initial local disease, which leads to a poor prognosis for CC patients. Necroptosis plays a key role in promoting tumor growth in different tumors. The purpose of this study was to construct a prognostic model composed of necroptosis-related genes (NRGs) in CC., Methods: The Cancer Genome Atlas was used to obtain information on clinical features and gene expression. Gene expression differential analysis, weighted gene co-expression network analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator regression algorithm were utilized to identify prognostic NRGs. Thereafter, a risk scoring model was established based on the NRGs. Biological processes and pathways were identified by gene ontology and gene set enrichment analysis (GSEA). Further, protein-protein interaction and ceRNA networks were constructed based on mRNA-miRNA-lncRNA. Finally, the effect of necroptosis related risk score on different degrees of immune cell infiltration was evaluated., Results: CALB1, CHST13, and SLC4A4 were identified as NRGs of prognostic significance and were used to establish a risk scoring model. The time-dependent receiver operating characteristic curve analysis revealed that the model could well predict the 1-, 3-, and 5-year overall survival (OS). Further, GSEA suggested that the NRGs may participate in biological processes, such as the WNT pathway and JAK-Stat pathway. Eight key hub genes were identified, and a ceRNA regulatory network, which comprised 1 lncRNA, 5 miRNAs and 3 mRNAs, was constructed. Immune infiltration analysis revealed that the low-risk group had significantly higher immune-related scores than the high-risk group. A nomogram of the model was constructed based on the risk score, necroptosis, and the clinicopathological features (age and TNM stage). The calibration curves implied that the model was effective at predicting the 1-, 3-, and 5-year OS of CC., Conclusion: Our NRG-based prognostic model can assist in the evaluation of CC prognosis and the identification of therapeutic targets for CC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Lu, Peng, Zhang, Zhang, Guo, Ma, Hua and Chen.)

Numerous studies have shown that long uncoded RNA (lncRNA) MSC-AS1 may play an important role in the occurrence and development of some types of cancer. However, its role in gastric cancer has rarely been discussed. This study aimed to clarify the association between lncRNA MSC-AS1 and gastric cancer using The Cancer Genome Atlas (TCGA) database. We determined the expression of MSC-AS1 using the Wilcoxon rank sum test; in addition, logistic regression was applied to evaluate the association between MSC-AS1 and clinicopathological characteristics. Also, Kaplan-Meier and Cox regression were used to evaluate the relationship between MSC-AS1 and survival. A nomogram was conducted to predict the impact of MSC-AS1 on prognosis. Moreover, Gene Set enrichment analysis (GSEA) was performed to annotate the biological function of MSC-AS1. Quantitative analysis of immune infiltration was carried out by single-set GSEA (ssGSEA). The MSC-AS1 level was elevated in gastric cancer tissues. An increased MSC-AS1 level was significantly correlated with T stage (odds ratio [OR] = 2.55 for T3 and T4 vs. T1 and T2), histological type (OR = 5.28 for diffuse type vs. tubular type), histological grade (OR = 3.09 for grade 3 vs. grades 1 and 2), TP53 status (OR = 0.55 for mutated vs. wild type), and PIK 3CA status (OR = 0.55 for mutated vs. wild type) (all p < 0.05) by univariate logistic regression. Kaplan-Meier survival analysis showed high MSC-AS1 expression had a poor overall survival [hazard ratio (HR) = 1.75; 95% confidence interval (CI): 1.25-2.45; p = 0.001] and progression-free interval (HR = 1.47; 95% CI: 1.03-2.10; p = 0.034). Multivariate survival analysis revealed that MSC-AS1 expression (HR = 1.681; 95% CI: 1.057-2.673; p = 0.028) was independently correlated with overall survival. GSEA demonstrated that the P38/MAPK pathway, the VEGF pathway, the cell adhesion molecules cams, the NOD-like receptor signaling pathway were differentially enriched in the high MSC-AS1 expression phenotype. SsGSEA and Spearman correlation revealed the relationships between MSC-AS1 and macrophages, NK cells, and Tems were the strongest. Coregulatory proteins were included in the PPI network. Upregulated lncRNA MSC-AS1 might be a potential biomarker for the diagnosis and prognosis of gastric cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Ge, Lu, Shan, Peng, Chai, Liu, Li, Zhang, Huang, Hua and Zhang.)

Background: Currently, the surgical approach to adenocarcinomas of esophago-gastric junction (AEG) remains controversial. Function-preserving gastric surgeries are becoming more popular, with proximal gastrectomy with double-tract anastomosis being one of the most important for AEG. Meanwhile, with the increasing use of laparoscopic techniques in the treatment of gastric cancer, the safety and effectiveness of laparoscopic-assisted proximal gastrectomy with double-tract anastomosis for Siewert type II-III AEG need to be further clarified., Methods: Data of patients with Siewert type II/III AEG was collected at our center from October 2010 to December 2019 were retrospectively analyzed. 61 patients underwent open proximal gastrectomy with double-tract anastomosis (OPG-DT group) and 52 underwent laparoscopic-assisted proximal gastrectomy with double-tract anastomosis (LAPG-DT group). The clinical features, surgery, and short-term outcomes of patients in these 2 groups were collected to assess the safety and feasibility of LAPG-DT., Results: A total of 113 patients were analyzed, there were 98 males and 15 females. No death during the operation. The differences in the number of lymph nodes, time to first flatus time to first eating, postoperative hospital stay, Additional analgesics were not statistically significant between two groups. Although the operative duration of LAPG-DT group was significantly longer than that of the OPG-DT group [(217±61) vs. (161±14) min, P=0.000), while less blood loss and less stress in LAPG-DT group. Early and late postoperative complications were similar between two groups., Conclusions: Although laparoscopic-assisted proximal gastrectomy with double-tract anastomosis requires long operative time, it is associated with less bleeding and milder stress. Therefore, it is a safe and feasible surgical method., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-21-165). All authors report funding supports from the Henan Provincial Science and Technology Key Task Program (no. 192102310311; no. 202102310414), the Henan Provincial Medical Science and Technology Key Task Program (no. LHGJ20190629), and the 1000 Talents Program of the Central Plains (No. 204200510023). The authors have no other conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

Introduction: Gallbladder cancer (GBC), the sixth most common gastrointestinal tract cancer, poses a significant disease burden in China. However, no national representative data are available on the clinical characteristics, treatment and prognosis of GBC in the Chinese population., Methods and Analysis: The Chinese Research Group of Gallbladder Cancer (CRGGC) study is a multicentre retrospective registry cohort study. Clinically diagnosed patient with GBC will be identified from 1 January 2008 to December, 2019, by reviewing the electronic medical records from 76 tertiary and secondary hospitals across 28 provinces in China. Patients with pathological and radiological diagnoses of malignancy, including cancer in situ, from the gallbladder and cystic duct are eligible, according to the National Comprehensive Cancer Network 2019 guidelines. Patients will be excluded if GBC is the secondary diagnosis in the discharge summary. The demographic characteristics, medical history, physical examination results, surgery information, pathological data, laboratory examination results and radiology reports will be collected in a standardised case report form. By May 2021, approximately 6000 patient with GBC will be included. The clinical follow-up data will be updated until 5 years after the last admission for GBC of each patient. The study aimed (1) to depict the clinical characteristics, including demographics, pathology, treatment and prognosis of patient with GBC in China; (2) to evaluate the adherence to clinical guidelines of GBC and (3) to improve clinical practice for diagnosing and treating GBC and provide references for policy-makers., Ethics and Dissemination: The protocol of the CRGGC has been approved by the Committee for Ethics of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (SHEC-C-2019-085). All results of this study will be published in peer-reviewed journals and presented at relevant conferences., Trial Registration Number: NCT04140552, Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To investigate the safety and merits of laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DT) for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG)., Methods: Retrospective analysis of the clinical data of 100 consecutive patients with Siewert II and III AEG treated at the Affiliated Tumor Hospital of Zhengzhou University from October 2010 to October 2019 was performed. Out of these patients, 69 underwent open proximal gastrectomy with double-tract reconstruction (OPG-DT), while 31 underwent LPG-DT. The clinicopathological characteristics, perioperative data, and short-term outcomes of the two groups were compared. A P value <0.05 was considered statistically significant., Results: Males accounted for 87% of all patients. Lymph nodes (LNs) count, time to first meal, postoperative length of stay, and postoperative complications were similar between the OPG-DT and LPG-DT group. flatus time was significantly shorter in the LPG-DT group (P<0.05), while the duration of operation was significantly shorter in the the OPG-DT group (P<0.001). Furthermore, the LPG-DT group has less blood loss, shorter flatus time, and lower postoperative-day-5 white blood cell (WBC) count and C-reactive protein (CRP) levels (P<0.05)., Conclusions: Although LPG-DT took longer to perform, its advantages of reduced blood loss and less surgical stress reflected on inflammatory markers supports an acceptable surgical option for Siewert II and III AEG., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-21-130). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: Total gastrectomy and proximal gastrectomy (PG) are both surgical options for the treatment of Siewert type III adenocarcinoma of the esophagogastric junction (AEG). Currently there is no consensus on selecting which procedure to perform; in particular, there are few reports of long-term outcomes for patients with local advanced AEG. The aim of this study was to validate the usefulness of PG with double-tract reconstruction in Siewert type III AEG., Methods: The clinical data of patients with Siewert type III AEG underwent PG with double-tract reconstruction (PG-DT) or total gastrectomy with Roux-en-Y anastomosis (TG-RY) at our hospital between October 2010 and October 2018. According to the defined inclusion and exclusion criteria, 2,146 cases were enrolled in this study. A 1-to-1 propensity score matching (PSM) was performed to compare the short and long-term outcomes between the 2 groups., Results: The operation time was longer in the PG-DT group, and the proportion rates of complications and recovery time was similar in the 2 groups. The rates of maintaining bodyweight and free-fat mass index were significantly higher in patients who underwent PG-DT compared to those who underwent TG-RY. While complications, recovery time and survival are similar between two groups., Conclusions: Regarding short-term outcomes, PG-DT seemed to be superior in terms of maintaining body weight and skeletal muscle compared to TG-RY, while both had similar complications. It was found that PG-DT enabled a potentially longer survival of pathological stage II and III Siewert type III AEG, although the finding was statistically insignificant. These results may help surgeons to determine the appropriate surgical approach and strategy for patients with early and locally advanced Siewert type III AEG., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo-20-475). The authors have no conflicts of interest to declare., (2020 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: Neoadjuvant chemotherapy (NAC) followed by surgery currently offers promise as a strategy for patients with locally advanced gastric cancer (GC). However, there is limited evidence to guide treatment for TRG 0 and 1 patients with locally advanced GC after R0 resection. This study set out to explore the optimal management for TRG 0 and 1 patients with locally advanced GC after R0 resection., Methods: The retrospective data of 154 TRG 0 and 1 patients with locally advanced GC following R0 resection who were treated between January 2012 and December 2018 were collected and analyzed. The Kaplan-Meier method was used to estimate the survival rate. Multivariate analysis was performed using the Cox proportional hazards model., Results: The median follow-up was 34.1 (range, 6.6-90.9) months. Six patients (3.9%) were lost during follow-up. Of the 27 patients who experienced relapse, 12 died, including 2 patients who died of non-neoplastic causes. The 5-year recurrence-free survival (RFS) and 5-year overall survival (OS) were 71.6% (95% CI: 68.5-79.6) and 82.9% (95% CI: 76.9-86.1) for the whole cohort, respectively. Univariate analysis revealed that patients with carcinoembryonic antigen (CEA) <5.0 ng/ml after NAC (77.7% vs. 20.1%, P<0.001), distal gastrectomy (91.7% vs. 67.5%, P=0.046) had higher 5-year RFS. Meanwhile, combined resection (55.6% vs. 73.1%, P=0.042), major complications (42.7% vs. 80.50%, P<0.001), and lymph node metastasis (ypN+) (52.0% vs. 83.7%, P<0.001) had lower 5-year RFS. The multivariate analysis showed that CEA level after NAC (HR =2.876, 95% CI: 1.051-7.872, P=0.040), major complications (HR =2.432, 95% CI: 1.062-5.567, P=0.035), and lymph node metastasis (ypN+) (HR =3.183, 95% CI: 1.242-8.161, P=0.016) were independent prognostic factors., Conclusions: TRG 0 and 1 patients with local GC after R0 resection following NAC had a good prognosis, especially patients with CEA <5.0 ng/mL after NAC, and those without major complications or lymph node metastasis. Monotherapy or no chemotherapy may offer options for treating TRG 0 and 1 patients without adverse prognostic factors., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-3986). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Objective: To investigate the prognostic value of tumor deposits(TD)in N0 stage gastric cancer., Methods: A retrospective case-control study was performed on clinicopathological data of 751 N0 stage gastric cancer patients who underwent subsequent R0 gastrectomy from January 2011 to February 2013 at Zhengzhou University Affiliated Tumor Hospital. Patients were divided into TD-negative group (688 cases) and TD-positive group (63 cases). Propensity score matching was used to balance the covariances between the two groups, such as age, gender, differentiation degree, tumor location, T stage, perineural invasion, lymphovascular invasion, extent of resection, tumor size, surgical procedure,and chemotherapy. Matching was performed by the minimal adjacent method of 1:2 pairing. The survival analysis was carried out using Kaplan-Meier method,and differences between the curves were detected by log-rank test. Cox proportional hazard model was used to perform univariate analysis and multivariate analysis., Results: After matching,56 patients were allocated into the TD-positive group and 112 patients into the TD-negative group, and the baseline of clinicopathological data of 2 groups matched well (all P>0.05). The median follow-up time was 55.2 (12.0-83.2) months, and 3 patients were lost to follow-up (died of other diseases). In TD-positive group, 38 patients died of gastric cancer and 1 died of other disease. In TD-negative group, 52 patients died of gastric cancer and 2 died of other diseases. The TD-positive group had lower 5-year survival rate than TD-negative group (31.0% vs. 52.9%,χ²=6.230, P=0.014). Subgroup analysis showed that the 5-year survival rate of T1-2 stage TD-positive patients was significantly lower than that of T1-2 stage TD-negative patients (47.1% vs. 92.6%, χ²=11.433,P<0.001),while the difference between two groups with T3-4 stage (23.8% vs. 40.0%, χ²=2.995,P=0.084)was not significant. In patients receiving chemotherapy, the 5-year survival rate of TD-positive group was significantly lower than that of TD-negative group(34.1% vs. 54.8%, χ²=4.122, P=0.042). Further subgroup analysis showed that patients receiving postoperative chemotherapy of TD-positive group both in T1-2 stage (63.6% vs. 100%, χ²=3.830,P=0.048) and in T3-4 stage (24.2% vs. 48.4%, χ²=4.740,P=0.029) had significantly lower 5-year survival rates than those of TD-negative group. However,T1-2 stage TD-positive patients receiving chemotherapy had significantly higher 5-year survival rate as compared to those without receiving chemotherapy(63.6% vs. 16.7%, χ²=5.474,P=0.019).Univariate analysis revealed T stage (HR=1.829, 95%CI:1.490-2.245, P<0.001),perineural invasion (HR=2.620, 95%CI:1.617-4.246,P<0.001),tumor size (HR=1.646, 95%CI:1.078-2.512, P=0.021),TD(HR=1.691,95%CI:1.112-2.572,P=0.014) were associated with the prognosis of patients with gastric cancer. Multivariate analysis showed TD-positive (HR=2.035, 95%CI:1.325-3.126, P=0.001), later T stage (HR=1.812, 95%CI: 1.419-2.313,P<0.001), perineural invasion (HR=1.782,95%CI:1.058-3.002,P=0.030) were independent risk factors for the prognosis of gastric cancer., Conclusions: TD is an independent risk factor for N0 stage gastric cancer,and may be closely related to T stage. Patients with TD-positive stage T1-2 should receive chemotherapy, but the prognosis of TD-positive patients undergoing adjuvant chemotherapy is poorer as compared to TD-negative patients. Therefore, more individualized treatments should be administrated.

Objective: To compare the effects of neoadjuvant chemotherapy and adjuvant chemotherapy on the prognosis of patients with locally advanced gastric cancer using propensity score matching method., Methods: Clinical data of patients with locally advanced gastric cancer undergoing open D2 radical gastrectomy between January 2012 and December 2014 at the Affiliated Tumor Hospital of Zhengzhou University were analyzed retrospectively. Sixty-five patients receiving neoadjuvant chemotherapy (NAC) were allocated into the NAC group and 1243 patients receiving postoperative adjuvant chemotherapy (AC) were allocated into the AC group., Inclusion Criteria: (1) age ranged from 18 to 75 years old, and biopsy specimen was confirmed as adenocarcinoma; (2) all the operative procedures were open D2 radical gastrectomy;(3)image examinations showed no distant metastasis or other unresectable factors., Exclusion Criteria: no open D2 radical gastrectomy, undergoing laparoscopic surgery, neoadjuvant chemotherapy course <2 cycles, without adjuvant chemotherapy, history of other malignancies, severe complications, incomplete data. SOX (tegafur-gimeracil-oteracil plus oxaliplatin) or XELOX (capecitabine plus oxaliplatin) was used as neoadjuvant and postoperative adjuvant chemotherapy regimen. One-to-two propensity score matching was performed to balance the covariance between two groups. Survival was analyzed using the Kaplan-Meier method. Differences between the curves were tested using log-rank test., Results: After balancing the covariates including gender, age, tumor location, degree of differentiation, clinical stage, chemotherapy regimen, chemotherapy course and surgical approach, 195 patients were enrolled, including 65 patients of the NAC group and 130 patients of the AC group. The number of harvested lymph nodes in NAC and AC group was 22.3±4.6 and 22.6±5.1 respectively, without statistically significant difference(t=1.125, P=0.263). Pathological response assessment for NAC group showed TRG0 in 6 cases, TRG1 in 8 cases, TRG2 in 17 cases, TRG3 in 34 cases; sensitive (TRG 0 to 2) in 31 cases (47.7%), non-sensitive in 34 cases (52.3%). The 3-year progression-free survival rate of NAC and AC group was 73.6%(95%CI: 62.8-84.3) and 69.9%(95%CI:62.1-77.7) respectively, which was not significantly different(P=0.361). The 3-year overall survival rate of NAC and AC group was 80.0%(95%CI:70.2-89.8) and 74.6%(95%CI:67.2-82.0) respectively, which was not significantly different as well(P=0.387). Subgroup analysis revealed that the 3-year progression-free survival rate and 3-year overall survival rate of sensitive patients in NAC group were 83.3%(95%CI:70.0-96.6) and 87.1%(95%CI:75.3-98.9) respectively, which were significantly higher than 62.4%(95%CI:46.1-78.7, P=0.037) and 70.2%(95%CI:54.7-85.7, P=0.033) of non-sensitive patients in NAC group, and those in AC group(P=0.044 and P=0.040)., Conclusions: Effects of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy on the prognosis of patients with locally advanced gastric cancer are similar. Patients who are sensitive to neoadjuvant chemotherapy have better prognosis. It may be beneficial to improve prognosis that some appropriate patients with locally advanced gastric cancer are screened for neoadjuvant chemotherapy.

Objective: To evaluate the clinical features and prognosis of gastric cancer patients with pathological complete response (pCR) after neoadjuvant chemotherapy (NAC)., Methods: Clinical data of 159 gastric cancer patients who received NAC followed by surgical resection between January 2012 and December 2014 at the Affiliated Tumor Hospital of Zhengzhou University were collected and clinical features of those with pCR were analyzed retrospectively. Kaplan-Meier method was used to estimate 3-year overall survival (OS) rate and recurrence-free survival (RFS) rate. Recurrence factors were analyzed by univariate and multivariate analysis with Cox proportional hazard model., Results: A total of 21 patients(13.2%) achieved pCR, including 13 male and 8 female cases, with the median age at diagnosis of 56 (40 to 70) years. Eleven cases were differentiated tumor and 10 were undifferentiated. Six cases were in clinical baseline stage II(, and 15 were in III(. Five cases received the mFOLFOX6 (oxaliplatin + leucovorin +5-FU), 6 received the SOX (oxaliplatin +S-1), 4 received the XELOX (oxaliplatin + capecitabine), 2 received the EOX (epirubicin + oxaliplatin +capecitabine) and 4 received the DOX (docetaxel + oxaliplatin +capecitabine) chemotherapy regimens. Two cases achieved CR, 18 achieved PR, and 1 was SD after NAC. The median (range) course of preoperative and postoperative chemotherapy were 4(2 to 5) and 2(0 to 5) . All the patients underwent R0 resection plus D2 lymphadenectomy, and 4 cases were performed with proximal gastrectomy, 3 cases were performed with distal gastrectomy, 13 cases were performed with total gastrectomy, and one case was performed with total gastrectomy plus pancreatic splenectomy. Pneumonia, abdominal bleeding and infection, anastomotic leakage, and gastroplegia occurred respectively in one case, who all were cured by conservative treatment. The median follow-up of the survivors was 39.3 (range 22.7 to 56.9) months. Three cases died of recurrence: 1 case in the liver, 1 in the lung, and 1 in the brain. Two cases developed recurrence and survived: 1 in the liver and 1 in celiac lymph nodes. The overall survival and 3-year recurrence-free survival rates were 90.2%(95%CI: 100 to 77.3) and 90.5%(95%CI: 100 to 78.0). Fourteen cases did not complete scheduled chemotherapy course, and the overall 3-year survival rate was 85.1%. Older age(>50 years old)(P=0.028, RR=0.063, 95%CI: 0.005 to 0.743) and no postoperative complication (P=0.023, RR=0.065, 95%CI: 0.006 to 0.689) were identified as independent prognostic factors with Cox multivariate analysis., Conclusion: Patients diagnosed as gastric cancer with pCR after NAC have good prognosis, but the pCR ratio is low, and those with younger age and more postoperative complications may have higher risk for recurrence and metastasis.

MicroRNAs (miRNAs) play a crucial role in the development and progression of human cancers, including gastric cancer (GC). The discovery of miRNAs may provide a new and powerful tool for studying the mechanism, diagnosis, and treatment of GC. In this study, we aimed to investigate the role of miR-326 in the development and progression of GC. Quantitative PCR (qPCR) was used to measure the expression level of miR-326 in GC tissues and cell lines. We found that miR-326 was significantly downregulated during GC. In addition, overexpression of miR-326 inhibited GC cell proliferation. Fluorescence-activated cell sorting (FACS) further showed that miR-326 significantly induced GC cell G2/M arrest. Subsequent dual-luciferase reporter assay identified one of the proto-oncogene NOB1 as a direct target of miR-326, and NOB1 can save growth inhibition caused by miR-326. We also confirmed that the growth inhibition caused by miR-326 is associated with AKT pathway activation. Taken together, our results indicate that miR-326 could serve as a potential diagnostic biomarker and therapeutic option for GC in the near future.

Cisplatin (DDP) based chemotherapy is still the main strategy of human gastric cancer (GC) treatment. However, drug resistance is a major obstacle for DDP chemotherapy. Recent studies indicated that the resistance could be modulated by the regulation of dysregulated microRNAs (miRs). Previous study also found miR-34a was associated with cell proliferation and apoptosis in human GC; however, the relationship between miR-34a and DDP resistance still remains unexplored. The purpose of this study was to investigate whether miR-34a is associated with DDP resistance in human GC cells. Our study found that the expression of miR-34a was significantly decreased in DDP resistance human GC tissues and DDP resistance human GC SGC7901/DDP cells compared with normal GC tissues and cells. Upregulation of miR-34a enhanced the DDP sensitivity of SGC7901/DDP cells to DDP through the inhibition of cell proliferation and induction of cell apoptosis; on the other hand downregulation of miR-34a could weaken the DDP sensitivity of SGC7901 cells to DDP. Further study found that MET was a direct target of miR-34a and the regulation of MET could affect the DDP sensitivity of SGC7901/DDP cells. Moreover, our study also indicated that up-regulation of miR-34a could decrease the expression of MET in SGC7901/DDP cells. Therefore, our findings suggested miR-34a could modulate human gastric cancer cell DDP sensitivity by regulation of cell proliferation and apoptosis via targeting MET, potentially benefiting human GC treatment in the future.