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Background: Cancer stem cells (CSCs) are critical factors that limit the effectiveness of gastric cancer (GC) therapy. Circular RNAs (circRNAs) are confirmed as important regulators of many cancers. However, their role in regulating CSC-like properties of GC remains largely unknown. Our study aimed to investigate the role of circUBA2 in CSC maintenance and the underlying mechanisms. Methods: We identified circUBA2 as an upregulated gene using circRNA microarray analysis. qRT-PCR was used to examine the circUBA2 levels in normal and GC tissues. In vitro and in vivo functional assays were performed to validate the role of circUBA2 in proliferation, migration, metastasis and CSC-like properties of GC cell. The relationship between circUBA2, miR-144-5p and STC1 was characterised using bioinformatics analysis, a dual fluorescence reporter system, FISH, and RIP assays. Results: CircUBA2 expression was significantly increased in GC tissues, and patients with GC with high circUBA2 expression had a poor prognosis. CircUBA2 enhances CSC-like properties of GC, thereby promoting cell proliferation, migration, and metastasis. Mechanistically, circUBA2 promoted GC malignancy and CSC-like properties by acting as a sponge for miR-144-5p to upregulate STC1 expression and further activate the IL-6/JAK2/STAT3 signaling pathway. More importantly, the ability of circUBA2 to enhance CSC-like properties was inhibited by tocilizumab, a humanised Interleukin-6 receptor (IL-6R) antibody. Thus, circUBA2 knockdown and tocilizumab synergistically inhibited CSC-like properties. Conclusions: Our study demonstrated the critical role of circUBA2 in regulating CSC-like properties in GC. CircUBA2 may be a promising prognostic biomarker for GC. [ABSTRACT FROM AUTHOR]

Objective: To study the historical global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. Methods: Incidence data were retrieved from the Cancer Incidence in Five Continents (CI5) volumes I-XI, and mortality data were obtained from the latest update of the World Health Organization (WHO) mortality database. We used join-point regression analysis to examine historical incidence and mortality trends and used the package NORDPRED in R to predict the number of deaths and mortality rates by 2035 by country and sex. Results: More than 1,089,000 new cases of gastric cancer and 769,000 related deaths were reported in 2020. The average annual percent change (AAPC) in the incidence of gastric cancer from 2003 to 2012 among the male population, South Korea, Japan, Malta, Canada, Cyprus, and Switzerland showed an increasing trend (P > 0.05); among the female population, Canada [AAPC, 1.2; (95%Cl, 0.5–2), P < 0.05] showed an increasing trend; and South Korea, Ecuador, Thailand, and Cyprus showed an increasing trend (P > 0.05). AAPC in the mortality of gastric cancer from 2006 to 2015 among the male population, Thailand [3.5 (95%cl, 1.6–5.4), P < 0.05] showed an increasing trend; Malta Island, New Zealand, Turkey, Switzerland, and Cyprus had an increasing trend (P > 0.05); among the male population aged 20–44, Thailand [AAPC, 3.4; (95%cl, 1.3–5.4), P < 0.05] showed an increasing trend; Norway, New Zealand, The Netherlands, Slovakia, France, Colombia, Lithuania, and the USA showed an increasing trend (P > 0.05). It is predicted that the mortality rate in Slovenia and France's female population will show an increasing trend by 2035. It is predicted that the absolute number of deaths in the Israeli male population and in Chile, France, and Canada female population will increase by 2035. Conclusion: In the past decade, the incidence and mortality of gastric cancer have shown a decreasing trend; however, there are still some countries showing an increasing trend, especially among populations younger than 45 years. Although mortality in most countries is predicted to decline by 2035, the absolute number of deaths due to gastric cancer may further increase due to population growth. [ABSTRACT FROM AUTHOR]

Robotic surgery may be an alternative to laparoscopic surgery for gastric cancer (GC). However, randomized controlled trials (RCTs) reporting the differences in survival between these two approaches are currently lacking. From September 2017 to January 2020, 300 patients with cT1-4a and N0/+ were enrolled and randomized to either the robotic (RDG) or laparoscopic distal gastrectomy (LDG) group (NCT03313700). The primary endpoint was 3-year disease-free survival (DFS); secondary endpoints reported here are the 3-year overall survival (OS) and recurrence patterns. The remaining secondary outcomes include intraoperative outcomes, postoperative recovery, quality of lymphadenectomy, and cost differences, which have previously been reported. There were 283 patients in the modified intention-to-treat analysis (RDG group: n = 141; LDG group: n = 142). The trial has met pre-specified endpoints. The 3-year DFS rates were 85.8% and 73.2% in the RDG and LDG groups, respectively (p = 0.011). Multivariable Cox regression model including age, tumor size, sex, ECOG PS, lymphovascular invasion, histology, pT stage, and pN stage showed that RDG was associated with better 3-year DFS (HR: 0.541; 95% CI: 0.314-0.932). The RDG also improved the 3-year cumulative recurrence rate (RDG vs. LDG: 12.1% vs. 21.1%; HR: 0.546, 95% CI: 0.302-0.990). Compared to LDG, RDG demonstrated non-inferiority in 3-year DFS rate. Robotic surgery has been demonstrated to improve short-term outcomes for patients with gastric cancer who received a gastrectomy, but the long-term effects are less clear. Here, the authors report the survival outcomes of their phase 2 randomized controlled trial comparing robotic to laparoscopic distal gastrectomy in patients with resectable gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Laparoscopy-assisted gastrectomy (LG) is rapidly gaining popularity owing to its minimal invasiveness. Previous studies have found that compared with two-dimensional (2D)-LG, three-dimensional (3D)-LG showed better short-term outcomes. However, the long-term oncological outcomes in patients with locally resectable gastric cancer (GC) remain controversial. Methods: In this noninferiority, open-label, randomized clinical trial, a total of 438 eligible GC participants were randomly assigned in a 1:1 ratio to either 3D-LG or 2D-LG from January 2015 to April 2016. The primary endpoint was operating time, while the secondary endpoints included 5-year overall survival (OS), disease-free survival (DFS), and recurrence pattern. Results: Data from 401 participants were included in the per-protocol analysis, with 204 patients in the 3D group and 197 patients in the 2D group. The 5-year OS and DFS rates were comparable between the 3D and 2D groups (5-year OS: 70.6% vs. 71.1%, Log-rank P = 0.743; 5-year DFS: 68.1% vs. 69.0%, log-rank P = 0.712). No significant differences were observed between the 3D and 2D groups in the 5-year recurrence rate (28.9% vs. 28.9%, P = 0.958) or recurrence time (mean time, 22.6 vs. 20.5 months, P = 0.412). Further stratified analysis based on the type of gastrectomy, postoperative pathological staging, and preoperative BMI showed that the 5-year OS, DFS, and recurrence rates of the 3D group in each subgroup were similar to those of the 2D group (all P > 0.05). Conclusions: For patients with locally resectable GC, 3D-LG performed by experienced surgeons in high-volume professional institutions can achieve long-term oncological outcomes comparable to those of 2D-LG. Registration number: NCT02327481 (http://clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Background: Chemoresistance is a major clinical challenge that leads to tumor metastasis and poor clinical outcome. The mechanisms underlying gastric cancer resistance to chemotherapy are still unclear. Methods: We conducted bioinformatics analyses of publicly available patient datasets to establish an apoptotic phenotype and determine the key pathways and clinical significance. In vitro cell models, in vivo mouse models, and numerous molecular assays, including western blotting, qRT-PCR, immunohistochemical staining, and coimmunoprecipitation assays were used to clarify the role of factors related to apoptosis in gastric cancer in this study. Differences between datasets were analyzed using the Student's t-test and two-way ANOVA; survival rates were estimated based on Kaplan–Meier analysis; and univariate and multivariate Cox proportional hazards models were used to evaluate prognostic factors. Results: Bulk transcriptomic analysis of gastric cancer samples established an apoptotic phenotype. Proapoptotic tumors were enriched for DNA repair and immune inflammatory signaling and associated with improved prognosis and chemotherapeutic benefits. Functionally, cyclin-dependent kinase 5 (CDK5) promoted apoptosis of gastric cancer cells and sensitized cells and mice to oxaliplatin. Mechanistically, we demonstrate that CDK5 stabilizes DP1 through direct binding to DP1 and subsequent activation of E2F1 signaling. Clinicopathological analysis indicated that CDK5 depletion correlated with poor prognosis and chemoresistance in human gastric tumors. Conclusion: Our findings reveal that CDK5 promotes cell apoptosis by stabilizing DP1 and activating E2F1 signaling, suggesting its potential role in the prognosis and therapeutic decisions for patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Background: The long-term dynamic recurrence hazard of locally advanced gastric cancer (LAGC) in the clinical setting of adjuvant chemotherapy (ACT) remains unclear. Purpose: This study aimed to investigate the dynamic recurrence risk of LAGC in patients who received ACT or not. Methods: The study assessed data from patients with LAGC who underwent radical gastrectomy between January, 2010 and October, 2015. Inverse probability of treatment weighting (IPTW) was performed to reduce selection bias between the ACT and observational (OBS) groups. Conditional recurrence-free survival (cRFS) and restricted mean survival time (RMST) were used to assess the survival differences. Results: In total, 1,661 LAGC patients were included (ACT group, n = 1,236 and OBS group, n = 425). The recurrence hazard gradually declined; in contrast, cRFS increased with RFS already accrued. Following IPTW adjustment, the cRFS rates were higher in the ACT group than those in the OBS group for patients at baseline or with accrued RFS of 1 and 2 years (p˂0.05). However, the cRFS rates of the ACT group were comparable with those of the OBS group for patients with accrued RFS of 3 or more years (p > 0.05). Likewise, the 5-year △RMST between the ACT and OBS groups demonstrated a similar trend. Moreover, the hematological metastasis rate of the ACT group was significantly lower than that of the OBS group for patients at baseline or with accrued RFS of 1 and 2 years, respectively (p˂0.05). Conclusions: Although ACT could provide substantial benefits for patients with LAGC, the differences in recurrence hazard between the ACT and OBS groups may attenuate over time, which could help guide surveillance and alleviate patients' anxiety. Further prospective large-scale studies are warranted. [ABSTRACT FROM AUTHOR]

Background: The accuracy of the eighth AJCC ypTNM staging system on the prognosis of gastric cancer (GC) patients after neoadjuvant therapy (NAT) is controversial. This study aimed to develop and validate a novel staging system using the log odds of positive lymph nodes scheme (LODDS). Methods: A retrospective analysis of 606 GC patients who underwent radical gastrectomy after neoadjuvant therapy was conducted as the development cohort. (Fujian Medical University Affiliated Union Hospital (n = 183), Qinghai University Affiliated Hospital (n = 169), Mayo Clinic (n = 236), Lanzhou University First Hospital (n = 18)). The validation cohort came from the SEER database (n = 1701). A novel ypTLoddsS (ypTLM) staging system was established using the 3-year overall survival. The predictive performance of two systems was compared. Results: Two-step multivariate Cox regression analysis in both cohorts showed that ypTLM was an independent predictor of overall survival of GC patients after neoadjuvant therapy (HR: 1.57, 95% CI: 1.30–1.88, p < 0.001). In the development cohort, ypTLM had better discrimination ability than ypTNM (C-index: 0.663 vs 0.633, p < 0.001), better prediction homogeneity (LR: 97.7 vs. 70.9), and better prediction accuracy (BIC: 3067.01 vs 3093.82; NRI: 0.36). In the validation cohort, ypTLM had a better prognostic predictive ability (C-index: 0.614 vs 0.588, p < 0.001; LR: 11,909.05 vs. 11,975.75; BIC: 13,263.71 vs 13,328.24; NRI: 0.22). The time-dependent ROC curve shows that the predictive performance of ypTLM is better than ypTNM, and the analysis of the decision curve shows that ypTLM achieved better net benefits. Conclusion: A LODDS-based ypTLM staging system based on multicenter data was established and validated. The predictive performance was superior to the eighth AJCC ypTNM staging system. [ABSTRACT FROM AUTHOR]

The effectiveness of neoadjuvant immune checkpoint inhibitor (ICI) therapy is confirmed in clinical trials; however, the patients suitable for receiving this therapy remain unspecified. Previous studies have demonstrated that the tumor microenvironment (TME) dominates immunotherapy; therefore, an effective TME classification strategy is required. In this study, five crucial immunophenotype‐related molecules (WARS, UBE2L6, GZMB, BATF2, and LAG‐3) in the TME are determined in five public gastric cancer (GC) datasets (n = 1426) and an in‐house sequencing dataset (n = 79). Based on this, a GC immunophenotypic score (IPS) is constructed using the least absolute shrinkage and selection operator (LASSO) Cox, and randomSurvivalForest. IPSLow is characterized as immune‐activated, and IPSHigh is immune‐silenced. Data from seven centers (n = 1144) indicate that the IPS is a robust and independent biomarker for GC and superior to the AJCC stage. Furthermore, patients with an IPSLow and a combined positive score of ≥5 are likely to benefit from neoadjuvant anti‐PD‐1 therapy. In summary, the IPS can be a useful quantitative tool for immunophenotyping to improve clinical outcomes and provide a practical reference for implementing neoadjuvant ICI therapy for patients with GC. [ABSTRACT FROM AUTHOR]

To develop and validate a simple metabolic score (Metabolic score, MS) for use in evaluating the prognosis of gastric cancer (GC) patients and dynamically monitor for early recurrence. We retrospectively collected general clinicopathological data of patients who underwent radical gastrectomy for GC between September 2012 and December 2017 in the Department of Gastric Surgery of the Fujian Medical University Union Hospital. Using a random forest algorithm to screen preoperative blood indicators into the Least absolute shrinkage and selection operator (LASSO) model, we developed a novel MS to predict prognosis. Data of 1974 patients were used to develop and validate the model. Total cholesterol (TCHO), bilirubin (TBIL), direct bilirubin (DBIL), and 15 other metabolic indicators had significant predictive value for the prognosis using the random forest algorithm. In the overall population, 533 patients (27.0%) had high and 1441 (73%) had low MS status. High MS status was related to tumor progression. The KM curves of 3-year OS and RFS for training set patients showed low MS had a better prognosis than high MS (OS: 79.4% vs 59.7%, P < 0.001; RFS: 76.0% vs 56.2%, P < 0.001). We have developed and validated MS to predict the long-term survival of GC patients and allow early monitoring of recurrence. This will provide physicians with simple, economical, and dynamic tumor monitoring information. Synopsis We've developed and validated MS to predict the long-term survival of GC patients and allow early monitoring of recurrence. This will provide economical, and dynamic tumor monitoring information. [ABSTRACT FROM AUTHOR]

This study aims to analyze the effect of textbook outcome (TO) on the long-term prognosis and adjuvant chemotherapy (AC) compliance of patients with gastric cancer (GC) in a single institute. Consecutive patients who underwent radical gastrectomy with pathological stage I-III at Union Hospital of Fujian Medical University from January 2010 to June 2017 were included. TO was defined as receiving a complete-potentially curative status, ≥15 lymph nodes examined, hospital stay ≤21 days, and freedom from intraoperative and postoperative complications, re-intervention in 30 days, 30-day readmission to the hospital or intensive care unit, and 30-day postoperative mortality. Totally 3993 patients were included, of which 3361 (84.2%) patients achieved TO. The overall, disease-specific, and recurrence-free survival of patients achieving TO were significantly better than those of patients without achieving TO (all P < 0.05). The total number of AC cycles was greater and the interval from surgery to first AC was shorter in the TO group compared with the Non-TO group. Age >65 years old, open surgery, pT3-4 stage, and total radical gastrectomy (TG) were identified as related high-risk factors for failure to achieve TO. Laparoscopic surgery facilitated TO achievement in high-risk groups. TO is a reliable indicator of favorable prognosis of patients with GC and contributes to postoperative chemotherapy compliance. Age ≤65 years old, non-TG, pT1-2 stage, and laparoscopic surgery may promote the achievement of TO. [ABSTRACT FROM AUTHOR]

Few studies have reported the association between the pattern and time point of recurrence in different groups stratified by age in postoperative survival of patients with gastric cancer. The clinicopathological data and recurrence data of 2028 patients with GC who underwent curative surgery from January 2010 to March 2015 were enrolled in this study. Patients were grouped according to age: young group (YG) (≤45 years old) (n = 180) and non-young group (OG) (>45 years old) (n = 1848). A total of 2028 patients were enrolled. The young group had better 5-year OS and DFS than the non-young group. In peritoneal recurrence, the cumulative incidence of recurrence in YG was higher than that in OG (P < 0.001). In distant recurrence, the cumulative incidence of recurrence YG was always lower than that of OG (P = 0.004). Recurrence hazard function varied over time between the two groups:in the peritoneal metastasis, the recurrence hazard for YG was higher and earlier than that of OG and the YG was observed during five years after surgery with two recurrence peaks in 8.5 months and in 41.5 months. In distant recurrence, the recurrence hazard for OG had an earlier and higher single peak than that of YG (6.0 months). The recurrence characteristics of patients with gastric cancer after curative resection between young group and older group are different. Personalized follow-up strategies should be developed according to the age and time point after operation for the early detection of recurrence and making decision for further treatment. [ABSTRACT FROM AUTHOR]

Effective classifiers for the prediction of individual adjuvant chemotherapy (AC) benefits are scarce. This study aimed to construct a useful classifier to predict the AC benefit and recurrence hazard based on preoperative hematological indices through a multicenter database. Multivariate analysis revealing GCRF (comprehensive deep learning classifier) as an independent prognostic factor associated with overall survival (OS) and disease-free survival (DFS). Locally advanced gastric cancer (LAGC) patients are categorized into the high-risk group (HRG) and low-risk group (LRG). In HRG, OS and DFS of the AC group are significantly higher than those of the non-AC group (all p˂0.05), whereas in LRG, OS and DFS of the AC group are comparable to those of the non-AC group (all p > 0.05). Furthermore, combined GCRF with 8th AJCC TNM staging system, only 650 (51.1%) patients can benefit most from AC among 1273 patients with pStage II-III. From the perspective of recurrence pattern, the recurrence rate of HRG is significantly higher than that of LRG in any recurrence type, including local recurrence, peritoneal recurrence, and distant recurrence (all p˂0.05). Furthermore, the mean time to peritoneal recurrence and lung metastasis in HRG is earlier than that in the LRG (p = 0.028 and 0.011, respectively). In summary, our novel classifier based on deep learning preoperative hematological indices can predict not only the AC benefit of LAGC patients, but also the recurrence hazard after surgery. This classifier is expected to be an effective supplement to the 8th AJCC TNM staging system for the prediction of AC benefits and is helpful for clinical decision in AC individual administration. Further large-scale western studies are warranted. [ABSTRACT FROM AUTHOR]

The impact of achieving textbook oncological outcome (TOO) as a multimodal therapy quality indicator on the prognosis of advanced gastric cancer (AGC) remains inadequately assessed. Patients with AGC who underwent curative gastrectomy between January 2010 and December 2017 at two East Asian medical centers were included. TOO was defined as achieving the textbook outcome (TO) and receiving neoadjuvant and/or adjuvant chemotherapy (NCT or ACT). Cox and logistic regression models were used to identify prognostic and non-TOO-associated risk factors. Among 3626 patients, 57.6% achieved TOO (TOO group), exhibiting significantly better 5-year overall survival (OS) and disease-free survival (DFS) than the non-TOO group (both p < 0.05). Multivariate Cox regression identified TOO as an independent prognostic factor for 5-year OS (HR, 0.67; 95% CI, 0.61–0.74; p < 0.001) and DFS (HR, 0.73; 95% CI, 0.66–0.81; p < 0.001). Multivariate logistic regression showed that open gastrectomy, lack of health insurance, age ≥65 years, ASA score ≥ Ⅲ, and tumor size ≥50 mm are independent risk factors for non-achievement of TOO (all p < 0.05). On a sensitivity analysis of TOO's prognostic value using varying definitions of chemotherapy parameters, a stricter definition of chemotherapy resulted in a decrease in the TOO achievement rate from 57.6 to 22.3%. However, the associated reductions in the risk of death and recurrence fluctuated within the ranges of 33–39% and 28–37%, respectively. TOO is a reliable and stable metric for favorable prognosis in AGC. Optimizing the surgical approach and improving health insurance status may enhance TOO achievement. [ABSTRACT FROM AUTHOR]

Background: It remains inconclusive whether laparoscopic gastrectomy (LG) has better long-term outcomes when compared with open gastrectomy (OG) for elderly gastric cancer (EGC). We attempted to explore the influence of the immune prognostic index (IPI) on the prognosis of EGCs treated by LG or OG to identify a population among EGC who may benefit from LG. Methods: We included 1539 EGCs treated with radical gastrectomy from January 2007 to December 2016. Propensity score matching was applied at a ratio of 1:1 to compare the LG and OG groups. The IPI based on dNLR ≥ cut-off value (dNLR) and sLDH ≥ cut-off value (sLDH) was developed, characterizing two groups (IPI = 0, good, 0 factors; IPI = 1, poor, 1 or 2 factors). Results: Of the 528 EGCs (LG: 264 and OG: 264), 271 were in the IPI = 0 group, and 257 were in the IPI = 1 group. In the entire cohort, the IPI = 0 group was associated with good 5-year overall survival (OS) (p = 0.001) and progression-free survival (PFS) (p = 0.003) compared to the IPI = 1 group; no significant differences in 5-year OS and PFS between the LG and OG groups were observed. In the IPI = 1 cohort, there was no significant difference in OS or PFS between the LG and OG groups across all tumor stages. However, in the IPI = 0 cohort, LG was associated with longer OS (p = 0.015) and PFS (p = 0.018) than OG in stage II EGC, but not in stage I or III EGC. Multivariate analysis showed that IPI = 0 was an independent protective factor for stage II EGC receiving LG, but not for those receiving OG. Conclusion: The IPI is related to the long-term prognosis of EGC. Compared with OG, LG may improve the 5-year survival rate of stage II EGC with a good IPI score. This hypothesis needs to be further confirmed by prospective studies. [ABSTRACT FROM AUTHOR]

Background: The oncologic efficacy of laparoscopic versus open surgery for advanced distal gastric cancer (ADGC) beyond 3 years after surgery remain obscure. Methods: A total of 1256 patients with ADGC at two teaching institutions in China from April 2007 to December 2014 were enrolled. The general data of the two groups were identified to enable rigorous estimation of propensity scores. Restricted mean survival time (RMST) and Landmark analysis was used to compare survival. Results: After matching 461 patients each in the open distal gastrectomy (ODG) and laparoscopic distal gastrectomy (LDG) groups, they were included into analysis. The 3- and 5-year overall survival (OS) and disease-free survival were comparable in two groups. RMST-stratified analysis showed that the 3-year RMST of ODG group was similar to that of LDG group in patients with cT4a (− 1.38 years, p = 0.163) or with cT4a and tumor size > 5 cm, whereas the 5-year RMST had significant differences between groups in cT4a patients(− 8.36 years, P = 0.005) or cT4a and tumor size > 5 cm patients(4.67 years, P = 0.042). In patients with cT4a and tumors > 5 cm, the number of peritoneal recurrences was significantly fewer in the ODG group than in the LDG group (4 vs. 17, P = 0.033), and the peritoneal recurrence time and multiple-site recurrence time were both later in the ODG group. Conclusion: By reducing recurrence, ODG achieves a better survival for GC patients with serous infiltration and tumors larger than 5 cm beyond 3 years after surgery. The present findings can serve as a reference for surgical options and the setting of follow-up time point for clinical studies. [ABSTRACT FROM AUTHOR]

Background: Due to lacking evidence for confirming the efficacy of performing laparoscopic surgery for locally advanced gastric cancer (LAGC). Therefore, this study aimed to compare the static and dynamic failure patterns after laparoscopic gastrectomy (LG) and open gastrectomy (OG) in LAGC. Methods: A total of 1792 LAGC patients who underwent radical resection between January 2010 and January 2017 were divided into the LG group (n = 1557) and the OG group (n = 235). Propensity score matching was performed to balance the two groups. Dynamic hazard rates of failure were calculated using the hazard function. Early and late failure were defined as failure occurring before and after 2 years since surgery, respectively. Results: A total of 1175 patients with LAGC were included after matching (LG group, n = 940; OG, n = 235). The failure rate of the whole cohort was 43.2% (508/1175), accounting for 41.4% (389/940) and 50.6% (119/235) in the LG and OG groups, respectively. Although the two groups showed no significant differences in failure rate for any failure type, landmark analysis showed a lower early distant recurrence rate in the stage IIa–IIIb subgroup of the LG group (OG versus LG: 30.3% versus 21.1%, P = 0.004). The dynamic hazard rate peaked at 9.4 months (peak rate = 0.0186) before gradually declining. In stage IIa–IIIb patients, the hazard rate of the OG group remained significantly higher than that of the LG group within the first 2 years in terms of distant recurrence (peak rate: OG versus LG, 0.0091 versus 0.0055). Conclusion: Given the differences in early failure between LG and OG, more intensive surveillance for distant recurrence within the first 2 years should be considered for patients with stage IIa–IIIb after OG. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the safety, effectiveness, and feasibility of indocyanine green (ICG) tracing in guiding lymph-node (LN) dissection during laparoscopic D2 radical gastrectomy in patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NAC). Method: We retrospectively analyzed data on 313 patients with clinical stage of cT1-4N0-3M0 who underwent laparoscopic radical gastrectomy after NAC between February 2010 and October 2020 from two hospitals in China. Grouped according to whether ICG was injected. For the ICG group (n = 102) and non-ICG group (n = 211), 1:1 propensity matching analysis was used. Results: After matching, there was no significant difference in the general clinical pathological data between the two groups (ICG vs. non-ICG: 94 vs. 94). The average number of total LN dissections was significantly higher in the ICG group and lower LN non-compliance rate than in the non-ICG group. Subgroup analysis showed that among patients with LN and tumor did not shrink after NAC, the number of LN dissections was significantly more and LN non-compliance rate was lower in the ICG group than in the non-ICG group. Intraoperative blood loss was significantly lesser in the ICG group than in the non-ICG group, while the recovery and complications of the two groups were similar. Conclusion: For patients with poor NAC outcomes, ICG tracing can increase the number of LN dissections during laparoscopic radical gastrectomy, reduce the rate of LN non-compliance, and reduce intraoperative bleeding. Patients with AGC should routinely undergo ICG-guided laparoscopic radical gastrectomy. [ABSTRACT FROM AUTHOR]

Background: Application of indocyanine green (ICG) fluorescence imaging is effective in guiding laparoscopic radical lymphadenectomy for gastric cancer. However, the optimal approach for indocyanine green injection is controversial. Therefore, the objective of this study was aimed to compare the efficacy and ICG injection between the preoperative submucosal and intraoperative subserosal approaches for lymph node (LN) tracing during laparoscopic gastrectomy.Method: This randomized controlled trial (ClinicalTrials.gov, NCT04219332) included 266 patients with potentially resectable gastric cancer (cT1-T4a, N0/+, M0) enrolled from a tertiary teaching center between December 2019 and October 2020. The primary endpoint was total number of retrieved LNs.Results: In total, 259 patients (n = 130 and n = 129 in the submucosal and subserosal groups, respectively) were included in the per-protocol analysis. There are no significant differences in total number of retrieved LNs between the two groups (49.8 vs. 49.2, P = 0.713). The rate of LN noncompliance in the submucosal group was comparable to that in the subserosal group (32.3% vs. 33.3%, P = 0.860). No significant difference was found between the submucosal and subserosal groups in terms of the incidence (17.7% vs. 16.3%; P = 0.762) or severity of postoperative complications. The mean fluorescence cost in the submucosal group was higher than that in the subserosal group ($335.3 vs. $182.4; P < 0.001). The overall treatment satisfaction score was lower in the submucosal group than in the subserosal group (70.5 vs. 76.1%, P = 0.048).Conclusion: ICG administered by subserosal injection was comparable to that administered by submucosal injection for lymph node tracing in gastric cancer. However, the former approach imposed a lower economic and mental burden on patients undergoing laparoscopic D2 lymphadenectomy.Trial Registration: ClinicalTrials.gov, NCT04219332 . [ABSTRACT FROM AUTHOR]

Background: The efficacy and benefits of adjuvant chemotherapy (AC) for patients with gastric cancer pT3N0M0 remain controversial. Methods: We prospectively collected and retrospectively analyzed 235 patients with pT3N0M0 gastric cancer who underwent radical resection between February 2010 and January 2016. Patients were divided into two groups: the surgery-alone (SA) group (n = 82) and the AC group (n = 153). We analyzed the effects of AC on the overall survival (OS) and recurrence-free survival (RFS), and the relationship between the number of chemotherapy cycles (CC) and recurrence rate (RR). Results: The 5-year OS and RFS of the participants were 80.9% and 87.7%, respectively, and those in the AC group were significantly higher than those in the SA group (86.9% vs. 69.5%, p = 0.003). The RFS of the AC and SA groups were 88.9% and 85.4%, respectively; the difference was not statistically significant (p = 0.35). The independent risk factors affecting the OS were perineural invasion-positive (PNI+) (HR = 2.64, 95%CI: 1.45–4.82, p = 0.003) and age ≥ 65 years (HR = 2.58, 95%CI: 1.39–4.8, p = 0.003). The independent risk factor affecting the RFS was also PNI+ (HR3.11; 95%CI: 1.48–6.54, p = 0.003). Stratified analysis revealed that postoperative AC can significantly improve the OS of PNI+ patients (AC group versus SA group: 84.1% vs. 45.5%, p = 0.001) and RFS (86.4% vs. 63.6%, p = 0.017). However, perineural invasion negative (PNI-) patients did not show the same results (p = 0.13 and p = 0.48, respectively). According to the number of CC, divided into CC < 3 groups and CC ≥ 3 groups, the cumulative RR in the CC ≥ 3 group of patients with PNI+ was significantly lower than that of the CC < 3 group (7.4% vs. 28.2%, p = 0.037). Conclusion: For pT3N0M0 gastric cancer patients with PNI+, at least three cycles of postoperative AC can significantly reduce the overall RR. This finding should be verified by using large external sample data. [ABSTRACT FROM AUTHOR]

Objective: To validate the prognostic value of tumor regression grading (TRG) and to explore the associated factors of TRG for advanced gastric cancer (AGC) with neoadjuvant chemotherapy (NACT) plus surgery. Methods: Two hundred forty-nine AGC patients treated with NACT followed by gastrectomy at the Mayo Clinic, USA and the Fujian Medical University Union Hospital, China between January 2000 and December 2016 were enrolled in this study. Cox regression was used to identify covariates associated with overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to reveal factors predicting tumor regression grading. Results: For patients with TRG 0-1, the 3- and 5-year OS rates were 85.2% and 74.5%, respectively, when compared to 56.1% and 44.1% in patients with TRG 2 and 28.2% and 23.0% in patients with TRG 3, respectively (p<0.001). TRGs were independent risk factors for OS. Similar findings were observed in RFS. Multivariable analysis revealed that an oxaliplatin-based regimen (p=0.017) was an independent predictor of TRG. The oxaliplatin-based regimen was superior to the nonoxaliplatin-based regimen for OS (38.4 months vs 19.5 months, respectively; p=0.01). Subgroup analyses by histological subtype indicated that the oxaliplatin-based regimen improved the OS in nonsignet ring cell carcinoma compared to the nonoxaliplatin-based regimen (53.7 months vs 19.5 months, respectively; p=0.011). However, similar findings were not observed in RFS. Conclusion: TRG was an independent factor of AGC treated with neoadjuvant chemotherapy plus surgery. Oxaliplatin-based neoadjuvant chemotherapy regimens improve tumor response and may have an overall survival benefit for patients with nonsignet ring cell carcinoma. [ABSTRACT FROM AUTHOR]

Background: Whether the change of the pre- and postoperative systemic inflammatory response (SIR) levels will affect the prognosis of gastric cancer (GC) is unclear. We aimed to investigate the dynamic changes in the pre- and postoperative SIR and their prognostic value for GC. Methods: The clinicopathological data from 2257 patients who underwent radical gastrectomy between January 2009 and December 2014 at Fujian Medical University Union Hospital (FMUUH) were analyzed. Perioperative SIR changes were reported as changes in the lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Results: The SIR levels showed different trends from postoperative months 1 to 12. Multivariate analysis showed that preoperative (pre)-LMR was an independent predictor for the prognosis (P = 0.024). The postoperative 12-month (post-12-month) LMR predicted the 5-year overall survival (OS) rate with the highest accuracy (areas under the curve [AUC] 0.717). Patients were divided into four groups according to the optimal cutoff of the preoperative and post-12-month LMR: high pre-LMR to high postoperative (post)-LMR group, high pre-LMR to low post-LMR group, low pre-LMR to high post-LMR group, and low pre-LMR to low post-LMR group. The survival analysis showed 5-year OS rate was significantly higher in patients with high post-12-month LMR than in patients with low post-12-month LMR, regardless of pre-LMR levels (81.6% vs. 44.2%, P < 0.001). The prognostic accuracy was significantly improved by incorporating the post-12-month LMR in the tumor-node-metastasis (TNM) staging system (P = 0.003). Conclusions: The remeasurement of LMR at post-12-month is helpful in predicting the long-term survival of GC. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have shown that the short-term efficacy of three-dimensional (3D) laparoscopic radical gastrectomy (LG) is comparable to that of two-dimensional (2D)-LG. Whether 3D-LG affects the recurrence patterns of gastric cancer (GC) patients has not been investigated. Methods: From January 2015 to April 2016, a total of 419 patients were recruited for a phase III clinical trial (NCT02327481), which compared the short-term outcomes between the 2D and 3D groups. The long-term efficacy including recurrence patterns was compared between the 2D and 3D groups in this retrospective study. Multivariate analyses were performed to determine whether 3D-LG affects the recurrence patterns. Results: Ultimately, 401 patients were analyzed (197 in the 2D-LG group and 204 in the 3D-LG group), and no differences were observed in the clinicopathological data between the two groups. There were no significant differences between the two groups in the recurrence types, first recurrence time or recurrence-free survival (RFS) (all p > 0.05). According to the 7th American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system, both groups were stratified into pathological stages I, II, and III. The stratified analysis showed no significant differences in RFS or overall survival (OS) among patients in each subgroup (all p > 0.05). The multivariate analysis of RFS showed that tumor diameter, pTNM stage, lymphovascular invasion, and adjuvant chemotherapy were independent factors (all p < 0.05). The multivariate analysis of post-recurrence survival (PRS) showed that adjuvant chemotherapy was an independent protective factor (p = 0.043). Conclusions: 3D-LG for GC did not differ significantly from 2D-LG in the effects on 3-year recurrence patterns, RFS and OS, which provides more tumor-related evidence for 3D technology. And due to the technological similarity, it may have certain reference value for robotic-assisted gastrectomy. Further multicenter, large-scale clinical trials are warranted. [ABSTRACT FROM AUTHOR]

Immunosuppressive molecules are extremely valuable prognostic biomarkers across different cancer types. However, the diversity of different immunosuppressive molecules makes it very difficult to accurately predict clinical outcomes based only on a single immunosuppressive molecule. Here, we establish a comprehensive immune scoring system (ISSGC) based on 6 immunosuppressive ligands (NECTIN2, CEACAM1, HMGB1, SIGLEC6, CD44, and CD155) using the LASSO method to improve prognostic accuracy and provide an additional selection strategy for adjuvant chemotherapy of gastric cancer (GC). The results show that ISSGC is an independent prognostic factor and a supplement of TNM stage for GC patients, and it can improve their prognosis prediction accuracy; in addition, it can distinguish GC patients with better prognosis from those with high prognostic nutritional index score; furthermore, ISSGC can also be used as a tool to select GC patients who would benefit from adjuvant chemotherapy independent of their TNM stages, MSI status and EBV status. Expression patterns of immune checkpoints in patients with gastric cancer remain poorly characterized. Here the authors propose an immune scoring system based on the expression of six immunosuppressive ligands to improve the prognostic accuracy in gastric cancer patients and drive the selection of candidates for adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

To investigate a reasonable lymph node (N) staging system for gastric cancer patients with ≤15 retrieved lymph nodes (LNs). The clinicopathological and follow-up data of patients with ≤15 LNs were obtained from the US Surveillance, Epidemiology, and End Results (SEER) database to analyze the impact of the number of retrieved LNs and metastatic status on the prognosis. In addition, external validation was achieved with data from two medical centers in China. A total of 18,139 gastric cancer patients with 1–15 retrieved LNs from the SEER database were enrolled and randomly divided into the training group and the internal validation group. A new LN staging system, mNr staging (mNr0-4; 5 stages), was established according to the number of retrieved LNs and the metastatic rate. Compared with the TNM and TNrM staging systems (established by Wang J; misclassification rates of 50.4% and 62.5%, respectively), the mTNrM staging system had a lower misclassification rate (23.4%). Furthermore, there was a significant difference in the 5-year overall survival (OS) rate between the mTNrM staging subgroups (p < 0.05); however, no significant difference was found in the 5-year OS rate of partial adjacent stages in the TNM (8th edition) and TNrM (p > 0.05) staging systems. Similar results were obtained in the external validation cohort. Conclusion: mNr and mTNrM staging systems can efficiently distinguish a survival difference in patients who undergo gastrectomy with ≤15 retrieved LNs, with more accurate predictions of the 5-year OS rate of patients compared with the TNM and TNrM staging systems. [ABSTRACT FROM AUTHOR]

Background: The benefit of adjuvant chemotherapy varies widely among patients with stage II/III gastric cancer (GC), and tools predicting outcomes for this patient subset are lacking. We aimed to develop and validate a nomogram to predict recurrence-free survival (RFS) and the benefits of adjuvant chemotherapy after radical resection in patients with stage II/III GC. Methods: Data on patients with stage II/III GC who underwent R0 resection from January 2010 to August 2014 at Fujian Medical University Union Hospital (FMUUH) (n = 1,240; training cohort) were analyzed by Cox regression to identify independent prognostic factors for RFS. A nomogram including these factors was internally and externally validated in FMUUH (n = 306) and a US cohort (n = 111), respectively. Results: The multivariable analysis identified age, differentiation, tumor size, number of examined lymph nodes, pT stage, pN stage, and adjuvant chemotherapy as associated with RFS. A nomogram including the above 7 factors was significantly more accurate in predicting RFS compared with the 8th AJCC-TNM staging system for patients in the training cohort. The risk of peritoneal metastasis was higher and survival after recurrence was significantly worse among patients calculated by the nomogram to be at high risk than those at low risk. The nomogram's predictive performance was confirmed in both the internal and external validation cohorts. Conclusion: A novel nomogram is available as a web-based tool and accurately predicts long-term RFS for GC after radical resection. The tool can also be used to determine the benefit of adjuvant chemotherapy by comparing scores with and without this intervention. [ABSTRACT FROM AUTHOR]

Background: Well-designed retrospective studies (RSs) and small-sample prospective studies (PSs) evaluating the efficacy of interventions have received much attention. This study was designed to evaluate the differences between well-designed RSs and small-sample randomized controlled trials based on the efficacy of laparoscopic distal gastrectomy (LDG) and open distal gastrectomy (ODG) for advanced gastric cancer (GC).Methods: The clinicopathological data of 1360 patients with GC who underwent DG were analysed. After propensity score matching (1:1), 380 cases (ODG = 190, LDG = 190) were finally selected in a RS. Meanwhile, data from 120 patients (ODG = 60, LDG = 60) who enrolled in a PS were analysed.Results: In the PS, the LDG group had less intraoperative blood loss, shorter time to first flatus, and shorter time to fluid diet than the ODG group. In the RS, the LDG group had less intraoperative blood loss, and a shorter postoperative hospital stay than the ODG group. In the PS, the 3-year overall survival (OS) rate was 83.3% in the LDG group and 83.2% in the ODG group (p = 0.877). In the RS, the 3-year OS rate was 68.7% in the LDG group and 66.6% in the ODG group (p = 0.752). No significant interactions were observed between the two groups and any of the variables examined, either in the PS or RS. The recurrence patterns were similar in the two groups. Furthermore, Cox regression analysis showed that surgical method (LDG/ODG) was not a prognostic factor affecting OS or DFS, either prospectively or retrospectively.Conclusions: The oncologic efficacy of laparoscopic and open distal gastrectomy for advanced GC is comparable. Well-designed RSs can be similar to small sample of PSs in assessing long-term oncologic outcomes of surgical interventions, but the short-term outcomes obtained should be treated with caution. [ABSTRACT FROM AUTHOR]

Background and Objective: No specialized prognostic model for patients with gastric cancer with peritoneal metastasis (GCPM) exists for intraoperative clinical decision making. This study aims to establish a new prognostic model to provide individual treatment decisions for patients with GCPM. Method: This retrospective analysis included 324 patients with GCPM diagnosed pathologically by laparoscopy from January 2007 to January 2018 who were randomly assigned to different sets (227 in the training set and 97 in the internal validation set). A nomogram was established from preoperative and intraoperative variables determined by a Cox model. The predictive ability and clinical applicability of the PM nomogram (PMN) were compared with the 15th Japanese Classification of Gastric Carcinoma (JCGC) Staging Guidelines for PM (P1abc). Additional external validation was performed using a dataset (n = 39) from the First Affiliated Hospital of University of Science and Technology of China. Results: The median survival time was 8 (range, 1–90) months. In the training set, each PMN substage had significantly different survival curves (P < 0.001), and the PMN was superior to the P1abc based on the results of time-dependent receiver operating characteristic curve, C-index, Akaike information criterion and likelihood ratio chi-square analyses. In the internal and external validation sets, the PMN was also better than the P1abc in terms of its predictive ability. Of the PMN1 patients, those undergoing palliative resection had better overall survival (OS) than those undergoing exploratory surgery (P < 0.05). Among the patients undergoing exploratory surgery, those who received chemotherapy exhibited better OS than those who did not (P < 0.05). Among the patients who received palliative resection, only PMN1 patients exhibited better OS following chemotherapy (P < 0.05). Conclusion: We developed and validated a simple, specific PM model for patients with GCPM that can predict prognosis well and guide treatment decisions. [ABSTRACT FROM AUTHOR]

The expression pattern and role of circular RNAs (circRNAs) in the pathogenesis of gastric cancer (GC) and their underlying mechanisms remain unresolved. In this study, we identified differentially expressed circRNAs by a circRNA microarray and verified the results by quantitative reverse transcription‐polymerase chain reaction using 117 clinical samples. Cell Counting Kit‐8, wound healing, Transwell, and tumorsphere formation assays were conducted to assess the effects of circ‐CEP85L on cell proliferation and invasion in vitro. Mouse intraperitoneal injection models were used to assess the functions of circ‐CEP85L in vivo. Luciferase reporter assays, fluorescence in situ hybridization, and rescue experiments were performed to elucidate the underlying mechanism of circ‐CEP85L. We found that circ‐CEP85L, which has not been studied in GC, was significantly downregulated in GC tissues and that decreased circ‐CEP85L expression correlated significantly with a worse prognosis. The knockdown of circ‐CEP85L promoted the proliferation and invasion of GC cells, which was reversed by overexpression of circ‐CEP85L. Furthermore, inhibition of circ‐CEP85L promoted tumor growth in vivo. Mechanistically, circ‐CEP85L was confirmed to be a direct target of miR‐942‐5p. In addition, rescue experiments indicated that circ‐CEP85L is able to inhibit the proliferation and invasion of GC cells by sponging miR‐942‐5p. Finally, western blot assays verified that the downregulation of miR‐942‐5p efficiently reversed the inhibition of NFKBIA induced by circ‐CEP85L overexpression. Therefore, we conclude that circ‐CEP85L promotes NFKBIA expression by acting as a sponge of miR‐942‐5p; thus, inhibiting GC proliferation and invasion. circ‐CEP85L is a potential target in the treatment of GC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of three nutritional scoring systems: Prognostic Nutritional Index (PNI), Controlling Nutritional Status (CONUT), and Naples Prognostic Score (NPS) on the short- or long-term prognosis of gastric cancer (GC) patients who underwent radical gastrectomy.Methods: The clinicopathological data of 2182 patients who underwent radical gastrectomy at the Fujian Medical University Union Hospital (FMUUH) from 2009 to 2014 were retrospectively analyzed. The effects of the PNI, CONUT, and NPS on the short- or long-term prognosis of GC patients were analyzed.Results: Overall, 359 (16.5%) patients had postoperative complications. There was no significant association between the PNI, CONUT, and NPS and postoperative complications (P > 0.05); however, high CONUT and NPS were significantly associated with severe postoperative complications (P < 0.05). Univariate analysis showed that PNI, CONUT, and NPS were all associated with overall survival (OS) (P < 0.001). However, multivariate analysis showed that only PNI was an independent risk factor for OS (P = 0.004), and the 5-year OS rate in the low PNI group was significantly lower than that in the normal PNI group (55.5% vs 75.4%, P < 0.05). The area under the curve (AUC) and the c-index of PNI were significantly higher than those of CONUT and NPS. The prognostic efficiency of combining PNI and TNM stage was also significantly better than that of TNM staging alone (P < 0.05).Conclusion: The current study demonstrated that CONUT and NPS are important for assessing the risk of severe postoperative complications. However, PNI is an independent risk factor for the long-term prognosis of GC patients who underwent radical gastrectomy and can improve the prognostic efficiency of TNM staging. [ABSTRACT FROM AUTHOR]

Background: To investigate the prognostic effects and risk factors of the omission and delay of postoperative chemotherapy of stage II/III gastric cancer (GC). Methods: The clinicopathological data of 1,520 patients undergoing radical gastrectomy for stage II/III GC were collected and retrospectively analyzed. We defined the chemotherapy delayed until more than 60 days after radical gastrectomy and the complete omission of chemotherapy as unacceptable chemotherapy initiation (UAC), whereas the chemotherapy conducted within 60 days of radical gastrectomy was defined as acceptable chemotherapy initiation (AC). The survival between the two groups was compared, and the trends and risk factors of UAC were analyzed. Results: There were 539 (35.5%) patients with UAC. The overall survival (OS) and disease-free survival of the UAC group patients were significantly inferior to those in the AC group (p < 0.001). Cox multivariate analysis demonstrated that UAC is an independent predictor of OS (p < 0.05). The OS and disease-free survival of the patients in the UAC group were close to those of the patients without chemotherapy (p > 0.05). Logistic analysis showed that female, old age, a self-paid status, a very low social status, high American Society of Anesthesiologists scores, intra-abdominal surgery history, and serious postoperative complications were independent risk factors of UAC (all p < 0.05). The radar chart shows the risk factors of UAC changed with time. Conclusions: UAC after radical gastrectomy is an independent risk factor for the prognosis of stage II/III GC patients. However, no significant decline of UAC has been achieved recently and should call for the attention of both government and clinicians. [ABSTRACT FROM AUTHOR]

Background: BATF2, also known as SARI, has been implicated in tumor progression. However, its role, underlying mechanisms, and prognostic significance in human gastric cancer (GC) are elusive. Methods: We obtained GC tissues and corresponding normal tissues from 8 patients and identified BATF2 as a downregulated gene via RNA-seq. qRT-PCR and western blotting were applied to examine BATF2 levels in normal and GC tissues. The prognostic value of BATF2 was elucidated using tissue microarray and IHC analyses in two independent GC cohorts. The functional roles and mechanistic insights of BATF2 in GC growth and metastasis were evaluated in vitro and in vivo. Results: BATF2 expression was significantly decreased in GC tissues at both the mRNA and protein level. Multivariate Cox regression analysis revealed that BATF2 was an independent prognostic factor and effective predictor in patients with GC. Low BATF2 expression was remarkably associated with peritoneal recurrence after curative gastrectomy. Moreover, elevated BATF2 expression effectively suppressed GC growth and metastasis in vitro and in vivo. Mechanistically, BATF2 binds to p53 and enhances its protein stability, thereby inhibiting the phosphorylation of ERK. Tissue microarray results indicated that the prognostic value of BATF2 was dependent on ERK activity. In addition, the N6-methyladenosine (m6A) modification of BATF2 mRNA by METTL3 repressed its expression in GC. Conclusions: Collectively, our findings indicate the pivotal role of BATF2 in GC and highlight the regulatory function of the METTL3/BATF2/p53/ERK axis in modulating GC progression, which provides potential prognostic and therapeutic targets for GC treatment. [ABSTRACT FROM AUTHOR]

Background: Many studies have found that use of aspirin can lengthen survival in patients with gastrointestinal cancer. The aim of this study was to assess the survival benefit of aspirin use compared with non-aspirin use for patients with esophageal, gastric or colorectal cancer.Methods: We searched online databases, including PubMed, the Cochrane Library, Embase and www.clinicaltrials.gov for studies that were conducted, before April 30th, 2020, to identify relevant studies. Overall survival and cancer-specific survival of esophageal, gastric and colorectal cancers among aspirin users were compared with those among non-aspirin users. Data extraction and quality evaluation were independently conducted by 2 investigators. A meta-analysis was performed to calculate the pooled risk ratios (RRs) for overall survival and cancer-specific survival by using either a fixed-effects model or a random-effects model.Results: A total of 18 studies were included in this meta-analysis, with more than 74,936 patients. There were no significant differences between postdiagnosis aspirin use and overall survival for esophageal and gastric cancers. For colorectal cancer, a benefit that was associated with postdiagnosis aspirin use was observed for overall survival and cancer-specific survival [HR = 0.83, 95%CI(0.75, 0.9.);HR = 0.78, 95%CI(0.66, 0.92), respectively. However, a prediagnosis of aspirin use did not provide a benefit for overall or cancer-specific survival in colorectal cancer. HR values for overall and cancer-specific survival benefits for colorectal cancer associated with both prediagnosis and postdiagnosis aspirin were as follows: HR = 0.75, 95%CI(0.61, 0.92) and HR = 0.78, 95%CI(0.73, 0.85), respectively. In addition, the survival benefit of postdiagnosis aspirin use appeared to be confined to patients with mutated PIK3CA tumors [HR = 0.78, 95%CI(0.50, 0.99)] and was positive for PTGS2 (COX-2) expression [HR = 0.75, 95%CI(0.43, 1.30)].Conclusions: These findings provide further indications that postdiagnosis aspirin use improves overall survival and cancer-specific survival in colorectal cancer, especially for patients who are positive for PTGS2 (COX-2) expression and PIK3CA-mutated tumors. However, aspirin therapy does not improve overall survival in esophageal and gastric cancers, although the meta-analysis was mainly limited to retrospective studies. [ABSTRACT FROM AUTHOR]

and purpose: For gastric cancer patients with peritoneal metastasis (GCPM), there is no universally accepted prognostic staging system. This study aimed to validate the predictive ability of the 15th peritoneal metastasis staging system (P1abc) of the Japanese Classification of Gastric Carcinoma (JCGC). The data of 309 GCPM patients from July 2007 to July 2017 were retrospectively analyzed. This study compared the prognosis prediction performances of P1abc, the previous JCGC PM staging (P123) and Gilly staging systems. The survival curve revealed a significant difference in overall survival (OS) predicted by P1abc, P123 and Gilly staging (all P < 0.05), and the survival of the two adjacent substages were well distinguished by P1abc but not by P123 and Gilly staging. Both P123 and Gilly staging were substituted with P1abc staging in a 2-step multivariate analysis. The results showed that P1abc staging was superior to both P123 and Gilly staging in its discriminatory ability (C-index), predictive accuracy (AIC) and predictive homogeneity (likelihood ratio chi-square). A stratified analysis by different therapies indicated that for the P1a and P1b patients, OS following palliative resection combined with palliative chemotherapy (PRCPC) was better than that after palliative resection (PR) or palliative chemotherapy (PC) alone (P < 0.05). For the P1c patients, OS after receiving PC was significantly superior to that after receiving PRCPC or PR (P = 0.021). P1abc staging is superior to P123 and Gilly staging in predicting the survival of GCPM patients. Surgeons can provide these patients with appropriate treatment options according to the corresponding substages within P1abc. [ABSTRACT FROM AUTHOR]

Background: Our study investigated the effect of lymph node (LN) noncompliance on the long-term prognosis of patients after laparoscopic total gastrectomy (LTG) and explored the risk factors of LN noncompliance. Methods: The clinicopathological data of gastric cancer (GC) patients who underwent LTG with D2 lymphadenectomy from June 2007 to December 2013 were prospectively collected and retrospectively analyzed. The effects of LN noncompliance on the long-term prognosis of patients with GC after LTG were explored. Results: The overall LN noncompliance rate was 51.9%. The survival rate of patients after LTG with LN compliance was significantly superior to that of patients with LN noncompliance (p = 0.013). The stratified analysis of TNM stage indicated that there was no difference between the OS of stage I patients with LN compliance and those with LN noncompliance; OS of stage II/III patients with LN compliance was significantly better than that of those with LN noncompliance. Cox regression analyses showed that LN noncompliance was an independent risk factor for OS. Logistic regression analysis showed that high BMI (≥ 25 kg/m2) was an independent risk factor for preoperative prediction of LN noncompliance in cStage II/III patients. Patients with a high BMI were more likely to have LN noncompliance during surgery, especially during the dissections of #6, #8a, and #12a LN stations. Conclusions: LN noncompliance was an independent risk factor for poor prognosis in patients with advanced gastric cancer (AGC) after LTG. Patients with high BMI were more likely to have LN noncompliance, especially during the dissections of #6, #8a, and #12a LN stations. LN tracing was recommended for these patients to reduce the rate of LN noncompliance. [ABSTRACT FROM AUTHOR]

Background: We sought to investigate the prognostic value of complete blood count (CBC)-based biomarkers for patients with resectable gastric cancer (GC).Methods: Patients with GC who underwent primary surgical resection between December 2008 and December 2013 were included. The estimated area under the curve (AUC) and multivariate Cox regression models were used to identify the best CBC-based biomarker. Time-dependent receiver operating characteristic (t-ROC) curve analysis was used to predict overall survival and compare the prognostic impact.Results: In the 1810 patients analyzed, the median follow-up period was 51.0 months (range 1-101 months). Based on multivariate analysis, the lymphocyte-monocyte ratio (LMR) and hemoglobin (Hb) level were independent prognostic factors (both P < 0.05). Based on the LMR and Hb level, we established the CBC-based inflammatory score (CBCS). A higher CBCS was associated with older age, female sex, higher American Society of Anesthesiologists (ASA) score, proximal tumor location, larger tumor size, later stage and vascular involvement (all P < 0.05). Univariate analyses showed that a higher CBCS was also associated with worse overall survival (OS), which was consistent in each stage (all P < 0.05). Multivariate analysis revealed that the CBCS was a significant independent biomarker (P < 0.05). The AUC for the CBCS (0.627) was significantly higher than the AUCs for the LMR (0.573) and Hb level (0.605) (both P < 0.05). Furthermore, the t-ROC curve of the CBCS was superior to that of the prognostic nutritional index (PNI), systemic immune-inflammation index (SII), modified Glasgow prognostic score (mGPS) and C-reactive protein/albumin ratio (CRP/Alb) throughout the observation period.Conclusion: The preoperative LMR and Hb level were optimal CBC-based biomarkers for predicting OS in GC patients after curative resection. Based on the LMR and Hb, we developed a novel and easily obtainable prognostic score called the CBCS, which may improve the prediction of clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Increasing number of clinical studies have shown that laparoscopic distal gastrectomy (LDG) with D2 lymph node (LN) dissection is an effective method for the treatment of advanced gastric cancer (AGC). However, reports on the technical feasibility and oncology efficacy of laparoscopic total gastrectomy (LTG) in the treatment of AGC are rare. Methods: A retrospective analysis of the clinicopathologic data of 1313 patients with clinical stage of cT2-4aN0-3M0 undergoing laparoscopic radical gastrectomy with D2 LN dissection from June 2007 to December 2013 was performed. Noncompliance was defined as patients with more than one LN station absence as described in the protocol for D2 lymphadenectomy in the Japanese Gastric Cancer Association (JGCA). According to the literature, it was subdivided into LN compliance group (all LN stations were detected), minor LN noncompliance group (1–2 LN stations were not detected), major LN noncompliance group (more than 2 LN stations were not detected). Based on the LN noncompliance, the surgical indications of LTG were analyzed with LDG as control. Results: Among the 1313 patients, 197 (39.20%) patients and 321(39.71%) patients in the LDG group and the LTG group had minor LN noncompliance, 59(11.70%) patients and 163(20.10%) patients had major LN noncompliance. The difference in the extent of LN noncompliance between the two groups was statistically significant (p < 0.001). COX proportional hazards regression analysis elucidated that the LN noncompliance was an independent prognostic factor for overall survival (OS). BMI ≥ 25 kg/m2 and the history of previous abdominal surgery (PAS) were independent risk factors for major LN noncompliance in LTG group (p < 0.05), with which patients were defined as a LN noncompliance high-risk group. With the exception of LN noncompliance high-risk group, the difference in the extent of LN noncompliance between LTG group and LDG group was still statistically significant (p = 0.008). Tumor diameter > 60 mm is a preoperative risk factor for station #5 LN noncompliance, and no preoperative risk factors for station #6 LN noncompliance were found, with which patients were defined as LN noncompliance middle-risk group. Conclusion: LN noncompliance is an independent prognostic factor for poor prognosis in patients after LTG. Based on this finding, patients with BMI ≥ 25 kg/m2, history of PAS and tumor diameter > 60 mm in the advanced stage of upper-middle gastric cancer represent high/middle-risk groups with LN noncompliance in LTG surgery, which should be carefully selected. [ABSTRACT FROM AUTHOR]

To examine the associations of the Age-Adjusted Charlson Comorbidity Index (ACCI) and preoperative systemic inflammation with survival in gastric cancer (GC) patients who underwent radical gastrectomy. Data from patients with GC who underwent radical gastrectomy between January 2009 and December 2014 in Fujian Medical University Union Hospital were retrospectively analyzed. Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors. The relationship between the ACCI and systemic inflammation of the patients was explored, and the prognostic value of a new scoring system based on the ACCI and systemic inflammation (ANLR) was evaluated. A total of 2257 patients with GC were included. The ACCI and neutrophil to lymphocyte ratio (NLR) were independent prognostic factors for overall survival (both P < 0.001) by multivariate analysis. A higher ACCI was an independent predictor of the increase in preoperative NLR (P < 0.001). Based on the preoperative ACCI and NLR, we established a novel marker, ANLR. Multivariate analysis showed that the ANLR was a significant independent predictor of 5-year OS (P < 0.001). The Harrell's C-statistics (C-index) of a model combining the ANLR and pTNM was 0.744 (95% CI: 0.728–0.760), which was significantly higher than the pTNM stage (0.717, 95% CI: 0.702–0.731; P < 0.001). The ACCI of patients with gastric cancer was associated with preoperative systemic inflammation. The ACCI combined with the NLR, which are commonly collected biomarkers, could enhance prognostication for GC patients. [ABSTRACT FROM AUTHOR]

To investigate the factors related to positive surgical margins of gastric cancer and their correlation with the prognosis of these patients. The clinicopathological data of gastric cancer patients undergoing gastrectomy were collected, and the relationship between surgical margins status and patient outcome was analyzed. A total of 10080 patients were included, among which 311 (3.1%) had positive surgical margins. pT3-4, pN+ and M1 were independent risk factors for positive margins, and a tumor in the middle of the stomach was a protective factor (p < 0.05). The 5-year overall survival (OS) rates of the patients with positive and negative margins after propensity score matching (PSM) were 24.2% and 36.8%, respectively (p < 0.001). For M0 patients, the 5-year OS of the margin-positive patients was lower than that of the margin-negative patients, and was higher than that of patients with M1. For the M1 patients, no statistically significant difference in 5-year OS was noted between patients with positive and negative margins. Age, positive margins, tumor location, pN+, and M1 were independent prognostic factors for OS in patients undergoing gastrectomy, and pN2-3 and M1 stages were independent prognostic factors for patients with positive surgical margins. Postoperative chemotherapy could improve the 5-year OS in pN2-3 and M1 margin-positive patients (p < 0.05). The prognosis of M0 gastric cancer patients with positive surgical margins is poor, and it is recommended that these patients should undergo routine intraoperative frozen-section pathological examination to reduce the risk of positive surgical margins. [ABSTRACT FROM AUTHOR]

Previous studies have elucidated that on average, long-term cancer survivors have better prognoses than newly diagnosed individuals. This study aimed to devise a nomogram to predict the conditional probability of cancer-specific survival (CPCS) in gastric cancer (GC) patients after D2 lymphadenectomy. Clinicopathological data for 2,596 GC patients who underwent D2 lymphadenectomy in an Eastern institution (the training cohort) were retrospectively analysed. Cancer-specific survival (CSS) was predicted using Cox regression models. A nomogram was constructed to predict CPCS at 3 and 5 years post-gastrectomy. Two external validations were performed using a cohort of 2,198 Chinese patients and a cohort of 504 Italian patients. In the training cohort, the 5-year CPCS was 59.2% immediately post-gastrectomy and increased to 68.8%, 79.7%, and 88.8% at 1, 2, and 3 years post-gastrectomy, respectively. Multivariate Cox regression analyses showed that age; tumour site, size and invasion depth; numbers of examined and metastatic lymph nodes; and surgical margins were independent prognostic factors of CSS (all P < 0.05) and formed the nomogram predictor variables. Internal validation showed that the conditional nomogram exhibited good discrimination ability at 3 and 5 years post-gastrectomy (concordance index, 0.794 and 0.789, respectively). External validation showed a 3- and 5-year concordance index of 0.788 and 0.785, respectively, in the Chinese cohort, and 0.792 and 0.787, respectively, in the Italian cohort. Calibration of the nomogram predicted that survival corresponded closely with actual survival. Conclusions: we developed a robust nomogram to predict CPCS after D2 lymphadenectomy for GC based on survival duration. [ABSTRACT FROM AUTHOR]

Background: Three-dimensional (3D) systems for laparoscopy provide surgeons with additional information on spatial depth not found in two-dimensional (2D) systems.Methods: This study enrolled 156 spleen-preserving splenic hilar lymphadenectomy (LSPSHL) patients in a randomized controlled trial (ClinicalTrials.gov Identifier NCT02327481) at the department of gastric surgery at Fujian Medical University Union Hospital between January 2015 and April 2016. The short-term efficacies were compared between the treatment groups. The unedited videos of 80 LSPSHL (40 procedures each for 3D and 2D) were rated for technical performance using the Generic Error Rating Tool.Results: The data for 156 LSPSHL patients indicate that the estimated blood loss (EBL) (3D vs 2D = 66.3 vs. 99.0, P = 0.046) was significantly less in the 3D group. The postoperative recovery and complication rates were similar (P > 0.05). And there were no deaths within 30 days of surgery. Two observers analyzed 80 videos of LSPSHL. The results showed that there were fewer grasping-errors made in the 3D group than in the 2D group when dissecting the inferior pole region of spleen (IPRS) (P = 0.016) and the superior pole region of spleen (SPRS) (P = 0.022). Additionally, the inter-rater reliability was high regarding grasping-errors in the IPRS (intraclass correlation coefficient (ICC) 0.92) and in the SPRS (ICC 0.83). The ICC for the total number of errors was 0.82. The mean of errors in the 3D group (3D vs. 2D = 20.7 vs. 23.5, P = 0.022) was less than the 2D group.Conclusions: Compared with 2D LSPSHL, 3D technology reduces EBL and technical errors during splenic hilar dissection. [ABSTRACT FROM AUTHOR]

To identify the risk factors for intraoperative laparoscopic hemostasis during laparoscopic spleen-preserving splenic hilar lymph node dissection (LSPSD) for proximal gastric cancer (GC) and to develop and validate a model to estimate the risk of intraoperative laparoscopic hemostasis. Between January 2011 and December 2014, we prospectively collected and retrospectively analyzed the medical records of 398 patients with proximal GC who underwent LSPSD. The data were split 75/25, with one group used for model development and the other for validation testing. Of the 398 patients enrolled in this study, 174 (43.7%) required laparoscopic hemostasis treatment. A multivariate analysis determined that the risk factors for the model group were gender, preoperative N stage, and terminal branches of the splenic artery (SpA), and each factor contributed 1 point to the risk score. The intraoperative laparoscopic hemostasis rates were 11.5%, 33.6%, 58.5%, and 73.5% for the low-, intermediate-, high-, and extremely high-risk categories, respectively (p < 0.001). Blood loss volume (BLV) and operative time (in min) for LSPSD increased significantly (p < 0.001) as the risk increased. The area under the receiver operating characteristic curve for the intraoperative laparoscopic hemostasis score was 0.700. The observed and predicted incidence rates were parallel for intraoperative laparoscopic hemostasis in the validation set. This simple, efficient scoring system using the factors for gender, preoperative N stage, and terminal SpA branches can accurately predict the risk of intraoperative laparoscopic hemostasis during LSPSD to improve surgical safety. • This simple efficient scoring system using the factors of gender, preoperative N stage, and terminal branches of the SpA could accurately predict the risk factors of intraoperative laparoscopic hemostasis during LSPSD to improve surgical safety. [ABSTRACT FROM AUTHOR]

Objective. Circular RNAs (circRNAs) have been reported to be widely involved in pathological processes of various cancers. However, little is known about their diagnostic values in early gastric cancer (EGC). This study is aimed at exploring whether circulating circRNAs in plasma could act as biomarkers for EGC diagnosis. Materials and Methods. Mass spectrometry (MS) was performed to identify the proteins that at significantly aberrantly levels in gastric cancer (GC) tissues. The target circRNA was identified by bioinformatics analysis. A receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic utility. Results. MS revealed that the ribosomal protein L6 (RPL6) expression was significantly downregulated only in EGC tissues vs. nontumorous tissues; this was validated by western blotting (n=30, p=0.0094). Bioinformatics analysis predicted that there is a hsa_circ_0006848/hsa_miR-329-5p/RPL6 axis in GC progression. The hsa_circ_0006848 expression was significantly downregulated in EGC tissues (vs. nontumorous tissues, n=30, p=0.0073) and plasma samples from EGC patients (vs. paired healthy volunteers, n=30, p=0.0089). In addition, the hsa_circ_0006848 plasma level in postoperative patients was significantly higher than that of preoperative patients (n=30, p=0.047). Furthermore, the decreased hsa_circ_0006848 expression in plasma was negatively correlated with poor differentiation (p=0.037) and tumor size (p=0.046). The area under the ROC curve (AUC) of hsa_circ_0006848 in plasma was 0.733, suggesting a good diagnostic value. The plasma hsa_circ_0006848 level combined with the carcinoembryonic antigen (CEA), carbohydrate-associated antigen 19-9 (CA19-9), and carbohydrate-associated antigen 72-4 (CA72-4) level increased the AUC to 0.825. Conclusion. Our results indicated that plasma hsa_circ_0006848 may be a novel noninvasive biomarker in EGC diagnosis. [ABSTRACT FROM AUTHOR]

Background: The definition and predictors of early recurrence (ER) for gastric cancer (GC) patients after radical gastrectomy are unclear. Methods: A minimum-p value approach was used to evaluate the optimal cutoff value of recurrence-free survival to determine ER and late recurrence (LR). Receiver operating characteristic curves were generated for inflammatory indices. Potential risk factors for ER were assessed with a Cox regression model. A decision curve analysis was performed to evaluate the clinical utility. Results: A total of 401 patients recruited in a clinical trial (NCT02327481) from January 2015 to April 2016 were included in this study. The optimal length of recurrence-free survival to distinguish between ER (n = 44) and LR (n = 52) was 12 months. Factors associated with ER included a preoperative C-reactive protein–albumin ratio (CAR) ≥ 0.131, stage III and postoperative adjuvant chemotherapy (PAC) > 3 cycles. The risk model consisting of both the CAR and TNM stage had a higher predictive ability and better clinical utility than TNM stage alone. Further stratification analysis of the stage III patients found that for the patients with a CAR < 0.131, both PAC with 1–3 cycles (p = 0.029) and > 3 cycles (p < 0.001) could reduce the risk of ER. However, for patients with a CAR ≥ 0.131, a benefit was observed only if they received PAC > 3 cycles (54.2% vs 16.0%, p = 0.004), rather than 1–3 cycles (58.3% vs 54.2%, p = 0.824). Conclusions: A recurrence-free interval of 12 months was found to be the optimal threshold for differentiating between ER and LR. Preoperative CAR was a promising predictor of ER and PAC response. PAC with 1–3 cycles may not exert a protective effect against ER for stage III GC patients with CAR ≥ 0.131. [ABSTRACT FROM AUTHOR]

Background: There is a lack of data on the effect of high postoperative body temperature on disease-free survival (DFS) in patients who underwent radical gastrectomy. Methods: Patients who underwent radical gastrectomy from January 2006 to December 2011 were selected. The highest body temperature within 1 week after operation was used to establish diagnostic thresholds for high and low body temperature through X-tile software. Results: A total of 1396 patients were included in the analysis. The diagnostic threshold for high body temperature was defined as 38 °C; 370 patients were allocated to the high-temperature group (HTG), while another 1026 patients were allocated to the low-temperature group (LTG). For all patients, survival analysis showed that 5-year DFS in the HTG was significantly lower than that for the LTG (55.6% vs 63.9%, P = 0.007). Multivariate analysis revealed that high postoperative body temperature was an independent prognostic risk factor for 5-year DFS (HR = 1.288 (1.067–1.555), P = 0.008). For patients without complications, survival analysis showed that the 5-year DFS rate in the HTG was lower than that for the LTG (57.5% vs 64.4%, P = 0.051), especially in patients with stage III gastric cancer (31.3% vs 41.7%, P = 0.037). For patients with complications or infectious complications, there were no significant differences between the HTG and LTG regarding 5-year DFS (49.3% vs 58.2%, P = 0.23 and 49.4% vs 55.1%, P = 0.481, respectively). Conclusion: For stage III gastric cancer patients without complications, high postoperative body temperature can significantly reduce the 5-year DFS. These patients may benefit from more aggressive adjuvant therapy and postoperative surveillance regimens. [ABSTRACT FROM AUTHOR]

Background: The metro-ticket prognostic tool for hepatocellular carcinoma has been proven to predict outcome, but a similar concept has not been investigated for GC. The objective of the current study was to apply the principles of the metro-ticket paradigm to develop a novel TNM staging system (nTNM) for gastric cancer (GC). Methods: The nTNM considered the distance from the origin on a Cartesian plane incorporating the pN (x-axis) and pT (y-axis) stages. GC patients undergoing radical resection at Fujian Medical University Union Hospital (FMUUH) (n = 4267) were included. The nTNM was validated using 2 external cohorts from the Sun Yat-sen University Cancer Center (SYSUCC) (n = 1800) and Surveillance, Epidemiology, and End Results (SEER) (n = 3227) databases. Results: nTNM classes with the same distance from the origin have same stage; the stage increases with this distance. Among all patients, 48.0% (n = 2049) were restaged in the nTNM compared with the 7th edition of the AJCC-TNM classification; 26.2% (n = 1116) were downstaged in the nTNM compared with the 8th edition. The nTNM provides significant survival differences between stages (all P < 0.001). The survival difference between stages IB and IIA was especially large for the nTNM (P < 0.001) compared to the 7th and 8th editions (P = 0.073). The concordance index and hazard ratio increased successively with the nTNM stage. Similar findings were observed in both external cohorts. Conclusion: Compared with the AJCC-TNM classification, the nTNM for GC is easier to remember and provides some improvements; therefore, the nTNM may be considered for adoption in future editions of the AJCC-TNM classification. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the prognostic value of the eighth AJCC TNM staging classification for patients with gastric cancer who had already survived for 5 years. Patients who underwent radical gastrectomy at a large eastern center were considered. The prognostic value of staging systems were assessed and compared. Additional external validation was performed using a dataset from the Surveillance, Epidemiology, and End Result (SEER) database. The 5-year overall survival (OS) rate for patients in the training set was 59.4%. With the prolongation of the survival time after surgery, the 5-year OS improved significantly (P < 0.05). However, there were no significant differences in survival curves among patients who have survived 5 years after surgery. The AUC and χ2 of the eighth AJCC classification for predicting of 5-year OS decreased gradually after surgery and appeared stable after 5 years. For patients who survived 5 years after surgery, we constructed a new TNM staging system (nTNM) according to the survival curves of T stage and N stage. A 2-step multivariate analysis showed that nTNM, age and sex were independent prognostic factors. The nTNM demonstrated superior prognostic stratification, with higher c-statistic and likelihood ratio chi-square scores and lower AIC values than those of the AJCC classification. Similar results were observed in the external validation set. The nTNM predicted an additional survival more accurately than did the AJCC classification for patients who have survived 5 years after surgery; this may guide decisions regarding surveillance. [ABSTRACT FROM AUTHOR]

Background: Whether the tumor‐node‐metastasis (TNM) staging system is appropriate for patients with node‐negative gastric cancer (GC) is still inconclusive. The modified staging system developed by recursive partitioning analysis (RPA) showed good prognostic performance in a variety of cancers. The application of RPA has not been reported in the prognostic prediction of GC. Methods: Node‐negative GC patients who underwent radical resection at Fujian Medical University Union Hospital (n = 862) and Sun Yat‐sen University Cancer Center (n = 311) with at least 5 years of follow‐up were selected as the training set. RPA was used to develop a modified staging system. Patients from the Surveillance, Epidemiology, and End Results database (n = 1415) were selected as the validation set. Results: The 5‐year overall survival (OS) rates of patients with 8th AJCC‐TNM stage IA‐IIIA in the training set were IA 95.2%, IB 87.1%, IIA 78.3%, IIB 75.8%, and IIIA 72.6%. Multivariate analysis (MVA) showed that larger tumor size, elder age, and deeper depth of invasion were independent predictors for OS in patients with node‐negative GC (all P < 0.05). Patients were reclassified into RPA I, RPA II, RPA III, and RPA IV stages based on RPA; the 5‐year OS rates were 96.1%, 87.2%, 81.0%, and 64.3%, respectively, with significant difference (P < 0.05). Two‐step MVA showed that the RPA staging system was an independent predictor of OS (P < 0.05). Compared with the 8th AJCC‐TNM staging system, the RPA staging system had a smaller AIC value (2544.9 vs 2576.2), higher χ2 score (104.2 vs 69.6) and higher Harrell's C‐index (0.697 vs 0.669, P = 0.007). The similar results were found in the validation set. Conclusions: A new prognostic predictive system based on RPA was successfully developed and validated, which may be suggested for staging node‐negative GC in future. [ABSTRACT FROM AUTHOR]

Background: Serum prealbumin (PALB) can predict the prognosis of patients with gastric cancer (GC). However, the prognostic value of combination of C-reactive protein and PALB (CRP/PALB) remains unclear. Methods: A total of 419 gastric cancer patients included in a clinical trial (NCT02327481) were analyzed. The present study is a substudy of the trial. Receiver operating characteristic (ROC) curves were generated, and by calculating the areas under the curve (AUC) and the C-index, the discriminative ability of each inflammatory index was compared, including CRP/PALB, C-reactive protein/albumin, Glasgow prognostic score (GPS), modified GPS, systemic immune-inflammation index, neutrophil–lymphocyte ratio, and platelet–lymphocyte ratio. Results: Ultimately, 401 patients were included in this study. The optimal cutoff value of CRP/PALB was 17.7. According to this cutoff point, the entire sample was divided into a CRP/PALB < 17.7 (LCP) group and a CRP/PALB ≥ 17.7 (HCP) group, comprising 245 and 156 patients, respectively. There were 54 and 22 patients experienced recurrence in the HCP and LCP group, respectively, p < 0.001. Compared with traditional inflammatory indices, CRP/PALB had the highest AUC (0.707) and C-index (0.716), all p < 0.05. The post-recurrence survival (PRS) of patients in the HCP group was significantly shorter than that in the LCP group (p = 0.010), especially for pathological stage III patients (p = 0.015) or patients with distant (p = 0.018) or local (p = 0.023) recurrences. Conclusions: The predictive value of preoperative CRP/PALB for the recurrence of GC is significantly better than traditional inflammatory indices. HCP significantly reduces the PRS, especially for pathological stage III patients or patients with distant or local recurrences. [ABSTRACT FROM AUTHOR]