Search

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]

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: Sarcopenic obesity may affect the health outcome of people with obesity after laparoscopic sleeve gastrectomy (LSG). To assess the impact of sarcopenic obesity (SO) on weight loss outcomes and improvement of quality of life after LSG. Materials and Methods: This observational study included patients who underwent LSG with SO (99 patients) or without SO (146 patients) from a single center. The primary endpoint was weight loss and disease-specific quality of life in patients with or without SO after the operation. Fat-free mass (FFM) and fat mass (FM) were calculated based on the L3-level images of preoperative CT scans. SO was diagnosed if FM/FFM ≥ 0.80. Results: Operative time and postoperative hospital stay days were longer in the SO group (p < 0.001). After LSG, weight, BMI, and EBMI were significantly lower in the NSO group than in the SO group (all P < 0.05), while %EWL and the number of patients with %EWL ≥ 100% were significantly lower in the SO group (both p < 0.05). The total BAROS scores of patients in the NSO group were higher than those in the SO group (p < 0.05). Additionally, the MA II questionnaire assessment showed a lower percentage of "very good" and "good" outcomes in the SO group (p < 0.05). Conclusions: Patients with SO take a slower rate, longer time to reach the ideal weight, and lower quality of life self-ratings than NSO patients after LSG. Thus, preoperative evaluation and tailoring rehabilitation guidance for people with SO should be accounted. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of preoperative sarcopenia on the short-term and long-term outcomes in older patients with locally advanced gastric cancer (LAGC). Methods: Clinicopathological data of older patients with LAGC who underwent radical surgery were retrospectively analyzed. Sarcopenia was defined as a skeletal muscle index of less than 36.4 cm2/m2 for men and less than 28.4 cm2/m2 for women. Comparing the postoperative complications and survival between sarcopenia and non-sarcopenia groups using multicenter data. Results: A total of 406 older patients with LAGC were included in the analysis, including 145 (35.7%) with sarcopenia and 261 (64.3%) with non-sarcopenia. Multivariate logistic regression analysis showed that sarcopenia was an independent risk factor for postoperative complications with CD grade ≥ II (OR 1.616; P < 0.05). Kaplan–Meier survival curve analysis showed that the 5-year overall survival (OS) and 5-year recurrence-free survival (RFS) in the sarcopenia group were lower than those in the non-sarcopenia group (P both < 0.05). Multivariate Cox regression analyses showed that sarcopenia was an independent prognostic factor for 5-year OS and RFS (P both < 0.05). The 5-year recurrence rate in the sarcopenia group was 57.2%, which was significantly higher than that in the non-sarcopenia group (46.4%; P = 0.036). Recurrence pattern analysis showed that the incidence of distant metastases in patients with sarcopenia (42.8%) was significantly higher than non-sarcopenia (31.4%; P = 0.022). Conclusion: Sarcopenia serves as a valuable predictor of both short-term and long-term outcomes in older patients with LAGC. Therefore, the significance of assessing preoperative nutritional status and implementing thorough postoperative follow-up for older LAGC patients with sarcopenia should be emphasized. [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]

Importance: It is largely unclear whether robotic distal gastrectomy (RDG) is cost-effective for locally advanced gastric cancer (LAGC). Objective: To evaluate the cost-effectiveness of RDG, laparoscopic distal gastrectomy (LDG), and open distal gastrectomy (ODG) for patients with LAGC. Design, setting, and participants: Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. A decision-analytic model was constructed to evaluate the cost-effectiveness of RDG, LDG, and ODG. Exposures: RDG, LDG, and ODG. Main outcomes and measures: Incremental cost-effectiveness ratio (ICER) and quality-adjusted life year (QALY). Results: This pooled analysis of two randomized controlled trials included 449 patients: 117, 254, and 78 patients in the RDG, LDG, and ODG groups, respectively. After IPTW, RDG demonstrated its priority in terms of less blood loss, postoperative length, and complication rate (all P < 0.05). RDG also showed higher QOL with more cost, representing an ICER of $85,739.73 per QALY and $42,189.53 per QALY compared to LDG and ODG, respectively. In probabilistic sensitivity analysis, RDG achieved the best cost-effectiveness for patients with LAGC only when the willingness-to-pay threshold was > $85,739.73 per QALY, which significantly exceeded 3 times Chinese per capita GDP. Furthermore, one of the most important factors was the indirect costs of robotic surgery in terms of the cost-effectiveness of RDG compared to that of LDG or ODG. Conclusions and relevance: Although improved short-term outcomes and QOL were seen in patients underwent RDG, the economic burden should be considered in the clinical decision-making regarding robotic surgery use for patients with LAGC. Our findings may vary in different health care settings and affordability. Trial registration CLASS-01 trial (ClinicalTrials.gov, CT01609309) and FUGES-011 trial (ClinicalTrials.gov, NCT03313700). [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]

Objective: To investigate the effect of intraoperative lymph node (LN) dissection and postoperative adjuvant chemotherapy on the overall survival (OS) of gastric cancer (GC) patients and their reciprocity. Methods: LN noncompliance was defined as the absence of more than one LN station, as described in the protocol for D2 lymphadenectomy in the Japanese Gastric Cancer Association. The definition of adjuvant chemotherapy (AC) noncompliance was that the chemotherapy planned dose does not meet the requirements. Results: Kaplan–Meier survival curves showed that the OS of patients with major LN noncompliance was significantly lower than that of patients with nonmajor LN noncompliance, and the OS of AC noncompliance patients was significantly lower than that of AC compliance patients. If there was nonmajor LN noncompliance during surgery, the OS of patients with AC compliance was significantly higher than that of patients with AC noncompliance (P = 0.035). In the case of major LN noncompliance during surgery, there was no statistically significant difference in OS between those with AC compliance and those with AC noncompliance (P = 0.682). Multivariate Cox regression analysis including AC noncompliance indicated that major LN noncompliance was an independent prognostic factor for poor OS (P = 0.012), while AC noncompliance was not an independent prognostic factor for OS (P = 0.609). Conclusion: Adequate lymph node dissection and adjuvant chemotherapy are both key steps to improve the awful prognosis of GC patients. Adjuvant chemotherapy may fail to remedy the poor prognosis caused by major LN noncompliance. [ABSTRACT FROM AUTHOR]

Background: Robotic surgery may be advantageous for complex surgery. We aimed to compare the intraoperative and postoperative short-term outcomes of spleen-preserving splenic hilar lymphadenectomy (SPSHL) during robotic and laparoscopic total gastrectomy. Methods: From July 2016 to December 2020, the clinicopathological data of 115 patients who underwent robotic total gastrectomy combined with robotic SPSHL (RSPSHL) and 697 patients who underwent laparoscopic total gastrectomy combined with laparoscopic SPSHL (LSPSHL) were retrospectively analyzed. A 1:2 ratio propensity score matching (PSM) was used to balance the differences between the two groups to compare their outcomes. The Generic Error Rating Tool was used to evaluate the technical performance. Results: After PSM, the baseline preoperative characteristics of the 115 patients in the RSPSHL and 230 patients in the LSPSHL groups were balanced. The dissection time of the region of the splenic artery trunk (5.4 ± 1.9 min vs. 7.8 ± 3.6 min, P < 0.001), the estimated blood loss during SPSHL (9.6 ± 4.8 ml vs. 14.9 ± 7.8 ml, P < 0.001), and the average number of intraoperative technical errors during SPSHL (15.1 ± 3.4 times/case vs. 20.7 ± 4.3 times/case, P < 0.001) were significantly lower in the RSPSHL group than in the LSPSHL group. The RSPSHL group showed higher dissection rates of No. 10 (78.3% vs. 70.0%, P = 0.104) and No. 11d (54.8% vs. 40.4%, P = 0.012) lymph nodes and significantly improved postoperative recovery results in terms of times to ambulation, first flatus, and first intake (P < 0.05). The splenectomy rates of the two groups were similar (1.7% vs. 0.4%, P = 0.539), and there was no significant difference in morbidity and mortality within postoperative 30 days (13.0% vs. 15.2%, P = 0.589). Conclusion: Compared to LSPSHL, RSPSHL has more advantages in terms of surgical qualities and postoperative recovery process with similar morbidity and mortality. For complex SPSHL, robotic surgery may be a better choice. [ABSTRACT FROM AUTHOR]

Objective: There is insufficient evidence to evaluate the long-term outcomes of robotic radical gastrectomy. The aim of this study was to compare the radical results and long-term outcomes of robotic and laparoscopic radical gastrectomy. Methods: We prospectively collected and retrospectively analyzed the general clinicopathological data of gastric cancer patients treated with robotic radical gastrectomy (RG) and laparoscopic radical gastrectomy (LG) from July 2016 to July 2018 at Fujian Medical University Union Hospital. The RG cohort was matched 1:3 with the LG cohort by using propensity score matching (PSM). The primary endpoints of the study were 3-year overall survival (OS) and 3-year relapse-free survival (RFS). Results: The study included 221 patients treated with RG and 1106 patients treated with LG for gastric cancer. After PSM, 211 patients were included in the RG cohort, and 663 patients were included in the LG cohort. The 3-year OS rate was 81.0% in the robotic cohort and 79.3% in the laparoscopic cohort (log-rank test, P = 0.516). The 3-year RFS rate was 78.7% in the robotic cohort and 75.6% in the laparoscopic cohort (log-rank test, P = 0.600). In the subgroup analyses, no significant differences were noted between the RG and LG cohorts in terms of 3-year OS and 3-year RFS (all P > 0.05). The therapeutic value index of each lymph node station dissection in the robotic cohort was comparable to that in the laparoscopic cohort. Conclusion: Robotic radical gastrectomy can achieve radical results and long-term outcomes comparable to laparoscopic surgery, and further multicenter prospective studies can be conducted to assess the clinical efficacy of robotic radical gastrectomy. [ABSTRACT FROM AUTHOR]

Background: The tumor immunosuppressive microenvironment can influence treatment response and outcomes. A previously validated immunosuppression scoring system (ISS) assesses multiple immune checkpoints in gastric cancer (GC) using tissue-based assays. We aimed to develop a radiological signature for non-invasive assessment of ISS and treatment outcomes. Methods: A total of 642 patients with resectable GC from three centers were divided into four cohorts. Radiomic features were extracted from portal venous–phase CT images of GC. A radiomic signature for predicting ISS (RISS) was constructed using the least absolute shrinkage and selection operator (LASSO) regression method. Moreover, we investigated the value of the RISS in predicting survival and chemotherapy response. Results: The RISS, which consisted of 10 selected features, showed good discrimination of immunosuppressive status in three independent cohorts (area under the curve = 0.840, 0.809, and 0.843, respectively). Multivariate analysis revealed that the RISS was an independent prognostic factor for both disease-free survival (DFS) and overall survival (OS) in all cohorts (all p < 0.05). Further analysis revealed that stage II and III GC patients with low RISS exhibited a favorable response to adjuvant chemotherapy (OS: hazard ratio [HR] 0.407, 95% confidence interval [CI] 0.284–0.584); DFS: HR 0.395, 95% CI 0.275–0.568). Furthermore, the RISS could predict prognosis and select stage II and III GC patients who could benefit from adjuvant chemotherapy independent of microsatellite instability status and Epstein–Barr virus status. Conclusion: The new, non-invasive radiomic signature could effectively predict the immunosuppressive status and prognosis of GC. Moreover, the RISS could help identify stage II and III GC patients most likely to benefit from adjuvant chemotherapy and avoid overtreatment. [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: Neuroinflammation is thought to be a cause of Alzheimer's disease (AD), which is partly caused by inadequate mitophagy. As a receptor of mitophagy, we aimed to reveal the regulatory roles of optineurin (OPTN) on neuroinflammation in the pathogenesis of AD.Methods: BV2 cells and APP/PS1 transgenic (Tg) mice were used as in vitro and in vivo experimental models to determine the regulatory roles of OPTN in neuroinflammation of AD. Sophisticated molecular technologies including quantitative (q) RT-PCR, western blot, enzyme linked immunosorbent assay (ELISA), co-immunoprecipitation (Co-IP) and immunofluorescence (IF) were employed to reveal the inherent mechanisms.Results: As a consequence, key roles of OPTN in regulating neuroinflammation were identified by depressing the activity of absent in melanoma 2 (AIM2) inflammasomes and receptor interacting serine/threonine kinase 1 (RIPK1)-mediated NF-κB inflammatory mechanisms. In detail, we found that expression of OPTN was downregulated, which resulted in activation of AIM2 inflammasomes due to a deficiency in mitophagy in APP/PS1 Tg mice. By ectopic expression, OPTN blocks the effects of Aβ oligomer (Aβo) on activating AIM2 inflammasomes by inhibiting mRNA expression of AIM2 and apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), leading to a reduction in the active form of caspase-1 and interleukin (IL)-1β in microglial cells. Moreover, RIPK1 was also found to be negatively regulated by OPTN via ubiquitin protease hydrolysis, resulting in the synthesis of IL-1β by activating the transcriptional activity of NF-κB in BV2 cells. As an E3 ligase, the UBAN domain of OPTN binds to the death domain (DD) of RIPK1 to facilitate its ubiquitination. Based on these observations, ectopically expressed OPTN in APP/PS1 Tg mice deactivated microglial cells and astrocytes via the AIM2 inflammasome and RIPK-dependent NF-κB pathways, leading to reduce neuroinflammation.Conclusions: These results suggest that OPTN can alleviate neuroinflammation through AIM2 and RIPK1 pathways, suggesting that OPTN deficiency may be a potential factor leading to the occurrence of AD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by the production and deposition of β-amyloid protein (Aβ) and hyperphosphorylated tau, leading to the formation of β-amyloid plaques (APs) and neurofibrillary tangles (NFTs). Although calcium ions (Ca2+) promote the formation of APs and NFTs, no systematic review of the mechanisms by which Ca2+ affects the development and progression of AD has been published. Therefore, the current review aimed to fill the gaps between elevated Ca2+ levels and the pathogenesis of AD. Specifically, we mainly focus on the molecular mechanisms by which Ca2+ affects the neuronal networks of neuroinflammation, neuronal injury, neurogenesis, neurotoxicity, neuroprotection, and autophagy. Furthermore, the roles of Ca2+ transporters located in the cell membrane, endoplasmic reticulum (ER), mitochondria and lysosome in mediating the effects of Ca2+ on activating neuronal networks that ultimately contribute to the development and progression of AD are discussed. Finally, the drug candidates derived from herbs used as food or seasoning in Chinese daily life are summarized to provide a theoretical basis for improving the clinical treatment of AD. [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 application of splenic hilar lymph node (no. 10 LN) dissection (no. 10 LND) for proximal gastric cancer (PGC) remains controversial. This study aimed to investigate the clinical relevance of no. 10 LND from the perspective of long-term survival. Methods: The main study population included 995 previously untreated patients who underwent laparoscopic radical total gastrectomy between January 2008 and December 2014. Of these 995 patients, 564 underwent no. 10 LND (no. 10D+ group) and the remaining 431 patients did not (no. 10D– group). Propensity score-matching was applied to reduce the effects of confounding factors. The study end points were overall survival (OS) and disease-free survival (DFS). Additionally, 39 patients who received neoadjuvant chemotherapy during the same period also were included as a separate population for analysis. Results: The metastasis rate for no. 10 LN was 10.5 % (59/564). No significant differences were observed in intra- and postoperative complications nor in mortality between the no. 10D+ and no. 10D– groups (all P > 0.05). After 1:1 matching, the two groups were comparable in clinicopathologic characteristics. The no. 10D+ group had significantly better survival than the no. 10D– group (5-year OS: 63.3 % vs 52.2 %, P = 0.003; 5-year DFS: 60.4 % vs 48.1 %, P = 0.013). For the patients who received neoadjuvant chemotherapy, the 5-year OS rates in the no. 10D+ and no. 10D– groups were respectively 50.6 % and 31.3 % (P = 0.150) and the 5-year DFS rates were respectively 51.5 % and 31.3 % (P = 0.123). Conclusions: Patients with untreated PGC may achieve the benefit of long-term survival from no. 10 LND. For patients with PGC who undergo neoadjuvant chemotherapy, no. 10 LND may not bring survival benefits. However, further validation with a large-sample study is needed. [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]

Clinical studies have found that some Alzheimer's disease (AD) patients suffer from Cushing's syndrome (CS). CS is caused by the long-term release of excess glucocorticoids (GCs) from the adrenal gland, which in turn, impair brain function and induce dementia. Thus, we investigated the mechanism of the effect of corticosterone (CORT) on the development and progression of AD in a preclinical model. Specifically, the plasma CORT levels of 9-month-old APP/PS1 Tg mice were abnormally increased, suggesting an association between GCs and AD. Long-term administration of CORT accelerated cognitive dysfunction by increasing the production and deposition of β-amyloid (Aβ). The mechanism of action of CORT treatment involved stimulation of the expression of BACE-1 and presenilin (PS) 1 in in vitro and in vivo. This observation was confirmed in mice with adrenalectomy (ADX), which had lower levels of GCs. Moreover, the glucocorticoid receptor (GR) mediated the effects of CORT on the stimulation of the expression of BACE-1 and PS1 via the PKA and CREB pathways in neuroblastoma N2a cells. In addition to these mechanisms, CORT can induce a cognitive decline in APP/PS1 Tg mice by inducing apoptosis and decreasing the differentiation of neurons. [ABSTRACT FROM AUTHOR]

Background: The benefits of neoadjuvant therapy for patients with locally advanced gastric cancer (GC) are increasingly recognized. The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual first proposed ypTNM staging, but its accuracy is controversial. This study aims to develop a modified ypTNM staging. Patients and Methods: Clinicopathological data of 1,791 patients who underwent curative‐intent gastrectomy after neoadjuvant therapy in the Surveillance, Epidemiology, and End Results database, as the development cohort, were retrospectively analyzed. Modified ypTNM staging was established based on overall survival (OS). We compared the prognostic performance of the AJCC 8th edition ypTNM staging and the modified staging for patients after neoadjuvant therapy. Results: In the development cohort, the 5‐year OS for AJCC stages I, II, and III was 58.8%, 39.1%, and 21.6%, respectively, compared with 69.9%, 54.4%, 34.4%, 24.1%, and 13.6% for modified ypTNM stages IA, IB, II, IIIA, and IIIB. The modified staging had better discriminatory ability (C‐index: 0.620 vs. 0.589, p <.001), predictive homogeneity (likelihood ratio chi‐square: 140.71 vs. 218.66, p <.001), predictive accuracy (mean difference in Bayesian information criterion: 64.94; net reclassification index: 35.54%; integrated discrimination improvement index: 0.032; all p <.001), and model stability (time‐dependent receiver operating characteristics curves) over AJCC. Decision curve analysis showed that the modified staging achieved a better net benefit than AJCC. In external validation (n = 266), the modified ypTNM staging had superior prognostic predictive power (all p <.05). Conclusion: We have developed and validated a modified ypTNM staging through multicenter data that is superior to the AJCC 8th edition ypTNM staging, allowing more accurate assessment of the prognosis of patients with GC after neoadjuvant therapy. Implications for Practice: The 8th edition of the American Joint Committee on Cancer (AJCC) Staging Manual first proposed ypTNM staging, but its accuracy is controversial. Based on multi‐institutional data, this study developed a modified ypTNM staging, which is superior to the AJCC 8th edition ypTNM staging, allowing more accurate assessment of the prognosis of patients with gastric cancer after neoadjuvant therapy. The 8th edition of the AJCC Staging Manual first proposed ypTNM staging for gastric cancer, but its accuracy is controversial. Modified ypTNM staging is needed. This article reports a modified staging system that allows for a more accurate assessment of the prognosis of gastric cancer patients after neoadjuvant therapy. [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]

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]

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]

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]

Background: In clinical practice, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are the most common markers measured before and after surgery for gastric cancer (GC). However, which pre- or post-operative combined tumour markers (CEA and CA19-9) have more prognostic value remains unclear.Methods: Consecutive patients undergoing a resection for GC at the Fujian Medical University Union Hospital were included as a discovery database between January 2011 and December 2014. The prognostic impact of pre- and post-operative tumour markers was evaluated using Kaplan-Meier log-rank survival analysis and multivariable Cox regression analysis. The results were then externally validated.Results: A total of 735 and 400 patients were identified in the discovery cohort and in the validation cohort, respectively. Overall survival rates decreased in a stepwise manner in association with the number of pre- and post-operative positive tumour markers (both P < 0.001). Multivariable analysis revealed that the number of pre-operative positive tumour markers was an independent prognostic factor (P < 0.05). For patients with abnormal pre-operative tumour markers, normalisation of tumour markers after surgery is an independent prognostic protective factor (hazard ratio (HR) = 0.618; 95% confidence interval (CI) = 0.414-0.921), and patients with both positive post-operative tumour markers had double the risk of overall death (HR = 2.338; 95% CI = 1.071-5.101). Similar results were observed in the internal validation and external validation cohorts.Conclusion: Pre-operative tumour markers have a better discriminatory ability for post-operative survival in GC patients than post-operative tumour markers, and the normalisation of tumour markers after surgery was associated with better survival. [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]

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]

The present study was designed to evaluate the dynamic survival and recurrence of remnant gastric cancer (RGC) after radical resection and to provide a reference for the development of personalized follow‐up strategies. A total of 298 patients were analyzed for their 3‐year conditional overall survival (COS3), 3‐year conditional disease‐specific survival (CDSS3), corresponding recurrence and pattern changes, and associated risk factors. The 5‐year overall survival (OS) and the 5‐year disease‐specific survival (DSS) of the entire cohort were 41.2% and 45.8%, respectively. The COS3 and CDDS3 of RGC patients who survived for 5 years were 84.0% and 89.8%, respectively. The conditional survival in patients with unfavorable prognostic characteristics showed greater growth over time than in those with favorable prognostic characteristics (eg, COS3, ≥T3: 46.4%‐83.0%, Δ36.6% vs ≤T2: 82.4%‐85.7%, Δ3.3%; P < 0.001). Most recurrences (93.5%) occurred in the first 3 years after surgery. The American Joint Committee on Cancer (AJCC) stage was the only factor that affected recurrence. Time‐dependent Cox regression showed that for both OS and DSS, after 4 years of survival, the common prognostic factors that were initially judged lost their ability to predict survival (P > 0.05). Time‐dependent logistic regression analysis showed that the AJCC stage independently affected recurrence within 2 years after surgery (P < 0.05). A postoperative follow‐up model was developed for RGC patients. In conclusion, patients with RGC usually have a high likelihood of death or recurrence within 3 years after radical surgery. We developed a postoperative follow‐up model for RGC patients of different stages, which may affect the design of future clinical trials. [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]

Background: To compare the differences in occurrence rates, time intervals, main causes, and management strategies of early unplanned reoperations (EUROs) after gastrectomy for gastric cancer (GC) between laparoscopic and open surgery. Methods: From Jan. 2005 to Dec. 2014, 2608 and 1516 patients underwent laparoscopic-assisted gastrectomy (LAG) and open gastrectomy (OG), respectively. Perioperative outcomes and risk factors for EURO were analyzed. Results: The overall EURO rate was 1.3%, and the rate in LAG and OG groups was 1.1% and 1.6%, respectively. The EURO rate after 24 h postoperatively was significantly lower in LAG group than in OG group (p = 0.019). No significant correlation was identified between laparoscopic surgery and EURO rate (p = 0.157); age > 70 (p = 0.028), body mass index (BMI) > 25 kg/m2 (p = 0.009), and estimated blood loss > 100 ml (p = 0.029) were independent risk factors for EURO. The main cause of EURO was intra-abdominal bleeding, anastomotic bleeding, and anastomotic leakage in LAG group; and intra-abdominal bleeding, anastomotic leakage, and intestinal obstruction in OG group. The proportion of patients with intra-abdominal bleeding requiring EURO was markedly higher in LAG group than in OG group (p = 0.043). Transverse mesocolonic vessels and spleen were the most common bleeding sites necessitating EURO in LAG and OG groups, respectively. Six of 28 (21.4%) patients with EUROs in LAG group underwent laparoscopic procedure (p = 0.025). Mortality in patients requiring EURO was 3.6% and 20.8% in LAG and OG groups, respectively (p = 0.084). Conclusions: Compared to open surgery, laparoscopic surgery does not increase the incidence of EURO in patients undergoing gastrectomy for GC; however, laparoscopic surgery is associated with a lower EURO rate after 24 h postoperatively and a higher proportion of patients with intra-abdominal bleeding requiring EURO than open surgery. Effective and accurate intraoperative hemostasis for intra-abdominal vessels and anastomotic sites will help further reduce the incidence of EURO following LAG within 24 h postoperatively. [ABSTRACT FROM AUTHOR]

Background: Most lymph node metastasis (LNM) models for early gastric cancer (EGC) include lymphovascular invasion (LVI) as a predictor. However, LVI must be confirmed by postoperative pathology. In this study, we aimed to develop a model for predicting the risk of LNM/LVI in EGC using preoperative factors.Methods: EGC patients who underwent radical gastrectomy at Fujian Medical University Union Hospital and Sun Yat-sen University Cancer Center (n = 1460) were selected as the training set. The risk factors of LNM/LVI were investigated. Data from the International study group on Minimally Invasive surgery for GASTRIc Cancer trial (n = 172) were selected as the validation set.Results: In the training set, the incidence of LNM/LVI was 21.6%. The 5-year cancer-specific survival rates of patients with and without LNM/LVI were 92.4 and 95.0%, respectively, with significant difference (P = 0.030). Multivariable logistic regression analysis showed that the four independent risk factors for LNM/LVI were female, tumor larger than 20 mm, submucosal invasion and undifferentiated tumor histological type (all P <  0.05); the area under the curve (AUC) was 0.694 (95% confidence interval [CI]: 0.659-0.730). Patients were divided into low-risk, intermediate-risk, high-risk and extremely high-risk groups by recursive partitioning analysis; the incidences of LNM/LVI were 5.4, 12.6, 24.2 and 37.8%, respectively (P <  0.001). The AUC of the validation set was 0.796 (95%CI, 0.662-0.851) and the predictive performance of the LNM/LVI risk in the validation set was consistent with that in the training set.Conclusions: The risk of LNM/LVI in differentiated mucosal EGC is low, which indicated that endoscopic resection is a treatment option. The risk of LNM/LVI in undifferentiated mucosal EGC and submucosa EGC are high and gastrectomy with lymph node dissection is suggested. [ABSTRACT FROM AUTHOR]

Copyright of Oncologist is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Previous studies have suggested that preoperative anemia negatively influences survival in patients with gastric cancer (GC). We sought to investigate which anemic markers can better predict the prognosis of patients with resectable GC. Methods: The study involved 2277 GC patients who underwent curative resection between December 2008 and December 2014. Cox regression models were used to identify the best anemic markers associated with prognosis. Time-dependent receiver operating characteristics analysis (t-ROC) and the estimated area under the curve (AUC) were used to compare the prognostic values. Results: Of all patients, 1709 (75.1%) were male, and the median age was 61 years. Univariate analyses showed that preoperative hematocrit (HCT), hemoglobin, and mean corpuscular volume were associated with OS (all P < 0.05). However, in a separate analysis of individual stages, only HCT was shown to be significantly prognostic across all tumor stages (all P < 0.05). In the multivariate analysis, preoperative HCT remained an independent prognostic factor for GC. Low HCT was significantly associated with older age, female sex, lower body mass index, higher American Society of Anesthesiologists score, higher preoperative transfusion rate, 90-day mortality, adjuvant chemotherapy, larger tumor size, lymph node metastasis, later stage, and vascular involvement. The t-ROC curve and AUC for HCT were similar to those for the controlling nutritional status and prognostic nutritional index throughout the observation period. Conclusions: The preoperative HCT is a novel, simple, and powerful prognostic indicator of poor outcome in patients with GC and can be used as a part of the preoperative risk stratification process. [ABSTRACT FROM AUTHOR]