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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: For patients with locally advanced proximal gastric cancer (LAPGC), the individualized selection of patients with highly suspected splenic hilar (No. 10) lymph node (LN) metastasis to undergo splenic hilar lymphadenectomy, is a clinical dilemma. This study aimed to re-evaluate the feasibility and safety of laparoscopic spleen-preserving splenic hilar lymphadenectomy (LSPSHL) and to identify the population who would benefit from it. Methods: A total of 1068 patients (D2 group = 409; D2 + No. 10 group = 659) who underwent laparoscopic total gastrectomy from four prospective trials between January 2015 and July 2019 were analyzed. Results: No significant difference in the incidence (16.9% vs. 16.4%; P = 0.837) of postoperative complications were found between the two groups. The metastasis rate of No. 10 LN among patients in the D2 + No. 10 group was 10.3% (68/659). Based on the decision tree, patients with LAPGC with tumor invading the greater curvature (Gre), patients with non-Gre-invading LAPGC with a tumor size > 5 cm and clinical positive locoregional LNs were defined as the high-priority No. 10 dissection group. The metastasis rate of No. 10 LNs in the high-priority group was 19.4% (41/211). In high-priority group, the 3-year overall survival of the D2 + No. 10 group was better than that of the D2 group (74.4% vs. 42.1%; P = 0.005), and the therapeutic index of No. 10 was higher than the indices of most suprapancreatic stations. Conclusions: LSPSHL for LAPGC is safe and feasible when performed by experienced surgeons. LSPSHL could be recommended for the high-priority group patients even without invasion of the Gre. [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: Laparoscopic spleen-preserving Splenic hilar lymphadenectomy (LSPL) is required in laparoscopy-assisted total gastrectomy for advanced proximal gastric cancer. However, it is considerably difficult and risk in clinical practice. Thus, we explore the application of LSPL performed by following the perigastric fascias and the intrafascial space in D2 radical gastrectomy for advanced upper-third gastric cancer. Methods: From July 2010 to December 2012, 109 patients with T2–3 upper-third gastric cancer underwent LSPL. Of these patients, 55 underwent classic LSPL (classic group), and the remaining 54 patients underwent LSPL performed by following the fascias and intrafascial space (fascia group). Clinicopathologic characteristics and intraoperative and postoperative variables were compared between the two groups. Results: There were no significant differences in clinicopathological characteristics between the two groups (P>0.05). All of the operations were successful without conversion to laparotomy. The operation time, mean splenic hilar lymph node (LN) dissection time, mean total blood loss and mean blood loss from splenic hilar LN dissection were significantly lower in the fascia group than in the classic group (P<0.05), whereas the times to first flatus, fluid diet and soft diet and the duration of hospital stay were similar in both groups. The mean number of harvested LNs (No. 10 and No. 11d) was slightly higher in the fascia group, but the difference was not significant. No significant difference in morbidity was found between the fascia group and the classic group (9.3% vs.10.9%, P>0.05). At a median follow-up of 12 months(range 5 to 35 months), none of the patients had died or experienced recurrent or metastatic disease. Conclusion: LSPL performed by following the fascias and intrafascial space is an optimal and safe technique based on anatomical logic, and it reduces the difficulties associated with LSPL, making it easier to master and allowing its widespread adoption. [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: The role of minimally invasive surgery using robotics versus laparoscopy in resectable gastric cancer patients with a high body mass index (BMI) remains controversial. Methods: A total of 482 gastric adenocarcinoma patients with BMI ≥ 25 kg/m2 who underwent minimally invasive radical gastrectomy between August 2016 and December 2019 were retrospectively analyzed, including 109 cases in the robotic gastrectomy (RG) group and 321 cases in the laparoscopic gastrectomy (LG) group. Propensity score matching (PSM) with a 1:1 ratio was performed, and the perioperative outcomes, lymph node dissection, and 3-year overall survival (OS) and disease-free survival (DFS) rates were compared. Results: After PSM, 109 patients were included in each of the RG and LG groups, with balanced baseline characteristics. Compared with the LG group, the RG group had similar intraoperative estimated blood loss [median (IQR) 30 (20–50) vs. 35 (30–59) mL, median difference (95%CI) − 5 (− 10 to 0)], postoperative complications [13.8% vs. 18.3%, OR (95%CI) 0.71 (0.342 to 1.473)], postoperative recovery, total harvested lymph nodes [(34.25 ± 13.43 vs. 35.44 ± 14.12, mean difference (95%CI) − 1.19 (− 4.871 to 2.485)] and textbook outcomes [(81.7% vs. 76.1%, OR (95%CI) 1.39 (0.724 to 2.684)]. Among pathological stage II–III patients receiving chemotherapy, the initiation of adjuvant chemotherapy in the RG group was similar to that in the LG group [median (IQR): 28 (25.5–32.5) vs. 32 (27–38.5) days, median difference (95%CI) − 3 (− 6 to 0)]. The 3-year OS (RG vs. LG: 80.7% vs. 81.7%, HR = 1.048, 95%CI 0.591 to 1.857) and DFS (78% vs. 76.1%, HR = 0.996, 95%CI 0.584 to 1.698) were comparable between the two groups. Conclusion: RG conferred comparable lymph node dissection, postoperative recovery, and oncologic outcomes in a selected cohort of patients with BMI ≥ 25 kg/m2. [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: Textbook outcome (TO) has been widely employed as a comprehensive indicator to assess the short-term prognosis of patients with cancer. Preoperative malnutrition is a potential risk factor for adverse surgical outcomes in patients with gastric cancer (GC). This study aimed to compare the TO between robotic-assisted gastrectomy (RAG) and laparoscopic-assisted gastrectomy (LAG) in malnourished patients with GC. Methods: According to the diagnostic consensus of malnutrition proposed by Global Leadership Initiative on Malnutrition (GLIM) and Nutrition Risk Index (NRI), 895 malnourished patients with GC who underwent RAG (n = 115) or LAG (n = 780) at a tertiary referral hospital between January 2016 and May 2021 were included in the propensity score matching (PSM, 1:2) analysis. Results: After PSM, no significant differences in clinicopathological characteristics were observed between the RAG (n = 97) and LAG (n = 194) groups. The RAG group had significantly higher operative time and lymph nodes harvested, as well as significantly lower blood loss and hospital stay time compared to the LAG group. More patients in the RAG achieved TO. Logistic regression analysis revealed that RAG was an independent protective factor for achieving TO. There were more adjuvant chemotherapy (AC) cycles in the RAG group than in the LAG group. After one year of surgery, a higher percentage of patients (36.7% vs. 22.8%; P < 0.05) in the RAG group recovered from malnutrition compared to the LAG group. Conclusions: For malnourished patients with GC, RAG performed by experienced surgeons can achieved a higher rate of TO than those of LAG, which directly contributed to better AC compliance and a faster restoration of nutritional status. [ABSTRACT FROM AUTHOR]

Background: To evaluate the prevalence of the accessory left hepatic artery (ALHA; defined as a vessel arising from the left gastric artery, which, together with a typical left hepatic artery, supplies blood to the left lobe of the liver) and its short-term clinical implications in patients undergoing radical gastrectomy for gastric cancer. Methods: Clinical data of 1173 patients with gastric cancer who underwent laparoscopy-assisted radical gastrectomy were retrospectively analyzed. Groups of patients with and without ALHA were compared to identify differences in intraoperative and postoperative variables and changes in liver function. Results: Of the 1173 patients, 135 (11.5%) had an ALHA and 1038 (88.5%) did not. There were no significant between-group differences in clinicopathological and intraoperative characteristics, postoperative recovery, and morbidity and mortality rates (P>0.05 each). None of the patients had postoperative symptoms associated with impaired liver function. Glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and total bilirubin (TBIL) concentrations were similar preoperatively. TBIL concentrations on postoperative days 1, 3, and 7 were similar (P>0.05), while GOT and GPT activities were higher in the ALHA than in the non-ALHA group on days 1 and 7 (P<0.05), with all three markers similar in the two groups on day 14. In patients without chronic liver disease (CLD), GOT, GPT and TBIL concentrations were similar in patients with and without ALHA; whereas, in patients with CLD, GOT and GPT concentrations on days 1 and 3 and GOT on day 7 were higher in patients with than without ALHA. Conclusion: ALHA is a common anomaly that was found in 11.5% of patients. It can be safely severed during radical gastrectomy in patients without CLD, but should be left intact in patients with CLD to prevent liver dysfunction. If severed in the latter, the patient should be monitored and liver-protecting therapy may be necessary. [ABSTRACT FROM AUTHOR]

Abstract: Objective: MicroRNA (miRNA) expression is deregulated in many types of human cancers. We sought to investigate the expression patterns of the miRNAs, miR-21, miR-145 and miR-155 in sporadic gastric cancer in a Chinese population. Methods: Total RNA was extracted from archived gastric cancer tissues and adjacent non-cancerous tissues from 20 pairs of paraffin-embedded specimens. Expression levels of miR-21, miR-145 and miR-155 were detected by quantitative reverse transcriptase PCR using a specific stem-loop primer, with U6 as the internal reference gene. Results: The expression of miR-21 and miR-155 in gastric cancer samples was significantly higher than in paired non-cancerous samples (P < 0.05). There was no statistically significant difference in expression levels of miR-145 between cancerous and non-cancerous tissues (P > 0.05). Conclusion: In Chinese sporadic gastric cancer tissues, the expressions of the oncogenic miR-21 and miR-155 were significantly up-regulated, while the expression of the tumor suppressor miR-145 was decreased, although this decrease was not statistically significant. Thus there is specificity in the miRNA expression pattern in gastric cancers in the Chinese population. [ABSTRACT FROM AUTHOR]

Background: Surgical quality control is a crucial determinant of evaluating the tumor efficacy. Objective: To assess the ClassIntra grade for quality control and oncological outcomes of robotic radical surgery for gastric cancer (GC). Methods: Data of patients undergoing robotic radical surgery for GC at a high-volume center were retrospectively analyzed. Patients were categorized into two groups, the intraoperative adverse event (iAE) group and the non-iAE group, based on the occurrence of intraoperative adverse events. The iAEs were further classified into five sublevels (ranging from I to V according to severity) based on the ClassIntra grade. Surgical performance was assessed using the Objective Structured Assessment of Technical Skill (OSATS) and the General Error Reporting Tool. Results: This study included 366 patients (iAE group: n = 72 [19.7%] and non-iAE group: n = 294 [80.3%]). The proportion of ClassIntra grade II patients was the highest in the iAE group (54.2%). In total and distal gastrectomies, iAEs occurred most frequently in the suprapancreatic area (50.0% and 54.8%, respectively). In total gastrectomy, grade IV iAEs were most common during lymph node dissection in the splenic hilum area (once for bleeding [grade IV] and once for injury [grade IV]). The overall survival (OS) and disease-free survival of the non-iAE group were significantly better than those of the iAE group (Log rank P < 0.001). Uni- and multi-variate analyses showed that iAEs were key prognostic indicators, independent of tumor stage and adjuvant chemotherapy (P < 0.001). Conclusion: iAEs in patients who underwent robotic radical gastrectomy significantly correlated with the occurrence of postoperative complications and a poor long-term prognosis. Therefore, utilization and inclusion of ClassIntra grading as a crucial surgical quality control and prognostic indicator in the routine surgical quality evaluation system are recommended. [ABSTRACT FROM AUTHOR]

For tumor treatment, the ultimate goal in tumor therapy is to eliminate the primary tumor, manage potential metastases, and trigger an antitumor immune response, resulting in the complete clearance of all malignant cells. Tumor microenvironment (TME) refers to the local biological environment of solid tumors and has increasingly become an attractive target for cancer therapy. Neutrophils within TME of gastric cancer (GC) spontaneously undergo ferroptosis, and this process releases oxidized lipids that limit T cell activity. Enhanced photodynamic therapy (PDT) mediated by di‐iodinated IR780 (Icy7) significantly increases the production of reactive oxygen species (ROS). Meanwhile, neutrophil ferroptosis can be triggered by increased ROS generation in the TME. In this study, a liposome encapsulating both ferroptosis inhibitor Liproxstatin‐1 and modified photosensitizer Icy7, denoted LLI, significantly inhibits tumor growth of GC. LLI internalizes into MFC cells to generate ROS causing immunogenic cell death (ICD). Simultaneously, liposome‐deliver Liproxstatin‐1 effectively inhibits the ferroptosis of tumor neutrophils. LLI‐based immunogenic PDT and neutrophil‐targeting immunotherapy synergistically boost the anti‐PD‐1 treatment to elicit potent TME and systemic antitumor immune response with abscopal effects. In conclusion, LLI holds great potential for GC immunotherapy. [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: 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: 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: 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: Few studies have investigated the efficacy of comprehensive therapies, including immunotherapy, for gastric cancer with synchronous liver metastases (GCLM). We retrospectively compared the effect of immunochemotherapy and chemotherapy alone as conversion therapies on the oncological outcomes of patients with GCLM. Methods: The clinicopathological data of 100 patients with GCLM from February 2017 to October 2021 at our institution were retrospectively analyzed. Patients were divided into immunochemotherapy (n = 33) and chemotherapy‐alone (n = 67) groups. Results: Baseline clinicopathological data did not differ significantly between the two groups. The immunochemotherapy group had a higher overall response rate (59.4% vs. 44.0%, p = 0.029) and disease control rate (71.9% vs. 49.2%, p = 0.036) than the chemotherapy group. The immunochemotherapy group showed better tumor regression in the gastric mass, metastatic lymph nodes, and liver lesions than the chemotherapy group. Ten (30.3%) patients in the immunochemotherapy group and 13 (19.4%) patients in the chemotherapy group underwent surgery after conversion therapy. However, the difference was not statistically significant. The overall survival (OS) and progression‐free survival (PFS) rates were better in the immunochemotherapy group than in the chemotherapy group. Treatment‐related adverse events occurred in 24 (72.7%) and 47 (70.1%) patients in the immunochemotherapy and chemotherapy groups, respectively. Conclusions: As a conversion therapy for GCLM, immunotherapy yielded better primary and metastatic tumor regression and survival benefits, with no increase in adverse events compared to chemotherapy. [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: 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: Helicobacter pylori (H. pylori) infection and its related diseases are substantial public health burden for highly infected areas. Recently, a novel family‐based H. pylori infection control and management (FBCM) strategy is introduced for H. pylori infection prevention and control. However, its cost‐effectiveness has not been evaluated. We conducted this health economic evaluation to investigate the cost‐effectiveness of FBCM, screen‐and‐treat, and no‐screen strategies in Chinese population. Materials and Methods: Cost‐effectiveness analysis was performed using decision tree and Markov model. Parameters required for the model were from published literatures and public databases, including health state utility, screening characteristics, treatment effectiveness, and medical costs for the three strategies. Outcomes were cost, quality‐adjusted life year (QALY), incremental cost‐effectiveness ratio (ICER). Uncertainty analysis was performed to verify the robustness of this model. Results: To prevent gastric cancer in a cohort of 1 million asymptomatic Chinese families, FBCM and screen‐and‐treat strategies prevented 1010 and 1201 new gastric cancer cases, reduced 2809 and 3339 gastric cancer‐related death, and saved 956,971 and 1,137,549 QALYs, respectively, when compared with no‐screen strategy. Cost‐effectiveness analysis showed that FBCM strategy cost $9.18/QALY, and screen‐and‐treat strategy cost $12.08/QALY for gastric cancer prevention when compared with no‐screen strategy. One‐way sensitivity analysis revealed that screening from younger age by both strategies are more cost‐effective. When compared with FBCM strategy, screen‐and‐treat strategy saved 5.98% gastric cancer cases and 5.78% of gastric cancer deaths, but costed $9348 to reduce a gastric cancer case. Results are not sensitive to any variables, and probabilistic sensitivity analysis confirmed robustness of the results. Conclusions: Both FBCM and screen‐and‐treat strategies are cost‐effective for gastric cancer prevention compared with no‐screen strategy. Since FBCM is more practical and convenient, it may be an efficient and excellent cost‐effective strategy for gastric cancer prevention in H. pylori and gastric cancer prevalent areas. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II–III locally AGC and explore the associated risk factors.Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established.In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II–III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets.Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II–III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy.Methods: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II–III locally AGC and explore the associated risk factors.Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established.In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II–III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets.Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II–III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy.Results: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II–III locally AGC and explore the associated risk factors.Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established.In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II–III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets.Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II–III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy.Conclusion: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II–III locally AGC and explore the associated risk factors.Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established.In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II–III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets.Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II–III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy.Graphical abstract: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II–III locally AGC and explore the associated risk factors.Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established.In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II–III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets.Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II–III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy. [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]

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: 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]

The biological functions of circular RNAs (circRNAs) in gastric cancer (GC) remain largely unexplored. Here, we identified that circ-RanGAP1 was significantly upregulated in both GC tissues and exosomes from the plasma of GC patients. High circ-RanGAP1 expression was closely associated with an advanced TNM stage, lymph node metastases, and worse survival. Inhibition of circ-RanGAP1 decreased GC cell invasion and migration in vitro. Overexpression of circ-RanGAP1 had the opposite effect. Additionally, circ-RanGAP1 silencing remarkably suppressed tumor growth and metastasis of GC in vivo. Mechanistically, circ-RanGAP1 sponged miR-877-3p to upregulate VEGFA expression. Overexpression of miR-877-3p reversed the biological functions mediated by circ-RanGAP1 in GC cells. Interestingly, we demonstrated that circ-RanGAP1 was upregulated in plasma exosomes from preoperative GC patients. More importantly, the plasma exosomes derived from these patients enhanced the migration and invasion potential of GC cells. Overall, the circ-RanGAP1-mediated miR-877-3p/VEGFA axis promotes GC progression. Our findings suggest that circ-RanGAP1 might act as a potential prognostic biomarker and therapeutic target for GC treatment. [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: 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: 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]

Purpose: To determine the indications for adjuvant chemotherapy (AC) in patients with stage IIa gastric cancer (T3N0M0 and T1N2M0) according to the 7th American Joint Committee on Cancer (AJCC).Methods: A total of 1593 patients with T3N0M0 or T1N2M0 stage gastric cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) database for the period 1988.1-2012.12. Cox multiple regression, nomogram and decision curve analyses were performed. External validation was performed using databases of the Fujian Medical University Union Hospital (FJUUH) (n = 241) and Italy IMIGASTRIC center (n = 45).Results: Cox multiple regression analysis showed that the risk factors that affected OS in patients receiving AC were age > 65 years old, T1N2M0, LN dissection number ≤ 15, tumor size > 20 mm, and nonadenocarcinoma. A nomogram was constructed to predict 5-year OS, and the patients were divided into those predicted to receive a high benefit (points ≤ 188) or a low benefit from AC (points > 188) according to a recursive partitioning analysis. OS was significantly higher for the high-benefit patients in the SEER database and the FJUUH dataset than in the non-AC patients (Log-rank < 0.05), and there was no significant difference in OS between the low-benefit patients and non-AC patients in any of the three centers (Log-rank = 0.154, 0.470, and 0.434, respectively). The decision curve indicated that the best clinical effect can be obtained when the threshold probability is 0-92%.Conclusion: Regarding the controversy over whether T3N0M0 and T1N2M0 gastric cancer patients should be treated with AC, this study presents a predictive model that provides concise and accurate indications. These data show that high-benefit patients should receive AC. [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]

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]

Abstract Gastric cancer (GC) is still a major aggressive malignancy worldwide. While the importance of circular RNAs (circRNAs) involved in carcinogenesis has gradually been acknowledged, their role in human cancers is not largely understood, including in GC. Here, we focused on hsa_circ_0001368 in GC, a novel circRNA that has not been previously reported. In the current study, we found a broad downregulation of hsa_circ_0001368 in GC tissues and cells, which correlates with a worse prognosis in GC patients. Functional experiments suggested that the knockdown of hsa_circ_0001368 promoted cell viability and motility by cell proliferation and invasion assays. In addition, the knockdown of hsa_circ_0001368 led to accelerated tumor growth in vivo. Mechanically, we demonstrated that hsa_circ_0001368 served as a competing endogenous RNA (ceRNA) to sponge miR-6506–5p. Subsequently, FOXO3 may act as the functional target of miR-6506–5p, and the knockdown of hsa_circ_0001368 decreased the expression of the tumor-suppressive gene FOXO3. Taken together, our study revealed that hsa_circ_0001368 plays a tumor-suppression role in GC via the miR-6506–5p/FOXO3 axis and may serve as a potential target for GC therapy. Highlights • In this study, we performed high-throughput circRNA microarray assays using gastric cancer (GC) patient samples to investigate the potential involvement of circRNAs in GC, and we revealed that lower levels of circRNA hsa_circ_0001368 were expressed in GC tissues than in normal adjacent tissues. • Functionally, knockdown of hsa_circ_0001368 dramatically promoted the ability of GC cells to proliferate and invasion in vitro and in vivo. • Regarding the mechanism, we found that hsa_circ_0001368 was mainly observed in the cytoplasm and was capable of sponging miR-6506–5p to increase the expression of the tumor-suppressive gene FOXO3. • Our study first revealed a novel signaling pathway of hsa_circ_0001368/miR-6506-5p/FOXO3 involved in GC progression. [ABSTRACT FROM AUTHOR]

Background: This study sought to explore whether lymphovascular invasion can affect the prognosis of patients with stage N0 gastric cancer and to evaluate the survival benefit of adjuvant chemotherapy for such patients.Method: From January 2006 to December 2011, a total of 2102 gastric cancer patients undergoing radical gastric resection were enrolled in this study. Homogeneity, discriminatory ability, and monotonicity of gradients in the combination of lymphovascular invasion and the 8th edition of the AJCC staging system and the 8th edition of the AJCC staging system alone were compared using linear trend χ2, likelihood ratio χ2 statistics, and Akaike information criterion (AIC) calculations. The Kaplan-Meier method and the log-rank test were used to analyze between-group differences in survival rate.Result: The median follow-up time of the whole group was 58 months, and the average age of the whole group was 63.9 years (range 21-89 years). The 3-year and 5-year overall survival rates in N0 patients with lymphovascular invasion were lower than those in N0 patients without lymphovascular invasion (3-year OS: 78.3% vs 92.5%, 5-year OS: 70.0% vs 88.3%, p < 0.001). A multivariate analysis showed that age (p < 0.001), lymphovascular invasion (p < 0.001), and pT (p < 0.001) were independent risk factors for the prognosis of N0 patients. Compared with the 8th edition of the AJCC staging system alone, the 8th AJCC staging system combined with lymphovascular invasion demonstrated a better linear trend χ2, likelihood ratio χ2 statistics, and AIC value (68.99 vs 58.58, 70.18 vs 58.36, 1473.38 vs 1485.04). In pT3N0M0 patients with lymphovascular invasion, the 3-year and 5-year overall survival rates of the adjuvant chemotherapy group were higher than those of the surgery alone group (3-year OS: 83.3% vs 68.2%, 5-year OS: 72.3% vs 50.0%, p = 0.048).Conclusion: Lymphovascular invasion is an independent prognostic factor in N0 patients. The 8th AJCC staging system combined with lymphovascular invasion can improve the accuracy of the AJCC staging system for N0 patients. Moreover, adjuvant chemotherapy improves the survival of pT3N0M0 patients with lymphovascular invasion. [ABSTRACT FROM AUTHOR]

Background: The systemic inflammation score (SIS), based on preoperative serum albumin (Alb) level and lymphocyte-to-monocyte ratio (LMR), has been shown to be a novel prognostic score for some tumors. We investigate the prognostic value of the SIS in patients with resectable gastric cancer (GC).Methods: Patients with GC who underwent curative resection between December 2008 and December 2013 were included. Time-dependent receiver operating characteristics analysis (t-ROC), concordance index (C-index) and AUC were used to compare the prognostic impact.Results: Totally, 1786 patients with resectable GC were included in the study. By multivariate analysis, the SIS was not an independent prognostic factor. However, the normal Alb level (≥ 40 g/l) and LMR ≥ 3.4 both remained independent protective factors for GC (both P < 0.05). Due to the similar survival of patients with LMR ≥ 3.4 and LMR < 3.4 in the normal Alb group, we combined the two subgroups to establish the modified SIS (mSIS). Multivariate analysis revealed that the mSIS was the only significant independent biomarker (P < 0.05). The t-ROC curve and C-index for the mSIS were superior to those of the SIS throughout the observation period. Furthermore, the AUC of the mSIS was significantly greater than that of the SIS at 3 and 5 years after operation (both P < 0.05).Conclusion: The preoperative mSIS is a novel, simple and useful prognostic factor for postoperative survival in patients with GC and can be used as a part of the preoperative risk stratification process to improve the prediction of clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: To determine whether laparoscopic surgery can be used in high-risk patients with gastric cancer.Methods: The clinicopathological data of 3743 patients with primary gastric adenocarcinoma, collected from January 2007 to December 2014, were retrospectively analyzed. Patients who had ≥ 1 of the following conditions were defined as high-risk patients: (1) age ≥ 80 years; (2) BMI ≥ 30 kg/m2; (3) ASA (American Society of Anesthesiologists) grade ≥ 3; or (4) clinical T stage 4 (cT4). Propensity score matching (PSM) was used to reduce confounding bias; then, we compared the short-term and long-term efficacy of laparoscopic gastrectomy (LG) with open gastrectomy (OG) in high-risk patients with gastric cancer.Results: A total of 1296 patients were included in PSM. After PSM, no significant difference in clinicopathological data was observed between the LG group (n = 341) and the OG group (n = 341). The operative time (181.70 vs. 266.71 min, p < 0.001) and blood loss during the operation (68.11 vs. 225.54 ml, p < 0.001) in the LG group were significantly lower than those in the OG group. In the LG and OG groups, postoperative complications occurred in 39 (11.4%) and 63 (18.5%) patients, respectively, p = 0.010. Multivariate analysis showed that laparoscopic surgery was an independent protective factor against postoperative complications (p = 0.019). The number of risk factors was an independent risk factor for postoperative complications (p = 0.021). The 5-year overall survival rate in the LG group was comparable to that in the OG group (55.0 vs. 52.0%, p = 0.086). Hierarchical analysis further confirmed that the LG and OG groups exhibited comparable survival rates among patients with stages cI, pI, cII, pII, cIII, and pIII (all p > 0.05).Conclusions: For high-risk patients with gastric cancer, LG not only exhibits better short-term efficacy than OG but also has a comparable 5-year survival rate to OG. [ABSTRACT FROM AUTHOR]

Abstract: Skeletal muscle index (SMI) and the controlling nutritional status (CONUT) score are useful for evaluating nutritional status, which is closely associated with cancer prognosis. This study compared the prognostic value of these indicators in patients with gastric cancer (GC) after radical gastrectomy (RG). We retrospectively enrolled 532 patients between 2010 and 2011. SMI was measured via CT images to determine low SMI. The CONUT score was calculated based on serum albumin, total lymphocyte count, and cholesterol. Patients were grouped according to SMI and the CONUT score based on previous research. Spearman's correlation coefficient, the Kaplan‐Meier method, and Cox regression were used. There was no significant correlation between SMI and the CONUT score. Five‐year overall survival (OS) and recurrence‐free survival (RFS) in patients with low SMI were significantly worse than those in patients with high SMI (P < .001). The normal nutrition group had better OS and RFS than did the light and moderate or severe malnutrition groups (P < .05), but the OS and RFS were not significantly different between the light and moderate or severe malnutrition groups (P = .726). Univariate analysis showed that SMI and the CONUT score were associated with OS and RFS, but only SMI remained prognostic in multivariate analysis. Preoperative SMI based on CT images is a more objective predictor than the CONUT score of long‐term survival in GC after RG, but this finding must be confirmed by prospective trials. [ABSTRACT FROM AUTHOR]

Background: Robotic-assisted gastrectomy (RAG) has been rapidly adopted for gastric cancer (GC) treatment. However, whether RAG provides any significant outcome/cost advantages over laparoscopy-assisted gastrectomy (LAG) for the experienced laparoscopist remains unclear.Methods: A retrospective review of a prospectively collected database identified 768 consecutive patients who underwent either RAG (n = 103) or LAG (n = 667) for GC between July 2016 and June 2017 at a large center. A 1:3 matched propensity score analysis was performed. The short-term outcomes and hospital costs between the two groups were compared.Results: A well-balanced cohort of 404 patients was analyzed (RAG:LAG = 1:3 match). The mean operation times were 226.6 ± 36.2 min for the RAG group and 181.8 ± 49.8 min for the LAG group (p < 0.001). The total numbers of retrieved lymph nodes were similar in the RAG and LAG groups (means 38 and 40, respectively, p = 0.115). The overall and major complication rates (RAG, 13.9% vs. LAG, 12.5%, p = 0.732 and RAG, 3.0% vs. LAG, 1.3%, p = 0.373, respectively) were similar. RAG was much more costly than LAG (1.3 times, p < 0.001) mainly due to the amortization and consumables of the robotic system. According to cumulative sum (CUSUM), the learning phases were divided as follows: phase 1 (cases 1-21), phase 2 (cases 22-63), and phase 3 (cases 64-101), in the robotic group. The surgical stress (SS) was higher in the robotic group compared with the laparoscopic group in phase 1 (p < 0.05). However, the SS did not differ significantly between the two groups in phase 3.Conclusions: RAG is a feasible and safe surgical procedure for GC, especially in the post-learning curve period. However, further studies are warranted to evaluate the long-term oncological outcomes and to elucidate whether RAG is cost-effective when compared to LAG. [ABSTRACT FROM AUTHOR]

Cisplatin (DDP) is the first line chemotherapeutic drug for several cancers, including gastric cancer (GC). Unfortunately, the rapid development of drug resistance remains a significant challenge for the clinical application of cisplatin. There is an urgent need to develop new strategies to overcome DDP resistance for cancer treatment. In this study, four types of human GC cells have been divided into naturally sensitive or naturally resistant categories according to their responses to cisplatin. PARP1 activity (poly (ADP-ribose), PAR) was found to be greatly increased in cisplatin-resistant GC cells. PARP1 inhibitors significantly enhanced cisplatin-induced DNA damage and apoptosis in the resistant GC cells via the inhibition of PAR. Mechanistically, PARP1 inhibitors suppress DNA-PKcs stability and reduce the capability of DNA double-strand break (DSB) repair via the NHEJ pathway. This was also verified in BGC823/DDP GC cells with acquired cisplatin resistance. In conclusion, we identified that PARP1 is a useful interceptive target in cisplatin-resistant GC cells. Our data provide a promising therapeutic strategy against cisplatin resistance in GC cells that has potential translational significance. [ABSTRACT FROM AUTHOR]

The 8th edition of the TNM was released in 2016 and included major revisions, especially for stage III. We aimed to compare the prognostic value of the 7th and 8th editions of the AJCC TNM classification for stage III gastric cancer. Clinical data from 1557 patients operated on for stage III gastric cancer according to the 7th edition between 2007 and 2014 were analyzed and compared using the 7th and 8th TNM classifications. A proposed staging system was established, and the three systems were compared in terms of prognostic performance. The stage shifted for 669 (42.96%) patients. It shifted from IIIA to IIIB (one patient, 0.06%), IIIB to IIIA (230 patients, 14.8%), IIIB to IIIC (94 patients, 6.0%), and IIIC to IIIB (344 patients, 22.1%). However, the new AJCC subgroupings did not prove distinctive for survival levels between T3N3aM0 (stage IIIB) and T3N3bM0 (stage IIIC) or between T4aN3aM0 (stage IIIB) and T4aN3bM0 (stage IIIC) when <30 lymph nodes ( LNs) were resected. The performance of the 8th edition (c-index, 0.614; 95% confidence interval [ CI], 0.596-0.633) revealed no relevant improvement compared to the 7th edition (c-index, 0.624; 95% CI, 0.605-0.643). The proposed staging system generated the best prognostic stratification. The 8th TNM edition may not provide better accuracy in predicting the prognosis of stage III gastric cancer. The proposed staging system, comprised of a combination of the number of LNs harvested and the 7th and 8th AJCC classifications, may improve predictive capacities for stage III gastric cancer. [ABSTRACT FROM AUTHOR]

Objective: In this study, we evaluated the short-term outcomes following three-dimensional (3D) or two-dimensional (2D) laparoscopic surgery for patients with gastric cancer.Background: There is a lack of prospective evidence regarding the safety and efficacy of 3D versus 2D laparoscopic surgery for patients with gastric cancer. Therefore, we conducted a phase III single-center, prospective, randomized, controlled trial to compare 3D and 2D laparoscopic surgery for patients with gastric cancer.Methods: We compared operation time, intraoperative blood loss, number of lymph node dissections, morbidity, and mortality between the 3D and 2D groups following laparoscopic surgery for gastric cancer. The study is registered at ClinicalTrials.gov with ID number NCT02327481.Results: A total of 228 patients were randomized (3D group 115 cases; 2D group 113 cases) between January 1, 2015 and September 1, 2015. Seven patients who underwent exploratory operations were excluded. Finally, a total of 221 patients were analyzed (3D group 109 cases, 2D group 112 cases). There were no significant differences between the two groups regarding the clinical pathological characteristics, operating time (3D vs. 2D, 184 ± 36 vs. 178 ± 37 min, P = 0.288), number of lymph node dissections (36 ± 14 vs. 37 ± 13, P = 0.698), time to first ambulation (2.27 ± 1.60 vs. 2.04 ± 0.84, P = 0.18), flatus (3.89 ± 1.49 vs. 3.69 ± 1.12, P = 0.255), liquid diet (4.88 ± 1.88 vs. 4.79 ± 1.57, P = 0.684), or duration of postoperative hospital stay (12.52 ± 4.83 vs. 12.63 ± 7.32, P = 0.903). The postoperative complication rates of the 3D and 2D groups were 18.3 and 16.1%, respectively, P = 0.723. No patients died during the postoperative hospital stay. However, the intraoperative blood loss in the 3D group was significantly lower than the 2D group (58 ± 75 vs. 78 ± 72 ml, P = 0.047).Conclusion: There was no significant difference in operation time and number of lymph node harvested between the 3D and 2D groups; however, 3D laparoscopic surgery may reduce the intraoperative blood loss compared to 2D procedure. Therefore, we conclude that this trial is safe and is thus ongoing. [ABSTRACT FROM AUTHOR]

Background: Comorbidity is a predictor of postoperative complications in gastrectomy. However, it remains unclear which comorbidities are predictors of postoperative complications in gastric cancer patients who have undergone laparoscopy-assisted total gastrectomy (LATG). The purpose of this study was to evaluate the effect of comorbidities on the surgical outcomes of patients with gastric cancer after LATG.Methods: We retrospectively collected data on 1657 gastric cancer patients who underwent LATG between January 2008 and December 2015. We investigated the incidences, types, and risk factors for postoperative complications after LATG. Patients were enrolled in analysis to evaluate the effects of comorbidities on postoperative complications.Results: The number of postoperative complications was associated with the number of comorbidities in the gastric cancer patients according to the operative period. Of the 1657 patients included in this study, 714 (43.1 %) had one or more comorbidities. Postoperative complications occurred in 283 patients (17.1 %), and 6 patients (0.4 %) died during hospitalization. With an increasing number of comorbidities, the incidence of local and systemic complications also increased. Univariate and multivariate analyses revealed that comorbidity was a predictive risk factor for local complications (OR 1.204, 1.014-1.431) and systemic complications (OR 1.237, 1.039-1.474). Diabetes mellitus, anemia, pulmonary disease, and renal dysfunction were found to be associated with postoperative complications, including abdominal bleeding, anastomotic leakage, and pneumonia.Conclusions: Our study has revealed that comorbidities could be a predictive risk factor for postoperative complications after LATG. Surgeons should carefully assess patients with full perioperative attention to some specific types of comorbidities. [ABSTRACT FROM AUTHOR]

PD-L1 is a member of the B7 family co-inhibitory molecules and plays a critical role in tumor immune escape. In this study, we found a polymorphism rs10815225 in the PD-L1 promoter region was significantly associated with the occurrence of gastric cancer. The GG homozygous frequency was higher in the cancer patients than that in the precancerous lesions, which was higher than that in the health controls. This polymorphism locates in the binding-site of Sp1 transcription factor (SP1). The expression level of PD-L1 mRNA in the GG homozygous cancer patients was apparently higher than that in the GC heterozygotes. Luciferase reporter results showed that SP1 bonded to rs10815225 G-allelic PD-L1 promoter instead of C-allelic. Upregulation and knockdown of SP1 resulted in elevation and attenuation of PD-L1 in SGC-7901 cells, respectively. The chromatin immunoprecipitation results further confirmed the binding of SP1 to the promoter of PD-L1. Additionally, rs10815225 was found to be in disequilibrium with a functional polymorphism rs4143815 in the PD-L1 3′-UTR, and the haplotypes of these two polymorphisms were also markedly related to gastric cancer risk. These results revealed a novel mechanism underlying genetic polymorphisms influencing PD-L1 expression modify gastric cancer susceptibility. [ABSTRACT FROM AUTHOR]

Potential predictive biomarker(s) to respond to chemotherapy in gastric cancer are unclear. Excision repair cross-complementing 1 (ERCC1), a DNA repair enzyme, is associated with clinical outcomes in gastric cancer. Here, we investigated the expression of ERCC1 in gastric cancer with platinum-based chemotherapy after surgery, and the association between ERCC1 expression and clinical parameters was analyzed. Our data showed that high levels of ERCC1 expression were positively associated with resistance to platinum-based chemotherapy but not with lymph node metastasis and pathological stage. In addition, patients with resistance to platinum-based chemotherapy probably had lymph node metastasis and pathological stage. [ABSTRACT FROM PUBLISHER]

CDK5RAP3 was isolated as a binding protein of the Cdk5 activator p35. Although CDK5RAP3 has been implicated in cancer progression, its expression and function have not been investigated in gastric cancer. Our study demonstrated that the mRNA and protein levels of CDK5RAP3 were markedly decreased in gastric tumor tissues when compared with respective adjacent non-tumor tissues. CDK5RAP3 in gastric cancer cells significantly reduced cell proliferation, migration, invasion and tumor xenograft growth through inhibition of β-catenin. Secondly, CDK5RAP3 was found to suppress the phosphorylation of GSK-3β (Ser9), leading to the phosphorylation (Ser37/Thr41) and subsequent degradation of β-catenin. Lastly, the prognostic value of CDK5RAP3 for overall survival was found to be dependent on β-catenin cytoplasm/nucleus localization in human gastric cancer samples. Collectively, our results demonstrated that CDK5RAP3 negatively regulates the β-catenin signaling pathway by repressing GSK-3β phosphorylation and could be a potential therapeutic target for gastric cancer. [ABSTRACT FROM AUTHOR]

Reprimo (RPRM) is a p53-induced tumor suppressor gene. Its aberrant DNA methylation is correlated with carcinogenesis and may be used as a surrogate marker for the early detection of gastric cancer. However, the detail information regarding its DNA methylation has not been revealed. Here, we investigated the RPRM gene methylation in gastric cancer tumor and plasma samples by methylation-sensitive melt curve analysis (MS-MCA) and bisulfite sequencing in depth. We developed a semi-quantitative method based on MS-MCA for detecting DNA methylation and unraveled the RPRM gene methylation pattern in gastric cancer. This study provides a solid foundation for the future application of detecting RPRM gene methylation in human plasma or serum samples to help diagnose gastric cancer or for prognosis evaluation. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a leading cause of cancer death and an important barrier to increasing life expectancy in China. Early detection of GC can significantly reduce its mortality rate. A new plasma-based multiplex DNA methylation assay combining simultaneous detection of three biomarkers (KCNQ5 , C9orf50 and CLIP4) and one control gene (ACTB) was developed. It was used to examine 12 paired tissue samples and a training cohort of 151 plasma samples. Its performance was subsequently confirmed in validation cohort 1 (n = 105) and validation cohort 2 (n = 139). Three methylation markers showed significantly higher methylation levels in GC tissues than in paired adjacent tissues. The assay showed a sensitivity of 67.9 % with a specificity of 86.6 % for GC detection in the training cohort, and the AUC was 0.786 (95 % CI: 0.701–0.855). The methylation levels in GC patients were significantly higher than those in benign gastric tumors and in control group. Meanwhile, the assay achieved a sensitivity of 65.5 % with a specificity of 90.0 % in the validation cohort 1, and the AUC was 0.805 (95 % CI: 0.716–0.876). In the validation cohort 2, its sensitivity and specificity were 73.7 % and 84.1 %, respectively, and the AUC was 0.851 (95 % CI: 0.776–0.909). The plasma-based multiplex DNA methylation assay was highly specific for GC early detection. It has the potential to become an alternative approach to improve diagnosis of GC in the clinics. [ABSTRACT FROM AUTHOR]