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Purpose: Since the relationship between postoperative platelet count and prognosis is still unclear, we designed a standardized index of platelet count to predict the prognosis of gastric cancer (GC). Methods: We designed a development validation cohort for the pre/post platelet ratio. We determined the ability of PPR to predict mortality in gastric cancer patients and validated them by a separate cohort. Survival was assessed by Kaplan–Meier analysis and associations explored by multivariate and multivariate analyses. The usefulness of the prediction was estimated by measuring the time-dependent ROC. Decision-curve analysis was used to validate the net clinical benefit. Results: The sample distribution was similar in the two cohorts, and the 1-, 3-, and 5-year OS evaluation of the postoperative/preoperative platelet ratio was the largest for AUC in the two cohorts. Meanwhile, PPR has a good predictive value and a net clinical benefit. Conclusions: PPR has been identified and validated to be independently concerned about OS of patients with GC and was a reliable and economic indicator to evaluate the prognosis. [ABSTRACT FROM AUTHOR]

The albumin‐bilirubin (ALBI) score was originally used to accurately assess liver dysfunction and predict the prognoses of patients with hepatocellular carcinoma. Following its more recent application to patients with gastrointestinal tumors, this study analyzed the prognostic value of the ALBI score in Chinese patients with advanced resectable (tumor‐node‐metastasis [TNM] stages I–III) gastric cancer (GC). This study investigated 1185 patients with advanced GC, including 429 with TNM stage I. The patients were divided into training and verifications groups (593 and 592 patients, respectively) in which these patients were classified as high risk (ALBI score ≥ −2.65) or low risk (ALBI score < −2.65). Univariate and multivariate Cox regression analyses were performed, and a visual survival prediction model (nomogram) was created. On Kaplan–Meier analysis, patients who were low‐risk and high‐risk according to their ALBI scores had significantly different survival rates in both the training and verification groups (p < 0.01). The difference was also significant when analyzing only patients with TNM stage I GC (p = 0.031). Univariate and multivariate analyses showed that the ALBI score (p = 0.014), age (p < 0.001), Nutritional Risk Screening 2002 score (p = 0.024), sarcopenia (p = 0.049), tumor differentiation (p = 0.027), and TNM stage (p < 0.001) were independent risk factors for survival. Our survival prediction model that incorporated the ALBI score accurately predicted the 5‐year survival rate of Chinese patients with GC. Therefore, the ALBI score is a valid clinical indicator and good predictor of survival after surgery for progressive GC. Moreover, this score is simple to derive and does not burden patients with additional costs. [ABSTRACT FROM AUTHOR]

Malnutrition is common in the patients with gastric cancer. Radical gastrectomy remained the primary strategy of curable treatment for gastric cancer. This study is performed to explore the effect of laparoscopic radical gastrectomy on clinical outcomes in gastric cancer patients with malnutrition. Gastric cancer patients with GLIM-defined malnutrition between 2014 and 2019 at our center were enrolled. The patients were divided into two groups according to the different type of surgery. Propensity score match analysis was used to balance the clinicopathologic characteristics of two groups. Postoperative outcomes and survival were compared. Multivariate analysis was used to independent risk factors of complication, overall survival (OS), and disease-free survival (DFS). Compared with patients underwent open radical gastrectomy, patients who underwent laparoscopic radical gastrectomy had lower rate of total, surgical and severe complications. They also had shorter postoperative hospital stay with better OS and DFS. Hypoalbuminemia (P = 0.003) was the independent risk factor of complications. Old age (≥75, P = 0.035) and TNM stage (III: P < 0.001, II: P = 0.015) were the independent risk factors of OS. Combined resection (P = 0.003) and TNM stage (III: P < 0.001, II: P = 0.001) posed independent risk factors of lacking DFS. Laparoscopic surgery proved to be the independent protective factor of complications (P = 0.014), OS (P < 0.001) and DFS (P < 0.001). Laparoscopic radical gastrectomy was relative safe and showed favorable outcomes in malnourished gastric cancer patients. [ABSTRACT FROM AUTHOR]

Motivation The molecular subtyping of gastric cancer (adenocarcinoma) into four main subtypes based on integrated multiomics profiles, as proposed by The Cancer Genome Atlas (TCGA) initiative, represents an effective strategy for patient stratification. However, this approach requires the use of multiple technological platforms, and is quite expensive and time-consuming to perform. A computational approach that uses histopathological image data to infer molecular subtypes could be a practical, cost- and time-efficient complementary tool for prognostic and clinical management purposes. Results Here, we propose a deep learning ensemble approach (called DEMoS) capable of predicting the four recognized molecular subtypes of gastric cancer directly from histopathological images. DEMoS achieved tile-level area under the receiver-operating characteristic curve (AUROC) values of 0.785, 0.668, 0.762 and 0.811 for the prediction of these four subtypes of gastric cancer [i.e. (i) Epstein–Barr (EBV)-infected, (ii) microsatellite instability (MSI), (iii) genomically stable (GS) and (iv) chromosomally unstable tumors (CIN)] using an independent test dataset, respectively. At the patient-level, it achieved AUROC values of 0.897, 0.764, 0.890 and 0.898, respectively. Thus, these four subtypes are well-predicted by DEMoS. Benchmarking experiments further suggest that DEMoS is able to achieve an improved classification performance for image-based subtyping and prevent model overfitting. This study highlights the feasibility of using a deep learning ensemble-based method to rapidly and reliably subtype gastric cancer (adenocarcinoma) solely using features from histopathological images. Availability and implementation All whole slide images used in this study was collected from the TCGA database. This study builds upon our previously published HEAL framework, with related documentation and tutorials available at http://heal.erc.monash.edu.au. The source code and related models are freely accessible at https://github.com/Docurdt/DEMoS.git. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is an age-related syndrome that may have negative impact on surgical outcomes and long-term survival of patients with gastric cancer. Serum creatinine/cystatin C (Cr/CysC) ratio has attracted attention as a surrogate marker for sarcopenia but has not been adequately studied in patients with gastric cancer. The purpose of this study was to investigate the validity of serum Cr/CysC ratio as a predictor of sarcopenia, evaluate a statistical cut-off value, and assess the relationship between Cr/CysC ratio and prognosis of patients with gastric cancer.Methods: We retrospectively studied 327 patients who underwent surgery for gastric cancer from June 2009 to October 2021. The skeletal muscle mass index was calculated using computed tomography (CT). We determined the relevance of serum Cr/CysC ratio as a surrogate maker for sarcopenia by comparing it with various biomarkers. The Concordance index (C-index) was calculted to measure whether the Cr/CysC ratio can prognosis of patients with gastric cancer.Results: Serum Cr/CysC was significantly correlated with with Skeletal Muscle Index (SMI) (r = 0.221, p < 0.001) and Skeletal Muscle Area (SMA) (r = 0.258, p < 0.001). The area under the curve for sarcopenia was significantly larger for serum Cr/CysC ratio than for other biomarkers (Cr/CysC: 0.644, CysC: 0.535, Cr: 0.556). Patients in the high-Cr/CysC group have longer survival time than that in low-Cr/CysC group, defined by the cutoff value 0.67. The C-index of both Cr/CysC ratio and SMI with OS was 0.63.Conclusions: Serum Cr/CysC ratio can be used accurately, inexpensively, and easily to evaluate sarcopenia in male patients with gastric cancer. Our study shows that patients with Cr/CysC below 0.67 had possibility of sarcopenia and would be poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Asians have the highest incidence of gastric cancer (GC), and the prognosis of Asian GC is poor. Furthermore, the therapeutics for Asian GC is limited because of genetic heterogeneity and screening difficulty at the early stage. This study aimed to develop an immune-related gene (IRG)-based prognostic signature and to explore prognosis-related regulatory mechanism and therapeutic target for Asian GC. Methods: To elucidate the prognostic value of IRGs in Asian GC, a comprehensive analysis of IRG expression profiles and overall survival times in 364 Asian GC patients from the Asian Cancer Research Group (ACRG) and The Cancer Genome Atlas (TCGA) databases was performed, and a novel prognostic index was established. To further explore regulatory prognosis mechanisms and therapeutic targets, a tumor immunogenomic landscape analysis, including stromal and immune subcomponents, cell types, panimmune gene sets, and immunomodulatory genes, was performed. Result: Our analysis allowed the creation of an optimal risk assessment model, the Asian-specific IRG-based prognostic index (ASIRGPI), which showed a high accuracy in predicting survival in Asian GC. We also developed an ASIRGPI-based nomogram to predict the 3- and 5-year overall survival (OS) of Asian GC patients. The impact of the ASIRGPI on the worse prognosis of Asian GC was possibly related to the stromal component remodeling. Specifically, TGFβ gene sets were significantly associated with the ASIRGPI and worse prognosis. Immunomodulatory gene analysis further revealed that TGFβ1 and EDNRB may be the novel potential therapeutic targets for Asian GC. Conclusions: As a tumor microenvironment-relevant gene set-based prognostic signature, the ASIRGPI model provides an effective approach for evaluating the prognosis of Asian GC and may even prolong OS by enabling the selection of individualized therapy with the novel targets. [ABSTRACT FROM AUTHOR]

Background: Currently, there are shortcomings in diagnosing gastric cancer with or without serous invasion, making it difficult for patients to receive appropriate treatment. Therefore, we aimed to develop a radiomic nomogram for preoperative identification of serosal invasion. Methods: We selected 315 patients with gastric cancer, confirmed by pathology, and randomly divided them into two groups: the training group (189 patients) and the verification group (126 patients). We obtained patient splenic imaging data for the training group. A p-value of <0.05 was considered significant for features that were selected for lasso regression. Eight features were chosen to construct a serous invasion prediction model. Patients were divided into high- and low-risk groups according to the radiologic tumor invasion risk score. Subsequently, univariate and multivariate regression analyses were performed with other invasion-related factors to establish a visual combined prediction model. Results: The diagnostic accuracy of the radiologic tumor invasion score was consistent in the training and verification groups (p<0.001 and p=0.009, respectively). Univariate and multivariate analyses of invasion risk factors revealed that the radiologic tumor invasion index (p=0.002), preoperative hemoglobin <100 (p=0.042), and the platelet and lymphocyte ratio <92.8 (p=0.031) were independent risk factors for serosal invasion in the training cohort. The prediction model based on the three indexes accurately predicted the serosal invasion risk with an area under the curve of 0.884 in the training cohort and 0.837 in the testing cohort. Conclusions: Radiological tumor invasion index based on splenic imaging combined with other factors accurately predicts serosal invasion of gastric cancer, increases diagnostic precision for the most effective treatment, and is time-efficient. [ABSTRACT FROM AUTHOR]

Recent findings have demonstrated the superiority and utility of microRNAs (miRNAs) as new biomarkers for cancer diagnosis, therapy, and prognosis. In this study, to explore the prognostic value of immune-related miRNAs in gastric cancer (GC), we analyzed the miRNA-expression profiles of 389 patients with GC, using data deposited in The Cancer Genome Atlas database. Using a forward- and backward-variable selection and multivariate Cox regression analyses model, we identified a nine-miRNA signature (the "ImmiRSig," consisting of miR-125b-5p , miR-99a-3p , miR-145-3p , miR-328-3p , miR-133a-5p , miR-1292-5p , miR-675-3p , miR-92b-5p , and miR-942-3p) in the training cohort that enabled the division of patients into high- and low-risk groups with significantly different survival rates. The ImmiRSig was successfully validated with an independent test cohort of 193 GC patients. Univariate and multivariate Cox regression analyses indicated that the ImmiRSig would serve as an independent prognostic factor after adjusting for other clinical covariates. Pending further prospective validation, the identified ImmiRSig appears to have significant clinical importance in terms of improving outcome predictions and guiding personalized treatment for patients with GC. Finally, significant associations between the ImmiRSig and the half-maximal inhibitory concentrations of chemotherapeutic agents were observed, suggesting that ImmiRSig may predict the clinical efficacy of chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Liver dysfunction and chronic inflammation influence the prognosis of many tumors and surgical outcomes. This study was performed to determine whether the Fibrosis-4 (FIB-4) index, originally defined as a noninvasive fibrosis marker, can predict the prognosis of patients with gastric cancer undergoing radical gastric cancer surgery. Methods: We have retrospectively analyzed 594 consecutive patients with gastric cancer who underwent gastrectomy in our database. The FIB-4 index was calculated using laboratory data and age before gastrectomy. The clinical utility of FIB-4 was evaluated by X-tile. Patients were divided into two groups (high and low FIB-4 index groups), and their overall survival (OS) was investigated. Cox regression analysis was used to identify the independent parameters associated with prognosis. Finally, we developed a prognostic prediction model by using R statistical software. Results: A total of 556 patients, including 422 men and 134 women, were enrolled. Of these, 61 (11.0%) and 495 (89.0%) patients had low and FIB-4 indexes, respectively. In addition to the indicators of FIB-4, preoperative age, tumor site, surgical procedure, TNM stage, and postoperative complications were found to be independent predictors of prognosis (P < 0.05). Among patients, the FIB-4 index group had significantly shorter OS (log-rank P = 0.01) than the low FIB-4 index group. This association was also confirmed in the multivariate analysis (hazard ratio, 4.65; 95% confidence interval, 1.07-4.29; P = 0.031). Conclusions: Preoperative FIB-4 index can predict long-term outcomes of gastric cancer patients who had undergone gastrectomy. [ABSTRACT FROM AUTHOR]

Objectives: Nutrition status is of great significance to the clinical outcome after major abdominal surgery. However, the effect of preoperative short‐term parenteral nutrition (PN) support among gastric cancer (GC) patients remains unknown and was evaluated in the current study. Methods: We retrospectively analyzed 455 nutritionally at‐risk GC patients after radical resection from 2010 to 2016. We matched patients with 3–7 days of PN support to those without PN support. χ2 And Mann‐Whitney U tests were used to compare differences between the PN and control groups. Results: The propensity‐matched sample included 368 GC patients (PN group, n = 184; control group, n = 184). The PN and control groups did not differ regarding postoperative complications (P =.528). The incidence of anastomotic leakage in the PN group was lower than in the control group (P =.011), whereas other complications were not found to differ between the groups. The hospitalization cost of the PN group was significantly higher than that of the control group (P <.001), whereas other outcome indicators were similar. Subgroup analysis showed that short‐term PN support may have an improved benefit for patients with serum albumin level <35 g/L, but not at the level of statistical significance (P =.17). Conclusion: Short‐term PN support did not significantly improve the short‐term clinical outcomes of nutritionally at‐risk GC patients, with the exception of a lower incidence of anastomotic leakage. Considering that short‐term PN support increases economic burden, PN should not be the preferred method among these patients. [ABSTRACT FROM AUTHOR]

Malnutrition in patients with gastric cancer (GC) with normal body mass index (BMI) is often ignored. This study aimed to explore the role of sarcopenia in predicting postoperative complication and long‐term survival in patients with GC with normal BMI. We included patients with normal BMI (18.5 kg/m2 ≤ BMI < 23 kg/m2) who underwent radical gastrectomy between July 2014 and December 2016. Sarcopenia was assessed by muscle mass, handgrip strength, and gait speed. Kaplan–Meier survival analysis was used to analyze the association between sarcopenia and the prognosis of patients with GC. Univariate and multivariate analyses were used to identify risk factors contributing to postoperative complications and long‐term survival. Overall, 267 patients with GC with normal BMI were included in this study; of which 49 (18.35%) patients were diagnosed with sarcopenia. Patients with sarcopenia had higher incidence of a major postoperative complication, longer postoperative hospital stays, and greater hospital costs. The Kaplan–Meier survival analysis showed that patients with sarcopenia had poorer overall survival than non‐sarcopenia patients. Univariate and multivariate analyses showed that sarcopenia was an independent predictor for postoperative complication and long‐term survival in such patients. Sarcopenia is an independent predictor for postoperative complications and long‐term survival in patients with normal BMI after radical gastrectomy for GC. We recommend that patients with normal BMI should perform nutritional risk screening by sarcopenia. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) is an oncogenic virus associated with tumorigenesis. Our previous study revealed that the HCMV US31 gene interacted with NF-κB2 and mediated inflammation through macrophages. However, there are few reports on the role of US31 in gastric cancer (GC). The aim of this study was to investigate the expression of the US31 gene in GC tissue and assess its role in the occurrence and development of GC. US31 expression in 573 cancer tissues was analyzed using immunohistochemistry. Results showed that US31 was significantly associated with tumor size (P = 0.005) and distant metastasis (P < 0.001). Higher US31 expression indicated better overall survival in GC patients. Overexpression of US31 significantly inhibited the proliferation, migration, and invasion of GC cells in vitro (P < 0.05). Furthermore, expression levels of CD4, CD66b, and CD166 were positively correlated with US31, suggesting that it was involved in regulating the tumor immune microenvironment of GC. RNA sequencing, along with quantitative real-time polymerase chain reaction, confirmed that the expression of US31 promoted immune activation and secretion of inflammatory cytokines. Overall, US31 inhibited the malignant phenotype and regulated tumor immune cell infiltration in GC; these results suggest that US31 could be a potential prognostic factor for GC and may open the door for a new immunotherapy strategy. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the most common malignancies with high mortality and substantial morbidity. Although the traditional treatment strategies for GC revolve around surgery, radiotherapy, and chemotherapy, none have been able to optimally treat most affected patients. To improve clinical outcomes and overcome potential GC resistance, we established a three-dimensional (3D) culturing platform that accurately predicts drug responses in a time- and cost-effective manner. We collected tumor tissues from patients following surgeries and cultured them for 3 days using our protocol. We first evaluated cell proliferation, viability, and apoptosis using the following markers: Ki67 and cleaved caspase 3 (Cas3). We demonstrated that cell viability was maintained for 72 h in culture and that the tumor microenvironments and vascular integrities of the tissues were intact throughout the culture period. We then administered chemotherapeutics to assess drug responses and found differential sensitivity across different patient-derived tissues, enabling us to determine individualized medication plans. Overall, our study validated this rapid, cost-effective, scalable, and reproducible protocol for GC tissue culture that can be employed for drug response assessments. Our 3D culture platform paves a new way for personalized medication in GC and other tumors and can greatly impact future oncological research. [ABSTRACT FROM AUTHOR]

Background: Curing locally advanced gastric cancer through surgery alone is difficult. Adjuvant and neoadjuvant chemotherapy bring potential benefits to more patients with gastric cancer based on several clinical trials. According to phase II studies and guidelines, SOX regimen as neoadjuvant chemotherapy is efficient. However, the optimal duration of neoadjuvant chemotherapy has not been established. In this study, we will evaluate the efficacy and safety of different cycles of SOX as neoadjuvant chemotherapy for patients with locally advanced gastric cancer.Methods: RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study which will enroll 524 patients in total. Eligible patients will be registered, pre-enrolled and receive three cycles of SOX, after which tumor response evaluations will be carried out. Those who show stable disease or progressive disease will be excluded. Patients showing complete response or partial response will be enrolled and assigned into either group A for another three cycles of SOX (six cycles in total) followed by D2 surgery; or group B for D2 surgery (three cycles in total). The primary endpoint is the rate of pathological complete response and the secondary endpoints are R0 resection rate, three-year disease-free survival, five-year overall survival, and safety.Discussion: This study is the first phase III randomized trial to compare the cycles of neoadjuvant chemotherapy using SOX for resectable locally advanced cancer. Based on a total of six to eight cycles of perioperative chemotherapy usually applied in locally advanced gastric cancer, patients in group A can be considered to have completed all perioperative chemotherapy, the results of which may suggest the feasibility of using chemotherapy only before surgery in gastric cancer.Trial Registration: Registered prospectively in the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) with registration number ChiCTR1900023293 on May 21st, 2019. [ABSTRACT FROM AUTHOR]

Sarcopenia and metabolic syndrome (MetS) are associated with the prognosis from malignant tumors. However, evidence of the relationship between sarcopenia and MetS among gastric cancer (GC) patients following radical gastrectomy is lacking. This study assessed the association between preoperative sarcopenia and MetS among GC patients and analyzed the prognosis of patients with different malnutrition statuses. We prospectively assessed the preoperative statuses of sarcopenia and MetS among patients who underwent radical gastrectomy from July 2014 to December 2017. We combined sarcopenia and MetS to generate four groups: MetS-related sarcopenia group (MSS), sarcopenia group (S), MetS group (MS), and normal group (N). A total of 749 patients with resectable GC were included in this study. Preoperative MetS was associated with sarcopenia (p < 0.001). Multivariate logistic regression presented that MetS-related sarcopenia (OR = 2.445; p = 0.010) and sarcopenia alone (OR = 2.117; p = 0.001) were independent predictors of grade Ⅱ and above complications, while MetS alone was not (p = 0.342). Cox regression analysis revealed that MetS-related sarcopenia led to the worst prognosis in the four groups (MSS vs MS: HR = 3.555, p < 0.001; MSS vs N: HR = 2.020, p = 0.003; MSS vs S: HR = 1.763, p = 0.021). However, the MetS group had better prognosis than the normal group (MS vs N: HR = 0.568, p = 0.048). Preoperative MetS was associated with sarcopenia among GC patients. MetS-related sarcopenia resulted in a significantly worse prognosis. The long-term prognoses of patients with sarcopenia were impaired by preoperative MetS, while patients without sarcopenia benefited. Thus, patients with both sarcopenia and MetS require more medical interventions. • Preoperative MetS was associated with sarcopenia among GC patients. • MetS-related sarcopenia resulted in a significantly worse prognosis. • Prognoses of patients with sarcopenia were impaired by preoperative MetS. • Prognoses of patients without sarcopenia were benefited from MetS. • Patients with both sarcopenia and MetS require more medical interventions. [ABSTRACT FROM AUTHOR]

Radiomics allows for mining of imaging data to examine tissue characteristics non-invasively, which can be used to predict the prognosis of a patient. This study explored the use of imaging techniques to evaluate splenic tissue characteristics to predict the prognosis of patients with gastric cancer. Computed tomography images from patients with gastric cancer were collected retrospectively. Splenic image characteristics, extracted with pyradiomics, of patients in the training group were randomly divided. Characteristics with a P value < 0.1 were selected for lasso regression to construct a survival risk model. Models for high-and low-risk groups were established. Patients were divided into the high- and low-risk groups for univariate and multivariate regression analysis of survival-related factors, and a visual prognostic prediction model was established. The splenic characteristic prognostic model was consistent in the training and verification groups (p < 0.001 and p = 0.016, respectively). The two groups that displayed different splenic characteristics showed no statistical difference in other basic data except the tumour-node-metastasis (pTNM) stage (p = 0.007). Univariate and multivariate analysis of survival risk factors showed that splenic characteristics (p = 0.042), age (p < 0.001), tumor location (p = 0.002), and pTNM stage (p < 0.001) were independent risk factors for survival. The prognostic prediction model combined with splenic characteristics significantly improved the accuracy of prognosis, predicting one-and three-year survival rates. Splenic features extracted from imaging technology can accurately predict the long-term survival of patients with gastric cancer. Splenic characteristic grouping can effectively improve the accuracy of survival prediction and gastric cancer prognosis. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MetS), a public health problem, is reportedly related to an increased risk of postoperative complications after surgery. However, whether MetS have an effect on complications after gastric cancer (GC) surgery are unknown. This study aimed to investigate the effects of preoperative MetS on complications after gastrectomy. Methods: Altogether, 718 gastric cancer patients who planned to receive radical gastrectomy between June 2014 and December 2016 were enrolled, demographic and clinicopathological characteristics were analyzed. Univariate and multivariate analyses were performed to identify potential risk factors for postoperative complications. A predictive model for postoperative complications was constructed in the form of a nomogram, and its clinical usefulness was assessed. Results: Of the 628 patients ultimately included in the study (mean age 62.92 years, 450 men and 178 women), 84 were diagnosed with MetS preoperatively. Severe postoperative complications (Clavien‐Dindo grade ≥II) were significantly more common in patients with MetS (41.7% versus 23.7%, P <.001). Predictors of postoperative complications included MetS (odds ratio [OR] = 1.800, P =.023), age (OR = 1.418, P =.050), Charlson score (OR = 1.787, P =.004 for 1‐2 points) and anastomosis type (OR = 1.746, P =.007 for Billroth II reconstruction). The high‐risk rating had a high AUC (ROC I = 0.503, ROC Ib = 0.544, ROC IIa = 0.601, ROC IIb = 0.612, ROC IIc = 0.638, ROC III = 0.735), indicating that the risk‐rating model has good discriminative capacity and clinical usefulness. Conclusions: MetS was an independent risk factor for complications after gastrectomy. The nomogram and rating model incorporating MetS, Billroth II anastomosis, age, and Charlson score was useful for individualized prediction of postoperative complications. [ABSTRACT FROM AUTHOR]

Purpose: Although peritoneal metastasis (PM) is associated with poor prognosis in gastric cancer (GC) patients, it is difficult to discriminate preoperatively. Our previous study has demonstrated visceral fat area (VFA) is a better obesity index than body mass index (BMI) in predicting abdominal metastasis. This study aimed to further explore the relationship between obesity and PM. Patients and Methods: VFA was retrieved for 859 consecutive patients undergoing radical gastrectomy between January 1, 2009, and December 31, 2013. A receiver operating characteristic curve analysis was used to determine the BMI-specific cutoff values for VFA. Univariate and multivariate analyses evaluating the risk factors for PM at different BMI levels were performed. Results: The optimal cutoff values for VFA were 67.28, 88.03, and 175.32 cm2 for low, normal, and high BMI patients, respectively, and 18 (15.52%), 220 (40.15%), and 61 (31.28%) patients were classified as having high VFA in each group. Univariate logistic regression revealed that the association between high VFA and PM was not dependent on BMI (odds ratio [OR]=9.048, P=0.007 for low BMI, OR=3.827, P< 0.001 for normal BMI, and OR=2.460, P=0.049 for high BMI). In multivariate logistic regression analysis, high VFA (OR=3.816, P< 0.001) and vascular invasion (OR=1.951, P=0.039) were independent risk factors for PM only in the normal BMI group. Conclusion: VFA only effectively predicted PM for GC patients with normal BMI, rather than those with low and high BMI. More attentions should be paid to those GC patients with high VFA and normal BMI. [ABSTRACT FROM AUTHOR]

Objectives: The present study aimed to explore the association between spleen density and post-operative outcomes of patients after curative gastrectomy. Methods: From June 2014 to December 2015, we conducted a retrospective study to analyze pertinent clinical data from gastric cancer patients who underwent gastrectomy at the First and the Second Affiliated Hospital of Wenzhou Medical University. Spleen density was determined via computed tomography scans. Univariate and multivariate analyses were performed to determine the risk factors associated with post-operative outcomes after gastric cancer surgery. Results: Three hundred and ninety five patients were included, of whom 98 (24.8%) were defined as having a diffuse reduction of spleen density based on diagnostic cutoff values (spleen density ≤43.89 HU). Multivariate analysis revealed diffuse reduction of spleen density as an independent risk factor for post-operative complications and long-term overall survival. Conclusions: Spleen density can predict severe postoperative complications and long-term overall survival in gastric cancer patients. As an imaging evaluation method, spleen density is a novel tool can be used in clinical as a prognostic predictor for patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Purpose: We previously found that human cytomegalovirus (HCMV) infection is associated with gastric cancer (GC) development. UL111A plays a role during HCMV productive or latent infection. However, UL111A expression profiles in GC tissues and their relationship with this disease are unknown. Methods: PCR and nested RT-PCR were performed to verify UL111A expression in 71 GC tissues and its transcripts in 16 UL111A-positive GC samples. UL111A expression levels in GC patients were evaluated by immunohistochemistry on a tissue microarray for 620 GC patients. The correlations among UL111A expression levels, clinicopathological characteristics, and prognosis were analyzed. Further, the effects of overexpression of latency-associated viral interleukin-10 (LAcmvIL-10) and cmvIL-10 on GC cell proliferation, colony formation, migration, and invasion were assessed. Results: The UL111A detection rate in GC tissues was 32.4% (23/71) and that of its mRNA expression was 68.75% (11/16). High expression of UL111A was also related to better overall and disease-free survival in GC patients. GC patients with TNM II/III stage expressing higher UL111A levels might benefit from adjuvant chemotherapy (ACT) after surgery. Moreover, high UL111A expression was also associated with increased CD4+ , CD8+ T-lymphocyte and Foxp3+ T-cell infiltration. In vitro assays further demonstrated that LAcmvIL-10 and cmvIL-10 overexpression inhibits GC cell line proliferation, colony formation, migration, and invasion. Conclusions: High UL111A expression changes the number of infiltrating T cells and is associated with favorable survival. Therefore, UL111A could be used as an independent prognostic biomarker and might be a potential therapeutic target for GC. [ABSTRACT FROM AUTHOR]

Background: Hyponatremia and hypocalcemia are common in patients with cancer, but their prognostic impact in patients who underwent gastric cancer (GC) surgery has not been investigated. Therefore, this study aimed to determine the postoperative prognostic impact of hyponatremia and hypocalcemia in patients undergoing curative gastrectomy by age group. Materials and methods: GC patients preoperatively diagnosed with hyponatremia or hypocalcemia who underwent elective radical gastrectomy were retrospectively evaluated. The patients were divided into the elderly group (≥60 years) and the young group (<60 years), and then further based on their sodium and calcium levels. The effect of preoperative hyponatremia or hypocalcemia on postoperative complications (PCs) by age was determined using univariate and multivariate analyses. Overall survival (OS) was compared between the two groups using log rank test and Cox proportional hazards regression. Results: Of the 842 patients evaluated, 36 (4.3%) were categorized into the younger hyponatremia group; 64 (7.6%), the elderly hyponatremia group; 48 (5.7%), the young hypocalcemia group; and 128 (15.2%), the elderly hypocalcemia group. Hyponatremia (P=0.001) and hypocalcemia (P=0.038) were independent risk factors for PCs in the elderly group. Further, hypocalcemia (hazard ratio (HR), 0.676; P=0.037) was independently associated with shorter OS. Conclusion: Preoperative hyponatremia and hypocalcemia predict poor outcomes in the elderly, but not in young GC patients. Further, hyponatremia and hypocalcemia in elderly GC patients should be corrected in the earliest time possible to obtain better clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Cachexia affects nearly 50–80% of cancer patients, and most studies have only focused on elderly patients. We investigated preoperative cachexia in gastric cancer (GC) patients by age group and comprehensively analyzed the impact of preoperative cachexia on the prognosis of GC patients in all age groups. Methods: In total, 575 patients were prospectively analyzed. The effect of preoperative cachexia on overall survival (OS) in all the patients and in patients with different age groups were investigated using log-rank test and Cox proportional hazards regression, respectively. Results: In total, 35.8% (206 of 575) individuals were diagnosed with cachexia. The median survival of cachexia patients (29.2 months) was shorter than that of non-cachexia patients (35.7 months). Cachexia (HR =1.976, P<0.001), age (HR =1.811, P<0.001), readmission (HR =2.559, P<0.001), tumor size (HR =1.639, P=0.003), TNM stage (stage II: HR =2.215, P=0.017; stage III: HR =5.758, P<0.001), whole stomach cancer (HR =2.639, P<0.001), and combined operation (HR =1.598, P=0.032) were independently associated with worse OS. After grouping by age, cachexia was associated with OS in patients younger than 50 years old (HR =4.947, P=0.029), patients 51–60 years old (HR =2.232, P=0.026), and patients 61–70 years old (HR =1.806, P=0.032), but not in patients older than 71 years (HR =1.411, P=0.119). Further, cachexia only significantly affected the postoperative length of stay (P=0.015) and hospitalization costs (P=0.032) in patients younger than 50 years old. Conclusions: Preoperative cachexia predicts poor outcome in younger GC patients, and greater attention should be paid to these patients. [ABSTRACT FROM AUTHOR]

The association between sarcopenia and postoperative outcomes in patients who undergo laparoscopic-assisted gastrectomy is unclear. We aimed to determine the predictive value of sarcopenia for adverse postoperative outcomes after laparoscopic-assisted gastrectomy for gastric cancer. We prospectively collected the clinical data of patients who underwent elective radical laparoscopic-assisted gastrectomy for gastric cancer in two large centers from August 2014 to October 2017. The third lumbar vertebra skeletal muscle index, handgrip strength, and 6-m usual gait speed were measured to diagnose sarcopenia. Subsequently, we aimed to identify the risk factors for postoperative complications. The study included 313 patients and 37 (11.8%) patients were classified as sarcopenic. Compared with non-sarcopenic patients, sarcopenic patients were significantly older (P < 0.001), had higher nutritional risk screening 2002 scores (P = 0.013), Charlson comorbidity index (CCI) scores (P = 0.033), and neutrophil to lymphocyte ratio (P = 0.004), and lower body mass index (P < 0.001), preoperative serum albumin (P < 0.001), and hemoglobin (P < 0.001). Sarcopenic patients had higher postoperative complication rate (P = 0.002), longer postoperative hospital stays (P = 0.020) and higher total cost of hospitalization (P = 0.001). Multivariate analysis revealed that CCI score ≥1 (odds ratio [OR]: 2.424, 95% confidence interval [CI]: 1.309–4.487; P = 0.005) and sarcopenia (OR: 2.752, 95% CI: 1.274–5.944; P = 0.010) were independent risk factors for short-term postoperative complications. Sarcopenia is an independent clinical predictor of short-term postoperative complications after laparoscopic-assisted gastrectomy. [ABSTRACT FROM AUTHOR]

Abnormal regulation of long non‑coding RNAs (lncRNAs) appears to be a primary feature of numerous types of human cancer. However, the association between the dysregulation of lncRNAs and functional alterations in gastric cancer (GC) remains unclear. In previous studies, we applied microarray and bioinformatics analyses to screen for key lncRNAs from the tumor tissues and matched adjacent non‑tumor tissues of 10 patients with GC. There were seven key lncRNAs demonstrated to be significantly different between carcinoma tissues and adjacent non‑tumor tissues. In the present study, the expression of these seven selected lncRNAs were validated in 82 patients with GC to further investigate the association between lncRNAs and GC clinical characterization. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) results demonstrated that RP5‑919F19, MCPH1 antisense RNA 1 (CTD‑2541M15) and urothelial carcinoma‑associated 1 (UCA1) exhibited consistent upregulation in cancer compared with adjacent non‑tumor tissues, whereas AP000459, LOC101928316, tumor suppressor candidate 8 (LINC01071) and maternally expressed 3 (MEG3) showed consistent downregulation. The results from the microarray and RT‑qPCR experiments achieved 100% agreement. A correlation analysis indicated that RP5‑919F19, LOC101928316 and MEG3 were significantly associated with tumor differentiation degree, RP5‑919F19, UCA1 and MEG3 were significantly associated with lymph node metastasis, and RP5‑919F19, CTD‑2541M15 and UCA1 were significantly associated with tumor‑node‑metastasis stage (P<0.05). In addition, it was identified that the differential expression of LINC01071 and LOC101928316 significantly correlated with the age and gender of the GC patients, respectively (P<0.05). The results suggest that the lncRNAs RP5‑919F19, LOC101928316, CTD‑2541M15, UCA1 and MEG3 are closely associated with the invasion and metastasis of GC, which reveals these indicators as potential specificity biomarkers for the diagnosis, prognosis and classification of GC. Thus, these lncRNAs merit further study as novel candidate biomarkers for the clinical diagnosis of GC and as potential targets for therapy. [ABSTRACT FROM AUTHOR]

In addition to regulating apoptosis via its interaction with the death domain of Fas receptor, death domain associated protein 6 (Daxx) is also known to be involved in transcriptional regulation, suggesting that the function of Daxx depends on its subcellular localization. In this study, we aimed to explore Daxx subcellular localization in gastric cancer ( GC) cells and correlate the findings with clinical data in GC patients. Seventy pairs of tissue samples ( GC and adjacent normal tissue) were analyzed immunohistochemically for Daxx expression and localization (nuclear and cytoplasmic). The Daxx Nuclear/Cytoplasmic ratio (Daxx NCR) values in tissue microarray data with 522 tumor samples were further analyzed. The defined Prior cohort ( n = 277, treatment between 2006 and 2009) and Recent cohort ( n = 245, treatment between 2010 and 2011) were then used to examine the relationship between Daxx NCR and clinical data. The Daxx NCR was found to be clinically informative and significantly higher in GC tissue. Using Daxx NCR (risk ratio = 2.0), both the Prior and Recent cohorts were divided into high- and low-risk groups. Relative to the low-risk group, the high-risk patients had a shorter disease free survival ( DFS) and overall survival ( OS) in both cohorts. Importantly, postoperative chemotherapy was found having differential effect on high- and low-risk patients. Such chemotherapy brought no survival benefit, (and could potentially be detrimental,) to high-risk patients after surgery. Daxx NCR could be used as a prognosis factor in GC patients, and may help select the appropriate population to benefit from chemotherapy after surgery. [ABSTRACT FROM AUTHOR]

Transmembrane protease serine 4 (TMPRSS4) is a type-II transmembrane serine protease that is frequently upregulated in human cancers. However, little is known about the biological roles of TMPRSS4 in gastric cancer. In this study, we examined the effect of TMPRSS4 on gastric cancer cell proliferation, migration, and invasion. The expression and secretion of matrix metalloproteinase-9 (MMP-9) and activation of nuclear factor-κB (NF-κB) were determined. The involvement of NF-κB/MMP-9 signaling was checked. Our data showed that TMPRSS4 silencing significantly ( P < 0.05) reduced the migration and invasion of AGS and MKN-45 gastric cancer cells, without affecting cell proliferation. Overexpression of TMPRSS4 significantly promoted cell migration and invasion. The expression and secretion of MMP-9 was significantly ( P < 0.05) enhanced in TMPRSS4-overexpressing cells. TMPRSS4-overexpressing cells had a significantly ( P < 0.05) lower level of IκBα and higher level of nuclear NF-κB. Luciferase reporter assay confirmed that overexpression of TMPRSS4 resulted in a 3–5-fold increase in NF-κB-dependent luciferase activity. Downregulation of MMP-9 significantly ( P < 0.05) reversed the invasiveness of gastric cancer cells induced by TMPRSS4 overexpression. Moreover, pharmacological inhibition of NF-κB attenuated the invasion of TMPRSS4-overexpressing cells and the expression of MMP-9. Upregulation of TMPRSS4 enhances the invasiveness of gastric cancer cells, largely through activation of NF-κB and induction of MMP-9 expression. Our study provides the rationale for targeting TMPRSS4 in the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: As a pro-inflammatory cytokine, IL-33 has been demonstrated to play an important role in tumor progression. It is reported that IL-33 is highly expressed in the serum and tumor tissues of patients with gastric cancer. However, the function of IL-33 in gastric cancer remains elusive. We here tried to elucidate the effects of IL-33 on gastric cancer cell invasion and migration. Methods: Invasion assay and migration assay were performed to assess the effects of IL-33 on gastric cancer cell invasion and migration. ST2 receptor was silenced by siRNA, and ERK1/2 pathway was inhibited by U0126. Protein levels of MMP-3 and IL-6 in cell supernatant were measured by ELISA. Results: IL-33 promoted the invasion and migration of gastric cancer cells, in a dose-dependent manner. Knockdown of the IL-33 receptor ST2 attenuated the IL-33-mediated invasion and migration. Furthermore, via ST2 receptor, IL-33 induced the activation of ERK1/2 and increased the secretion of MMP-3 and IL-6. In addition, blockage of ERK1/2 pathway resulted in inhibition of invasion and migration induced by IL-33, and downregulation of MMP-3 and IL-6 production. Conclusions: IL-33 promotes gastric cancer cell invasion and migration by stimulating the secretion of MMP-3 and IL-6 via ST2-ERK1/2 pathway. Thus, IL-33 may be a useful marker for the diagnosis and treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the significance of MAGE-A3 novel immunodominant epitopes in serological diagnosis of gastric cancer. Methods: B cell, CTL, and Th epitopes of MAGE-A3 were analyzed using computer-assisted techniques. Three possible immunodominant epitope peptides located at 5aa-23aa (QRSQHCKPEEGLEARGEAL), 112aa-131aa (KVAELVHFLLLKYRAREPVT), and 232aa-246aa (EGREDSILGDPKKLL) with potential B cell-dominant epitope, high-score HLA-A2 and A24 restriction CTL epitope, and HLA-DRB restriction Th epitope were selected. After optimized by prokaryotic codon, these genes were expressed as Trx-His-tag recombinant proteins in Escherichia coli and purified by Ni-NTA agarose beads. Three recombinant proteins were identified by Western blotting using His-tag monoclonal antibody and the serum antibodies from the patient of gastric cancer. The level of specific antibodies in the sera from 210 patients with gastric cancer, 56 patients with chronic gastritis, and 116 healthy controls was further analyzed by indirect ELISA. Results: Three MAGE-A3 epitope recombinant proteins about 20 kDa molecular weight were specifically recognized by His-tag monoclonal antibody and the serum of gastric cancer patients. ELISA based on the epitope recombinant protein indicated that gastric cancer patients had significantly higher reactivity to these immunodominant epitope proteins compared with chronic gastritis and healthy individuals ( P < 0.05). Furthermore, the serum antibody positive rate in the gastric cancer group was also significantly higher than that in the chronic gastritis patients and healthy controls ( P < 0.05), while there was no significant difference in gastritis group and the healthy control group ( P > 0.05). Conclusions: These study results demonstrated that these three predictive epitopes may be potential targets for applications in the design of serological diagnosis tools for gastric cancer. [ABSTRACT FROM AUTHOR]

Recognized as a group I carcinogen for gastric cancer (GC) and a factor involved in the development of GC, Helicobacter pylori serves a major part in GC research. However, most studies have focused on H. pylori itself, ignoring the complicated pathogenic microbiological environment of GC and neglecting the synergistic or antagonistic effects of H. pylori with other pathogenic microorganisms. Increasing evidence has revealed that the human cytomegalovirus (HCMV) is present in several types of tumors and serves an important role in the neoplastic process of certain human malignant tumors, including GC. The aim of the present study was to explore the role of HCMV and H. pylori co-infection in GC. HCMV and H. pylori infection was analyzed in paired gastric tumor and peri-tumoral tissues from 134 (98 male and 36 female) patients using PCR. The results revealed that a total of 74 (55.2%) patients had H. pylori infection, 58 patients (43.3%) had HCMV infection, and 34 (25.4%) patients had both HCMV and H. pylori infection. Univariate and multivariate analyses demonstrated that H. pylori infection was independently associated with advanced lymphatic metastasis [P=0.007; odds ratio (OR)=3.51]. Furthermore, compared with HCMV−/H. pylori−, neither HCMV+/H. pylori− nor HCMV+/H. pylori+ were associated with metastasis, but HCMV−/H. pylori+ co-infection status was an independent risk factor for advanced lymphatic metastasis (P=0.005; OR=6.00). In conclusion, GC co-infected with HCMV and H. pylori exhibited a low tendency of lymph node metastasis. HCMV may interact with H. pylori to inhibit the process of lymphatic metastasis, and the mechanism requires further investigation. [ABSTRACT FROM AUTHOR]

Gastric cancer is the fifth most frequently diagnosed malignant neoplasm and the third leading cause of cancer-related mortality. Nevertheless, the therapeutic efficacy of conventional surgical and chemotherapeutic interventions in clinical practice is often unsatisfactory. Curcumin (Cur) has shown promise as a therapeutic agent in prior studies. However, its progress in this context has been impeded by challenges including low solubility, instability in aqueous environments, and rapid metabolism. In this study, we develop methacrylate fish gelatin (FGMA) hydrogel microparticles (FGMPs@Cur) encapsulating Cur via microfluidic electrospray technology for postoperative comprehensive treatment of gastric cancer. Comprehensive characterizations and analyses were conducted to assess the cytotoxicity against gastric cancer cells and potential tissue reparative effects of FGMPs@Cur. In vitro experiments revealed that FGMPs@Cur exhibited a remarkable cytotoxic effect on nearly 80 % of gastric cancer cells while maintaining at least 95 % viability of normal cells in cell compatibility tests. In vivo results demonstrated that FGMPs@Cur significantly reduced tumor volume to 47 % of the control group, and notable tissue regeneration was observed at the surgical site. These properties indicated that such a hydrogel microparticle system is a promising candidate for postoperative gastric cancer treatment in practical application. [Display omitted] [ABSTRACT FROM AUTHOR]

Accurate evaluation of muscle strength and function is difficult. Commonly known as sarcopenia, skeletal muscle loss is closely correlated with the prognosis of patients diagnosed with gastric cancer (GC). We wondered the correlation between skeletal muscle measures combined with computed tomography and grip strength (GS) and short-term outcomes after radical gastrectomy (RG) in patients with GC. We analyzed 594 patients with GC who underwent RG. The skeletal muscle index (SMI), skeletal muscle density (Hounsfield unit average calculation [HUAC]), and GS were measured. The skeletal muscle gauge (SMG) was created by multiplying SMI and HUAC. Logistic regression modeling and multivariate analysis were used. Univariate analysis showed that low SMI, low HUAC, low GS, and low SMG were predictors of short-term complications after surgery. Compared with other muscle-related factors (AUC HUAC = 0.559, AUC SMI = 0.575, AUC GS = 0.580, AUC SMG = 0.598, AUC SMI+GS = 0.559), low GS plus SMG (AUC GS plus SMG = 0.614, P < 0.01) was a more accurate independent risk factor for postoperative complications. Moreover, the risk model with SMG plus GS for the diagnosis of skeletal muscle loss was superior to the other models (c-index = 0.729). Skeletal muscle measures using computed tomography and GS are closely correlated with short-term outcomes of patients diagnosed with GC after RG. The model contained SMG plus GS could effectively predict for patients with GC after RG at high risk of short-term outcomes. SMG plus GS has the highest accuracy for the several evaluation methods of sarcopenia. [ABSTRACT FROM AUTHOR]

Background Precise determination of the lymph node status is critical for determining appropriate treatment for early gastric cancer (EGC). This study attempted to establish a simple, effective risk scoring system to predict lymph node metastasis (LNM) in EGC by investigating the relationship between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) and EGC LNM. Materials and methods We retrospectively reviewed 312 operable patients with EGC. The clinical utility of PLR and NLR was tested by receiver operating characteristic curves. The scoring system was developed using independent risk factors. Finally, 89 EGC patients were collected from prospective database to validate the scoring system's accuracy. Results The optimal PLR and NLR cut-off values were 106 and 2.97, respectively. High NLR ( P = 0.009) and PLR ( P = 0.007) values were associated with LNM of EGC in univariate analyses, although only high PLR ( P = 0.025) was an independent risk factor in multivariate analyses, together with age ( P = 0.009), differentiation ( P = 0.017), invasive depth ( P < 0.001), and tumor size ( P = 0.003). The scoring system's accuracy for retrospective and prospective data was 0.781 (95% confidence interval: 0.721-0.841) and 0.817 (95% confidence interval 0.714-0.920), respectively. Conclusions Preoperative PLR and NLR correlate with EGC LNM. Our scoring system is reliable, accurate, and effective in predicting LNM in EGC patients. [ABSTRACT FROM AUTHOR]

• Microcapsules can serve as drug carriers for local delivery. • We prepare suspended bubble microcapsules to improve their retention at stomach. • The bubble microcapsules are generated via microfluidics and a cavitation process. • Both hydrophilic and hydrophobic drugs are encapsulated. • The bubble microcapsules demonstrate good therapeutic efficacy to gastric cancer. Microcapsules are promising drug carriers for disease treatment. Specifically, for drug delivery in the stomach, a key point is to enable retention of the carriers regardless of gastric emptying and peristalsis. Here, we designed novel drug-loaded bubble microcapsules, which were prepared by microfluidic technology and used for oral drug delivery. The bubble microcapsules were composed of a PLGA shell and a bubble core, which was derived from osmotic-triggered cavitation. The PLGA shell ensured efficient drug encapsulation and sustained release; the bubble core enabled retention of the microcapsules in the stomach and thus facilitated long-term treatment. Based on this, we confirmed anti-tumor effects of drug-loaded bubble microcapsules in vivo and in vitro. The drug-loaded bubble microcapsules significantly inhibited the growth and metastasis of tumors. These results suggest that the suspended bubble microcapsules can be used as an ideal drug release platform for cancer therapy. It is foreseeable that the suspension bubble microcapsules prepared by this method would have broader application prospects as oral delivery vehicles for the treatment of gastrointestinal diseases. [ABSTRACT FROM AUTHOR]