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

BackgroundSerum 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.MethodsA 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.ResultsUltimately, 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.ConclusionsThe 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.

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 .

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

Purpose – Effective and efficient supply chain coordination requires the integration of all product flow processes. However, inconsistent empirical results have been obtained with respect to the relationships between supply chain integration (SCI) and performance. Drawing on efficiency-flexibility arguments, this paper seeks to develop a SCI model that includes buyer-supplier-supplier relationships, and proposes a contingency framework for reexamining the SCI-supplier performance relationship under demand and technological uncertainties. Design/methodology/approach – A two-stage data collection process was conducted, and a total of 878 suppliers that listed in the Taiwanese “Center-Satellite Production System” with supply contract were contacted for this study. Finally 164 suppliers were gathered and screened as valid responses. Hierarchical regression analysis was used to test the hypotheses in this study. Findings – Evidence indicates that SCI has a significant positive effect on the suppliers' performance. The positive SCI-performance relationship can be moderately weakened by demand uncertainty; however, this positive SCI-performance relationship will be strengthened by technological uncertainty. Originality/value – While supply chain management is needed to manage the vertical and horizontal relationships simultaneously, this study offers a framework to solve efficiency-flexibility dilemma arguments when dealing with “exploitation” and “exploration” alternatives to help to reexamine the inconsistent SCI-performance relationship. Furthermore, based on transaction cost theory, this paper takes the nature of uncertainty into account for improving the theoretical background of the SCI-performance relationship arguments. Empirical results indicate the existence of an ambidextrous supply chain integration strategy which justifies the choice of which one is preferable in efficiency-flexibility dilemma arguments.

Indocyanine green (ICG) fluorescence imaging-guided lymphadenectomy has been demonstrated to be effective in increasing the number of lymph nodes (LNs) retrieved in laparoscopic gastrectomy for gastric cancer (GC). Previously, we reported the primary outcomes and short-term secondary outcomes of a phase 3, open-label, randomized clinical trial (NCT03050879) investigating the use of ICG for image-guided lymphadenectomy in patients with potentially resectable GC. Patients were randomly (1:1 ratio) assigned to either the ICG or non-ICG group. The primary outcome was the number of LNs retrieved and has been reported. Here, we report the primary outcome and long-term secondary outcomes including three-year overall survival (OS), three-year disease-free survival (DFS), and recurrence patterns. The per-protocol analysis set population is used for all analyses (258 patients, ICG [n = 129] vs. non-ICG group [n = 129]). The mean total LNs retrieved in the ICG group significantly exceeds that in the non-ICG group (50.5 ± 15.9 vs 42.0 ± 10.3, P  < 0.001). Both OS and DFS in the ICG group are significantly better than that in the non-ICG group (log-rank P  = 0.015; log-rank P  = 0.012, respectively). There is a difference in the overall recurrence rates between the ICG and non-ICG groups (17.8% vs 31.0%). Compared with conventional lymphadenectomy, ICG guided laparoscopic lymphadenectomy is safe and effective in prolonging survival among patients with resectable GC. Due to high rate of metastasis, lymphadenectomy is a cornerstone of the surgical treatment of gastric cancer however the accurate dissection of lymph nodes (LN) can be challenging. Here, the authors present the long-term outcomes of a randomised control trial investigating indocyanine green fluorescence image-guided LN retrieval in gastric cancer patients undergoing laparoscopic gastrectomy.

Background Tumor-infiltrating immune cells are present in various malignant tumors, but their clinical significance in gastric cancer (GC) remains unclear. This study aimed to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). Methods Using a prospective database containing 401 cases of GC, we evaluated TIL (cluster of differentiation 8 (CD8) expression) and TAM (cluster of differentiation 68 (CD68) expression) statuses via immunohistochemical staining. Results Compared with CD8+ TIL-negative cases ( n  = 196, 48.6%), CD8+ TIL-positive cases ( n  = 205, 51.1%) showed significantly better recurrence-free survival (RFS) [log-rank p <0.001; multivariate HR: 0.372; 95% confidence interval (CI): 0.239–0.579, p <0.001]. In contrast, compared with CD68+ TAM-negative cases ( n  = 217, 54.1%), CD68+ TAM-positive cases ( n  = 184, 45.9%) had significantly poor RFS [log-rank p <0.001; multivariate HR: 2.182; 95% CI: 1.435–3.318, p <0.001]. Thus, patients with a positive CD8+ TIL and negative CD68+ TAM status exhibited significantly increased RFS. Multivariate analysis demonstrated that CD8+ TILs and CD68+ TAMs may serve as independent prognostic markers for RFS. Incorporating CD8+ TIL and CD68+ TAM statuses into the AJCC TNM system generated a predictive model with better predictive accuracy for RFS. More importantly, patients with a positive TIL and negative TAM status showed a tendency of improved RFS after postoperative adjuvant chemotherapy (PAC). Similar results were obtained by overall survival (OS) analysis. Conclusions CD8+ TIL and CD68+ TAM statuses were identified as independent prognostic factors that may be integrated into the current TNM staging system to refine risk stratification and to better predict the survival benefit from PAC in patients with GC. Trial registration The current controlled trial was registered at ClinicalTrials.gov (ID: NCT02327481 ) on December 30, 2014.

This study extends the idea of subsidiary ambidexterity as a subsidiary’s attempt to obtain a fit between its dual embeddedness (i.e. ambidextrous contexts) and its learning strategy (i.e. ambidextrous behaviors). We design a dyadic survey to collect data from Taiwanese MNEs and their Chinese subsidiaries to test our arguments. First, we redefine subsidiary ambidexterity as a three-step mechanism in which three different types of dual embeddedness will cause different legitimacy effects (resource or conformity effect), which will then result in a subsidiary’s different learning strategies. Second, we propose three different subsidiary ambidexterity patterns: (1) a subsidiary will prefer in maintaining higher external than internal political embeddedness, which leads to their focusing on exploitation (an adaptability case of ambidexterity); (2) a subsidiary will intend to develop both high external and high internal cultural embeddedness and that will cause them to explore and exploit simultaneously (an alignment case of ambidexterity); and (3) in sometimes a subsidiary will prefer to maintain higher external than internal cognitive embeddedness and that will lead the subsidiary to emphasize exploration, whereas in other times a subsidiary will prefer to have higher internal cognitive than external cognitive embeddedness and that will lead the subsidiary to emphasize exploitation (a balancing case of ambidexterity). Our view can largely contribute to the subsidiary learning literature.

Prospective evidence regarding the combination of programmed cell death (PD)−1 and angiogenesis inhibitors in treating locally advanced gastric cancer (LAGC) is limited. In this multicenter, randomized, phase 2 trial (NCT04195828), patients with gastric adenocarcinoma (clinical T2-4N + M0) were randomly assigned (1:1) to receive neoadjuvant camrelizumab and apatinib combined with nab-paclitaxel plus S-1 (CA-SAP) or chemotherapy SAP alone (SAP) for 3 cycles. The primary endpoint was the major pathological response (MPR), defined as <10% residual tumor cells in resection specimens. Secondary endpoints included R0 resection rate, radiologic response, safety, overall survival, and progression-free survival. The modified intention-to-treat population was analyzed (CA-SAP [ n  = 51] versus SAP [ n  = 53]). The trial has met pre-specified endpoints. CA-SAP was associated with a significantly higher MPR rate (33.3%) than SAP (17.0%, P  = 0.044). The CA-SAP group had a significantly higher objective response rate (66.0% versus 43.4%, P  = 0.017) and R0 resection rate (94.1% versus 81.1%, P  = 0.042) than the SAP group. Nonsurgical grade 3-4 adverse events were observed in 17 patients (33.3%) in the CA-SAP group and 14 (26.4%) in the SAP group. Survival results were not reported due to immature data. Camrelizumab and apatinib combined with chemotherapy as a neoadjuvant regimen was tolerable and associated with favorable responses for LAGC. Neoadjuvant treatment represents a therapeutic option for locally advanced gastric cancer (LAGC). Here the authors report the results of a randomized phase 2 trial of camrelizumab (anti-PD1) and apatinib (anti-VEGFR2) combined with nab-paclitaxel plus S-1 versus chemotherapy alone as neoadjuvant treatment for LAGC.

BackgroundThe definition and predictors of early recurrence (ER) for gastric cancer (GC) patients after radical gastrectomy are unclear.MethodsA 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.ResultsA 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).ConclusionsA 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.