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Background: Clinical T4 (cT4) stage gastric cancer presents with frequent postoperative recurrence and poor prognosis. This study is to evaluate the oncological efficacy of laparoscopic radical total gastrectomy combined with postoperative prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with cT4N + M0 gastric cancer who received neoadjuvant chemotherapy. Methods: We reviewed the clinicopathological data of 174 patients with clinical T4 gastric cancer who underwent neoadjuvant chemotherapy followed by laparoscopic radical total gastrectomy between June 2017 and December 2021. Among them, 142 were included in the non-HIPEC group, and 32 in the HIPEC group. Patients in both groups were paired based on propensity score in a 2:1 ratio to assess disparities in tumor recurrence and long-term survival. Results: After matching, there were no significant differences in the clinicopathological data between the two groups. The peritoneum (16.1%) and distant organs (10.9%) were the most frequent locations for recurrence. Prior to matching, the recurrence rates were similar at all sites for both groups. Compared with those in the non-HIPEC cohort, the recurrence rates at all sites, the lung, and the peritoneum were notably lower in the HIPEC cohort. Prior to matching, the 3-year overall survival and disease-free survival rates were similar between the two groups; following matching, the HIPEC group exhibited notably greater survival rates than did the non-HIPEC group. The disparities in survival rates between the groups became even more pronounced after conducting a stratified analysis among patients with stage III disease. Conclusions: Neoadjuvant chemotherapy combined with prophylactic HIPEC after laparoscopic radical gastrectomy can effectively reduce the rate of peritoneal metastasis in patients with cT4N + M0 advanced gastric cancer and significantly improve the prognosis of such patients, which is of great clinical value. [ABSTRACT FROM AUTHOR]

Background: The roles of the transcriptional factor SIX2 have been identified in several tumors. However, its roles in gastric cancer (GC) progression have not yet been revealed. Our objective is to explore the impact and underlying mechanisms of SIX2 on the stemness of GC cells. Methods: Lentivirus infection was employed to establish stable expression SIX2 or PFN2 in GC cells. Gain- and loss-of-function experiments were conducted to detect changes of stemness markers, flow cytometry profiles, tumor spheroid formation, and tumor-initiating ability. ChIP, RNA-sequencing, tissue microarray, and bioinformatics analysis were performed to reveal the correlation between SIX2 and PFN2. The mechanisms underlying the SIX2/PFN2 loop-mediated effects were elucidated through tissue microarray analysis, RNA stability assay, IP-MS, Co-Immunoprecipitation, and inhibition of the JNK signaling pathway. Results: The stemness of GC cells was enhanced by SIX2. Mechanistically, SIX2 directly bound to PFN2's promoter and promoted PFN2 activity. PFN2, in turn, promoted the mRNA stability of SIX2 by recruiting RNA binding protein YBX-1, subsequently activating the downstream MAPK/JNK pathway. Conclusion: This study unveils the roles of SIX2 in governing GC cell stemness, defining a novel SIX2/PFN2 regulatory loop responsible for this regulation. This suggests the potential of targeting the SIX2/PFN2 loop for GC treatment (Graphical Abstracts). [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is a major health problem worldwide, with a high incidence among older adults. Given the aging overall population, it was crucial to understand the current burden and prospective trend of older gastric cancer. This study aimed to analyze the temporal trends of the incidence, mortality, and survival of older gastric cancer in the highest gastric cancer risk area in China from 2010 to 2019, and to predict the future burden of older gastric cancer up to 2024. Methods: The study was conducted in Gansu province, an area characterized by the highest gastric cancer incidence and mortality in China. The registration data of gastric cancer incidence and mortality from 2010 to 2019 were pooled from registries in the Gansu Cancer Registration System, while survival data were collected from the First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Cancer Hospital. Chinese standard population in 2000 and the Segi's world standard population were applied to calculate the age-standardized rate. Joinpoint regression was used to analyze the average annual percentage change (AAPC) in cancer incidence and mortality. Autoregressive Integrated Moving Average (ARIMA) models were employed to generate forecasts for incidence and mortality from 2020 to 2024. Results: Based on registry data from 2010 to 2019, the incidence and mortality rates of gastric cancer among older adults remained stable. The incidence rates declined from 439.65 per 100,000 in 2010 to 330.40 per 100,000 in 2019, with an AAPC of -2.59% (95% confidence interval[CI], -5.14 to 0.04, P = 0.06). Similarly, the mortality rate changed from 366.98 per 100,000 in 2010 to 262.03 per 100,000 in 2019, with an AAPC of -2.55% (95% CI, -8.77–4.08%, P = 0.44). In the hospital-based cohort, the decline in survival rates was reported among older patients with gastric cancer in the highest gastric cancer risk area in China, with the 3-year overall survival (OS) decreasing from 58.5% (95% CI, 53.5–63.2%) in 2010 to 34.4% (95%CI, 32.1–36.7%) in 2019, and the 3-year progression-free survival (PFS) decreasing from 51.3% (95%CI, 47.5–55.1%) in 2010 to 34.2% (95%CI, 32.0–36.3%) in 2019, respectively. Moreover, forecasts generated by ARIMA models revealed a significant decline in the incidence and mortality of older gastric cancer in China from 2020 to 2024. Specifically, the incidence rate of older gastric cancer was expected to decrease from 317.94 per 100,000 population in 2020 to 205.59 per 100,000 population in 2024, while the anticipated mortality rate was estimated to decrease from 222.52 per 100,000 population in 2020 to 186.22 per 100,000 population in 2024. Conclusion: From 2010 to 2019, the incidence and mortality of older gastric cancer remained stable in the highest gastric cancer risk area in China, while the survival rates showed a decline. Based on the ARIMA models, it was anticipated that there might be a continued decline in older gastric cancer incidence and mortality in the highest-risk area in China over the next five years. [ABSTRACT FROM AUTHOR]

Cells sense and respond to various mechanical forces from the extracellular matrix primarily by modulating the actin cytoskeleton. Mechanical forces can be translated into biochemical signals in a process called mechanotransduction. Yes-associated protein (YAP) is an effector of Hippo signaling and a mediator of mechanotransduction, but how mechanical forces regulate Hippo signaling is still an open question. We propose that retinoic acid-induced protein 14 (RAI14) responds to mechanical forces and regulates Hippo signaling. RAI14 positively regulates the activity of YAP. RAI14 interacts with NF2, a key component of the Hippo pathway, and the interaction occurs on filamentous actin. When mechanical forces are kept low in cells, NF2 dissociates from RAI14 and filamentous actin, resulting in increased interactions with LATS1 and activation of the Hippo pathway. Clinical data show that tissue stiffness and expression of RAI14 and YAP are upregulated in tumor tissues and that RAI14 is strongly associated with adverse outcome in patients with gastric cancer. Our data suggest that RAI14 links mechanotransduction with Hippo signaling and mediates Hippo-related biological functions such as cancer progression. Synopsis: Cells sense and respond to mechanical forces primarily by modulating the actin cytoskeleton. Retinoic acid-induced protein 14 (RAI14) is responsive to extracellular mechanical forces, thereby regulating cell proliferation by modulating the Hippo signaling pathway. The positive regulation of YAP/TAZ activity by RAI14 is mainly mediated through NF2. Interactions between RAI14, NF2, and LATS, in response to ECM stiffness and F-actin integrity, regulate YAP/TAZ activity. RAI14 promotes cell proliferation in a Hippo signaling-dependent manner. The RAI14-Hippo signaling axis plays a pivotal role in gastric cancer progression. Cells sense and respond to mechanical forces primarily by modulating the actin cytoskeleton. Retinoic acid-induced protein 14 (RAI14) is responsive to extracellular mechanical forces, thereby regulating cell proliferation by modulating the Hippo signaling pathway. [ABSTRACT FROM AUTHOR]

Background: CT-detected Extramural venous invasion (EMVI) is known as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). However, the molecular basis is not clear. In colorectal cancer, M2 macrophages plays a vital role in determining EMVI. This study aimed to investigate the relationship between CT-detected EMVI and the M2 macrophages as well as prognosis predictionusing a radiogenomic approach. Method: We utilized EMVI-related genes (from mRNA sequencing of 13 GC samples correlated with EMVI score by spearman analysis, P < 0.01) to overlap the co-expression genes of WGCNA module and M2 macrophages related genes (from mRNA data of 371 GC patients in TCGA database), generating a total of 136 genes. An EMVI-M2-prognosis-related hub gene signature was constructed by COX and least absolute shrinkage and selection operator (LASSO) analysis from a training cohort TCGA database (n = 371) and validated it in a validation cohort from GEO database (n = 357). High- and low-risk groups were divided by hub gene (EGFLAM and GNG11) signature-derived risk scores. We assessed its predictive ability through Kaplan-Meier (K-M) curve and COX analysis. Furthermore, we utilized ESTIMATE to detect tumor mutation burden (TMB) and evaluate sensitivity to immune checkpoint inhibitors (ICIs). Expression of hub genes was tested using western blotting and immunohistochemistry (IHC) analysis. Results: The overall survival (OS) was significantly reduced in the high-risk group (Training/Validation: AUC = 0.701/0.620; P < 0.001/0.003). Furthermore, the risk score was identified as an independent predictor of OS in multivariate COX regression analyses (Training/Validation: HR = 1.909/1.928; 95% CI: 1.225–2.974/1.308–2.844). The low-risk group exhibited significantly higher TMB levels (P = 1.6e− 07) and greater sensitivity to ICIs. Significant higher expression of hub-genes was identified on multiple GC cell lines and original samples. Hub-genes knockdown in gastric cancer cell lines inhibited their proliferation, metastatic and invasive capacity to varying degrees. In vivo experiments indicate that EGFLAM, as one of the hub genes, its high expression can serve as a biomarker for low response to immunotherapy. Conclusion: Our study demonstrated EMVI-M2 gene signature could effectively predict the prognosis of GC tissue, reflecting the relationship between EMVI and M2 macrophages. [ABSTRACT FROM AUTHOR]

Background/Aims: Gastric cancer (GC) ranks among the prevalent types of cancer, and its progression is influenced by the tumor microenvironment (TME). A comprehensive comprehension of the TME associated with GC has the potential to unveil therapeutic targets of significance. Methods: The complexity and heterogeneity of TME interactions were revealed through our investigation using an integrated analysis of single-cell and bulk-tissue sequencing data. Results: We constructed a single-cell transcriptomic atlas of 150,913 cells isolated from GC patients. Our analysis revealed the intricate nature and heterogeneity of the GC TME and the metabolic properties of major cell types. Furthermore, two cell subtypes, LOX+ Fibroblasts and M2 Macrophages, were enriched in tumor tissue and related to the outcome of GC patients. In addition, LOX+ Fibroblasts were significantly associated with M2 macrophages. immunofluorescence double labeling indicated LOX+ Fibroblasts and M2 Macrophages were tightly localized in GC tissue. The two cell subpopulations strongly interacted in a hypoxic microenvironment, yielding an immunosuppressive phenotype. Our findings further suggest that LOX+ Fibroblasts may act as a trigger for inducing the differentiation of monocytes into M2 Macrophages via the IL6-IL6R signaling pathway. Conclusions: Our study revealed the intricate and interdependent communication network between the fibroblast and macrophage subpopulations, which could offer valuable insights for targeted manipulation of the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Multiple investigations have demonstrated the crucial involvement of T-cell exhaustion (TEX) in anti-tumor immune response and their strong correlation with prognosis. This study aimed at creating a strong signature using TEX for gastric cancer through bioinformatics analysis and experimental validation. We utilized data from The Cancer Genome Atlas (TCGA) databases to retrieve RNA-seq data from patients with stomach adenocarcinoma (STAD). Genes related to TEX were discovered using gene set variance analysis (GSVA) and weighted gene correlation network analysis (WGCNA). Subsequently, prognostic signature based on TEX was developed using LASSO-Cox analysis. Relationship between key genes and immune cells were examined. Finally, biological function of a key TEX-related gene PTPRT in gastric cancer was verified by in vivo experiment. A total of 29 TEX-related biomarkers were screened by WGCNA and random forest. Among them, five core signatures (PTPRT, CAV2, PPIH, PRDM2, and FGF1), further identified by LASSO-Cox, were considered as strong predictors of prognosis for gastric cancer and associated with immune infiltration. PTPRT gene had the largest number of SNPs, with the most mutation types. In vivo experiments revealed that PTPRT overexpression significantly inhibited tumor malignant progression and accelerated apoptosis through stimulating the secretion of killer cytokines such as TNF-α and IFN-γ. In addition, flow cytometry revealed that PTPRT overexpression alleviated TEX by increasing the abundance of CD8+ T cells, with inhibition of cell surface PD-1 and Tim-3. The predictive prognostic value of TEX gene expression levels was evaluated in patients with gastric cancer, providing a new perspective for precision immuno-oncology studies. [ABSTRACT FROM AUTHOR]

Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) gastric cancer (GC) exhibits an immune-active tumor microenvironment (TME) compared to MMR proficient (pMMR)/microsatellite stable/Epstein-Barr virus-negative [EBV (−)] GC. The tumor cell-intrinsic cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway has been considered a key regulator of immune cell activation in the TME. However, its significance in regulating the immune-active TME in dMMR/MSI-H GC remains unclear. Here, we demonstrated that tumor cell-intrinsic cGAS–STING was highly expressed in dMMR GC compared to pMMR/EBV (−) GC. The expression of tumor cell-intrinsic STING was significantly and positively associated with the number of CD8+ tumor-infiltrating lymphocytes in GC. Analysis of TCGA datasets revealed that the expression of interferon-stimulated genes and STING downstream T-cell attracting chemokines was significantly higher in MSI-H GC compared to other subtypes of GC with EBV (−). These results suggest that tumor cell-intrinsic STING signaling plays a key role in activating immune cells in the dMMR/MSI-H GC TME and might serve as a novel biomarker predicting the efficacy of immunotherapy for GC treatment. [ABSTRACT FROM AUTHOR]

Background: β-glucan has been reported to be a potential natural immune modulator for tumor growth inhibition. We aimed to evaluate the efficacy and safety of b-glucan plus immunotherapy and chemotherapy in the first-line treatment of advanced gastric adenocarcinoma. Methods: This is a phase IB, prospective, single-arm, investigator-initiated trail. Advanced gastric adenocarcinoma patients received β-glucan, camrelizumab, oxaliplatin, oral S-1 every 3 weeks. The curative effect was evaluated every 2 cycles. The primary endpoints were objective response rate (ORR) and safety, with secondary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). The exploratory endpoint explored biomarkers of response to treatment efficacy. Results: A total of 30 patients had been enrolled, including 20 (66.7%) males and all patients with an ECOG PS score of ≥1. The ORR was 60%, the mPFS was 10.4 months (95% confidence interval [CI], 9.52-11.27), the mOS was 14.0 months (95% CI, 11.09-16.91). A total of 19 patients (63.3%) had TRAEs, with 9 patients (30%) with grade ≥ 3. The most common TRAEs were nausea (53.3%). After 2 cycles of treatment, the levels of IL-2, IFN-γ and CD4+ T cells significantly increased (P < 0.05). Furthermore, biomarker analysis indicated that patient with better response and longer OS exhibited lower GZMA expression at baseline serum. Conclusions: This preliminary study demonstrates that β-glucan plus camrelizumab and SOX chemotherapy offers favorable efficacy and a manageable safety profile in patients with advanced gastric adenocarcinoma, and further studies are needed to verify its efficacy and safety. [ABSTRACT FROM AUTHOR]

Acetyl CoA acetyltransferase 1 (ACAT1), a mitochondrial enzyme, is mainly involved in the formation and decomposition of ketones, isoleucine, and fatty acids. Previous clinical studies showed that mutations in the ACAT1 gene lead to ketoacidosis, Notably the role of ACAT1 in human cancer' pathogenesis varies depending on cancer type, and its specific role in gastric cancer remains largely unknown. In the current study, we found that the expression of ACAT1 in primary late-stage gastric cancer tumor tissues was significantly lower than in early-stage tumors. This observation was further confirmed in high-grade gastric cancer cell line MKN45. The expression of CD44 and OCT4 was decreased, while CD24 expression was increased by overexpressing ACAT1 in MKN45 gastric cancer cells. Moreover, the ability of gastric cancer cells to form colonies on soft agar was also reduced by ACAT1 overexpression. Likewise, overexpression of ACAT1 inhibited epithelial mesenchymal transition (EMT) in gastric cancer cells evidenced by increased expression of the epithelial marker E-Cadherin, decreased expression of mesenchymal marker vimentin, and decreased expression levels of SNAI 1/3. In addition, ACAT1 overexpression inhibited cell migration and invasion, improved the response to 5-Fluorouracil (5-FU) and etoposide. In contrast, inhibition of ACAT1 activity promoted the proliferation of gastric cancer cells. The xenotransplantation results in nude mice showed that overexpression of ACAT1 in gastric cancer cells inhibited tumor growth in vivo. In addition, the low expression of ACAT1 in gastric cancer was further validated by searching public databases and conducting bioinformatic analyses. Mechanistically, bioinformatic analysis found that the inhibitory effect of ACAT1 in gastric cancer may be related to the Adipocytokine Signaling Pathway, Ppar Signaling Pathway, Propanoate Metabolism and P53 Signaling Pathway. Correlation analysis indicated ACAT1 mRNA expression was correlated with immune infiltrates. Collectively, our data show that ACAT1 induces pronounced inhibitory effects on gastric cancer initiation and development, which may impact future strategies to treat this aggressive cancer. [ABSTRACT FROM AUTHOR]

Introduction: Patients with renal insufficiency are more prone to postoperative complications (PCs). Studies have shown that minor changes in serum creatinine (SCr), immediately post-surgery, can aid in assessing patients' renal function. This study aimed to explore the relationship between the changes in SCr and PCs in patients with gastric cancer (GC). Materials and methods: We prospectively collected data regarding the SCr of 530 GC patients, within 2 weeks before surgery and within 24 hours after surgery in our hospital (2014-2016). The patients were divided into three groups according to the level of SCr change after surgery: reduced (<10%), normal (10%), and elevated (>10%) creatinine groups. Univariate and multivariate logistic analysis were performed to evaluate its correlation with short-term PCs in the patients. The R language was used to construct a nomogram. Results: 83, 217, and 230 patients were assigned to the elevated, reduced, and normal SCr groups, respectively. Multivariate analysis showed that the reduced and elevated SCr groups were independently associated with the occurrence of PCs and severe postoperative complications (SPCs), respectively. Additionally, postsurgical SCr change, age, hypoalbuminemia, total gastrectomy, combined resection, and laparoscopy, were independently related to PCs. Combining the above influential factors, the predictive model can distinguish patients with PCs more reliably (c-index is 0.715). Conclusion: Post-surgery, reduced SCr is a protective factor for PCs, while elevated serum creatinine is an independent risk factor for SPCs. Our nomogram can identify GC patients with high risks of PCs. [ABSTRACT FROM AUTHOR]

Background: Although anti-HER2 therapies have been widely used against gastric carcinoma, the prognostic significance of HER2 overexpression remains unclear. Previous studies failed to provide convincible evidence due to inconsistent HER2 evaluation criteria and heterogeneous clinical characteristics. Objectives: To figure out the prognostic significance of HER2 expression in gastric cancer, we rigorously designed and conducted this study. Design: Meta-analysis. Data sources and methods: Record retrieval was performed by searching PubMed, Web of Science, Cochrane Library, Embase, ASCO, and ESMO meeting libraries from inception to November 2022. Cohort studies investigating overall survival comparison between HER2-positive and HER2-negative gastric cancer patients were included. Both resectable and advanced cases were separately collected while HER2 evaluation standards should be consistent across eligible studies. Newcastle–Ottawa Scale was used for quality assessment. Overall survival was the only endpoint and effect size was presented by hazard ratio (HR) with its 95% confidence interval. The pooled calculation was conducted on Review Manager 5.4. Results: Thirty studies were eligible, including 9945 patients. Eligible studies were mostly high quality (n = 31). Regarding resectable cases (n = 22), HER2-positive groups had significantly worse prognosis than HER2-negative counterparts (HR 1.56, 95%CI 1.32–1.85, p < 0.00001). For HER2-positive patients with advanced gastric cancer (n = 10), HER2 overexpression was also an unfavorable survival indicator (HR 1.70, 95%CI 1.23–2.35, p = 0.001). Potential heterogeneous studies had been eliminated while outcomes remained stable by sensitivity analysis. Subgroup analysis suggested HER2-positive patients had a poorer prognosis in both East Asian (resectable: HR 1.56; advanced: HR 1.32) and non-East Asian countries (HR 1.58; HR 3.27). Conclusion: As a novel survival biomarker in gastric cancer, HER2 overexpression indicates unfavorable prognosis among both resectable and advanced patients, irrespective of East Asian or non-East Asian populations. Trial registration: PROSPERO (CRD42020168051). [ABSTRACT FROM AUTHOR]

Background: Myeloid-derived suppressor cells (MDSCs) are the major factor in gastric cancer (GC) immune evasion. Nevertheless, the molecular process underlying the expansion of MDSCs induced by tumor-derived exosomes (TDEs) remains elusive. Methods: The levels of exosomal and soluble PD-L1 in ninety GC patients were examined via enzyme-linked immunosorbent assay (ELISA) to determine their prognostic value. To investigate the correlation between exosomal PD-L1 and MDSCs, the percentage of MDSCs in the peripheral blood of 57 GC patients was assessed via flow cytometry. Through ultracentrifugation, the exosomes were separated from the GC cell supernatant and detected via Western blotting, nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). The function of exosomal PD-L1 in MDSCs was evaluated via immunofluorescence, Western blotting and flow cytometry in a GC cell-derived xenograft (CDX) model. Results: The overall survival (OS) of GC patients in the high exosomal PD-L1 group was significantly lower than that of patients in the low exosomal PD-L1 group (P = 0.0042); however, there was no significant correlation between soluble PD-L1 and OS in GC patients (P = 0.0501). Furthermore, we found that the expression of exosomal PD-L1 was positively correlated with the proportions of polymorphonuclear MDSCs (PMN-MDSCs, r = 0.4944, P < 0.001) and monocytic MDSCs (M-MDSCs, r = 0.3663, P = 0.005) in GC patients, indicating that exosomal PD-L1 might induce immune suppression by promoting the aggregation of MDSCs. In addition, we found that exosomal PD-L1 might stimulate MDSC proliferation by triggering the IL-6/STAT3 signaling pathway in vitro. The CDX model confirmed that exosomal PD-L1 could stimulate tumor development and MDSC amplification. Conclusions: Exosomal PD-L1 has the potential to become a prognostic and diagnostic biomarker for GC patients. Mechanistically, MDSCs can be activated by exosomal PD-L1 through IL-6/STAT3 signaling and provide a new strategy against GC through the use of exosomal PD-L1 as a treatment target. [ABSTRACT FROM AUTHOR]

Background: Patients with gastric cancer (GC) who underwent radical surgery require long-term follow-up (usually 5 years). The purpose of this study was to explore individualized follow-up strategies for patients with GC. Methods: This is a retrospective cohort study that established a clinicopathologic database of patients who underwent gastrectomy from January 2010 to December 2020 at Ningbo No. 2 Hospital. Follow-up was performed until March 2023. The rate of new-onset recurrence of patients with GC was explored annually according to different pTNM stages, defining a recurrence rate of less than 1% as adequate follow-up time. Results: Of the 1606 patients who were eligible, the total number of patients who completed the 5- and 10-year follow-up was 1107 and 586, respectively. A total of 444 cases were diagnosed with recurrence. The recurrence rate for stage IA patients was consistently less than 1% during the follow-up time. The adequate follow-up time (the rate of new-onset recurrence less than 1%) was 5 years for stage IB and IIA patients, and 8 years for stage IIB and IIIA patients, respectively. In contrast, stage IIIB patients were always at risk of recurrence during the follow-up time (>1%). Time to a new recurrence rate for stage IIIC patients was 6 years. Conclusion: Among patients who underwent radical gastrectomy, the rate of new-onset recurrence varied among patients with different pTNM stages. This study suggests that the follow-up of GC can be individualized and refer to pTNM stage. [ABSTRACT FROM AUTHOR]

Background: Potentially curative therapy for locally advanced gastric cancer consists of gastrectomy, usually in combination with perioperative chemotherapy. An oncological resection includes a radical (R0) gastrectomy and modified D2 lymphadenectomy; generally, a total omentectomy is also performed, to ensure the removal of possible microscopic disease. However, the omentum functions as a regulator of regional immune responses to prevent infections and prevents adhesions which could lead to bowel obstructions. Evidence supporting a survival benefit of routine complete omentectomy during gastrectomy is lacking. Methods: OMEGA is a randomized controlled, open, parallel, non-inferiority, multicenter trial. Eligible patients are operable (ASA < 4) and have resectable (≦ cT4aN3bM0) primary gastric cancer. Patients will be 1:1 randomized between (sub)total gastrectomy with omentum preservation distal of the gastroepiploic vessels versus complete omentectomy. For a power of 80%, the target sample size is 654 patients. The primary objective is to investigate whether omentum preservation in gastrectomy for cancer is non-inferior to complete omentectomy in terms of 3-year overall survival. Secondary endpoints include intra- and postoperative outcomes, such as blood loss, operative time, hospital stay, readmission rate, quality of life, disease-free survival, and cost-effectiveness. Discussion: The OMEGA trial investigates if omentum preservation during gastrectomy for gastric cancer is non-inferior to complete omentectomy in terms of 3-year overall survival, with non-inferiority being determined based on results from both the intention-to-treat and the per-protocol analyses. The OMEGA trial will elucidate whether routine complete omentectomy could be omitted, potentially reducing overtreatment. Trial registration: ClinicalTrials.gov NCT05180864. Registered on 6th January 2022. [ABSTRACT FROM AUTHOR]

Background: Totally robotic distal gastrectomy (TRDG) is being used more and more in gastric cancer (GC) patients. The study aims to evaluate the short-term efficacy of TRDG and robotic-assisted distal gastrectomy (RADG) in the treatment of GC. Methods: We retrospectively collected the clinical data of patients who underwent TRDG or RADG, of which 60 patients were included in the study: 30 cases of totally robotic and 30 cases of robotic-assisted. The short-term efficacy of the two groups was compared. Results: There was no significant difference in the clinicopathological data between the two groups. Compared to RADG, TRDG had less intraoperative blood loss(P = 0.019), less postoperative abdominal drainage(P = 0.031), shorter time of exhaust(P = 0.001) and liquid diet(P = 0.001), shorter length of incision(P<0.01), shorter postoperative hospital stays(P = 0.033), lower postoperative C-reactive protein(CRP)(P = 0.024) and lower postoperative Visual Analogue Scale(VAS) scores(P = 0.048). However, no significant statistical differences were found in terms of total operation time(P = 0.108), number of lymph nodes retrieved(P = 0.307), time for anastomosis(P = 0.450), proximal resection margin(P = 0.210), distal resection margin(P = 0.202), postoperative complication(P = 0.506), total hospital cost(P = 0.286) and postoperative white blood cell(WBC)(P = 0.113). Conclusions: In terms of security and technology, TRDG could serve as a better treatment method for GC. [ABSTRACT FROM AUTHOR]

Introduction: Mutated human epidermal growth factor receptor 2 (HER2) is an oncogene with critical pathogenic roles in breast cancer. HER2-low-positive breast cancer is a recently described subtype. We aimed to explore the clinical and molecular characteristics of gastric cancer with low HER2 expression, drawing on recent developments in breast cancer subtypes. Materials and methods: This retrospective study involved 129 patients with HER2-non-amplified gastric cancer treated in Iwate prefectural Iwai Hospital from 2013 to 2019. Tumors were classified as HER2-null or low-positive based on immunohistochemistry score 0 or 1 + or 2 + with HER2 negativity in situ hybridization, respectively. Statistical analyses, including Kaplan–Meier analyses and Cox proportional hazards model were conducted. Results: Low HER2 expression was present in 26% (33/129) of the patients. Clinicopathological characteristics were not significantly different between the HER2-low and null groups. Kaplan–Meier analysis of overall survival was significantly longer in the HER2-low group than in the HER2-null group (P = 0.01). In multivariate Cox regression analysis, HER2-null status was associated with worse survival (hazard ratio 3.01; 95% confidence interval 1.18–7.65; and P = 0.02). Conclusion: This study highlights the prognostic importance of low HER2 expression in gastric cancer, similar to that observed in HER2-low-positive breast cancer, and suggests reclassification of gastric cancer to improve personalized treatment. Future studies should elucidate the molecular underpinnings of low HER2 expression in gastric cancer to guide novel therapeutic strategies and improve outcomes. [ABSTRACT FROM AUTHOR]

Rutin is a natural flavonoid compound that is widely found in a variety of plants and has a variety of biological effects, including anti-inflammatory, antioxidant, and anti-tumor effects. Rutin has been shown to have anti-tumor effects in a variety of cancers, but its effects on gastric cancer need to be further explored. The aim of this study was to explore the effects of Rutin on gastric cancer cells and the potential molecular regulatory mechanisms. Gastric cancer cells (AGS and MGC803) were treated with different concentrations of Rutin. Cell proliferation, apoptosis, migration, and invasion were determined by MTT, flow cytometry, scratch assay, and Transwell analysis, respectively. Cell epithelial mesenchymal transition (EMT) markers and Wnt/β-catenin pathway were analyzed by RT-qPCR and western blot assay. The results showed that Rutin significantly inhibited the proliferation, migration and invasion ability of gastric cancer cells, induced apoptosis, and suppressed the EMT process. Further experiments revealed that Rutin achieved the effect of inhibiting the biological behavior of gastric cancer cells by suppressing the activation of the Wnt/β-catenin pathway. Therefore, Rutin may become a potential therapeutic candidate for gastric cancer. [ABSTRACT FROM AUTHOR]

The aim of this meta-analysis was to compare the efficacy of robot distal gastrectomy (RDG) versus laparoscopic distal gastrectomy (LDG) for gastric cancer. Studies included only those that utilized propensity score matching (PSM). A systematic literature search was conducted in several major global databases, including PubMed, Embase, and Google Scholar, up to June 2024. Articles were screened based on predefined inclusion and exclusion criteria. Baseline data and primary and secondary outcome measures (e.g., operative time, estimated blood loss, lymph-node yield dissection, length of hospital stay, and time to first flatus) were extracted. The quality of PSM studies was assessed using the ROBINS-I, and data were analyzed using Review Manager 5.4.1 software. A total of 12 propensity score-matched studies involving 3688 patients were included in this meta-analysis. Robot-assisted surgery resulted in a longer operative time (WMD 30.64 min, 95% CI 15.63 – 45.66; p < 0.0001), less estimated blood loss (WMD 29.54 mL, 95% CI − 47.14 − 11.94; p = 0.001), more lymph-node yield (WMD 5.14, 95% CI 2.39 − 7.88; p = 0.0002), and a shorter hospital stay (WMD − 0.36, 95% CI − 0.60 − 0.12; p = 0.004) compared with laparoscopic surgery. There were no significant differences between the two surgical methods in terms of time to first flatus, overall complications, and major complications. Robot distal gastrectomy for gastric cancer reduces intraoperative blood loss, increases lymph-node yield, and shortens hospital stay compared with laparoscopic surgery, despite a longer operative time. There are no significant differences in time to first flatus and complication rates between the two groups. [ABSTRACT FROM AUTHOR]

Objectives: Supplemental parenteral nutrition (SPN) is recommended to add when enteral nutrition alone is not sufficient. This research aims to evaluate the effect of preoperative SPN in patients with gastric cancer. Methods: A total of 180 patients with gastric cancer were divided into three groups (60 patients per group) according to different nutritional support scheme. The primary endpoint was the changes in nutrition and inflammatory, while the secondary endpoint included the changes in prognosis. Results: Compared with the control group, there were significant differences in nutrition and inflammation related indicators in the oral nutrition supplement (ONS) group and the SPN + ONS group (P < 0.05). Compared with the ONS group, the SPN + ONS group showed significant differences in the above indicators (P < 0.05). However, no significant changes were observed in the incidence of complications, the postoperative exhaust time, and the hospitalization time. Conclusions: Preoperative SPN had a positive effect on nutrition and inflammation of gastric cancer patients undergoing surgery, but had no significant effect on their prognosis. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the fourth most common malignant cancer and is a lifethreatening disease worldwide. Phytochemicals have been shown to be a rational, safe, non-toxic, and very promising approach to the prevention and treatment of cancer. It has been found that phytochemicals have protective effects against GC through inhibiting cell proliferation, inducing apoptosis and autophagy, suppressing cell invasion and migration, anti-angiogenesis, inhibit Helicobacter pylori infection, regulating the microenvironment. In recent years, the role of phytochemicals in the occurrence, development, drug resistance and prognosis of GC has attracted more and more attention. In order to better understand the relationship between phytochemicals and gastric cancer, we briefly summarize the roles and functions of phytochemicals in GC tumorigenesis, development and prognosis. This review will probably help guide the public to prevent the occurrence and development of GC through phytochemicals, and develop functional foods or drugs for the prevention and treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC), a prevalent malignant tumor which is a leading cause of death from malignancy around the world. Peritoneal metastasis accounts for the major cause of mortality in patients with GC. Despite hyperthermia intraperitoneal chemotherapy (HIPEC) improves the therapeutic effect of GC, it’s equivocal about the mechanism under HIPEC. Methods: MiR-183-5p expression was sifted from miRNA chip and detected in both GC patients and cell lines by qRT-PCR. Gene interference and rescue experiments were performed to identified biological function in vitro and vivo. Next, we affirmed PPP2CA as targeted of miR-183-5p by dual luciferase reporter assay. Finally, the potential relationship between HIPEC and miR-183-5p was explored. Results: MiR-183-5p is up-regulated in GC and associated with advanced stage and poor prognosis. MiR-183-5p accelerate GC migration in vitro which is influenced by miR-183-5p/PPP2CA/AKT/GSK3β/β-catenin Axis. HIPEC exerts migration inhibition via attenuating miR-183-5p expression. Conclusion: MiR-183-5p can be used as a potential HIPEC biomarker in patients with CC. [ABSTRACT FROM AUTHOR]

Purpose: In recent years, clinicians have focused on the importance of preventing hypoglycemia. We evaluated the impact of different reconstruction procedures after proximal gastrectomy on glycemic variability in non-diabetic patients with gastric cancer. Methods: This prospective observational study was conducted between April 2020 and March 2023. Flash continuous glucose-monitoring, a novel method for assessing glycemic control, was used to evaluate the glycemic profiles after gastrectomy. A flash continuous glucose-monitoring sensor was placed subcutaneously at the time of discharge, and glucose trends were evaluated for 2 weeks. Results: The anastomotic methods for proximal gastrectomy were esophagogastrostomy in 10 patients and double-tract reconstruction in 10 patients. The time below this range (glucose levels < 70 mg/dL) was significantly higher in the double-tract reconstruction group than in the esophagogastrostomy group (p = 0.049). A higher nocturnal time below this range was significantly correlated with an older age and double-tract reconstruction (p = 0.025 and p = 0.025, respectively). Conclusion: These findings provide new insights into reconstruction methods after proximal gastrectomy by assessing postoperative hypoglycemia in non-diabetic patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Purposes: The present study evaluated the impact of clinical guidelines for gastric cancer surgery on surgeons' choice of procedure in real-world practice. We focused on the 2014 guideline revision recommending laparoscopic surgery and the evidence concerning splenectomy for prophylactic lymphadenectomy reported in 2015 using the National Clinical Database, which is the most comprehensive database in Japan. Methods: We investigated the monthly percentages of laparoscopic distal gastrectomies performed for stage I gastric cancer (LDG%) and splenectomies performed during total gastrectomy for advanced cancer (TGS%) between 2014 and 2017. We evaluated the descriptive statistics of the time-series changes in the LDG%, TGS%, and annual trends of outcomes. Results: In total, 124,787 patients were enrolled. The mean LDG% and TGS% were 69.8% and 9.2%, respectively. The LDG% and TGS% were 66.4% and 16.7%, respectively, in January 2014 and 73.1% and 5.9%, respectively, in December 2017. LDG% consistently increased, and TGS% showed a consistent downward trend throughout the observation period. There was no significant change in this trend after the publication of the guideline recommendations or clinical trial results. Conclusion: No significant changes in surgical procedures were observed after publication of the guidelines or results of clinical trials. [ABSTRACT FROM AUTHOR]

Background: Robot-assisted minimally invasive gastrectomy (RAMIG) is increasingly used as a surgical approach for gastric cancer. This study assessed the effectiveness of RAMIG and studied which stages of the IDEAL-framework (1 = Idea, 2A = Development, 2B = Exploration, 3 = Assessment, 4 = Long-term follow-up) were followed. Methods: The Cochrane Library, Embase, Pubmed, and Web of Science were searched for studies on RAMIG up to January 2023. Data collection included the IDEAL-stage, demographics, number of participants, and study design. For randomized controlled trials (RCTs) and long-term studies, data on intra-, postoperative, and oncologic outcomes, survival, and costs of RAMIG were collected and summarized. Results: Of the 114 included studies, none reported the IDEAL-stage. After full-text reading, 18 (16%) studies were considered IDEAL-2A, 75 (66%) IDEAL-2B, 4 (4%) IDEAL-3, and 17 (15%) IDEAL-4. The IDEAL-stages were followed sequentially (2A-4), with IDEAL-2A studies still ongoing. IDEAL-3 RCTs showed lower overall complications (8.5–9.2% RAMIG versus 17.6–19.3% laparoscopic total/subtotal gastrectomy), equal 30-day mortality (0%), and equal length of hospital stay for RAMIG (mean 5.7–8.5 days RAMIG versus 6.4–8.2 days open/laparoscopic total/subtotal gastrectomy). Lymph node yield was similar across techniques, but RAMIG incurred significantly higher costs than laparoscopic total/subtotal gastrectomy ($13,423–15,262 versus $10,165–10,945). IDEAL-4 studies showed similar or improved overall/disease-free survival for RAMIG. Conclusion: During worldwide RAMIG implementation, the IDEAL-framework was followed in sequential order. IDEAL-3 and 4 long-term studies showed that RAMIG is similar or even better to conventional surgery in terms of hospital stay, lymph node yield, and overall/disease-free survival. In addition, RAMIG showed reduced postoperative complication rates, despite higher costs. [ABSTRACT FROM AUTHOR]

Antibody–drug conjugates (ADCs) represent a crucial component of targeted therapies in gastric cancer, potentially altering traditional treatment paradigms. Many ADCs have entered rigorous clinical trials based on biological theories and preclinical experiments. Modality trials have also been conducted in combination with monoclonal antibody therapies, chemotherapies, immunotherapies, and other treatments to enhance the efficacy of drug coordination effects. However, ADCs exhibit limitations in treating gastric cancer, including resistance triggered by their structure or other factors. Ongoing intensive researches and preclinical experiments are yielding improvements, while enhancements in drug development processes and concomitant diagnostics during the therapeutic period actively boost ADC efficacy. The optimal treatment strategy for gastric cancer patients is continually evolving. This review summarizes the clinical progress of ADCs in treating gastric cancer, analyzes the mechanisms of ADC combination therapies, discusses resistance patterns, and offers a promising outlook for future applications in ADC drug development and companion diagnostics. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a common malignancy that presents challenges in patient care worldwide. The mismatch repair (MMR) system is a highly conserved DNA repair mechanism that protects genome integrity during replication. Deficient MMR (dMMR) results in an increased accumulation of genetic errors in microsatellite sequences, leading to the development of a microsatellite instability-high (MSI-H) phenotype. Most MSI-H/dMMR GCs arise sporadically, mainly due to MutL homolog 1 (MLH1) epigenetic silencing. Unlike microsatellite-stable (MSS)/proficient MMR (pMMR) GCs, MSI-H/dMMR GCs are relatively rare and represent a distinct subtype with genomic instability, a high somatic mutational burden, favorable immunogenicity, different responses to treatment, and prognosis. dMMR/MSI-H status is a robust predictive biomarker for treatment with immune checkpoint inhibitors (ICIs) due to high neoantigen load, prominent tumor-infiltrating lymphocytes, and programmed cell death ligand 1 (PD-L1) overexpression. However, a subset of MSI-H/dMMR GC patients does not benefit from immunotherapy, highlighting the need for further research into predictive biomarkers and resistance mechanisms. This review provides a comprehensive overview of the clinical, molecular, immunogenic, and therapeutic aspects of MSI-H/dMMR GC, with a focus on the impact of ICIs in immunotherapy and their potential as neoadjuvant therapies. Understanding the complexity and diversity of the molecular and immunological profiles of MSI-H/dMMR GC will drive the development of more effective therapeutic strategies and molecular targets for future precision medicine. [ABSTRACT FROM AUTHOR]

Background: For the elderly patients with gastric cancer, it may be more challenging to tolerate complete neoadjuvant therapy (NAT). The impact of discontinued NAT on the surgical safety and pathological outcomes of elderly patients with poor tolerance remains poorly understood. Methods: Gastric cancer patients received gastrectomy with curative intent from the Dutch upper GI cancer audit (DUCA) database were included in this study. The independent association of age with not initiating and discontinuation of NAT was assessed with restricted cubic splines (RCS). According to the RCS results, age ≥ 70 years was defined as elderly. Short-term postoperative outcomes and pathological results were compared between elderly patients who completed and discontinued NAT. Results: Between 2011- 2021, total of 3049 patients were included. The risk of not initiating NAT increased from 70 years. In 1954 (64%) patients receiving NAT, the risk of discontinuation increased from 55 years, reaching the peak around 74 years. In the elderly, discontinued NAT was not independently associated with worse 30-day mortality, overall complications, anastomotic leakage, re-intervention, and pathologic complete response, but was associated with a higher risk of R1/2 resection (p-value = 0.001), higher ypT stage (p-value = 0.004), ypN + (p-value = 0.008), and non-response (p-value = 0.012). Conclusion: A decreased utilization of NAT has been observed in Dutch gastric cancer patients from 70 years due to old age considerations, possibly because of their high risk of discontinuation. Increasing the utilization of NAT may not adversely impact the surgical safety of gastric cancer population ≥ 70 years and may contribute to better pathological results. [ABSTRACT FROM AUTHOR]

Cisplatin (DDP) is a basic chemotherapy drug for gastric cancer (GC). With the increase of DDP drug concentration in clinical treatment, cancer cells gradually became resistant. Therefore, it is necessary to find effective therapeutic targets to enhance the sensitivity of GC to DDP. Studies have shown that Transmembrane protein 205 (TMEM205) is overexpressed in DDP-resistant human epidermoid carcinoma cells and correlates with drug resistance, and database analyses show that TMEM 205 is also overexpressed in GC, but its role in cisplatin-resistant gastric cancer remains unclear. In this study, we chose a variety of experiments in vivo and vitro, aiming to investigate the role of TMEM 205 in cisplatin resistance in gastric cancer. The results showed that TMEM 205 promoted proliferation, stemness, epithelial–mesenchymal transition (EMT), migration and angiogenesis of gastric cancer cells through activation of the Wnt/β-catenin signaling pathway. In addition, TMEM205 promotes GC progression by inducing M2 polarization of tumor-associated macrophages (TAMs). These results suggest that TMEM205 may be an effective target to regulate the sensitivity of GC to DDP, providing a new therapeutic direction for clinical treatment. [ABSTRACT FROM AUTHOR]

Background: Limited data exist for global prevalence of claudin 18 isoform 2 (CLDN18.2) positivity and association of CLDN18.2 status with clinical and tumor characteristics in patients with locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. We report prevalence of CLDN18.2 positivity (phase 3; SPOTLIGHT, NCT03504397; GLOW, NCT03653507) and concordance of CLDN18.2 status between a subset of pair-matched tumor samples (phase 2, ILUSTRO, NCT03505320; phase 1, NCT03528629) from clinical studies of zolbetuximab. Methods: Tumor samples from patients with LA unresectable or mG/GEJ adenocarcinoma were tested for CLDN18.2 status by immunohistochemistry. Human epidermal growth factor receptor 2 (HER2) expression was tested per central or local assessment. Results: Across SPOTLIGHT and GLOW, the prevalence of CLDN18.2 positivity (≥ 75% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining) was 38.4%. Prevalence was similar in gastric versus GEJ adenocarcinoma samples and regardless of collection method (biopsy versus resection) or collection site (primary versus metastatic). CLDN18.2 positivity was most prevalent in patients with diffuse-type tumors. In ILUSTRO and the phase 1 study, concordance of CLDN18.2 positivity was 61.1% between archival (i.e., any time before treatment) and baseline (i.e., ≤ 3 months before first treatment) samples, and concordance of any CLDN18 staining (≥ 1% of tumor cells demonstrating moderate-to-strong membranous CLDN18 staining) was 88.9%. Conclusions: CLDN18.2 was a highly prevalent biomarker in patients with HER2-negative, LA unresectable or mG/GEJ adenocarcinoma. CLDN18.2 positivity remained relatively stable over time in many patients. Biomarker testing for CLDN18.2 should be considered in standard clinical practice in these patients. [ABSTRACT FROM AUTHOR]

Objective: To compare the risks of gastric cancer and other gastric diseases in patients with type-2 diabetes mellitus (T2DM) exposed to sodium-glucose cotransporter 2 inhibitors (SGLT2I), dipeptidyl peptidase-4 inhibitors (DPP4I) or glucagon-like peptide-1 receptor agonists (GLP1a). Design: This was a population-based cohort study of prospectively collected data on patients with T2DM prescribed SGLT2I, DPP4I or GLP1a between January 1st 2015 and December 31st 2020 from Hong Kong. The outcomes were new-onset gastric cancer, peptic ulcer (PU), acute gastritis, non-acute gastritis, and gastroesophageal reflux disease (GERD). Propensity score matching (1:1) using the nearest neighbour search was performed, and multivariable Cox regression was applied. A three-arm comparison between SGLT2I, DPP4I and GLP1a was conducted using propensity scores with inverse probability of treatment weighting. Results: A total of 62,858 patients (median age: 62.2 years old [SD: 12.8]; 55.93% males; SGLT2I: n = 23,442; DPP4I: n = 39,416) were included. In the matched cohort, the incidence of gastric cancer was lower in SGLT2I (Incidence rate per 1000 person-year, IR: 0.32; 95% confidence interval, CI 0.23–0.43) than in DPP4I (IR per 1000 person-year: 1.22; CI 1.03–1.42) users. Multivariable Cox regression found that SGLT2I use was associated with lower risks of gastric cancer (HR 0.30; 95% CI 0.19–0.48), PU, acute gastritis, non-acute gastritis, and GERD (p < 0.05) compared to DPP4I use. In the three-arm analysis, GLP1a use was associated with higher risks of gastric cancer and GERD compared to SGLT2I use. Conclusions: The use of SGLT2I was associated with lower risks of new-onset gastric cancer, PU, acute gastritis, non-acute gastritis, and GERD after matching and adjustments compared to DPP4I use. SGLT2I use was associated with lower risks of GERD and gastric cancer compared to GLP1a use. [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. Methods: 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. Results: 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. Conclusion: 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: In the FIGHT study (NCT03694522) bemarituzumab, a humanized monoclonal antibody selective for fibroblast growth factor receptor 2b (FGFR2b), plus mFOLFOX6 showed clinically meaningful efficacy in patients with FGFR2b-positive (2+/3+ membranous staining by immunohistochemistry) locally advanced unresectable/metastatic gastric/gastroesophageal cancer (G/GEJC). A meaningful proportion of patients in FIGHT were enrolled in East Asia, reflecting global epidemiology of G/GEJC. Methods: This subgroup analysis of the global, phase 2, double-blind FIGHT study included all patients enrolled in East Asian sites. Patients were randomized 1:1 to bemarituzumab-mFOLFOX6 (15 mg/kg and one 7.5 mg/kg dose on cycle 1, day 8) or matching placebo-mFOLFOX6. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate, and safety. Efficacy was evaluated after a minimum follow-up of 24 months. Results: The East Asian subgroup comprised 89 patients (57% of overall study population); 45 were randomized to bemarituzumab-mFOLFOX6 and 44 to placebo-mFOLFOX6. Median PFS (95% confidence interval [CI]) was 12.9 months (8.8–17.9) with bemarituzumab-mFOLFOX6 and 8.2 months (5.6–10.3) with placebo-mFOLFOX6 (HR 0.50, 95% CI 0.29–0.87); median OS (95% CI) was 24.7 months (13.8–33.1) vs 12.9 months (9.3–21.4), respectively (HR 0.56, 95% CI 0.32–0.96). Treatment benefit was more pronounced in patients with FGFR2b-positive G/GEJC in ≥ 10% of tumor cells. No new safety signals were reported. Conclusion: In East Asian patients with FGFR2b-positive advanced/metastatic G/GEJC enrolled in the global FIGHT study, bemarituzumab-mFOLFOX6 showed clinically meaningful outcomes over placebo-mFOLFOX6. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of local recurrence following gastric endoscopic submucosal dissection (ESD) remains a clinical concern. We aimed to evaluate the impact of narrow safety margin (< 1 mm) on the recurrence rate. Methods: A retrospective cohort study was conducted across two centers. Cases of R0-ESD with subsequent recurrence were compared to matched controls in a 1:2 ratio in a case-cohort analysis. Results: Over a median period of 25 months (IQR 14-43), a recurrence rate of 3% (95%CI 1.7-4.3) was observed, predominantly (13/21) following R0 resections with favourable histology. Endoscopic retreatment was feasible in 18 of 21 recurrences. The proportion of R0-cases where the safety margin in both horizontal (HM) and vertical (VM) margin exceeded 1 mm was similarly distributed in the recurrence and non-recurrence group, representing nearly 20% of cases. However, cases with HM less than 1 mm, despite VM greater than 1 mm, nearly doubled in the recurrence group (7.7% vs. 3.9%), and tripled when both margins were under 1 mm (23.1% vs. 7.7%). Despite this trend, statistical significance was not achieved (p = 0.05). In the overall cohort, the only independent risk factor significantly associated with local recurrence was the presence of residual tumor at the HM (HM1) or not assessable HM (HMx) (OR 16.5 (95%CI 4.4-61.7), and OR 11.7 (95%CI 1.1-124.1), respectively). Conclusions: While not common or typically challenging to manage, recurrence post-ESD warrants attention and justifies rigorous post-procedural surveillance, especially in patients with HM1, HMx, and probably also in those with R0 resections but narrow safety margin. [ABSTRACT FROM AUTHOR]

Background: Robotic distal gastrectomy (RDG) with Billroth I (BI) reconstruction is predominantly performed due to its physiological congruence and simplicity. The Intracorporeal Triangular Anastomotic Technique (INTACT) aims to reduce ischemic areas compared to the conventional Delta-shaped anastomosis using the unique characteristics of robotic surgery to standardize procedures, thereby ensuring safe, simple, and reliable reconstruction. This study aims to investigate the efficacy of the INTACT in RDG with BI reconstruction, focusing on its robotic precision in minimizing ischemic zones and improving surgical reliability. Surgical technique: The posterior duodenal wall is dissected before reconstruction, and the hepatoduodenal ligament is severed to facilitate passive duodenal manipulation. A quarter-circumference incision is created centrally on the anterior wall of the duodenal stump to avoid excessive tension during anastomosis and to ensure an adequate anastomotic diameter. A small opening is established on the greater curvature of the remaining stomach, and the posterior walls of the stomach and duodenum are joined using a Linear stapler in the first fire. A V-shape is created, and two EndoWrist instruments (robotic first and fourth arms) are utilized to grip and extend the anastomosis diameter, completing the anastomosis with a shared hole closure using the Linear stapler. The robotic arms' features improve the physiological integrity and stability of the BI reconstruction. Results: A total of 81 patients underwent RDG with INTACT from September 2020 to January 2024. The median age was 72 years (range: 31–91), with 49 males and 32 females. The median blood loss was 0 ml (range: 0–200 ml), and the median postoperative hospital stay was 8 days (range: 6–20 days). No cases required reanastomosis during surgery, and no postoperative anastomotic leakage, surgery-related reoperations, or anastomotic strictures were reported. Conclusion: INTACT in RDG can be safely performed. The characteristics of the EndoWrist instruments helped in stabilizing the technique, making it a viable option in robotic-assisted surgeries. [ABSTRACT FROM AUTHOR]

• Fibroblasts can be activated as cancer-associated fibroblasts in the tumourmicroenvironment. • Cancer-associated fibroblasts help promote gastric cancer metastasis. • Cancer-Associated Fibroblasts Form Signalling Network with Gastric Cancer Cells. • Multiple drugs targeting cancer-associated fibroblasts have been found to inhibit gastric cancer progression. Despite advances in surgery, radiotherapy and immunotherapy, the mortality rate for gastric cancer remains one of the highest in the world. A large body of evidence has demonstrated that cancer-associated fibroblasts (CAFs), as core members of the stroma, can secrete cytokines, proteins and exosomes to create a tumour microenvironment that is conducive to cancer cell survival. CAFs can also interact with cancer cells to form a complex signalling network, enabling cancer cells to more easily metastasise to other organs and tissues in the body and develop metastatic foci. In this review, we provide an overview of the CAFs concept and activators. We focus on elucidating their effects on immune cells, intratumoural vasculature, extracellular matrix, as well as cancer cell activity, metastatic power and metabolism, and on enhancing the metastatic ability of cancer cells through activation of JAK/STAT, NF/κB and CXCL12/CXCR4. Various therapeutic agents targeting CAFs are also under development and are expected to improve the prognosis of gastric cancer in combination with existing treatment options. [ABSTRACT FROM AUTHOR]

Cancers have emerged as a significant concern due to their impact on public health and society. The examination and interpretation of tissue sections stained with Hematoxylin and Eosin (H&E) play a crucial role in disease assessment, particularly in cases like gastric cancer. Microsatellite instability (MSI) is suggested to contribute to the carcinogenesis of specific gastrointestinal tumors. However, due to the nonspecific morphology observed in H&E-stained tissue sections, MSI determination often requires costly evaluations through various molecular studies and immunohistochemistry methods in specialized molecular pathology laboratories. Despite the high cost, international guidelines recommend MSI testing for gastrointestinal cancers. Thus, there is a pressing need for a new diagnostic modality with lower costs and widespread applicability for MSI detection. This study aims to detect MSI directly from H&E histology slides in gastric cancer, providing a cost-effective alternative. The performance of well-known deep convolutional neural networks (DCNNs) and a proposed architecture are compared. Medical image datasets are typically smaller than benchmark datasets like ImageNet, necessitating the use of off-the-shelf DCNN architectures developed for large datasets through techniques such as transfer learning. Designing an architecture proportional to a custom dataset can be tedious and may not yield desirable results. In this work, we propose an automatic method to extract a lightweight and efficient architecture from a given heavy architecture (e.g., well-known off-the-shelf DCNNs) proportional to a specific dataset. To predict MSI instability, we extracted the MicroNet architecture from the Xception network using the proposed method and compared its performance with other well-known architectures. The models were trained using tiles extracted from whole-slide images, and two evaluation strategies, tile-based and whole-slide image (WSI)-based, were employed and compared. Additionally, a visual explanation of the best convolutional neural network model is presented to validate numerical results. The MicroNet architecture achieved the best accuracy (0.85) and area under the curve-receiver operating characteristic curve (0.93), outperforming previous works for the study dataset. The proposed method can be utilized by developers to design lightweight and efficient problem-based neural network architectures, such as MicroNet, for MSI prediction. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 has been a pivotal biomarker for gastric cancer treatment strategies for many years. However, more than a decade after the ToGA trial demonstrated the efficacy of trastuzumab in improving survival, the development of treatments targeting human epidermal growth factor receptor 2 remains challenging. Several large-scale clinical trials of tyrosine kinase inhibitors, non-trastuzumab anti-human epidermal growth factor receptor 2 antibodies, and antibody–drug conjugates have failed to meet the primary endpoints. The concept of trastuzumab beyond progression and the complexity of resistance mechanisms to anti-human epidermal growth factor receptor 2 therapy after trastuzumab treatment presented significant obstacles, leading to trastuzumab being the sole therapy for human epidermal growth factor receptor 2-positive gastric cancer for some time. Nevertheless, the landscape has shifted in recent years, especially since the introduction of the antibody–drug conjugate trastuzumab deruxtecan in 2020. This has rekindled the interest in developing treatments targeting human epidermal growth factor receptor 2 in gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle (SM) is a key factor in cancer treatment. However, it is unclear whether pretreatment SM change affects the outcome of immune checkpoint inhibitors (ICIs) therapy in gastric cancer (GC). Methods: Advanced GCs treated with ICIs were retrospectively investigated. SM evaluated by psoas muscle area at the third lumbar vertebra was measured on CT acquired within 1 month from the start of ICIs therapy (CT-1), and on CT acquired 2.8 ± 0.84 months before CT-1. Monthly change rate of SM (MCR-SM) was defined as the change rate of SMs between those two CTs divided by the period between those CTs (month). Monthly change rate of body weight (MCR-BW) during the same period was also calculated. They were compared with disease-specific survival (DSS) and progression-free survival (PFS). MCR-SM was compared with pretreatment markers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein (CRP), and liver-to-spleen CT attenuation ratio (LSR) as a marker of liver lipid metabolism. Results: This study enrolled eighty-three GC patients. MCR-SM significantly correlated with DSS and PFS (P < 0.0001, 0.001, respectively), whereas MCR-BW did not. Kaplan–Meier analyses demonstrated that higher MCR-SM (MCR-SM ≥ −0.7185%) significantly associated with better DSS and PFS (P = 0.0002, 0.03, respectively). Patients with positive MCR-SM showed significantly lower NLR, MLR, and CRP than those with negative (P = 0.01, 0.006, 0.003, respectively). MCR-SM showed a significant positive correlation with LSR (P = 0.007, R = 0.30). Conclusions: Pretreatment SM loss, associated with high systemic inflammation and hepatic fat accumulation, related to poor outcome of ICIs therapy in GC. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWAS) pinpointed gastric cancer (GC)-associated single-nucleotide polymorphisms (SNPs) and other gene variants not only in genes of the human host but also in genes of the bacterial pathogen Helicobacter pylori. Functional studies unraveled the underlying mechanisms by which SNPs in H. pylori virulence factors CagA and serine protease HtrA promote GC development. The 171L/S SNP in HtrA originated in Asia 60 000 to 45 000 years ago after the human migration out-of-Africa and spread to all continents except Africa; the EPIYT mutation in CagA arose before the out-of-Africa migration. Several single-nucleotide polymorphisms (SNPs) in human chromosomes are known to predispose to cancer. However, cancer-associated SNPs in bacterial pathogens were unknown until discovered in the stomach pathogen Helicobacter pylori. Those include an alanine-threonine polymorphism in the EPIYA-B phosphorylation motif of the injected effector protein CagA that affects cancer risk by modifying inflammatory responses and loss of host cell polarity. A serine-to-leucine change in serine protease HtrA is associated with boosted proteolytic cleavage of epithelial junction proteins and introduction of DNA double-strand breaks (DSBs) in host chromosomes, which co-operatively elicit malignant alterations. In addition, H. pylori genome-wide association studies (GWAS) identified several other SNPs potentially associated with increased gastric cancer (GC) risk. Here we discuss the clinical importance, evolutionary origin, and functional advantage of the H. pylori SNPs. These exciting new data highlight cancer-associated SNPs in bacteria, which should be explored in more detail in future studies. [ABSTRACT FROM AUTHOR]

Dermatomyositis (DM) is associated with interstitial lung disease (ILD) and malignancy. However, the coexistence of ILD and malignancy (DM–ILD–malignancy) is rare, and limited information exists regarding its management. Herein, we report the case of a 70-year-old man who developed DM with rapidly progressive ILD and advanced gastric cancer and provide a literature review of managing DM–ILD–malignancy. The patient presented with typical DM skin rashes and shortness of breath, which worsened within 1 month, without muscular symptoms. Additionally, the patient tested negative for myositis-specific autoantibodies (MSAs). Computed tomography revealed ILD and advanced gastric cancer, which was confirmed on endoscopic examination to be a poorly differentiated adenocarcinoma. Although the patient's ILD progressed rapidly, surgical treatment of the cancer was prioritized. Prednisolone (PSL) 0.5 mg/kg was initiated 3 days before surgery and increased to 1 mg/kg at 7 days postoperative. Remarkable improvement in the skin rash and ILD was observed, and the PSL dose was tapered without immunosuppressants. A literature review revealed that anti-melanoma differentiation-associated gene 5 and anti-aminoacyl transfer RNA synthetase antibodies are the predominant MSAs in DM–ILD–malignancy, and the optimal treatment should be determined based on several factors, including ILD patterns, and malignancy type and stage. In particular, lung cancer may be a risk factor for the acute exacerbation of ILD, and preceding immunosuppression would be useful. Furthermore, prioritizing surgery for gastric cancer is effective because of its paraneoplastic nature. [ABSTRACT FROM AUTHOR]

The controlled nutritional status score (CONUT) and handgrip strength (HGS) were both predictive indexes for the prognosis of cancers. However, the combination of CONUT and HGS for predicting the prognosis of gastrointestinal cancer had not been developed. This study aimed to explore the combination of CONUT and HGS as the potential predictive prognosis in patients with gastric and colorectal cancer. A cohort study was conducted with gastric and colorectal cancer patients in multicenter in China. Based on the optimal HGS cutoff value for different sex, the HGS cutoff value was determined. The patients were divided into high and low HGS groups based on their HGS scores. A CONUT score of 4 or less was defined as a low CONUT, whereas scores higher than 4 were defined as high CONUT. The Kaplan-Meier method was used to create survival curves, and the log-rank test was used to compare time-event relationships between groups. A Cox proportional hazard regression model was used to determine independent risk factors for overall survival (OS). A total 2177 gastric and colorectal patients were enrolled in this study, in which 1391 (63.9%) were men (mean [SD] age, 66.11 [11.60] years). Multivariate analysis revealed that patients with high HGS had a lower risk of death than those with low HGS (hazard ratio [HR],0.87; 95% confidence interval [CI], 0.753–1.006, P = 0.06), while high CONUT had a higher risk of death than those with low CONUT (HR, 1.476; 95% CI, 1.227–1.777, P < 0.001). Patients with both low HGS and high CONUT had 1.712 fold increased risk of death (HR, 1.712; 95% CI, 1.364–2.15, P < 0.001). Moreover, cancer type and sex were stratified and found that patients with high CONUT and low HGS had lower survival rate than those with low CONUT and high HGS in both gastric or colorectal cancer, and both male and female. A combination of low HGS and high CONUT was associated with poor prognosis in patients with gastrointestinal cancer, which could probably predict the prognosis of gastrointestinal cancer more accurate than HGS or CONUT alone. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the association between low-dose aspirin use and the risk of GC and gastric adenoma according to a family history of GC. We conducted a population-based study of 7,596,003 participants screened for GC between 2013 and 2014. Aspirin users and non-users were matched in a 1:1 ratio through propensity score matching (PSM). After PSM, 51,818 participants with a family history of GC and 359,840 without a family history of GC were analyzed (mean follow-up periods: 4.9 ± 0.8 and 4.8 ± 0.8 years, respectively). In patients with a family history of GC, aspirin use was significantly associated with a reduced risk of GC (adjusted hazard ratio [aHR]=0.80; 95 % confidence interval [CI]=0.65–0.995) and gastric adenoma (aHR=0.81; 95% CI=0.69–0.94). In those without a family history of GC, aspirin use was associated with a reduced risk of gastric adenoma (aHR = 0.92; 95 % CI = 0.86–0.98), but not with that of GC (aHR = 0.99; 95 % CI = 0.90–1.08). Low-dose aspirin use was associated with a reduced risk of gastric adenoma, regardless of a family history of GC, and may play a role in the early stages of gastric carcinogenesis. However, the association between aspirin and GC was only observed in those with a family history of GC. [ABSTRACT FROM AUTHOR]

Background/Aim: We hypothesized that the hemoglobin, albumin, lymphocyte, and platelet (HALP) score may be a promising marker for the treatment and management of gastric cancer (GC). To test this hypothesis, we evaluated the clinical impact of the HALP score in patients with GC who received curative treatment. Patients and Methods: Consecutive patients who underwent curative resection for GC at the Yokohama City University between 2005 and 2020 were selected based on their medical records. The HALP score was calculated as follows: HALP=Hemoglobin (g/l) × albumin (g/l) × lymphocytes (109/l)/platelets (109/l). Results: The 3-year and 5-year overall survival (OS) rates were 88.6% and 85.8%, respectively, in patients with HALP scores of >40, and 70.3% and 57.2% in patients with HALP scores of ≤40. There were significant differences between the groups analyzed (p<0.001). In univariate analysis, age, T status, lymph node metastasis status, HALP score, lymphovascular invasion status, pathological type, and postoperative complication status were identified as significant prognostic factors for OS. In multivariate analysis, the HALP score remained a significant prognostic factor for OS [hazard ratio (HR)=2.679; 95% confidence interval (CI)=1.455-4.934, p=0.002]. Similar results were observed in the analysis of recurrence-free survival. In addition, the HALP score status affects the postoperative clinical course, including the occurrence of postoperative anastomotic leakage and the introduction of postoperative adjuvant chemotherapy. Conclusion: The HALP score affects both short- and long-term oncological outcomes. Thus, the HALP score may be a promising prognostic factor for the treatment and management of GC. [ABSTRACT FROM AUTHOR]

Background/Aim: To date, the different clinicopathological characteristics of gastric cancer (GC) in the lesser curvature and greater curvature remain unclear. The aim of this study was to investigate the different features of the tumors in the two sites and provide new strategy for a tailored therapy. Patients and Methods: Between January 2003 and December 2019, 121 patients with GC located in the lesser or greater curvature were surgically treated with curative intent. Data about clinico-pathological features were retrospectively analyzed. In addition, we analyzed the different lymph node patterns according to the lymph node (LN) metastasis between the two groups of patients. Results: No statistically significant differences were found regarding the 5-year overall survival (5y-OS) and 5y disease-free survival (5y-DFS) between patients with GC in the two sites (p=0.94 and p=0.98, respectively). Considering TNM pathological stage, patients with GC in the lesser curvature in stage II and III, showed a worse survival than those with GC in the greater curvature (stage II 5y-OS: 80 vs. 100% and stage III 5y-OS: 18.9 vs. 55.5%). Considering the median value of metastasis LNs, GC in the greater curvature metastasized more often to LN stations no. 8, 10, and 11, whereas GC in the lesser curvature to LN stations no. 8, 9, and 12. Conclusion: GC in the lesser curvature showed a worse prognosis than GC in the greater curvature. Therefore, GC in the lesser curvature could undergo a more aggressive surgery, including an extended lymphadenectomy, and a close follow-up. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to develop and validate a machine learning-based, multimodality fusion (MMF) model using 18F-fluorodeoxyglucose (FDG) PET/CT radiomics and kernelled support tensor machine (KSTM), integrated with clinical factors and nuclear medicine experts' diagnoses to individually predict peritoneal metastasis (PM) in advanced gastric cancer (AGC). Methods: A total of 167 patients receiving preoperative PET/CT and subsequent surgery were included between November 2006 and September 2020 and were divided into a training and testing cohort. The PM status was confirmed via laparoscopic exploration and postoperative pathology. The PET/CT signatures were constructed by classic radiomic, handcrafted-feature-based model and KSTM self-learning-based model. The clinical nomogram was constructed by independent risk factors for PM. Lastly, the PET/CT signatures, clinical nomogram, and experts' diagnoses were fused using evidential reasoning to establish the MMF model. Results: The MMF model showed excellent performance in both cohorts (area under the curve [AUC] 94.16% and 90.84% in training and testing), and demonstrated better prediction accuracy than clinical nomogram or experts' diagnoses (net reclassification improvement p < 0.05). The MMF model also had satisfactory generalization ability, even in mucinous adenocarcinoma and signet ring cell carcinoma which have poor uptake of 18F-FDG (AUC 97.98% and 89.71% in training and testing). Conclusions: The 18F-FDG PET/CT radiomics-based MMF model may have significant clinical implications in predicting PM in AGC, revealing that it is necessary to combine the information from different modalities for comprehensive prediction of PM. [ABSTRACT FROM AUTHOR]

Background: Despite a radical operation, about half of gastric cancer (GC) patients with advanced GC experience peritoneal metastasis (PM), and the patients with PM have a poor prognosis. However, because staging laparoscopy was a highly invasive procedure for patients, identification of PM using a liquid biopsy can be useful for patients with GC. Methods: This study analyzed two genome-wide miRNA expression profiling datasets (GSE164174 and TCGA). The study prioritized biomarkers in pretreatment plasma specimens from clinical training and validation cohorts of patients with GC. The authors developed an integrated exosomal miRNA panel and established a risk-stratification model, which was combined with the miRNA panel and currently used tumor markers (CEA, CA19-9, CA125, and CA72-4 levels). Results: The comprehensive discovery effort identified a four-miRNA panel that robustly predicted the metastasis with excellent accuracy in the TCGA dataset (area under the curve [AUC] 0.86). A circulating exosomal miRNA panel was established successfully with remarkable diagnostic accuracy in the clinical training (AUC 0.85) and validation (AUC 0.86) cohorts. Moreover, the predictive accuracy of the panel was significantly superior to that of conventional clinical factors (P < 0.01), and the risk-stratification model was dramatically superior to the panel and currently used clinical factors for predicting PM (AUC 0.94; univariate: odds ratio [OR] 77.00 [P < 0.01]; multivariate OR 57.71 [P = 0.01]). Conclusions: The novel risk-stratification model for predicting PM has potential for clinical translation as a liquid biopsy assay for patients with GC. The study findings highlight the potential clinical impact of the model for improved selection and management of patients with GC. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer poses a major diagnostic and therapeutic challenge as surgical resection provides the only opportunity for a cure. Specific labeling of gastric cancer could distinguish resectable and nonresectable disease and facilitate an R0 resection, which could improve survival. Methods: Two patient-derived gastric cancer lines, KG8 and KG10, were established from surgical specimens of two patients who underwent gastrectomy for gastric adenocarcinoma. Harvested tumor fragments were implanted into the greater curvature of the stomach to establish patient-derived orthotopic xenograft (PDOX) models. M5A (humanized anti-CEA antibody) or IgG control antibodies were conjugated with the near-infrared dye IRDye800CW. Mice received 50 µg of M5A-IR800 or 50 µg of IgG-IR800 intravenously and were imaged after 72 hr. Fluorescence imaging was performed by using the LI-COR Pearl Imaging System. A tumor-to-background ratio (TBR) was calculated by dividing the mean fluorescence intensity of the tumor versus adjacent stomach tissue. Results: M5A-IR800 administration resulted in bright labeling of both KG8 and K10 tumors. In the KG8 PDOX models, the TBR for M5A-IR800 was 5.85 (SE ± 1.64) compared with IgG-IR800 at 0.70 (SE ± 0.17). The K10 PDOX models had a TBR of 3.71 (SE ± 0.73) for M5A-IR800 compared with 0.66 (SE ± 0.12) for IgG-IR800. Conclusions: Humanized anti-CEA (M5A) antibodies conjugated to fluorescent dyes provide bright and specific labeling of gastric cancer PDOX models. This tumor-specific fluorescent antibody is a promising potential clinical tool to detect the extent of disease for the determination of resectability as well as to visualize tumor margins during gastric cancer resection. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the most frequent reasons for cancer‐related death worldwide. The multimodal therapeutic strategies are now pragmatically tailored to each patient, especially in advanced GC. A radical but safe gastrectomy remains the cornerstone of the GC treatment. Moreover, the quality‐of‐life (QoL) outcome measures are now routinely utilized in order to select optimal type of gastrectomy, as well as reconstruction method. Postoperative complications are frequent, and effective diagnosis and treatment of complications is crucial to lower the mortality rates. The postoperative complications prolong hospital stay and may result in poor QoL, thus eliminating the completion of perioperative adjuvant therapy. Therefore, avoiding morbidity is not only relevant for the immediate postoperative course, but can also affect long‐term oncological outcome. Measuring outcome enables surgeons to: monitor their own results; compare quality of treatment between centres; facilitate improvement both for surgery alone and combined treatment; select optimal procedure for an individual patient. Textbook oncological outcome is a composite quality measure representing the ideal hospitalization for gastrectomy, as well as stage‐appropriate (perioperative) adjuvant chemotherapy. Standardized system for recording complications and adherence to multimodality treatment guidelines are crucial for achieving the ultimate goal of surgical quality‐improvement that can benefit patients QoL and long‐term outcomes after fast and uneventful hospitalization for gastrectomy. [ABSTRACT FROM AUTHOR]