Gel immersion endoscopic mucosal resection for small gastric neoplastic lesions: A pilot study.

Gastric endoscopic mucosal resection is challenging due to the slippery mucosa, abundant blood vessels, and the presence of mucus. We developed gel immersion endoscopy to secure the visual field, even in a blood-filled gastrointestinal lumen in 2016. Clear gel with appropriate viscosity, instead of water, can prevent rapid mixture with blood and facilitate identification of the culprit vessel. We further optimized the gel for endoscopic treatment, and the resultant product, Viscoclear (Otsuka Pharmaceutical Factory) was first released in Japan in 2020. The viscosity of this gel has been optimized to maximize endoscopic visibility without compromising the ease of its irrigation. The aim of this study is to clarify the effectiveness of gel immersion endoscopic mucosal resection for small-sized early gastric neoplasms. Seven lesions in seven patients were treated by gel immersion endoscopic mucosal resection. The size of all lesions was under 10 mm. The median procedure time was 4.5 min. Intraoperative bleeding occurred in four of seven lesions immediately after snare resection and was easily controlled by endoscopic hemostatic forceps during the gel immersion endoscopy. The R0 resection rate was 100%. In conclusion, gel immersion endoscopic mucosal resection may be a straightforward, rapid, and safe technique for resecting superficial gastric neoplasms <10 mm in diameter.

Actinidia chinensis polysaccharide interferes with the epithelial-mesenchymal transition of gastric cancer by regulating the nuclear transcription factor-κB pathway to inhibit invasion and metastasis.

OBJECTIVE: To investigate the mechanisms of the effect of Actinidia chinensis polysaccharide (ACPS) on the invasion and metastasis of gastric cancer cells. METHODS: BGC-823-Luc gastric cancer cells stably transfected with a luciferase gene were used to establish an insitutransplanted tumor mouse model. A live mouse imaging system was used to observe tumor growth, and hematoxylin and eosin staining was applied to analyze tissue histopathology. Transwell and scratch wound assays were performed to examine the invasive and migratory ability of BGC-823 cells. Immunofluorescence, confocal microscopy, immunohistochemistry, and Western blot assays were used to analyze the expressions of the nuclear transcription factor-κB (NF-κB) signaling pathway and epithelial-mesenchymal transition (EMT)-related proteins. RESULTS: ACPS significantly inhibited the growth of subcutaneously transplanted BGC-823-Luc gastric cancer tumors in nude mice and reduced inflammatory cell infiltration in tumor tissues. ACPS inhibited Epidermal Growth Factor-induced invasion, migration, and morphological changes in the cytoskeleton of BGC-823 cells. ACPS inhibited gastric cancer EMT and decreased the expression of matrix metallopeptidase 9, N-cadherin and p-NF-κB p65 in transplanted tumor tissues. ACPS inhibited the expression of matrix metalloproteinases and vascular adhesion factors in BGC-823 cells, promoted p65-NF-κB nuclear translocation, and regulated proteins associated with the NF-κB p65 pathway. CONCLUSIONS: ACPS inhibited gastric cancer invasion and metastasis both in vivo and in vitro, which evidenced the inhibition of gastric cancer EMT viaregulating the NF-κB inflammatory pathway.

Weitiao No. 3 (3) enhances the efficacy of anti-programmed cell death protein-1 immunotherapy by modulating the intestinal microbiota in an orthotopic model of gastric cancer mice.

OBJECTIVE: To explore the effects of Weitiao No. 3 (3, WD-3) on anti-programmed cell death protein-1 (PD-1) immunotherapy in gastric cancer (GC). METHODS: The intestinal microbiota was analyzed by 16S rDNA sequencing of fecal samples from three groups: healthy people (Health), GC patients (GC), and WD-3-treated GC patients (WD-3). Next, we established an orthotopic model of GC mice, which were treated with anti-PD-1, WD-3, or an inoculation of intestinal bacteria. Immune markers CD3, CD4, CD8, and forkhead box protein P3 (FOXP3), and the cell proliferation marker Ki67, were evaluated by immunohistochemistry. Cell apoptosis in GC tumors was assessed by terminal-deoxynucleotidyl-transferase-mediated deoxyuridine triphosphate nick end labeling staining. Enzyme-linked immunosorbent assays (ELISAs) were performed to analyze the serum levels of the following cytokines in GC mice: tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, IL-10, interferon (IFN)-γ, and transforming growth factor (TGF)-ß. RESULTS: Sequencing data showed that there were significant differences in the composition of the gut microbial community among the three human groups. The gut bacteria in the three groups mainly comprised the phyla Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. At the genus level, the relative abundances of Bifidobacterium and Coprococcus showed significant decreases in the GC group, and an obvious increase in the WD-3 group, compared with the Health group. Interestingly, the relative abundance of Saccharopolyspora was only detected in the WD-3 group. The results of in vivo experiments in GC mice showed that WD-3 or anti-PD-1 treatment increased the levels of CD3+, CD4+, and CD8+ T cells, but decreased the levels of FOXP3+ regulatory T cells. Furthermore, WD-3 or PD-1 antibody treatment inhibited proliferation and promoted apoptosis of GC tumor cells. ELISA analysis showed that WD-3 or PD-1 antibody treatment facilitated TNF-α, IL-2, and IFN-γ expression, while suppressing IL-6, IL-10, and TGF-ß expression. Combination therapy with WD-3 and anti-PD-1 intensified all of these effects. CONCLUSION: WD-3 enhanced the immunotherapeutic efficacy of anti-PD-1 by modulating the intestinal microbiota in an orthotopic model of GC mice.

Introduction of LPIN1 as a potential diagnostic and prognostic biomarker for gastric cancer via integrative bioinformatics analysis of a competing endogenous RNA network and experimental validation.

Objectives: Identification of effective biomarkers is crucial for the heterogeneous disease of gastric cancer (GC). Recent studies have focused on the role of pseudogenes regulating gene expression through competing endogenous RNA (ceRNA) networks, however, the pseudogene-associated ceRNA networks in GC remain largely unknown. The current study aimed to construct and analyze a three-component ceRNA network in GC and experimentally validate a ceRNA. Materials and Methods: A comprehensive analysis was conducted on the RNA-seq and miRNA-seq data of The Cancer Genome Atlas (TCGA) stomach adenocarcinoma (STAD) dataset to identify differentially-expressed mRNAs (DEMs), pseudogenes (DEPs), and miRNAs (DEMis). Pseudogene-associated ceRNA and protein-protein interaction (PPI) networks were constructed, and functional enrichment analyses were performed. DEMs and DEPs with degree centralities≥2 were selected for survival analysis. A ceRNA was further selected for experimental validation. Results: 10,145 DEMs, 3576 DEPs, and 66 DEMis were retrieved and a ceRNA network was then constructed by including DEMis with concurrent interactions with at least a DEM and a DEP. Functional enrichment analysis demonstrated that DEMs of the ceRNA network were significantly enriched in cancer-associated pathways. LPIN1 and WBP1L were two mRNAs showing an association with STAD patients overall survival. Expression analysis of LPIN1 showed a significant decrease in GC tumors compared to non-tumor tissues (P=0.003). Conclusion: Our research emphasizes the significant implications of ceRNA networks in the development of new biomarkers for the detection and prognosis of cancer. Further examination is necessary to explore the functional roles of LPIN1 in the pathogenesis of GC.

Long-term Oncologic Outcomes of Robotic Total Gastrectomy for Advanced Gastric Cancer.

PURPOSE: Although laparoscopic distal gastrectomy has rapidly replaced open distal gastrectomy, laparoscopic total gastrectomy (LTG) is less frequently performed owing to technical difficulties. Robotic surgery could be an appropriate minimally invasive alternative to LTG because it alleviates the technical challenges posed by laparoscopic procedures. However, few studies have compared the oncological safety of robotic total gastrectomy (RTG) with that of LTG, especially for advanced gastric cancer (AGC). Herein, we aimed to assess the oncological outcomes of RTG for AGC and compare them with those of LTG. MATERIALS AND METHODS: We retrospectively reviewed 147 and 204 patients who underwent RTG and LTG for AGC, respectively, between 2007 and 2020. Long-term outcomes were compared using inverse probability of treatment weighting (IPTW). RESULTS: After IPTW, the 2 groups exhibited similar clinicopathological features. The 5-year overall survival was comparable between the 2 groups (88.5% [95% confidence interval {CI}, 79.4%-93.7%] after RTG and 87.3% [95% CI, 80.1%-92.0%]) after LTG; log-rank P=0.544). The hazard ratio (HR) for death after RTG compared with that after LTG was 0.73 (95% CI, 0.40-1.33; P=0.304). The 5-year relapse-free survival was also similar between the 2 groups (75.7% [95% CI, 65.2%-83.4%] after RTG and 76.4% [95% CI, 67.9%-83.0%] after LTG; log-rank P=0.850). The HR for recurrence after RTG compared with that after LTG was 0.93 (95% CI, 0.60-1.46; P=0.753). CONCLUSIONS: Our findings revealed that RTG and LTG for AGC had similar long-term outcomes. RTG is an oncologically safe alternative to LTG and has technical advantages.

Clinical implications of CT-detected ascites in gastric cancer: association with peritoneal metastasis and systemic inflammatory response.

OBJECTIVES: This study aimed to evaluate the diagnostic significance of computed tomography (CT) detected ascites in gastric cancer (GC) with peritoneal metastasis (PM) and investigate its association with systemic inflammatory response. METHODS: This retrospective study included 111 GCs with ascites (PM: n = 51; No PM: n = 60). Systemic inflammatory indexes, tumor markers, and the CT-assessed characteristics of ascites were collected. The differences in parameters between the two groups were analyzed. Diagnostic performance was obtained by receiver operating characteristic curve analysis. The association between the volume of ascites and clinical characteristics was evaluated with correlation analysis. RESULTS: In this study, over half of GCs with ascites were not involved with PM. The systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), five tumor markers, and the characteristics of ascites showed significant differences between the two groups (all p < 0.05). Among them, SII, NLR, PLR, and the volume of ascites achieved the areas under the curve of 0.700, 0.698, 0.704, and 0.903, respectively. Moreover, the volumes of ascites showed positive correlations with SII, NLR, and PLR in GCs with PM, and the volumes of ascites detected in the upper abdomen were more strongly correlated with CA125 level (all p < 0.05). CONCLUSION: Many GCs with CT-detected ascites did not occur with synchronous PM. The presence of upper abdominal ascites had certain clinical significance for diagnosing PM in GCs. Systemic inflammatory indexes were elevated and positively correlated with the volume of ascites in GCs with PM, which might suggest the enhanced systemic inflammatory response. CRITICAL RELEVANCE STATEMENT: CT-detected ascites in the upper abdomen played an indicative role in identifying synchronous PM in GCs, and the systemic inflammatory response was enhanced in GCs with PM, which might be helpful for clinical evaluation. KEY POINTS: Many GCs with CT-detected ascites did not occur with synchronous PM. CT-detected ascites in the upper abdomen help in identifying PM in GCs. GCs with PM showed elevated systemic inflammatory indexes and enhanced systemic inflammatory response.

Correlation between White Globe Appearance and Clinicopathologic Characteristics in Early Gastric Cancer.

Background/Aims: Magnifying endoscopy with narrow-band imaging (ME-NBI) enables the visualization of detailed microsurface (MS) and microvascular (MV) structures in the gastrointestinal tract. White globe appearance (WGA) is a small whitish lesion with a globular shape identified during ME-NBI for early gastric cancer (EGC). This study aimed to investigate the associations between WGA, clinicopathological characteristics, and other ME-NBI findings in patients with EGC. Methods: The presence or absence of WGA in 122 patients (126 lesions) with an endoscopic diagnosis of EGC who underwent ME-NBI before endoscopic or surgical resection was prospectively collected and retrospectively analyzed. During ME-NBI, the MS and MV patterns and the presence of WGA and white opaque substances (WOS) were investigated. EGC cases were categorized as differentiated or undifferentiated type, and mucosal, submucosal, or advanced. Results: Of 126 lesions, WGA was observed in 25 (19.8%). WGA was associated with tumor size (≤2 cm [17/63, 27.0%] vs >2 cm [8/63, 12.7%]; p=0.044), histologic type (differentiated type [22/89, 24.7%] vs undifferentiated type [3/37. 8.1%]; p=0.033), and tumor location (upper third [1/11, 9.1%] vs middle third [18/58, 31.0%] and lower third [6/57, 10.5%]; p=0.017). Although WGA was observed more frequently in lesions with an oval/tubular MS pattern, a fine-network MV pattern, and the absence of WOS, the difference was not statistically significant (MS pattern, p=0.358; MV pattern, p=0.212; WOS, p=0.121, respectively). Conclusions: WGA was associated with small tumor size, differentiated-type histology, and middle-third tumor location, and was more frequently observed in lesions with an oval/tubular MS and fine-network MV patterns and the absence of WOS.

Expression, DNA methylation pattern and transcription factor EPB41L3 in gastric cancer: a study of 262 cases.

PURPOSE: DNA methylation prominently inactivates tumor suppressor genes and facilitates oncogenesis. Previously, we delineated a chromosome 18 deletion encompassing the erythrocyte membrane protein band 4.1-like 3 (EPB41L3) gene, a progenitor for the tumor suppressor that is differentially expressed in adenocarcinoma of the lung-1 (DAL-1) in gastric cancer (GC). METHODS: Our current investigation aimed to elucidate EPB41L3 expression and methylation in GC, identify regulatory transcription factors, and identify affected downstream pathways. Immunohistochemistry demonstrated that DAL-1 expression is markedly reduced in GC tissues, with its downregulation serving as an independent prognostic marker. RESULTS: High-throughput bisulfite sequencing of 70 GC patient tissue pairs revealed that higher methylation of non-CpGs in the EPB41L3 promoter was correlated with more malignant tumor progression and higher-grade tissue classification. Such hypermethylation was shown to diminish DAL-1 expression, thus contributing to the malignancy of GC phenotypes. The DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) was found to partially restore DAL-1 expression. Moreover, direct binding of the transcription factor CDC5L to the upstream region of the EPB41L3 promoter was identified via chromosome immunoprecipitation (ChIP)-qPCR and luciferase reporter assays. Immunohistochemistry confirmed the positive correlation between CDC5L and DAL-1 protein levels. Subsequent RNA-seq analysis revealed that DAL-1 significantly influences the extracellular matrix and space-related pathways. GC cell RNA-seq post-5-Aza-CdR treatment and single-cell RNA-seq data of GC tissues confirmed the upregulation of AREG and COL17A1, pivotal tumor suppressors, in response to EPB41L3 demethylation or overexpression in GC epithelial cells. CONCLUSION: In conclusion, this study elucidates the association between non-CpG methylation of EPB41L3 and GC progression and identifies the key transcription factors and downstream molecules involved. These findings enhance our understanding of the role of EPB41L3 in gastric cancer and provide a solid theoretical foundation for future research and potential clinical applications.

The EPB41L3 gene, frequently exhibiting haplotype deletions and reduced expression in gastric cancer tissues, points to its potential role as a tumor suppressor. However, tumor suppressor genes are not only influenced by genomic deletions but also by their methylation status. Our study highlights the significantly lower expression of EPB41L3 in gastric cancer compared to adjacent non-cancerous tissues across 262 patients. We also discovered that elevated non-CpG island methylation of EPB41L3 correlates strongly with tumor malignancy progression, based on the analysis of 70 paired gastric cancer samples. Moreover, we identified CDC5L as a crucial transcription factor interacting with the EPB41L3 promoter. Integrative analyses of transcriptomic and single-cell sequencing data further revealed that AREG and COL17A1 are key downstream molecules regulated by DAL-1, with their expression tightly controlled by EPB41L3 methylation and expression levels. These insights enhance our understanding of EPB41L3's role in gastric cancer and could open new avenues for targeted therapies.

Survival among patients cured from gastric adenocarcinoma compared to the background population.

BACKGROUND: It is unknown if gastric adenocarcinoma survivors have longer, shorter, or similar survival compared to the background population. This knowledge could contribute to evidence-based monitoring strategies, healthcare recommendations, and information for patients and families. METHODS: This population-based cohort study included all patients who underwent gastrectomy for gastric adenocarcinoma between 2006-2015 in Sweden and survived ≥ 5 years after surgery. They were followed up until death, postoperative year 10, or end of study period (31 December, 2020). Division of the observed by the expected survival yielded relative survival rates with 95% confidence intervals (CIs) using the life table method. The expected survival was derived from the entire Swedish population of the corresponding age, sex, and calendar year. Data came from medical records and nationwide registers. RESULTS: The survival among all 767 gastric adenocarcinoma survivors was shorter than the expected. The reduction in relative survival increased for each follow-up year, from 97.3% (95% CI 95.4-99.1%) year 6 to 86.6% (95% CI 82.3-90.9%) year 10. The decline in relative survival was more pronounced among patients who had gastrectomy in earlier calendar years (82.9% [95% CI 77.4-88.4%] year 10 for years 2011-2015), shorter education (85.2% [95% CI 77.4-93.0%] year 10 for education ≤ 9 years), more comorbidities (78.0% [95% CI 63.9-92.0%] year 10 for Charlson comorbidity score ≥ 2), and no neoadjuvant therapy (83.2% [95% CI 77.4-89.0%] year 10). CONCLUSION: Gastric adenocarcinoma survivors seem to have poorer survival than the corresponding background population, particularly in certain subgroups.

Advanced diffusion-weighted MRI models for preoperative prediction of lymph node metastasis in resectable gastric cancer.

OBJECTIVE: To investigate the potential of six advanced diffusion-weighted imaging (DWI) models for preoperative prediction of lymph node metastasis (LNM) in resectable gastric cancer (GC). METHODS: Between Nov 2022 and Nov 2023, standard MRI scans were prospectively performed in consecutive patients with endoscopic pathology-confirmed gastric adenocarcinoma who were referred for direct radical gastrectomy. Six DWI models, including fractional order calculus (FROC), continuous-time random walk (CTRW), diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM), the mono-exponential model (MEM) and the stretched exponential model (SEM) were computed. Surgical pathologic diagnosis of LNM was the reference standard, and patients were classified into LNM-positive or LNM-negative groups accordingly. The morphological features and quantitative parameters of the DWI models in different LNM categories were analyzed and compared. Multivariable logistic regression was used to screen significant predictors. Receiver-operating characteristic curves and the area under the curve (AUC) were plotted to evaluate the performances, the Delong test was performed to compare the AUCs. RESULTS: In the LNM-positive group, tumor thickness and kurtosis (DKI_K) were significantly higher, while anomalous diffusion coefficient (CTRW_D), diffusivity (DKI_D), diffusion coefficient (FROC_D), pseudodiffusion coefficient (IVIM_D*), perfusion fraction (IVIM_f), and ADC were lower compared to the LNM-negative group. Clinical tumor staging (cT) and CTRW_D were independent predictors. Their combination demonstrated a superior AUC of 0.930, significantly higher than that of individual parameters. CONCLUSIONS: Tumor thickness, DKI_K, CTRW_D, DKI_D, FROC_D, IVIM_D*, IVIM_f and ADC were associated with LNM status. The combination of independent predictors of cT and CTRW_D further enhanced the performance.

Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts.

Surveillance recommendations for gastric cancer (GC) in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter community-based cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015-2017 and followed-up until 2021. Cumulative incidence rates (CIRs) of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixed-effects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic (atrophic gastritis/intestinal metaplasia) and neoplastic lesions (low-grade/high-grade dysplasia), respectively (Ptrend<0.001). Four predictors, including male, ⩾60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients (⩾3 risk factors) with non-neoplastic lesions showed higher GC risks (adjusted HR=7.73, 95%CI: 4.29-13.92), and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions (aHR=3.07, 95%CI: 1.67-5.64) and high-risk patients with mild lesions (aHR=7.29, 95%CI: 3.58-14.86) showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3-5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

Impact of the COVID-19 pandemic on cancer mortality in Brazil.

BACKGROUND: In the first year of the COVID-19 pandemic, data projections indicated an increase in cancer mortality for the following years due to the overload of health services and the replacement of health priorities. The first studies published with data from mortality records have not confirmed these projections. However, cancer mortality is not an outcome that occurs immediately, and analyses with more extended follow-up periods are necessary. This study aims to analyze the impact of the COVID-19 pandemic on the mortality from all types and the five most common types of cancer in Brazil and investigate the relationship between the density of hospital beds and mortality from COVID-19 in cancer patients in Brazil's Intermediate Geographic Regions (RGIs). METHODS: The Brazilian Mortality Information System provided data on the deaths from trachea, bronchus, and lung, colorectal, stomach, female breast, and prostate cancer and all types of cancer, and from COVID-19 in individuals who had cancer as a contributing cause of death. Predicted rates for 2020-2022 were compared with the observed ones, through a rate ratio (RR). An association analysis, through multivariate linear regression, was carried out between mortality from COVID-19 in cancer patients, the rate of hospital beds per 100,000 inhabitants, and the Human Development Index of the 133 RGIs of Brazil. RESULTS: In 2020, 2021, and 2022, mortality from all cancers in Brazil was lower than expected, with an RR of 0.95, 0.94, and 0.95, respectively, between the observed and predicted rates. Stomach cancer showed the largest difference between observed and expected rates: RR = 0.89 in 2020 and 2021; RR = 0.88 in 2022. Mortality from COVID-19 in cancer patients, which reached its peak in 2021 (6.0/100,000), was negatively associated with the density of hospital beds in the public health system. CONCLUSIONS: The lower-than-expected cancer mortality during 2020-2022 seems to be partly explained by mortality from COVID-19 in cancer patients, which was probably underestimated in Brazil. The findings suggested a protective role of the availability of hospital care concerning deaths due to COVID-19 in this population. More extensive follow-up is needed to understand the impact of the COVID-19 pandemic on cancer mortality.

Risk Prediction Models for Gastric Cancer: A Scoping Review.

Background: Gastric cancer is a significant contributor to the global cancer burden. Risk prediction models aim to estimate future risk based on current and past information, and can be utilized for risk stratification in population screening programs for gastric cancer. This review aims to explore the research design of existing models, as well as the methods, variables, and performance of model construction. Methods: Six databases were searched through to November 4, 2023 to identify appropriate studies. PRISMA extension for scoping reviews and the Arksey and O'Malley framework were followed. Data sources included PubMed, Embase, Web of Science, CNKI, Wanfang, and VIP, focusing on gastric cancer risk prediction model studies. Results: A total of 29 articles met the inclusion criteria, from which 28 original risk prediction models were identified that met the analysis criteria. The risk prediction model is screened, and the data extracted includes research characteristics, prediction variables selection, model construction methods and evaluation indicators. The area under the curve (AUC) of the models ranged from 0.560 to 0.989, while the C-statistics varied between 0.684 and 0.940. The number of predictor variables is mainly concentrated between 5 to 11. The top 5 most frequently included variables were age, helicobacter pylori (Hp), precancerous lesion, pepsinogen (PG), sex, and smoking. Age and Hp were the most consistently included variables. Conclusion: This review enhances understanding of current gastric cancer risk prediction research and its future directions. The findings provide a strong scientific basis and technical support for developing more accurate gastric cancer risk models. We expect that these conclusions will point the way for future research and clinical practice in this area to assist in the early prevention and treatment of gastric cancer.

Measurement of changes in serum-based inflammatory indicators to monitor response to nivolumab monotherapy in advanced gastric cancer: a multicenter retrospective study.

BACKGROUND: Nonresectable gastric cancer develops rapidly; thus, monitoring disease progression especially in patients receiving nivolumab as late-line therapy is important. Biomarkers may facilitate the evaluation of nivolumab treatment response. Herein, we assessed the utility of serum-based inflammatory indicators for evaluating tumor response to nivolumab. METHODS: This multicenter retrospective cohort study included 111 patients treated with nivolumab monotherapy for nonresectable advanced or recurrent gastric cancer from October 2017 to October 2021. We measured changes in the C-reactive protein (CRP)-to-albumin ratio (CAR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) in serum from baseline to after the fourth administration of nivolumab. Furthermore, we calculated the area under the receiver operating characteristic curves (AUC ROCs) for CAR, PLR, and NLR to identify the optimal cutoff values for treatment response. We also investigated the relationship between clinicopathologic factors and disease control (complete response, partial response, and stable disease) using the chi-squared test. RESULTS: The overall response rate (complete and partial response) was 11.7%, and the disease control rate was 44.1%. The median overall survival (OS) was 14.0 (95% CI 10.7‒19.2) months, and the median progression-free survival (PFS) was 4.1 (95% CI 3.0‒5.9) months. The AUC ROCs for CAR, PLR, and NLR before nivolumab monotherapy for patients with progressive disease (PD) were 0.574 (95% CI, 0.461‒0.687), 0.528 (95% CI, 0.418‒0.637), and 0.511 (95% CI, 0.401‒0.620), respectively. The values for changes in CAR, PLR, and NLR were 0.766 (95% CI, 0.666‒0.865), 0.707 (95% CI, 0.607‒0.807), and 0.660 (95% CI 0.556‒0.765), respectively. The cutoff values for the treatment response were 3.0, 1.3, and 1.4 for CAR, PLR, and NLR, respectively. The PFS and OS were significantly longer when the treatment response values for changes in CAR, PLR, and NLR were below these cutoff values (CAR: OS, p < 0.0001 and PFS, p < 0.0001; PLR: OS, p = 0.0289 and PFS, p = 0.0302; and NLR: OS, p = 0.0077 and PFS, p = 0.0044). CONCLUSIONS: Measurement of the changes in CAR, PLR, and NLR could provide a simple, prompt, noninvasive method to evaluate response to nivolumab monotherapy. TRIAL REGISTRATION: This study is registered with number K2023006.

Efficacy and safety of ramucirumab in gastric or gastroesophageal cancer: A systematic review and meta-analysis.

BACKGROUND: Ramucirumab is considered a potential treatment for gastric or gastroesophageal cancer; however, its safety has not been evaluated. This meta-analysis aimed to evaluate the efficacy and safety of ramucirumab for treating gastric or gastroesophageal cancer. METHODS: The databases of PubMed, Embase, and Cochrane Library were searched through October 2023. The search focused on randomized controlled trials (RCTs) comparing ramucirumab (with or without chemotherapy) to a placebo (with or without chemotherapy) in patients with gastric or gastroesophageal cancer. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were pooled. RESULTS: Seven RCTs with a total of 2613 patients were included. Compared with placebo (with or without chemotherapy), ramucirumab (with or without chemotherapy) significantly improved OS (HR: 0.90, 95% CI: 0.82-0.99, p = 0.030), PFS (HR: 0.74, 95% CI: 0.60-0.90, p = 0.003), ORR (OR: 1.39, 95% CI: 1.15-1.67, p < 0.001), and DCR (OR: 1.91, 95% CI: 1.38-2.63, p < 0.001). However, ramucirumab (with or without chemotherapy) also increased the incidence of decreased appetite (OR: 1.29, 95% CI: 1.09-1.53, p = 0.004), diarrhea (OR: 1.39, 95% CI: 1.01-1.91, p = 0.05), hypertension (OR: 3.13, 95% CI: 2.03-4.83, p < 0.00001), and bleeding or hemorrhage (OR: 2.34, 95% CI: 1.93-2.85, p < 0.00001). CONCLUSIONS: Ramucirumab (with or without chemotherapy) can improve OS, PFS, ORR and DCR in patients with gastric or gastroesophageal cancer. However, it may also increase the incidence of specific AEs.

Presence of RB1 or Absence of LRP1B Mutation Predicts Poor Overall Survival in Patients with Gastric Neuroendocrine Carcinoma and Mixed Adenoneuroendocrine Carcinoma.

Purpose: Neuroendocrine carcinomas (NECs) of the stomach are extremely rare, but fatal. However, our understanding of the genetic alterations in gastric NECs is limited. We aimed to evaluate genomic and clinicopathological characteristics of gastric NECs and mixed adenoneuroendocrine carcinomas (MANECs). Materials and Methods: Fourteen gastric NECs, 3 gastric MANECs, and 1381 gastric adenocarcinomas were retrieved from the departmental next-generation sequencing database between 2017 and 2019. Clinicopathological parameters and next-generation sequencing test results were retrospectively collected and reviewed. Results: Gastric NECs and MANECs frequently harbored alterations of TP53, RB1, SMARCA4, RICTOR, APC, TOP1, SLX4, EGFR, BRCA2, and TERT. In contrast, gastric adenocarcinomas exhibited alterations of TP53, CDH1, LRP1B, ARID1A, ERBB2, GNAS, CCNE1, NOTCH, and MYC. Mutations of AKT3, RB1, and SLX4; amplification of BRCA2 and RICTOR; and deletion of ADAMTS18, DDX11, KLRC3, KRAS, MAX, NFKBIA, NUDT7, and RB1 were significantly more frequent in gastric NECs and MANECs than in gastric adenocarcinomas. The presence of LRP1B mutation was significantly associated with longer overall survival (OS), whereas RB1 mutation and advanced TNM stage were associated with shorter OS. Conclusion: We identified frequently mutated genes and potential predictors of survival in patients with gastric NECs and MANECs.

Disappearing Signet Ring Cell Adenocarcinoma in Gastric Cancer Patients.

BACKGROUND: The incidence of diffuse-type gastric cancer is increasing steadily in the United States, Europe, and Asia. This subtype is known for aggressive clinical characteristics and transmural invasion. However, T1a diffuse-type cancers have been observed to have a better 5-year, disease-specific mortality than stage-matched intestinal tumors, supporting a clinical difference in these early-stage cancers. METHODS: Data on all living patients with T1a gastric adenocarcinoma with a finding of signet ring cell morphology on pathology and ≥1 year of follow-up from 2013 to 2023 at Memorial Sloan Kettering Cancer Center (MSK) was collected from a prospectively maintained database. Patients with known CDH1 or CTNNA1 mutations were excluded. RESULTS: In 7 of 30 patients, sporadic pathologically confirmed T1a signet ring cell (diffuse) cancer identified on initial biopsy was no longer detectable upon subsequent biopsy or resection with mean follow-up of 50 months. CONCLUSIONS: These cases allude to the distinct pathways of carcinogenesis in T1a signet ring cell cancers. Potential factors that may underlie the spontaneous regression of these T1a cancers include complete removal at initial biopsy, immune clearance, and lack of survival advantage conferred by signet ring cell genetic alterations in these cases. Given their more indolent behavior at an earlier stage, we suggest that these lesions can be closely followed by endoscopy in select circumstances with thorough disease assessment and an experienced care team.

Predicting tumor invasion depth in gastric cancer: developing and validating multivariate models incorporating preoperative IVIM-DWI parameters and MRI morphological characteristics.

INTRODUCTION: Accurate assessment of the depth of tumor invasion in gastric cancer (GC) is vital for the selection of suitable patients for neoadjuvant chemotherapy (NAC). Current problem is that preoperative differentiation between T1-2 and T3-4 stage cases in GC is always highly challenging for radiologists. METHODS: A total of 129 GC patients were divided into training (91 cases) and validation (38 cases) cohorts. Pathology from surgical specimens categorized patients into T1-2 and T3-4 stages. IVIM-DWI and MRI morphological characteristics were evaluated, and a multimodal nomogram was developed. The MRI morphological model, IVIM-DWI model, and combined model were constructed using logistic regression. Their effectiveness was assessed using receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC). RESULTS: The combined nomogram, integrating preoperative IVIM-DWI parameters (D value) and MRI morphological characteristics (maximum tumor thickness, extra-serosal invasion), achieved the highest area under the curve (AUC) values of 0.901 and 0.883 in the training and validation cohorts, respectively. No significant difference was observed between the AUCs of the IVIM-DWI and MRI morphological models in either cohort (training: 0.796 vs. 0.835, p = 0.593; validation: 0.794 vs. 0.766, p = 0.79). CONCLUSION: The multimodal nomogram, combining IVIM-DWI parameters and MRI morphological characteristics, emerges as a promising tool for assessing tumor invasion depth in GC, potentially guiding the selection of suitable candidates for neoadjuvant chemotherapy (NAC) treatment.

Effectiveness of the CANCER-AIMS intervention on nutritional status and symptom management in patients with gastric cancer following gastrectomy: A randomized controlled trial.

BACKGROUND: Dietary education and modification interventions are valuable and feasible strategies for enhancing nutritional status and managing symptoms in patients with gastric cancer following gastrectomy. In alignment with administrative policies prioritizing shorter hospital stays and enhanced postoperative self-management, the provision of a simplified nutritional management approach following gastrectomy holds promise for preventing weight loss and expanding resources for monitoring both the nutritional and symptomatic aspects of these patients. OBJECTIVE: This study evaluated the effectiveness of an integrative approach involving the five sequential steps of Conversation, Assessment, Nutrition plan, Complications, Evaluation, and Reassurance or Removal (CANCER) into Altering Intake and Managing Symptoms (AIMS), with specific focus on enhancing nutritional status and symptom management. DESIGN: A single-blind, two-arm, randomized controlled trial. SETTING: This study was conducted at a tertiary hospital in Shandong province, China. PARTICIPANTS: Patients with total or subtotal gastrectomy for gastric cancer. METHODS: The participants were randomly assigned to either the intervention or control group in a 1:1 ratio. The intervention group received a 16-week CANCER-AIMS intervention program. The control group received usual routine care dietary guidance. Questionnaires and electronic medical records of each patient were used to assess dietary intake, dietary symptoms, and subjective and objective nutritional status. Outcomes were assessed at four specific time points: the day before discharge and at 4-, 8-, and 16-weeks following hospital discharge. RESULTS: Thirty-eight participants completed the study. The findings revealed significant interaction effects between group and time for dietary intake, dietary symptoms, and nutritional status between intervention and control groups (P < 0.001). The intervention group had significantly higher dietary intake, fewer dietary symptoms, and better nutritional status post-intervention than the control group (P < 0.001). Moreover, there were significant differences in dietary intake, dietary symptoms, and nutritional status according to time in both the intervention and control groups. CONCLUSION: The CANCER-AIMS intervention for patients with gastric cancer following gastrectomy may be efficient at enhancing nutritional intake, reducing negative dietary symptoms, and thus improving both their subjective and objective nutritional status.

Demographic Comparison of the Burden of Endoscopically Screenable Cancers in the United States.

Background and Aims: Gastrointestinal cancer incidence varies by race and ethnicity. In the United States (US), there are screening guidelines for esophageal cancer (EC) and colorectal cancer (CRC), but not gastric cancer (GC). We compared GC, CRC, and EC incidence among the most populous racial and ethnic groups to inform US interception strategies. Methods: We used SEER∗Stat to compare GC, CRC, and EC incidence rates across non-Hispanic White (NHW), non-Hispanic Black, Hispanic, and the 8 largest Asian American populations using the Surveillance, Epidemiology, and End Results 9 registries (2010-2014). Results: Noncardia GC incidence was highest among Korean (18.7 cases per 100,000) and lowest among NHW (1.4 cases per 100,000) Americans. CRC incidence was highest among non-Hispanic Black, Southeast Asian, and Japanese (35.9, 34.2, and 33.8 per 100,000, respectively) Americans and lowest among South Asian Americans (18.9 per 100,000). EC incidence was greatest in NHW (4.7 per 100,000) and lowest in Filipino (1.2 per 100,000) Americans. The incidence of noncardia GC slightly exceeded colon cancer in Korean American men (25.5 vs 22.4 per 100,000). GC surpassed EC incidence in all non-White racial and ethnic groups. Conclusion: The burden of GC, CRC, and EC differs based on race and ethnicity. Non-White racial and ethnic groups experience a disproportionate burden of GC for which systematic programs for cancer interception, similar to CRC and EC, are needed.