Gastric Carcinoma Patients Research Articles

CDKN2A somatic copy number amplification in normal tissues surrounding gastric carcinoma reduces cancer metastasis risk in droplet digital PCR analysis.

The CDKN2A gene is frequently affected by somatic copy number variations (SCNVs, including deletions and amplifications [SCNdel and SCNamp]) in the cancer genome. Using surgical gastric margin tissue samples (SMs) as the diploid reference in SCNV analysis via CDKN2A/P16-specific real-time PCR (P16-Light), we previously reported that the CDKN2A SCNdel was associated with a high risk of metastasis of gastric carcinoma (GC). However, the status of CDKN2A SCNVs in SMs and their clinical significance have not been reported. Peripheral white blood cell (WBC) and frozen GC and SM tissue samples were collected from patients (n = 80). Droplet digital PCR (ddPCR) was used to determine the copy number (CN) of the CDKN2A gene in tissue samples using paired WBCs as the diploid reference. A novel P16-ddPCR system was initially established with a minimal proportion (or limit, 10%) of the detection of CDKN2A CN alterations. While CDKN2A SCNamp events were detected in both SMs and GCs, fewer CDKN2A SCNdel events were detected in SMs than in GCs (15.0% vs. 41.3%, P = 4.77E-04). Notably, significantly more SCNamp and fewer SCNdel of the CDKN2A gene were detected in SMs from GC patients without metastasis than in those from patients with lymph node metastasis by P16-ddPCR (P = 0.023). The status of CDKN2A SCNVs in SM samples was significantly associated with overall survival (P = 0.032). No cancer deaths were observed among the 11 patients with CDKN2A SCNamp. CDKN2A SCNVs in SMs identified by P16-ddPCR are prevalent and significantly associated with GC metastasis and overall survival.

Unveiling molecular clues: Exploring IFNγ, IL-10, and MMP7 blood levels in gastric carcinoma patients

Objective: Gastric carcinoma is a leading cause of morbidity and mortality worldwide. Early detection can help reduce mortality rates. Biomarkers are being investigated globally for their potential in disease screening, monitoring, and follow-up in various cancers. However, currently, there is insufficient data on the role of biomarkers in gastric carcinoma. Material and Methods: This single center case control study was conducted from June 2018 to March 2021 from South India. Blood samples were collected from 85 patients diagnosed with gastric carcinoma and 85 apparently healthy individuals serving as the control group. The samples were collected in a fasting state. The serum levels of biomarkers interferon gamma (IFNγ), interleukin 10 (IL-10), and matrix metalloproteinase 7 (MMP7) were measured using enzyme-linked immunosorbent assay (ELISA) and compared between the two groups. Additionally, the levels of biomarkers were compared within the gastric cancer group based on disease location, stage, and histotype. Results: The serum levels of IFNγ and IL-10 were found to be significantly elevated in gastric carcinoma patients compared to the healthy control group. Both biomarkers exhibited high sensitivity and specificity in detecting carcinoma of the stomach. However, there was no significant difference in the serum level of MMP7 between gastric cancer patients and control group. Conclusion: IFNγ and IL-10 show promise as potential molecular biomarkers for the detection of gastric carcinoma. Further, well designed studies, involving larger and more diverse populations matched for stage and histological types, are necessary to establish the screening and monitoring utility of these biomarkers in gastric carcinoma.

Feasibility and Efficacy of Sentinel Lymph Node Mapping in Gastric Cancer.

Lymph node metastasis is a critical prognostic factor for patients with gastric carcinoma (GC). Sentinel lymph node (SLN) mapping has the potential to identify the initial site of draining lymph node metastasis and reduce the extent of surgical lymphadenectomy. This study aimed to evaluate the diagnostic accuracy of SLN mapping in GC. The study enrolled 129 GC patients undergoing total or partial gastrectomy with D2 lymphadenectomy and indocyanine green fluorescence-guided SLN mapping. The primary outcomes were the negative predictive value (NPV) and sensitivity of SLN mapping. The secondary outcomes were clinicopathologic factors associated with SLN mapping accuracy and successful SLN mapping. The SLN detection rate in this study was 86.8 %. The study had an overall NPV of 83.1 % and an overall sensitivity of 65.8 %. The NPV was found to be significantly higher in the patients with no lymphovascular invasion (LVI) than in those with LVI (96.0 % vs 59.3 %; p < 0.001) and in the patients whose pathologic T (pT) stage lower than 3 than in those whose T stage was 3 or higher (92.0 % vs 66.7 %; p = 0.009). The sensitivity of SLN mapping was 50 % in the patients with no LVI and 33 % in the patients with a pT stage lower than 3. The study results showed that for patients with early-stage GC with no LVI, negative SLN findings may represent a potential additive predictor indicating the absence of regional LN metastasis. However, given the low sensitivity rates noted, further research is needed to identify specific patient populations that may benefit from SLN mapping in GC.

Effect of cetuximab plus FOLFOX4 regimen on clinical outcomes in advanced gastric carcinoma patients receiving evidence-based care

BACKGROUND Although chemotherapy is effective for treating advanced gastric carcinoma (aGC), it may lead to an adverse prognosis. Establishing a highly effective and low-toxicity chemotherapy regimen is necessary for improving efficacy and outcomes in aGC patients. AIM To determine the efficacy and safety of cetuximab (CET) combined with the FOLFOX4 regimen (infusional fluorouracil, folinic acid, and oxaliplatin) as first-line therapy for patients with aGC, who received evidence-based care (EBC). METHODS A total of 117 aGC patients who received EBC from March 2019 to March 2022 were enrolled. Of these, 60 in the research group (RG) received CET + FOLFOX4 as first-line therapy, whereas 57 in the control group (CG) received FOLFOX4. The efficacy [clinical response rate (RR) and disease control rate (DCR)], safety (liver and kidney dysfunction, leukopenia, thrombocytopenia, rash, and diarrhea), serum tumor marker expression [STMs; carbohydrate antigen (CA) 19-9, CA72-4, and carcinoembryonic antigen (CEA)], inflammatory indicators [interleukin (IL)-2 and IL-10], and quality of life (QOL) of the two groups were compared. RESULTS A markedly higher RR and DCR were observed in the RG compared with the CG, with an equivalent safety profile between the two groups. RG exhibited notably reduced CA19-9, CA72-4, CEA, and IL-2 levels following treatment, which were lower than the pre-treatment levels and those in the CG. Post-treatment IL-10 was statistically increased in RG, higher than the pre-treatment level and the CG. Moreover, a significantly improved QOL was evident in the RG. CONCLUSION The CET + FOLFOX4 regimen is highly effective as first-line treatment for aGC patients receiving EBC. It facilitates the suppression of STMs, ameliorates the serum inflammatory microenvironment, and enhances QOL, without increased adverse drug effects.

Identification of immunotherapy-related subtypes, characterization of tumor microenvironment infiltration, and development of a prognostic signature in gastric carcinoma.

Recent advances in immunotherapy have elicited a considerable amount of attention as viable therapeutic options for several cancer types, the present study aimed to explore the immunotherapy-related genes (IRGs) and develop a prognostic risk signature in gastric carcinoma (GC) based on these genes. IRGs were identified by comparing immunotherapy responders and non-responders in GC. Then, GC patients were divided into distinct subtypes by unsupervised clustering method based on IRGs, and the differences in immune characteristics and prognostic stratification between these subtypes were analyzed. An immunotherapy-related risk score (IRRS) signature was developed and validated for risk classification and prognosis prediction based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts. Besides, the predictive ability of the IRRS in immunotherapy response was also determined. A total of 63 IRGs were identified, and 371 GC patients were stratified into two molecular subgroups with significantly different prognosis and immune characteristics. Then, an IRRS signature comprised of three IRGs (CENP8, NRP1, and SERPINE1) was constructed to predict the prognosis of GC patients in TCGA cohort. Importantly, external validation in multiple GEO cohorts further confirmed the universal applicability of the IRRS in distinct populations. Furthermore, we found that the IRRS was significantly correlated with patient's responsiveness to immunotherapy, GC patients with low IRRS are more likely to benefit from existing immunotherapy. The risk score could serve as a robust prognostic biomarker, provide therapeutic benefits for immunotherapy and may be helpful for clinical decision making in GC patients.

Nucleobindin 2 inhibits senescence in gastric carcinoma

Here, we focused on the role of Nucleobindin 2 (NUCB2), a multifunctional protein, in gastric carcinoma (GC) progression. NUCB2 expression was investigated in 150 GC cases (20 non-invasive (pT1) and 130 invasive (pT2/pT3/pT4) tumors) by immunohistochemistry (IHC), and in situ hybridization for detection of the mRNA in 21 cases. Using GC cell lines, we determined whether NUCB2 expression was associated with specific cellular phenotypes. In GC clinical samples, NUCB2 was transcriptionally upregulated when compared to normal tissues. High NUCB2 expression was associated with clinicopathological factors including deep tumor invasion, lymphovascular invasion, lymph node metastasis, and advanced clinical stages, and was a significant independent predictor of unfavorable progression-free survival in 150 non-invasive and invasive GC patients. Similar findings were also evident in 72 invasive GC cases in which patients received post-operative chemotherapy, but not in 58 invasive tumors from patients who did not receive the chemotherapy. In cell lines, NUCB2 knockout inhibited proliferation, susceptibility to apoptosis, and migration capability by inducting cellular senescence; this was consistent with higher proliferation and apoptotic indices in the NUCB2 IHC-high compared to NUCB2 IHC-low GC cases. NUCB2-dependent inhibition of senescence in GC engenders aggressive tumor behavior by modulating proliferation, apoptosis, and migration.

Identification of Key Genes Associated with Tumor Microenvironment Infiltration and Survival in Gastric Adenocarcinoma via Bioinformatics Analysis.

Gastric carcinoma (GC) is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related deaths globally. The tumor microenvironment plays a significant role in the pathogenesis, prognosis, and response to immunotherapy. However, the immune-related molecular mechanisms underlying GC remain elusive. Bioinformatics analysis of the gene expression of GC and paracancerous healthy tissues from the same patient was performed to identify the key genes and signaling pathways, as well as their correlation to the infiltration of the tumor microenvironment (TME) by various immune cells related to GC development. We employed GSE19826, a gene expression profile from the Gene Expression Omnibus (GEO), for our analysis. Functional enrichment analysis of Differentially Expressed Genes (DEGs) was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database. Cytoscape software facilitated the identification of nine hub DEGs, namely, FN1, COL1A1, COL1A2, THBS2, COL3A1, COL5A1, APOE, SPP1, and BGN. Various network analysis algorithms were applied to determine their high connectivity. Among these hub genes, FN1, COL1A2, THBS2, COL3A1, COL5A1, and BGN were found to be associated with a poor prognosis for GC patients. Subsequent analysis using the TIMER database revealed the infiltration status of the TME concerning the overexpression of these six genes. Specifically, the abovementioned genes demonstrated direct correlations with cancer-associated fibroblasts, M1 and M2 macrophages, myeloid-derived suppressor cells, and activated dendritic cells. Our findings suggest that the identified hub genes, particularly BGN, FN1, COL1A2, THBS2, COL3A1, and COL5A1, play crucial roles in GC prognosis and TME cell infiltration. This comprehensive analysis enhances our understanding of the molecular mechanisms underlying GC development and may contribute to the identification of potential therapeutic targets and prognostic markers for GC patients.

COMPARATIVE ANALYSIS OF STAGING MODALITIES IN CARCINOMA STOMACH: UNRAVELING THE SYNERGY BETWEEN STAGING LAPAROSCOPY AND CECT ABDOMEN

&#x0D; Objective: Stomach carcinoma, a complex challenge in oncology, necessitates refined staging for optimal therapeutic strategies. The comparative analysis of staging laparoscopy and contrast-enhanced computed tomography (CECT) emerges as a key exploration in this context.&#x0D; Methods: Conducted at Indira Gandhi Medical College and Hospital, Shimla, this prospective study spanned one year. Biopsy-proven gastric carcinoma patients meeting inclusion criteria underwent extensive investigations, including CECT, staging laparoscopy, and diagnostic lavage. The study employed specific protocols for each procedure, ensuring comprehensive data collection.&#x0D; Results: Analysis of 32 cases revealed a prevalence in the 61-70 y age group, predominantly affecting males. Diverse symptoms included pain (68.75%) and palpable mass (81.2%). Well-differentiated adenocarcinoma (43.8%) dominated, with distinct age-related patterns. The study showcased the intricate nature of gastric carcinoma, demanding tailored diagnostic approaches.&#x0D; Conclusion: This study unravels the interplay between staging laparoscopy and CECT in gastric carcinoma, offering a comprehensive staging approach. The nuanced insights gained through their synergy address individual limitations, contributing to more precise evaluations and tailored interventions. The collaborative use of these modalities promises to enhance precision, ultimately improving patient outcomes in gastric carcinoma management.

ENHANCING STOMACH CARCINOMA STAGING: A COMPREHENSIVE REVIEW OF THE ROLE OF STAGING LAPAROSCOPY AS AN ADJUNCT TO CECT ABDOMEN

Objective: Stomach carcinoma poses challenges in accurate staging and treatment planning. This study explores the evolving role of staging laparoscopy as an adjunct to contrast-enhanced computed tomography (CECT) in enhancing stomach carcinoma staging.&#x0D; Methods: Conducted at Indira Gandhi Medical College and Hospital, Shimla, a one-year prospective study included biopsy-proven gastric carcinoma patients. Exclusion criteria involved neoadjuvant chemotherapy and proven metastasis. Investigations encompassed CECT, staging laparoscopy, and diagnostic lavage.&#x0D; Results: TNM staging revealed a predominance of Stage IIA (21.9%) and IIIA (25%). Locally advanced cases demonstrated infiltration into other organs (53.1%). Occult metastasis was present in 28.2%, with 66.7% in ascites cases. Staging laparoscopy detected occult metastasis in 28.2%, complementing CECT limitations. Significant associations were noted between occult metastasis and CECT staging, particularly in Stage III (88.9%).&#x0D; Conclusion: Integration of staging laparoscopy with CECT enhances precision in stomach carcinoma staging. Limitations of CECT in identifying occult metastasis are addressed by staging laparoscopy, providing valuable insights. Findings underscore the importance of CECT in advanced stages, contributing to comprehensive gastric cancer management. This study contributes to evolving diagnostic and therapeutic approaches, promising improved patient outcomes.

The Impact of the COVID-19 Pandemic on Esophageal and Gastric Cancer Surgery in Germany: A Four-Year Retrospective Single-Center Study of 287 Patients.

Background: Disruptions to surgical care for cancer patients during the COVID-19 pandemic remain an ongoing debate. This study assesses the effects of the COVID-19 pandemic on perioperative outcomes in a continuous series of surgically treated esophageal and gastric carcinoma patients at a large university hospital in Europe over 48 months. Methods: We conducted a retrospective single-center cohort study at a tertiary referral center. All patients who underwent oncologic esophageal or gastric resection between March 2018 and February 2022 were included in the analysis. The sample was split into a 24 months COVID-19 and an equivalent pre-COVID-19 control period. Outcome variables included caseload, in-hospital mortality, morbidity, treatment course, and disease stage at presentation. Results: Surgeons performed 287 operations, with around two-thirds (62%) of the cohort undergoing esophagectomy and one-third (38%) gastrectomy. The in-hospital mortality was 1% for the COVID-19 and the control periods. Patients did not present at a later disease stage nor did they wait longer for treatment. There was no decrease in caseload, and patients did not suffer from more perioperative complications during COVID-19. Conclusions: Esophageal and gastric carcinoma patients received safe and timely surgical care during the pandemic. Future pandemic protocols may streamline oncologic care towards tertiary referral centers.

Clinical value assessment for serum hsa_tsr013526 in the diagnosis of gastric carcinoma.

Gastric carcinoma (GC) is a malignant tumor that is detrimental to human health. Transfer RNA-derived small RNAs are a newly identified class of noncoding small RNAs with specific biological functions that are aberrantly expressed in cancer. The aim of this study was to investigate the potential of hsa_tsr013526 as a biomarker for GC. Quantitative real-time fluorescence polymerase chain reaction was used to detect the expression level of hsa_tsr013526. The molecular characteristics of hsa_tsr013526 were verified by agarose gel electrophoresis, Sanger sequencing, and separation of nuclear and cytoplasmic RNA fractions. By testing the receiver operating characteristic (ROC) curves, the diagnostic efficiency of GC using hsa_tsr013526 was determined. Finally, we predicted the downstream of hsa_tsr013526 using functional assays and bioinformatics analysis. Serum expression of hsa_tsr013526 was higher in GC patients than in healthy donors. Serum expression showed differential changes in GC patients, gastritis patients, and healthy donors. Chi-squared tests showed that high expression of hsa_tsr013526 was significantly correlated with T stage, lymphatic metastasis, and tumor node metastasis stage. ROC curve analysis indicated that GC patients could be discriminated from healthy donors or gastritis patients based on their serum levels of hsa_tsr013526. Furthermore, hsa_tsr013526 expression was significantly reduced in postoperative GC patients (p = .0016). High expression of hsa_tsr013526 promotes gastric cancer cell proliferation, invasion, and migration. Serum hsa_tsr013526 was stable and specific, and could be used for dynamic monitoring of GC patients. Therefore, hsa_tsr013526 may be a new biomarker for the diagnosis and postoperative monitoring of GC patients.

The role of the NY-ESO-1 in the prognosis of gastric cancer.

Gastric cancer (GC) is one of the most common malignancies worldwide and the fourth leading cause of cancer-related deaths. GC is a multifactorial disease influenced by both environmental and genetic factors. Its most critical features include invasiveness and high metastatic potential. Metastasis is a complex process, and our understanding of the mechanisms involved remains incomplete. Growing evidence suggests that cancer-testis antigens (CTAs) play a crucial role in the metastatic potential of various tumors. Several studies have linked CTA expression with lower tumor differentiation, higher metastatic potential, and poor chemotherapy response. New York esophageal squamous cell carcinoma-1 (NY-ESO-1) antigen, part of the CTA group, is expressed in tumor tissues, while its expression in normal tissues is restricted to spermatogonia. This study aimed to determine the expression of NY-ESO-1 in primary adenocarcinoma of the stomach, both with and without metastasis in regional lymph nodes, and to compare it with TNM stage, age, gender, and survival. We analyzed GC tissue from 53 node-negative and 55 node-positive primary gastric carcinoma patients for NY-ESO-1 expression using immunohistochemical assay. The results were correlated with clinicopathological parameters and survival. Patients with positive NY-ESO-1 expression in primary tumors had a median survival of 19.0 months (range 14.1-24.0), in contrast to those with negative expression, who had a median survival of 52.0 months (range 0.0-133.3) (chi-square 7.99, P=0.005). T status, N status, and NY-ESO-1 expression were all independently associated with shorter survival. No significant difference in NY-ESO-1 expression in primary tumors was observed concerning lymph node metastasis status. In summary, our findings suggest that increased expression of NY-ESO-1 could potentially serve as a prognostic biomarker for GC.

Development and validation of a predictive model associated with lymph node metastasis of gastric signet ring carcinoma patients.

The risk factors for lymph node metastasis (LNM) in patients with gastric signet ring cell carcinoma (GSRC) have not been well-defined. This study was designed to prognosticate LNM in patients with GSRC by constructing and verifying a nomogram. A total of 2789 patients with GSRC from the Surveillance, Epidemiology, and End Results (SEER) database and Yijishan Hospital of Wannan Medical College (YJS) were retrospectively reviewed. A predictive model was established using logistic regression based on the SEER cohort. The performance of the model was evaluated using the concordance index (C-index) and decision curve analysis (DCA). In addition, its robustness was validated using the YJS cohort. Four independent predictors of LNM were identified in the SEER cohort. Next, a nomogram was constructed by incorporating these predictors. The C-index were 0.800 (95% confidence interval [CI] = 0.781-0.819) and 0.837 (95% CI = 0.784-0.890) in the training and external validation cohorts, respectively. The outcomes of DCA supported good clinical benefits. The proposed model for evaluating the LNM in patients with GSRC can help to avoid the misdiagnosis risk of N-stage, assist to screen the population suitable for neoadjuvant therapy and help clinicians to optimize clinical decisions.

The clinical value of CT spectral imaging in preoperative evaluation of pathological types of gastric cancer.

Gastric cancer (GC) is the fifth most common cancer worldwide and the third leading cause of cancer death. Due to the low rate of early diagnosis, most patients are already in the advanced stage and lose the chance of radical surgery. To investigate the clinical value of computed tomography (CT) spectral imaging in preoperative evaluation of pathological types of gastric cancer patients. 121 patients with gastric cancer were selected. CT energy spectrum imaging was performed on the patients. The water and iodine concentration of the lesion were measured, and the standardized iodine concentration ratio was calculated. The iodine concentration, iodine concentration ratio and water concentration level of different pathological types were analyzed and compared. The iodine concentration and iodine concentration ratio of gastric mucinous carcinoma patients in venous phase and parenchymal phase were lower than those of gastric non-mucinous carcinoma patients, and the differences were statistically significant (P< 0.05). The iodine concentration and iodine concentration ratio of patients with mucinous adenocarcinoma in venous phase and parenchymal phase were lower than those of patients with choriocarcinoma, and the differences were statistically significant (P< 0.05). The iodine concentration and iodine concentration ratio of middle and high differentiated adenocarcinoma patients in venous phase and parenchymal phase were lower than those of low differentiated adenocarcinoma patients, and the differences were statistically significant (P< 0.05). However, there was no significant difference in water concentration levels among venous, arterial, and parenchymal phases in all pathological types of gastric cancer patients (P> 0.05). CT spectral imaging plays an important role in the preoperative evaluation of patients with gastric cancer. The pathological types of gastric cancer are different, and the iodine concentration will change accordingly. CT spectral imaging can effectively evaluate the pathological types of gastric cancer and has high clinical application value.

Comparison of human epidermal growth factor receptor 2 and cancer stem cell markers like CD44 and CD133 expressions with clinicopathological parameters in gastric cancer

Objectives: Gastric carcinoma (GC) is the fourth most common cause of cancer-related tumor deaths worldwide. The prognostic significance of CD44, CD133 and human epidermal growth factor receptor 2 (HER2) expression in GC remains controversial. Therefore, we aimed to investigate the relationship of CD44, CD133 and HER2 expression with clinicopathological features in metastatic and non-metastatic GC patients. Methods: A total of 139 patients with GC (68 with metastasis, 71 without metastasis) diagnosed were retrospectively analyzed. CD44 and CD133 expression were determined by immunohistochemical method in all cases. In addition, HER2 overexpression of the tumor was evaluated in patients with metastatic GC. Results: The CD133 positivity rate was 90.6% (n = 126) when all cases were considered, and that for CD44 was 84.9% (n = 118). There was no difference in CD133 and CD44 positivity (intensity or density) rates and between the total scores of metastatic and non-metastatic patients with GC (p &amp;gt; 0.05). HER2 positivity in metastatic cases was detected in 49 (70.1%) patients by immunohistochemical method. No correlation was found between CD133 total score and age, tumor size or depth, and HER2 scores in metastatic or non-metastatic cases (p &amp;gt; 0.05). In the correlation analyzes performed with CD44 scores, only a borderline significant correlation was found between CD44 scores and tumor size (r:0.175; p = 0.047) in non-metastatic cases. Conclusions: We demonstrated associations between CD44/CD133 expression and histological grade in all patients, between CD44 and tumor size in non-metastatic patients, and between HER2 and intestinal type (Lauren) in metastatic patients. The results of this study need to be confirmed by multicenter studies including large case series.

Immunonutrition supplementation for resectable gastric cancer during standard perioperative chemotherapy (CT) FLOT: A pivotal study, I–SUPPLY.

57 Background: Gastric carcinomas (GC) can be divided into immunogenic and immune-resistant based on the infiltration of the tumour microenvironment (TME) from different immune cells (ICs) such as Natural Killer (NK), activated CD8+, CD3+ and CD4+ memory T cells. High ImmunoScore (IS) (positive cells/mm2 for each marker (CD8+, CD3+, Foxp3+) in the Core Tumour and Invasive Margins) is strongly related to better prognosis of GC patients in terms of Disease-Free Survival and Overall Survival. ICs activation and consequent immunogenic TME requires high nutrient absorption and synthesis accumulation of protein, lipid and nucleotides. However, tumour cells (TCs) promote their own proliferation by stealing the available micronutrients to ICs therefore leading to an immunosuppressive TME phenotype. Methods: This is a translational, prospective, non-randomized study. Primary endpoint is to assess if enteral immune nutrition (EIN) supplementation during the acme of the activity of cytotoxic of perioperative FLOT (docetaxel, oxaliplatin and 5-fluorouracil) in stage II-III GC can revert the TME in favour of ICs over TCs, witnessed by an increase of IS in surgical specimen over biopsy controls. A steady amount of EIN with Arginine, Omega-3-fatty acids, Glutamine and ribonucleic acid, will be added to patient’s diet from day 3 to 8 of each FLOT cycle, twice a day. We plan to use Image analysis software for automatic tumor detection and quantification of CD3+ and CD8+ stained cells whose densities will be converted into IS with pre-defined cutoffs. IS utilizes standardized percentile values (0 to 100%). We identify IS as Low, Intermediate (Int) and High with a mean percentile of 0-25%, &gt;25-70%, &gt;70-100% respectively. Two-group classifications are planned, corresponding to IS Low and Int-High. To better define the kind of tumor infiltrating cells (TILs) and assess the amount of immune suppressive cells, more IHC scoring will be evaluated: helper T-cells CD4+, CD8 T memory (CD 103+), T regulatory (both CD4+ and Foxp3+/CD105+), Macrophages M1 (CD 68+) and M2 (CD 163+). Results: Based on historical controls the rate of Int-High IS (&gt;25-70%, &gt;70% respectively) is about 64%, we expect to find a 20% increase of Int-High IS GC over biopsy control (internal validation cohort). To detect an increase in the percentage of high IS among patients treated with EIN (estimated around 85%) compared to biopsy controls (estimated around 64%) assuming a probability α and β of 0.2, the required sample size will be of 21 patients with resectable GC receiving EIN supplementation plus standard CT. To define the sample size a single proportion test was used. Conclusions: Our hypothesis is that EIN given during perioperative CT might prevent the establishment of an unfavourable TME for ICs in both auxotrophic and non-auxotrophic malignancies, thus leading to an increase of GC immunogenic pattern.

Value of a preoperative prognostic nutritional index for the prognostic evaluation of gastric neuroendocrine carcinoma patients.

To study the value of Onodera's prognostic nutrition index (PNI) in patients with gastric neuroendocrine cancer (G-NEC). The clinical data on 148 cases of G-NEC presented between March 2010 and April 2022 were retrospectively analyzed. The relationship between the clinical characteristics of the patients and PNI was analyzed. Optimal PNI cutoff values for G-NEC prognosis prediction were calculated using the X-tile software. The survival curves were created using the Kaplan-Meier method. A Cox proportional hazards model was also established to identify independent prognostic factors that impact the prognosis of patients with G-NEC. The median overall survival (OS) rate was 30 months (range 6-127 months), and the OS rates at 1, 3 and 5 years were 89.2, 71.6 and 68.2%, respectively. The mean PNI of the 148 patients before the operation was 49.5 ± 8.0. The mean PNI of patients with anemia (p < 0.001) and abnormal carcinoembryonic antigen (p = 0.039) was significantly lower than that of patients without such comorbidities. The mean PNI of patients with Stage III tumors (p < 0.001) and postoperative complications was significantly lower (p = 0.005). PNI optimal cutoff values were 50 (p < 0.001). Based on the cut-off value of the PNI, these patients were divided into a PNI-high group (PNI ≥ 50.0, n = 77) and a PNI-low group (PNI < 50.0, n = 71). The PNI-high group had a significantly better 5-years OS rate compared with the PNI-low group (76.6% vs. 59.2%, χ2 = 14.7, p < 0. 001). Multivariate analysis demonstrated that PNI and pathological stage were independent prognostic factors for patients with G-NEC. In the subgroup analysis, OS rates were significantly lower in the PNI-low group than in the PNI-high group among patients with stage I and stage III of the disease. The PNI is a simple and useful marker for predicting long-term outcomes in G-NEC patients regardless of tumor stage. Based on our results, we suggest that PNI should be included in routine assessments of patients with G-NEC.

Prognostic nomograms for gastric carcinoma after D2 + total gastrectomy to assist decision-making for postoperative treatment: based on Lasso regression

ObjectiveThis study aimed to establish novel nomograms that could be used to predict the prognosis of gastric carcinoma patients who underwent D2 + total gastrectomy on overall survival (OS) and progression-free survival (PFS).MethodsLasso regression was employed to construct the nomograms. The internal validation process included bootstrapping, which was used to test the accuracy of the predictions. The calibration curve was then used to demonstrate the accuracy and consistency of the predictions. In addition, the Harrell’s Concordance index (C-index) and time-dependent receiver operating characteristic (t-ROC) curves were used to evaluate the discriminative abilities of the new nomograms and to compare its performance with the 8th edition of AJCC-TNM staging. Furthermore, decision curve analysis (DCA) was performed to assess the clinical application of our model. Finally, the prognostic risk stratification of gastric cancer was conducted with X-tile software, and the nomograms were converted into a risk-stratifying prognosis model.ResultsLASSO regression analysis identified pT stage, the number of positive lymph nodes, vascular invasion, neural invasion, the maximum diameter of tumor, the Clavien–Dindo classification for complication, and Ki67 as independent risk factors for OS and pT stage, the number of positive lymph nodes, neural invasion, and the maximum diameter of tumor for PFS. The C-index of OS nomogram was 0.719 (95% CI: 0.690–0.748), which was superior to the 8th edition of AJCC-TNM staging (0.704, 95%CI: 0.623–0.783). The C-index of PFS nomogram was 0.694 (95% CI: 0.654–0.713), which was also better than that of the 8th edition of AJCC-TNM staging (0.685, 95% CI: 0.635–0.751). The calibration curves, t-ROC curves, and DCA of the two nomogram models showed that the prediction ability of the two nomogram models was outstanding. The statistical difference in the prognosis between the low- and high-risk groups further suggested that our model had an excellent risk stratification performance.ConclusionWe reported the first risk stratification and nomogram for gastric carcinoma patients with total gastrectomy in Chinese population. Our model could potentially be used to guide treatment selections for the low- and high-risk patients to avoid delayed treatment or unnecessary overtreatment.

Prognostic significance of N6-methyladenosine-modified related chemotransferase METTL3 in gastric carcinoma: Evidence from meta-analysis.

N6-methyladenosine (m6A) methylation is known as the research hotspot for tumor epimodification, and its associated methyltransferase-like3 (METTL3) is significantly differentially expressed in gastric carcinoma, but its clinical value has not been summarized. This meta-analysis aimed to evaluate the prognostic significance of METTL3 in gastric carcinoma. Databases, including PubMed, EMBASE (Ovid platform), Science Direct, Scopus, MEDLINE, Google Scholar, Web of Science, and Cochrane Library, were used to identify relevant eligible studies. The endpoints included overall survival, progression-free survival, recurrence-free survival, post-progression survival, and disease-free survival. Hazard ratios (HR) with 95% confidence intervals (CI) were used to correlate METTL3 expression with prognosis. Subgroup and sensitivity analyses were performed. Seven eligible studies involving 3034 gastric carcinoma patients were recruited for this meta-analysis. The analysis showed that high METTL3 expression was associated with significantly poorer overall survival (HR = 2.37, 95% CI 1.66-3.39, P < 0.01) and unfavorable disease-free survival (HR = 2.58, 95% CI 1.97-3.38, P < 0.01), as did unfavorable progression-free survival (HR = 1.48, 95% CI 1.19-1.84, P < 0.01)/recurrence-free survival (HR = 2.62, 95% CI 1.93-5.62, P < 0.01)/post-progression survival (HR = 1.53, 95% CI 1.22-1.91, P < 0.01). Subgroup analysis found that high METTL3 expression was associated with worse overall survival in patients with Chinese (HR = 2.21, 95% CI 1.48-3.29, P < 0.01), in studies with sample source from formalin-fixed, paraffin-embedded tissues (HR = 2.66, 95% CI 1.79-3.94, P < 0.01), and the reported directly from articles group (HR = 2.42, 95% CI 1.66-3.53, P < 0.01). The subgroup analysis that was performed based on sample size, detected method, and follow-up showed the same results. High expression of METTL3 predicts poor prognosis in gastric carcinoma, indicating promise for METTL3 as a prognostic biomarker.Systematic review registration: https://www.crd.york.ac.uk/prospero, ID = CRD42023408519.

Pathologic exploration of neuroendocrine differentiation in carcinomas.

e16238 Background: Tumor with neuroendocrine differentiation (NED) has been verified in non-neuroendocrine organ adenocarcinomas. However, the incidence of NED in various studies varies greatly due to the different selection and criteria of NED markers. Further analysis of large clinical samples is still needed to reveal its biological characteristics and clarify the diagnosis and treatment of NED. Methods: From January 2017 to June 2018，a total of 450 histopathological samples were collected and analyzed retrospectively from patients with multiple malignant cancers, including gastric cancer (GC), colorectal cancer (CRC), lung cancer, breast cancer and prostate cancer treated in Cancer Hospital, Chinese Academy of Medical Sciences. Immunohistochemical staining for NED markers such as synaptophysin (Syn), chromogranin A (ChrA), and neural cell adhesion molecule (CD56) were performed to explore the incidence of different cancer types. Furthermore, NED or non-NED patients were evaluated comparatively in terms of pathological characteristics and prognosis. Results: Up to February 6, 2023, 129 CRC and GC samples were measured. 9 (15.3%) of 59 CRC patients were positive for NED markers, including 7 cases of Syn (+), 6 cases of ChrA (+) and 2 cases of CD56 (+). Moreover, 4 (6.8%) of 59 patients were positive for at least 2 NED markers in CRC. 18 (52.9%) of 34 gastric signer ring cell carcinoma patients were positive for NED markers, including 15 cases of Syn (+) and 14 cases of ChrA (+). Meanwhile, 10 (27.8%) of 36 gastric tubular adenocarcinoma patients were positive for NED markers, including 6 cases of Syn (+) and 10 cases of ChrA (+). Particularly, 17 (24.3%) (11/6, signer ring cell carcinoma/ tubular adenocarcinoma) of 70 GC patients were positive for at least two NED markers. Conclusions: NED is widely present in colorectal cancer and gastric cancer, especially in gastric signer ring cell carcinoma. The encouraging outcomes of the NED prevalence rate may shed light on the individualized treatments for patients with carcinomas. Further explorations are needed in the following research. [Table: see text]