The percentages of signet-ring cells (SRCs) affects the prognosis after radical gastrectomy for advanced gastric cancer.

PURPOSE: Only recently has the percentage of signet-ring cells (SRCs) been shown to affect the prognosis following gastric cancer surgery. It is uncertain whether the SRC percentage has a role in tumour biology or prognosis of gastric signet-ring cell carcinoma (GSRCC). For this research, we assessed the effect of the SRC percentage on the clinicopathological and prognostic characteristics of gastric cancer (GC) tumours and created and verified a prognostic nomogram to assess the overall survival (OS) of GSRCC patients. METHODS: In our study, 1100 GC patients with signet-ring cell carcinoma (SRCC) at Zhejiang Cancer Hospital from December 2013 to December 2018 who underwent curative gastric cancer resection were retrospectively analysed. The patients were separated into two groups: those with SRCC (SRC percentage >50%; n = 157) and those with partial signet-ring cell carcinoma (PSRCC) (SRC percentage ≤50%; n = 943). We compared the clinicopathological characteristics of both groups. To estimate OS and determine correlations with the SRC percentage, the Kaplan-Meier method and log-rank test were used. To develop the prognostic nomogram, independent prognostic indicators for OS were identified using Cox regression analyses. Predictions were assessed using the calibration curve and C-index. RESULTS: Our research showed that there was no discernible difference in OS between the two groups. The preoperative CA242 level, pT stage, pN stage, age, nerve invasion, neoadjuvant chemotherapy, postoperative chemotherapy, and maximum tumour diameter were independent prognostic risk factors for OS for GC (all p < 0.05). However, for advanced GC, the SRC percentage (HR = 1.571, 95% CI 1.072-2.302, p = 0.020) was an independent prognostic factor of OS. Other independent prognostic risk factors were age, pT stage, pN stage, nerve invasion, tumour location, neoadjuvant chemotherapy, postoperative chemotherapy, preoperative CA50 level, and preoperative CEA level (all p < 0.05). On these bases, nomograms were constructed for GC and advanced GC, with C-indexes of 0.806 (95%CI 0.782-0.830) and 0.728 (95%CI 0.697-0.759), respectively. CONCLUSIONS: In cases of advanced gastric cancer, the SRC percentage served as a standalone prognostic indicator for OS. An effective tool for assessing the prognosis of GSRCC was offered by the nomogram.

Clinicopathological characteristics of gastric neuroendocrine neoplasms: A comprehensive analysis.

OBJECTIVE: This study aimed to explore the clinicopathological characteristics and prognostic implications of gastric neuroendocrine neoplasms (g-NENs). METHODS: A retrospective enrollment of 142 patients diagnosed with g-NENs was conducted at Zhejiang Cancer Hospital between January 1, 2007 and December 31, 2021. The study compared essential clinicopathological features and survival rates. Additionally, the prognosis of gastric neuroendocrine carcinomas/mixed neuroendocrine-non-neuroendocrine neoplasms (g-NEC/MiNEN) were contrasted with those of gastric adenocarcinoma (GAC) and signet ring cell carcinoma (SRCC). RESULTS: The study comprised a total of 142 g-NENs cases, with a male-to-female ratio of approximately 2:1. The 5-year survival rates for g-NEC and g-MiNEN were 26.7% and 35.2%, respectively. Corresponding 5-year survival rates for G1 and G2 were observed at 100% and 80.0%, respectively. g-NEC/MiNEN showed a significantly worse prognosis compared to g-NET (p < 0.001). g-NEC/MiNEN exhibited a poor prognosis compared to GAC (p < 0.001), and within poorly differentiated GAC, g-NEC/MiNEN demonstrated a worse prognosis (p = 0.007). Additionally, patients receiving postoperative adjuvant therapy exhibited notably prolonged overall survival (OS) in the case of g-NEC/MiNEN (p = 0.010). CONCLUSION: In short, the prognosis of g-NEC/MiNEN was worse than that of g-NET, GAC and poorly differentiated GAC, but this group benefit from postoperative adjuvant therapy.

A retrospective study: exploring the optimal patient population for adjuvant chemotherapy after D2 gastrectomy.

BACKGROUND: Adjuvant chemotherapy (CT) constitutes the primary approach for treating resectable advanced gastric cancer (GC). However, the effectiveness of postoperative CT can differ across various patient groups. This retrospective study aimed to examine how variances in clinical and pathologic factors affect postoperative CT. METHODS: This study enrolled 2060 patients with GC who underwent curative gastrectomy at Zhejiang Cancer Hospital between January 2008 and December 2017, with 1277 receiving postoperative CT. This study used Kaplan-Meier to determine the effect of clinical and pathology factors on CT benefits. In addition, univariate and multivariate Cox regression analyses were used to identify independent prognosis risk factors. RESULTS: Both univariate and multivariate analyses demonstrated that the absence of postoperative CT is an independent factor associated with a poor prognosis in patients with GC. The Kaplan-Meier univariate analysis revealed that specific subgroups, including males, those with a normal body mass index (BMI), the elderly, individuals with gastric adenocarcinoma, cases of nerve invasion by the tumor, vascular invasion by the tumor, tumor size ≥ 5 cm, and Tumor, Node, Metastasis (TNM) stage III, exhibited improved treatment outcomes with the administration of postoperative CT. The creation of nomograms using Cox regression and the rms package holds significant clinical relevance. CONCLUSION: Postoperative CT is advantageous for prolonging the survival of advanced patients undergoing D2 gastrectomy, particularly in male patients, the elderly, individuals with a normal BMI score, those diagnosed with gastric adenocarcinoma, cases, in which the tumor invades nerves or blood vessels, patients with a tumor size of ≥5 cm, and those with a TNM stage of III, as it results in improved treatment outcomes within these subgroups.

Prognostic significance of serum tumor markers in various pathologic subtypes of gastric cancer.

PURPOSE: This study aimed to assess the utility of 6 serum tumor markers in prognosis between gastric adenocarcinoma and gastric signet ring cell carcinoma (SRCC). METHODS: A cohort of 3131 cases of gastric adenocarcinoma and 275 cases of gastric SRCC was assembled. The serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125, alpha fetoprotein (AFP), carbohydrate antigen 242 (CA242), and carbohydrate antigen 724 (CA724) were measured in all cases. The study analyzed the association between the levels of these 6 tumor markers and the prognosis of gastric adenocarcinoma and SRCC. RESULTS: The study revealed that gastric SRCC exhibited lower concentrations of CEA (P < .001) and CA19-9 (P = .002), along with reduced positive rates of CEA (P = .041), CA19-9 (P = .003), AFP (P < .001), and CA242 (P = .006), while displaying higher positive rates of CA724 (P = .024) than gastric adenocarcinoma. Nevertheless, the receiver operating characteristic curve demonstrated that serum tumor markers did not hold clinical significance in differentiating between gastric adenocarcinoma and SRCC. Survival analysis substantiated that the combined criteria of serum tumor markers stood as an independent risk factor for both gastric adenocarcinoma and SRCC. Notably, the nomogram indicated that serum tumor markers exerted a more substantial influence on the prognosis of gastric adenocarcinoma than on gastric SRCC. CONCLUSION: The study concluded that the combined criteria of serum tumor markers emerge as independent risk factors for both subtypes of gastric cancer. Furthermore, this combined approach exhibited enhanced efficacy in prognosticating the outcome of gastric adenocarcinoma compared with gastric SRCC.

Revolutionizing T3-4N0-2M0 gastric cancer staging with an innovative pathologic N classification system.

BACKGROUND: The current pathologic N (pN) classification exhibits limitations in the prognostic stratification of patients with pT3-4N0-2M0 gastric cancer (GC). Therefore, this study aimed to develop and validate a new lymph nodal staging method based on the number of examined lymph nodes (ELNs) and lymph node ratio (LNR). METHODS: Data from 7883 patients with pT3-4N0-2M0 GC were collected from the Surveillance, Epidemiology, and End Results (SEER) database and Zhejiang Cancer Provincial Hospital. Optimal cutoff values for ELNs and LNR were determined using X-tile software. Kaplan-Meier methods, Log-rank tests, and Cox regression analyses were employed in this study. Patients were categorized into 3 new pN stages: new pN0 (pN0 with ELNs of >16), new pN1 (pN0 with ELNs of ≤16 or pN1-2 with LNR of ≤0.15), and new pN2 (pN1-2 with LNR of >0.15). The prognostic predictive power of both current and new pN staging was evaluated using the Akaike information criterion (AIC), Bayesian information criterion, concordance index (C-index), and receiver operating characteristic curve. RESULTS: The new pN classification exhibited excellent performance in Kaplan-Meier survival analysis. After adjusting for confounding factors, the new pN staging emerged as an independent prognostic indicator in patients with GC. In the SEER cohort, the new pN staging demonstrated enhanced prognostic prediction accuracy over the American Joint Committee on Cancer pN staging (AIC: 75578.85 vs 75755.06; C-index: 0.642 vs 0.630; P < .001). Similar findings were validated in the Chinese cohort. CONCLUSION: This study developed and validated an improved pN classification for patients with pT3-4N0-2M0 GC. Surgeons should consider ELNs and LNR when assessing postoperative prognosis in patients with GC.

Targeting CLDN18.2 in cancers of the gastrointestinal tract: New drugs and new indications.

Cancers of the gastrointestinal (GI) tract greatly contribute to the global cancer burden and cancer-related death. Claudin-18.2(CLDN18.2), a transmembrane protein, is a major component of tight junctions and plays an important role in the maintenance of barrier function. Its characteristic widespread expression in tumour tissues and its exposed extracellular loops make it an ideal target for researchers to develop targeted strategies and immunotherapies for cancers of the GI tract. In the present review, we focus on the expression pattern of CLDN18.2 and its clinical significance in GI cancer. We also discuss the tumour-promoting and/or tumour-inhibiting functions of CLDN18.2, the mechanisms regulating its expression, and the current progress regarding the development of drugs targeting CLDN18.2 in clinical research.

A literature review on the potential clinical implications of streptococci in gastric cancer.

Streptococcus is widely found in nature and the human body, and most species are not pathogenic. In recent years, studies have found that Streptococcus is associated with gastric cancer. Streptococcus was found to be enriched in the oral cavity, stomach and intestine of gastric cancer patients and found to be increased in gastric cancer tissues, suggesting that Streptococcus may be the pathogenic bacteria underlying gastric cancer. This review discusses the discovery of Streptococcus, the relationship between Streptococcus and gastric cancer, and the possible carcinogenic mechanism of Streptococcus and summarizes the progress of the research on the role of Streptococcus in gastric cancer to provide new ideas for the early detection, diagnosis and treatment of gastric cancer.

Discovery of 6-Arylurea-2-arylbenzoxazole and 6-Arylurea-2-arylbenzimidazole Derivatives as Angiogenesis Inhibitors: Design, Synthesis and in†vitro Biological Evaluation.

We embarked on a structural optimization campaign aimed at the discovery of novel anti-angiogenesis agents with previously reported imidazole kinase inhibitors as a lead compound. A library of 29 compounds was synthesized. Several title compounds exhibited selective inhibitory activities against vascular endothelial growth factor receptor 2 (VEGFR-2) over epidermal growth factor receptor (EGFR) kinase; these compounds also displayed selective and potent antiproliferative activity against three cancer cell lines. The newly synthesized compounds were evaluated for anti-angiogenesis activity by chick chorioallantoic membrane (CAM) assay. Among them, 1-(2-(2-chlorophenyl)benzo[d]oxazol-5-yl)-3-(4-(trifluoromethoxy)phenyl)urea (compound 5 n) showed the most potent anti-angiogenesis capacity, efficient cytotoxic activities (in vitro against human umbilical vein endothelial cells (HUVEC), H1975, A549, and HeLa cell lines, with respective IC50 values of 8.46, 1.40, 7.61, and 0.28 µm), and an acceptable level of VEGFR-2 kinase inhibition (IC50 =0.25 µm). Molecular docking analysis revealed 5 n to be a type II inhibitor of VEGFR-2 kinase. In general, these results indicate that these 6-arylurea-2-arylbenzoxazole/benzimidazole derivatives are promising inhibitors of VEGFR-2 kinase for potential development into anti-angiogenesis drugs.