Positive peritoneal lavage fluid cytology based on isolation by size of epithelial tumor cells indicates a high risk of peritoneal metastasis.

Background: Peritoneal metastasis (PM) is the most prevalent type of metastasis in patients with gastric cancer (GC) and has an extremely poor prognosis. The detection of free cancer cells (FCCs) in the peritoneal cavity has been demonstrated to be one of the worst prognostic factors for GC. However, there is a lack of sensitive detection methods for FCCs in the peritoneal cavity. This study aimed to use a new peritoneal lavage fluid cytology examination to detect FCCs in patients with GC, and to explore its clinical significance on diagnosing of occult peritoneal metastasis (OPM) and prognosis. Methods: Peritoneal lavage fluid from 50 patients with GC was obtained and processed via the isolation by size of epithelial tumor cells (ISET) method. Immunofluorescence and fluorescence in situ hybridization (FISH) were used to identify FCCs expressing chromosome 8 (CEP8), chromosome 17 (CEP17), and epithelial cell adhesion molecule (EpCAM). Results: Using a combination of the ISET platform and immunofluorescence-FISH, the detection of FCCs was higher than that by light microscopy (24.0% vs. 2.0%). Samples were categorized into positive and negative groups, based on the expressions of CEP8, CEP17, and EpCAM. Statistically significant relationships were demonstrated between age (P = 0.029), sex (P = 0.002), lymphatic invasion (P = 0.001), pTNM stage (P = 0.001), and positivity for FCCs. After adjusting for covariates, patients with positive FCCs had lower progression-free survival than patients with negative FCCs. Conclusion: The ISET platform highly enriched nucleated cells from peritoneal lavage fluid, and indicators comprising EpCAM, CEP8, and CEP17 confirmed the diagnosis of FCCs. As a potential detection method, it offers an opportunity for early intervention of OPM and an extension of patient survival.

Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. BACKGROUND: Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. METHODS: Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. RESULTS: A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. CONCLUSION: Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.

IMPROVEMENT OF THE MODEL OF PREVENTION OF MALIGNANT NEOPLASM OF THE GASTRIC.

The fight against malignant neoplasms is one of the most important problems of health care in Ukraine; its relevance is due to the continuous growth of oncological morbidity in the population, the complexity of timely diagnosis and treatment, high cost, as well as quite high levels of disability and mortality of such patients. Gastric cancer, which remains one of the most common and deadly neoplasms in the world, occupies one of the leading positions among cancer. Aim - scientifically substantiate and develop a model for improving the organization of prevention of malignant neoplasms of the gastric. A study of performance indicators of oncology health care facilities and a survey of respondents was conducted: 180 respondents of patients with gastric cancer and precancerous diseases of the stomach using medical-statistical, sociological methods and questionnaires. A functional and organizational model for improving the prevention of malignant neoplasms of the stomach has been scientifically substantiated and developed. The features of the proposed model were the inclusion in it, in addition to the previously existing, innovative elements (an algorithm for early diagnosis and prevention of negative consequences of malignant neoplasms of the stomach at the level of primary medical care, reminders for primary medical care doctors regarding monitoring of risk factors and predictors of malignancy of precancerous stomach diseases, the allocation of a dynamic monitoring group due to the increased risk of precancerous gastric diseases becoming oncological), as well as previously existing, but functionally changed components (optimization of the functions of the primary care physician in relation to the information provision of the patient and his relatives; monitoring of risk factors for precancerous and cancerous stomach diseases, control and accounting for the implementation of the recommendations of specialist doctors and rehabilitation specialists), the interaction between which provided the model with a qualitatively new focus on achieving its strategic goal - preventing the occurrence and progression of the development of malignant neoplasms of the gastric. The proposed functional and organizational model will lead to a positive medical and social effect for the improvement of the organization of the prevention of gastric cancer in the main areas: systematicity, comprehensiveness and preventive direction. Its implementation will lead to an increase in early detection, coverage of dynamic monitoring of patients, as well as a projected economic effect due to a decrease in the specific weight of neglected forms of gastric cancer, improvement in survival and reduction in mortality.

Detection and Characterization of Methylated Circulating Tumor DNA in Gastric Cancer.

Gastric cancer is the fifth most common disease in the world and the fourth most common cause of death. It is diagnosed through esophagogastroduodenoscopy with biopsy; however, there are limitations in finding lesions in the early stages. Recently, research has been actively conducted to use liquid biopsy to diagnose various cancers, including gastric cancer. Various substances derived from cancer are reflected in the blood. By analyzing these substances, it was expected that not only the presence or absence of cancer but also the type of cancer can be diagnosed. However, the amount of these substances is extremely small, and even these have various variables depending on the characteristics of the individual or the characteristics of the cancer. To overcome these, we collected methylated DNA fragments using MeDIP and compared them with normal plasma to characterize gastric cancer tissue or patients' plasma. We attempted to diagnose gastric cancer using the characteristics of cancer reflected in the blood through the cancer tissue and patients' plasma. As a result, we confirmed that the consistency of common methylated fragments between tissue and plasma was approximately 41.2% and we found the possibility of diagnosing and characterizing cancer using the characteristics of the fragments through SFR and 5'end-motif analysis.

[Advances in the application of intragastric flora in the diagnosis and treatment of gastric cancer].

Gastric cancer is one of the major causes of cancer-related deaths worldwide, and infection with Helicobacter pylori and EBV, smoking and a salt-heavy diet have been shown to be risk factors for the development of gastric cancer. Currently, numerous research has demonstrated that differences in the structure of the gastric flora can be exploited to distinguish the different stages of gastric mucosal lesions and to predict the progression of gastric cancer. Therefore, a new biomarker is presented for the diagnosis of gastric cancer based on the structural differences of the gastric flora. Gastric flora has also potential in the treatment of gastric cancer. The application of non-H. pylori flora to modulate immune cells may increase the sensitivity of tumour cells for chemotherapy, improve the efficacy of immune checkpoint inhibitors and significantly prolong the survival of patients. This review of advances in the application of gastric flora in the diagnosis and treatment of gastric cancer is aimed at providing a reference and basis for future research in this field.

[Key updates and interpretation of the ninth version of AJCC staging system for neuroendocrine tumors of the stomach].

The cancer staging system of the American Joint Committee on Cancer (AJCC) is the most widely used clinical basis for tumor staging. In October 2023, AJCC released the staging system (ninth version) for the neuroendocrine tumors of stomach (NET), which has been implemented in January 2024. The ninth version of NET staging system mainly updated the histopathologic classification, diagnosis and staging methods, clinical and pathological staging, prognosis grade, tumor and non-tumor prognostic features. The update and implementation of the staging system provide a more detailed reference for the accurate diagnosis, staging and precise treatment of gastric neuroendocrine tumors. Moreover, it is convenient for clinicians to carry out clinical practice. The purpose of our article is to provide a high-level overview of the major changes in AJCC staging system (version 9) for gastric NET based on the latest evidence-based medical research.

F11R RNA trinucleotide over-edited by ADAR in gastric and colorectal cancers: Cross-cohort validation, gene expression regulation, and diagnostic significance.

The F11 receptor (F11R) gene encoding junctional adhesion molecule A has been associated with gastric cancer (GC) and colorectal cancer (CRC), in which its role and regulation remain to be further elucidated. Recently F11R was also identified as a potential target of adenosine-to-inosine (A-to-I) mediated by the adenosine deaminases acting on RNA (ADARs). Herein, using RNA-Seq and experimental validation, our current study revealed an F11R RNA trinucleotide over-edited by ADAR, with its regulation of gene expression and clinical significance in four GC and three CRC cohorts. Our results found an over-edited AAA trinucleotide in an AluSg located in the F11R 3'-untranslated region (3'-UTR), which showed editing levels correlated with elevated ADAR expression across all GC and CRC cohorts in our study. Overexpression and knockdown of ADAR in GC and CRC cells, followed by RNA-Seq and Sanger sequencing, confirmed the ADAR-mediated F11R 3'-UTR trinucleotide editing, which potentially disrupted an RBM45 binding site identified by crosslinking immunoprecipitation sequencing (CLIP-seq) and regulated F11R expression in luciferase reporter assays. Moreover, the F11R trinucleotide editing showed promising predictive performance for diagnosing GC and CRC across GC and CRC cohorts. Our findings thus highlight both the potential biological and clinical significance of an ADAR-edited F11R trinucleotide in GC and CRC, providing new insights into its application as a novel diagnostic biomarker for both cancers.

Combined detection of serum EFNA1 and MMP13 as diagnostic biomarker for gastric cancer.

We previously identified that serum EFNA1 and MMP13 were potential biomarker for early detection of esophageal squamous cell carcinoma. In this study, our aim is to explore the diagnostic value of serum EFNA1 and MMP13 for gastric cancer. We used enzyme-linked immunosorbent assay (ELISA) to detect the expression levels of serum EFNA1 and MMP13 in 210 GCs and 223 normal controls. The diagnostic value of EFNA1 and MMP13 was evaluated in an independent cohorts of GC patients and normal controls (n = 238 and 195, respectively). Receiver operating characteristics were used to calculate diagnostic accuracy. In training and validation cohorts, serum EFNA1 and MMP13 levels in the GC groups were significantly higher than those in the normal controls (P < 0.001). The area under the curve (AUC) of the combined detection of serum EFNA1 and MMP13 for GC was improved (0.794), compared with single biomarker used. Similar results were observed in the validation cohort. Importantly, the combined measurement of serum EFNA1 and MMP13 to detect early-stage GC also had acceptable diagnostic accuracy in training and validation cohort. Combined detection of serum EFNA1 and MMP13 could help identify early-stage GC, suggesting that it may be a promising tool for the early detection of GC.

Screening for oncogenic AF1q expression predicts disease recurrence in gastric cancer patients.

AF1q associates with tumor progression and metastases upon WNT signaling. The downstream WNT target CD44 has demonstrated prognostic significance in gastric cancer (GC). This study evaluates the impact of AF1q on tumor stage and survival in GC patients. Immunohistochemical marker expression was analyzed and data were processed to correlation and survival analysis. Out of 182 GC samples, 178 (97.8%) showed moderate to high AF1q expression (p < 0.001), these samples correlated with positive lymph node stage (p = 0.036). In a subgroup analysis of patients with nodal-positive GC (n = 129, 70.9%), enhanced tumoral AF1q expression resulted in impaired recurrence-free survival (RFS, p = 0.030). Enhanced tumoral CD44 expression resulted in impaired disease-specific survival (DSS) in the subgroup of patients with nodal-positive GC (p = 0.031) as well as in the overall GC group (p = 0.005). AF1q demonstrated as an independent prognostic marker for RFS (p = 0.035) and CD44 for DSS (p = 0.036). AF1q has shown potential for prognostication of RFS in GC patients and is predominantly expressed in nodal-positive GC. Testing AF1q provides a possibility of identifying patients with locoregional (and advanced) disease, particularly at risk for disease recurrence. Implementing AF1q into the diagnostic process may facilitate screening, prognosis estimation as well as consideration of preoperative multimodal treatment in patients qualifying for elective upfront surgery.

Implementing an integrated molecular classification for gastric cancer from endoscopic biopsies using on-slide tests.

The availability of more effective biological therapy can improve outcomes of gastric cancer (GC), but most patients do not have access to personalized treatment. GC molecular classification helps identify patients suitable for specific therapies and provides useful prognostic information. To date, only a small number of patients have access to molecular classification. We proposed a working molecular classification that can be delivered using on-slide tests available in most histopathology laboratories. We used eight on-slide tests [in situ hybridization (ISH) for Epstein-Barr virus-encoded small ribonucleic acid (EBER) and immunohistochemistry (IHC) for MutL homolog 1 (MLH1), PMS1 homolog 2 (PMS2), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), E-cadherin, ß-catenin and p53] to classify GC into one of six categories: GC associated with Epstein-Barr virus (GC-EBV), GC mismatch repair deficient (GC-dMMR), GC with epithelial-mesenchymal transition (GC-EMT), GC with chromosomal instability (GC-CIN), GC genomically stable (GC-GS) and GC not otherwise specified (GC-NOS)∕indeterminate. The classification has provision also for current and future on-slide companion diagnostic (CDx) tests necessary to select specific biological therapies and, as proof of principle, in this study we used three CDx tests currently required for the management of GC [human epidermal growth factor receptor 2 (Her2), programmed cell death-ligand 1 (PD-L1) 22C3 and Claudin18.2 (CLDN18.2)]. This paper describes the necessary tissue pathways and laboratory workflow and assesses the feasibility of using this classification prospectively on small endoscopic biopsies of gastric and gastroesophageal junction adenocarcinoma. This work demonstrates that such molecular classification can be implemented in the context of a histopathology diagnostic routine with little impact on turnaround times and laboratory capacity. The widespread adoption of a molecular classification for GC will help refine prognosis and guide the choice of more appropriate biological therapy for these patients.

Gastroenteropancreatic neuroendocrine tumors in children and adolescents.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare in children and adolescents. Standard management of these tumors has not been well established due to their rarity in this age group. We aimed to report the clinical and pathological characteristics of patients with this rare disease followed and treated between the years 1993-2022. MATERIALS AND METHODS: The medical records of patients with GEP-NETs were reviewed. RESULTS: Fourteen patients (11 girls, 3 boys) were diagnosed with GEP-NET. The median age was 13 (9-18) years. Tumor localization was the appendix in 12, stomach in one and pancreas in one patient. Mesoappendix invasion was detected in four patients two of whom underwent right hemicolectomy (RHC) and lymph node dissection (LND). Of those, one patient had lymph node involvement. The other two had not further operations. Somatostatin was used in one with pancreatic metastatic disease and the other with gastric disease after surgery. No additional treatment was given in other patients. All patients are under follow-up without evidence of disease at a median follow-up of 85 months (7-226 months). CONCLUSION: GEP-NETs should be considered in the differential diagnosis of acute appendicitis and in cases with persistent abdominal pain. In children, there is invariably a favorable prognosis, and additional surgical interventions other than simple appendectomies generally do not provide benefits. Mesoappendix invasion may not necessitate RHC and LND.

Extraskeletal osteosarcoma infiltrating pancreas, spleen, gastric, and left kidney: a case report.

BACKGROUND: Extraskeletal osteosarcoma is an extremely rare malignancy that accounts for 1% of soft tissue sarcoma and 4.3% of all osteosarcoma. Extraskeletal osteosarcoma can develop in a patient between the ages of 48 and 60 years. The incidence of extraskeletal osteosarcoma is slightly higher in male patients than in females. CASE PRESENTATION: A 50-year-old Caucasian male patient presented with a 6-month history of intermittent lower-left back pain that limits his activity. Prior ultrasonography and abdominal computed tomography scan showed a diagnosis of kidney stone and tumor in the lower-left abdomen. The computed tomography urography with contrast revealed a mass suspected as a left retroperitoneal malignant tumor. Hence, the tumor was resected through laparotomy and the patient continued with histopathological and immunohistochemistry examination with the result of extraskeletal osteosarcoma. CONCLUSION: Extraskeletal osteosarcoma presents diagnostic challenges requiring multimodal examination, including histological and immunohistochemistry analyses. This case underscores the aggressive nature and poor prognosis despite undergoing the current suggested treatment.

Real-World Application of Artificial Intelligence for Detecting Pathologic Gastric Atypia and Neoplastic Lesions.

PURPOSE: Results of initial endoscopic biopsy of gastric lesions often differ from those of the final pathological diagnosis. We evaluated whether an artificial intelligence-based gastric lesion detection and diagnostic system, ENdoscopy as AI-powered Device Computer Aided Diagnosis for Gastroscopy (ENAD CAD-G), could reduce this discrepancy. MATERIALS AND METHODS: We retrospectively collected 24,948 endoscopic images of early gastric cancers (EGCs), dysplasia, and benign lesions from 9,892 patients who underwent esophagogastroduodenoscopy between 2011 and 2021. The diagnostic performance of ENAD CAD-G was evaluated using the following real-world datasets: patients referred from community clinics with initial biopsy results of atypia (n=154), participants who underwent endoscopic resection for neoplasms (Internal video set, n=140), and participants who underwent endoscopy for screening or suspicion of gastric neoplasm referred from community clinics (External video set, n=296). RESULTS: ENAD CAD-G classified the referred gastric lesions of atypia into EGC (accuracy, 82.47%; 95% confidence interval [CI], 76.46%-88.47%), dysplasia (88.31%; 83.24%-93.39%), and benign lesions (83.12%; 77.20%-89.03%). In the Internal video set, ENAD CAD-G identified dysplasia and EGC with diagnostic accuracies of 88.57% (95% CI, 83.30%-93.84%) and 91.43% (86.79%-96.07%), respectively, compared with an accuracy of 60.71% (52.62%-68.80%) for the initial biopsy results (P<0.001). In the External video set, ENAD CAD-G classified EGC, dysplasia, and benign lesions with diagnostic accuracies of 87.50% (83.73%-91.27%), 90.54% (87.21%-93.87%), and 88.85% (85.27%-92.44%), respectively. CONCLUSIONS: ENAD CAD-G is superior to initial biopsy for the detection and diagnosis of gastric lesions that require endoscopic resection. ENAD CAD-G can assist community endoscopists in identifying gastric lesions that require endoscopic resection.

A dual-gene panel of two fragments of methylated IRF4 and one of ZEB2 in plasma cell-free DNA for gastric cancer detection.

Early detection is crucial for increasing the survival rate of gastric cancer (GC). We aimed to identify a methylated cell-free DNA (cfDNA) marker panel for detecting GC. The differentially methylated CpGs (DMCs) were selected from datasets of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The selected DMCs were validated and further selected in tissue samples (40 gastric cancer and 36 healthy white blood cell samples) and in a quarter sample volume of plasma samples (37 gastric cancer, 12 benign gastric disease, and 43 healthy individuals). The marker combination selected was then evaluated in a normal sample volume of plasma samples (35 gastric cancer, 39 control diseases, and 40 healthy individuals) using real-time methylation-specific PCR (MSP). The analysis of the results compared methods based on 2-ΔΔCt values and Ct values. In the results, 30 DMCs were selected through bioinformatics methods, and then 5 were selected for biological validation. The marker combination of two fragments of IRF4 (IRF4-1 and IRF4-2) and one of ZEB2 was selected due to its good performance. The Ct-based method was selected for its good results and practical advantages. The assay, IRF4-1 and IRF4-2 in one fluorescence channel and ZEB2 in another, obtained 74.3% sensitivity for the GC group at any stage, at 92.4% specificity. In conclusion, the panel of IRF4 and ZEB2 in plasma cfDNA demonstrates good diagnostic performance and application potential in clinical settings.

Diagnostic Usefulness of p53 Immunostaining in Gastric Cancer and Dysplasia: A Real-world Clinical Experience.

BACKGROUND/AIM: Gastric cancer and its precancerous lesions represent a significant public health concern. A subset of gastric cancers exhibits mutations in the TP53 gene, often accompanying distinctive morphologic alterations. This study aimed to assess the diagnostic efficacy of p53 immunostaining in real-world clinical settings. PATIENTS AND METHODS: A retrospective analysis was conducted on 50 cases of gastric tumors and tumor-like lesions, wherein p53 immunostaining played a pivotal diagnostic role. The staining pattern of p53 was examined in conjunction with clinicopathologic parameters. RESULTS: Mutant p53 staining pattern demonstrated a significant association with high-grade nuclear atypia (p<0.001), high-grade dysplasia, and tubular adenocarcinoma (p<0.001), as well as microsatellite instability status (p=0.034). Furthermore, the diagnostic utility of p53 immunostaining was evident in scenarios where: 1) biopsy specimens contained few tumor cells, 2) pathologic evaluation of resection margins was limited by cauterization artifacts, and 3) distinction between low-grade and high-grade gastric dysplasia was challenging. CONCLUSION: P53 immunostaining can be helpful for the diagnosis of gastric tumor and tumor-like lesions, and accurate pathologic margin evaluation, particularly in lesions demonstrating intestinal-type differentiation and some degree of nuclear atypia.

Gastric Metastasis Mimicking Early Gastric Cancer from Invasive Ductal Carcinoma of the Breast: Case Report and Literature Review.

Backgound and Objectives: Gastric metastasis from invasive ductal breast cancer (BC) is rare. It mainly occurs in patients with lobular BC. The occurrence of multiple metastases is typically observed several years after the primary diagnosis. Endoscopic findings of gastric metastasis of the BC were usually the linitis plastic type. Case presentation: A 72-year-old women who underwent right modified radical mastectomy (MRM) 10 month ago was referred after being diagnosed with early gastric cancer (EGC) during systemic chemotherapy. EGC type I was found at gastric fundus, and pathologic finding showed poorly differentiated adenocarcinoma. Metachronous double primary tumor EGC was considered. Management and Outcome: A laparoscopic total gastrectomy was performed, and postoperative pathology revealed submucosa invasion and two lymph node metastases. A pathologic review that focused on immunohistochemical studies of selected antibodies such as GATA binding protein 3 (GATA3), gross cystic disease fluid protein-15 (GCDFP-15), cytokeratin 7 (CK7) was performed again, comparing previous results. As a result, gastric metastasis from BC was diagnosed. After totally laparoscopic total gastrectomy, palliative first-line chemotherapy with paclitaxel/CDDP was performed. Two months after gastrectomy, she was diagnosed with para-aortic lymph node metastasis and multiple bone metastases. She expired six months after gastrectomy. Conclusions: Gastric metastasis from invasive ductal carcinoma of the breast, which is clinically manifested as EGC, is a very rare condition. If there is a history of BC, careful pathological review will be required.